2015 ARS Supplement

Transcription

2015 ARS Supplement

A Supplement to:
PERSPECTIVES ON THE TREATMENT OF HEMATOLOGIC AND SOLID MALIGNANCIES
April 2015 | Volume 29 • Supplement No. 1
For ONCOLOGY online, go to
ONCOLOGY • APRIL 2015 • VOLUME 29 • SUPPLEMENT NUMBER 1
Integrating High-Tech
With High-Touch
in Radiation Oncology
Program Abstracts From the 97th Annual
Meeting of the American Radium Society
Kenneth E. Rosenzweig, MD, President
Mount Sinai School of Medicine, Department of Radiation Oncology,
New York, New York
Benjamin Movsas, MD, Chair, Scientific Program Committee
Henry Ford Hospital, Department of Radiation Oncology,
Detroit, Michigan
cancernetwork.com
SUPPORTED BY
THE AMERICAN
RADIUM SOCIETY
GRAND HYATT KAUAI
KAUAI, HAWAII
MAY 2–5, 2015
Committees of the ARS
EXECUTIVE COMMIT TEE
Kenneth E. Rosenzweig, MD, President
John “Drew” Ridge, MD, PhD, President-Elect
Ben J. Slotman, MD, PhD, Secretary
Quynh-Thu Le, MD, Treasurer
Kaled M. Alektiar, MD, Industry Relations Chair Kenneth B. Roberts, MD, Member-at-Large
Beth M. Beadle, MD, Member-at-Large
Benjamin Movsas, MD, 2015 SPC Chair
Elin R. Sigurdson, MD, PhD, Immediate Past President
2014-2015
2014-2015
2014-2015
2014-2015
2014-2015
2013-2015
2014-2016
2014-2015
2014-2015
CONSTITUTION AND BY-LAWS COMMIT TEE
Lynn D. Wilson, MD, MPH (Chair)2014-2017
Elin Sigurdson, MD, PhD (Ex officio)
Kenneth Russell, MD
2012-2015
2014-2016
Erich Sturgis, MD, MPH
EDUCATIOn and website RESOURCES COMMIT TEE
Jonathan J. Beitler, MD (Co-Chair) Elin R. Sigurdson, MD, PhD (Ex officio)
Roy Decker, MD
Jim Wallace, MD
Mike Kupferman, MD
David Wazer, MD
Peter A.S. Johnstone, MD
Cynthia Ballenger, MD
2014-2017
2014-2017
2012-2015
2014-2017
2012-2015
2014-2016
2014-2017
INDUSTRY RELATIONS/DEVELOPMENT COMMIT TEE
Kaled M. Alektiar, MD (Chair)2014-2015
Elin R. Sigurdson, MD, PhD (Ex officio)
Alan Pollack, MD, PhD
2012-2016
Sue S. Yom, MD, PhD
2014-2018
2015-2019
Meena S. Moran, MD
JANEWAY LECTURE COMMIT TEE
WEBSITE AND PUBLIC RELATIONS COMMIT TEE
Jonathan J. Beitler, MD (Chair)2011-2014
Thomas A. Buchholz, MD (Ex officio)
David Wazer, MD
2012-2015
2010-2013
John Ward, MD
Cynthia Ballenger, MD
2011-2014
SCIENTIFIC PROGRAM COMMIT TEE
Benjamin Movsas, MD (Program Chair)
Kenneth E. Rosenzweig, MD (President)
Matthew C. Abramowitz, MD
Beth M. Beadle, MD, PhD
Thomas A. Buchholz, MD
Todd J. Carpenter, MD
Indrin Chetty, PhD
Ted DeWeese, MD
Mohamed Elshaikh, MD
Mary Feng, MD
Thomas Galloway, MD
Mary K. Hayes, MD
Mark A. Henderson, MD
Joe Herman, MD
Andre Konski, MD, MBA, MA, FACR
W. Robert Lee, MD
Stella Ling, MD
Rahul R. Parikh, MD, PhD
Alan Pollack, MD, PhD
John "Drew" Ridge, MD, PhD
Kenneth Roberts, MD
Elin R. Sigurdson, MD, PhD
Charles B. Simone, II, MD
Jean Wright, MD
Sue S. Yom, MD, PhD
rePRESENTATIVE TO THE BOARD OF CHANCELLORS OF
THE AMERICAN COLLEGE OF RADIOLOGY
J. Frank Wilson, MD (Chair)2012-2015
John “Drew” Ridge, MD, PhD
2014-2015
2014-2017
MEMBERSHIP AND CREDENTIALS COMMIT TEE
Dr. James D. Cox, MD
Ben J. Slotman, MD (Chair)
Mack Roach, III, MD
Kelly K. Hunt, MD Erich Sturgis, MD, MPH
Quynh-Thu Le, MD
Meena S. Moran, MD
Matthew C. Abromowitz, MD
Arnold Paulino, MD
NOMINATING COMMIT TEE
Jay S. Cooper, MD
Sue S. Yom, MD, PhD Kenneth Russell, MD
2014-2016
2014-2017
The UICC Global Task Force on Radiotherapy
for Cancer Control (GTFRCC)
2013-2015
AMERICAN COLLEGE OF RADIOLOGY COUNCILOR
2012-2015
2014-2016
2012-2015
2014-2016
2014-2017
2014-2017
2012-2015
Andre Konski, MD 2012-2015
2014-2016
2014-2017
REPRESENTATIVE TO THE NATIONAL COUNCIL ON
RADIATION PROTECTION & MEASUREMENTS
RESIDENT AND AT TENDING EDUCATIONAL COMMIT TEE
Jeffrey Michalski, MD Elin R. Sigurdson, MD, PhD (Ex officio)
Ashesh B. Jani, MD Joe Herman, MD
2014-2015
2012-2015
2014-2017
2014-2017
2012-2015
AMERICAN COLLEGE OF RADIOLOGY ASSISTANT
COUNCILOR
Martin Colman, MD
2014-2015
REPRESENTATIVE TO THE COMMISSION ON CANCER
John “Drew” Ridge, MD, PhD
Ritsuko Komaki, MD 2012-2015
2014-2017
TRUSTEES OF THE AMERICAN BOARD OF RADIOLOGY
Lynn Wilson, MD
Kaled Alektiar, MD
2011-2015
2013-2017
New Membership Application
AMERICAN RADIUM SOCIETY
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ii 2016 CAll foR AbstRACts
The American Radium Society invites you and your colleagues to participate in the
ARS 98th Annual Meeting
April 16–19, 2016
Hilton Philadelphia
at Penn’s Landing
Philadelphia, PA
President: John “Drew” Ridge, MD, PhD
Program Chair: W. Robert Lee, MD
CALL FOR ABSTRACTS All authors who wish to present papers for the ARS 98th Annual
Meeting may submit an abstract online starting in summer 2015. Abstracts may be selected
for either oral or poster presentations.
Deadline for submission is November 2015.
We encourage everyone to submit an abstract, whether or not you are a member of the
ARS. Visit www.americanradiumsociety.org/abstracts for more information and complete
submission instructions.
Original contributions should be submitted for consideration; any work that has already
been accepted for publication or previously presented is not eligible.
For more information, please visit www.americanradiumsociety.org
or contact the ARS office: 11300 West Olympic Blvd, suite 600 | Los Angeles, CA 90064
Travel Grants and Essay Awards:
Trainees who submit a completed manuscript, dealing with subjects related to clinical, translational or basic research, by November 2015, are eligible for the Young Oncologist Essay Awards.
These awards provide an honorarium of $500 plus reimbursement up to $2,000 for travel. Young
Oncologist Travel Grants of $1,000 will also be available for outstanding abstracts that are reviewed favorably for presentation at the Annual Meeting.
Phone: (310) 437-0581 | Fax: (310) 437-0585 | Email: [email protected] |
Twitter: @RadiumSociety | Facebook: www.facebook.com/AmericanRadiumSociety
American Radium Society Scientific Papers and Posters 2015
SCIENTIFIC PAPERS
(S001) Tumor Control and Toxicity Outcomes for Head
and Neck Cancer Patients Re-Treated With IntensityModulated Radiation Therapy (IMRT)—A Fifteen-Year
Experience (S002) Prognostic Value of Intraradiation
Treatment FDG-PET Parameters in Locally
Advanced Oropharyngeal Cancer Erqi L. Pollom, MD, Jie Song, PhD, Madhu Sudhan, Benjamin Y. Durkee,
Sonya Aggarwal, BA, Rie von Eyben, Timothy T. Bui, BS, Ruijiang Li, PhD,
Billy Loo, Quynh-Thu X. Le, Wendy Y. Hara, MD; Stanford University
Vinita Takiar, MD, PhD, Dominic Ma, BS, Adam S. Garden, MD, Beth
M. Beadle, MD, PhD, Clifton D. Fuller, MD, PhD, Gary B. Gunn, MD,
William H. Morrison, MD, David I. Rosenthal, MD, Jack Phan, MD,
PhD; UT MD Anderson Cancer Center
BACKGROUND: To determine whether fluorodeoxyglucose (FDG)
positron emission tomography (PET) parameters measured at an
early time point during radiation for locally advanced oropharyngeal cancer (OPC) correlate with outcomes.
PURPOSE AND OBJECTIVES: The probability of locoregional failure
after definitive treatment for cancers in the head and neck (H&N)
area approaches 50%, with 80% of such failures occurring within
previously high-dose–treated radiation volumes, within 2 years of
treatment. Historically, H&N cancers arising in previously irradiated volumes were rarely re-treated with radiotherapy due to toxicity concerns. With improved precision in planning and delivery,
re-irradiation is now used with greater frequency. Here, we review
and analyze our 15-year institutional experience using only intensity-modulated radiation therapy (IMRT) to treat previously irradiated H&N carcinoma.
METHODS: Patients with stage III–IVB, intact OPC who were treated with definitive radiation with curative intent were included in
this study if they underwent both pre- and midtreatment PETcomputed tomography (CT) planning scans in our department. The
treatment-planning CT was registered with the PET from the same
session, and the metabolic tumor volume (MTV) was extracted
from within the primary and nodal tumor volumes contoured by
the treating physician. MTV was defined as the volume with standardized uptake value (SUV) > 2.5. MTV velocity was defined as the
difference between pre- and midtreatment nodal MTV divided by
time elapsed between these two scans. Extraction of imaging features was performed using MATLAB. MATERIALS AND METHODS: We retrospectively reviewed the
records of 227 patients who were re-irradiated to the H&N using
IMRT between 1999 and 2014. Radiation-related acute and late toxicity, including events requiring hospitalization or urgent intervention and death were recorded. Outcome variables included gender,
age, surgery, chemotherapy, radiotherapy dose, radiotherapy volume, and time between initial irradiation and re-irradiation. RESULTS: A total of 206 patients (91%) were treated with definitive
intent. Of them, 104 patients (50%) underwent salvage resection
and 136 patients (66%) received chemotherapy. Median follow-up
after re-irradiation for definitely treated patients was 24.7 months.
The 5-year rates of locoregional control, progression-free survival,
and overall survival for definitively treated patients were 54%, 25%,
and 39%, respectively. Actuarial rates of grade ≥ 3 toxicity were 32%
at 2 years and 48% at 5 years, with dysphagia or odynophagia requiring feeding tube placement representing the most common toxicity
of grade ≥ 3. On multivariate analysis, concurrent chemotherapy
and retreatment site influenced tumor control, whereas response to
induction chemotherapy and initial disease site influenced survival.
High-dose clinical tumor volume (CTV1) > 50 cc and concurrent
chemotherapy were significantly associated with increased grade ≥
3 toxicity. Notably, patients who were treated to a CTV1 < 25 cc
experienced no grade ≥ 3 toxicity.
CONCLUSIONS: Re-irradiation for H&N cancers with IMRT and
concurrent chemotherapy results in promising local control and
survival outcomes in selected patients. Treatment-related toxicity
continues to be significant despite improvements in systemic therapy and radiation dose conformality, warranting careful patient
selection and target volume delineation.
RESULTS: In total, 60 patients who fulfilled the inclusion criteria
were treated from February 2009 to January 2014 at Stanford.
Median age was 59 years (range: 27–83 yr). The p16 status was positive in 51 patients, negative in 8 patients, and unknown in 1 patient.
Nine patients received induction chemotherapy, and 59 patients
received concurrent chemotherapy (cisplatin: n = 26; cetuximab: n
= 25; carboplatin: n = 8). A total of 25 patients had a > 10-year
smoking history. Patients were treated to a median dose of 70 Gy (range: 63.6–70 Gy,
in 30–35 fractions). Patients underwent a planning PET at a median
of 11 days (range: 2–26 d) prior to radiation start and an intratreatment planning PET after receipt of a median of 16 fractions (range:
10–22 fractions).
Median pretreatment MTVs for the entire cohort at the primary,
nodal, and combined primary and nodal sites were 16.7 cc (range:
0.9–143.0 cc), 11.5 cc (range: 0–195.1 cc), and 32.7 cc (range: 2.0–
225.2 cc), respectively. Median intratreatment MTVs for the entire
cohort at the primary, nodal, and combined primary and nodal sites
were 7.6 cc (range: 0.4–150.2 cc), 3.8 cc (range: 0–95.6 cc), and 14.7
cc (range: 0.3–150.2 cc), respectively. Median follow-up was 17 months (range: 2–63 mo). One-year overall survival was 98%. Age, smoking status, chemotherapy, and stage
did not predict for survival. For the entire cohort, there was a trend
for worse survival with less metabolic response, as measured by
MTV velocity (P = .09; hazard ratio [HR] = 1.6). Within the p16+
patients, less metabolic response at the combined primary and nodal
sites was a significant predictor for worse survival (P = .03; HR = 2.2).
CONCLUSION: Metabolic response during radiotherapy predicts for
survival in p16+ OPC patients and may help in risk stratification of
these patients for potential treatment de-intensification.
1
(S003) Weekly IGRT Volumetric Response Analysis as
a Predictive Tool for Locoregional Control in Head and
Neck Cancer Radiotherapy (S004) Combination of Radiotherapy and Cetuximab for
Aggressive, High-Risk Cutaneous Squamous Cell Cancer
of the Head and Neck: A Propensity Score Analysis Raj Davuluri, MD, Jeff Krase, PharmD, Michael K. Cheung, MD, Brian
N. Allen, MS, Sun K. Yi, MD; Department of Radiation Oncology, University of Arizona Cancer Center
Joshua D. Palmer, MD, Jon Strasser, MD, Michael Dzeda, MD, Neil
Hockstein, MD, Charles Schneider, MD, Adam Raben, MD; Sidney Kimmel Medical College of Thomas Jefferson University; Helen F. Graham
Cancer Center of Christiana Care Health System
INTRODUCTION: Organ-preserving chemoradiation (CRT) has
become standard of care for head and neck squamous cell carcinoma (HNSCC). Volumetric image-guided radiotherapy (IGRT),
though primarily utilized for daily setup precision, may also allow
for treating physicians to evaluate disease response throughout
therapy. In other disease sites, such as lung, IGRT-measured tumor
response has been found to be predictive of oncologic outcome. To
our knowledge, no such study has been performed in patients treated for HNSCC.
METHODS: After institutional review board (IRB) approval, patients
who were treated definitively with CRT for stage III–IV HNSCC on
TomoTherapy (Madison, WI) with daily megavoltage cone-beam
computed tomography (MVCT) IGRT were retrospectively
reviewed for volumetric response. A resident physician (RD), alongside an expert HN radiation oncologist (SY), contoured identifiable
disease on representative weekly imaging while blinded to patient
outcome. Response was measured against formal posttreatment
clinical, radiological, and/or histological assessment. Data were
stratified according to primary site or largest nodal disease. Student
t-test was utilized to compare percent volume reduction in those
with recurrence vs those without recurrence.
RESULTS: Thirty-five patients were identified with a median followup of 15.8 months. Fifty-six percent of patients were HPV-positive,
and 67% was oropharyngeal, 12% was laryngeal, 9% was hypopharyngeal, and 6% was nasopharyngeal in origin. Twenty-six percent
of patients were T4, 26% was T3, 21% was T2, and 17% was T1.
Twelve percent of patients were N3, 65% was N2, 6% was N1, and
11% was N0. Eighty-five percent of patients had stage IV disease,
and 15% had stage III disease. The median dose to gross disease was
70 Gy in 35 fractions. A total of 6 recurrences at a median follow-up
of 8 months [range: ] were identified. Mean percent volume of disease at the end of treatment for those with recurrence vs those without recurrence was significantly different (31% vs 6%; P = .001). For
primary tumors, the difference in mean residual disease was 20% vs
5% (P = .005) for recurrences vs nonrecurrences, respectively. For
nodal disease, the difference in mean residual disease was 47% vs
6% (P = .0001) for recurrences vs nonrecurrences, respectively.
When percent residual disease was less than 30% of original volume,
the positive predictive value, negative predictive value, sensitivity,
and specificity were 100%, 93%, 66%, and 100%, respectively.
CONCLUSIONS: Assessment of volumetric IGRT disease response
for HNSCC that is treated with definitive CRT is valuable for predicting disease control. Patients with less than 70% volume reduction should be considered for early surgical intervention.
2
BACKGROUND: Locally advanced, high-risk cutaneous squamous
cell carcinoma (CSCC) of the head and neck is typically aggressive
and treated with combined modality therapy. These patients tend to
be older and frail, with multiple comorbidities, which makes chemotherapy difficult to tolerate. Cetuximab is a monoclonal antibody
against the epidermal growth factor (EGF) receptor and has demonstrated activity in CSCC. We investigate the safety and preliminary efficacy of combined therapy in advanced, high-risk CSCC
with the addition of cetuximab.
METHODS: Patients who were identified with locally advanced CSCC
with high-risk or very-high-risk features were treated with cetuximab
and radiotherapy between 2006 and 2013. A matched cohort over the
same time period was identified that was treated with radiation.
Propensity score analysis was performed with weighted factors, including Charlson comorbidity index score (age-adjusted), age, Karnofsky
performance status (KPS), primary location, T and N stage, recurrent
status, margin status, lymphovascular space invasion (LVSI), perineural invasion (PNI), and grade. Overall survival (OS), progression-free
survival, and freedom from local or distant recurrence were evaluated
with the Kaplan-Meier method for both the unadjusted and propensity score-adjusted groups. Multivariate analysis was performed using
Cox proportional hazard models.
RESULTS: A total of 29 patients were in the cetuximab group, and 39
were in the control group. Median follow-up for living patients was
30 months. Patients in the cetuximab group were more likely to have
advanced N stage, positive margins, and recurrent disease. After
matching of propensity scores, the groups were well balanced. OS
was not statistically significantly different between the two groups,
but there were approximately 20% more long-term survivors in the
cetuximab group after matching, with 80% vs 61% surviving at 4
years. Local control rate was 76% and 79% in the cetuximab and
control groups, respectively. The rate of distant metastases was lower
in the cetuximab group (6.8% vs 10%). The incidence of grade 2–3
toxicity was 41% in the cetuximab group. There was one grade 3
toxicity (cetuximab-induced acneiform rash), one grade 4 toxicity
(dysphagia), and no grade 5 toxicity.
CONCLUSIONS: Although limited by small numbers, we found that
there were more long-term survivors and less distant metastasis in
the cetuximab group. This is the largest report of CSCC patients
treated with cetuximab. In the absence of prospective data, we
believe that these data reveal that the addition of cetuximab is well
tolerated and reveal signs of efficacy in this typically poorly performing group of patients and should be pursued in clinical trials.
(S005) Radiotherapy for Carcinoma of the Hypopharynx
Over Five Decades: Experience at a Single Institution Julian Johnson, MD, Stephen Shiao, MD, PhD, Vivian Weinberg, PhD,
Jeanne Quivey, MD, Sue Yom, MD, PhD; University of California, San
Francisco; Cedars Sinai
BACKGROUND AND PURPOSE: To determine the effect of treat-
ment decade and utilization of intensity-modulated radiation therapy (IMRT) on locoregional control and overall survival in patients
with squamous cell carcinoma of the hypopharynx.
METHODS: Between 1962 and 2008, 116 patients with squamous
cell carcinoma of the hypopharynx underwent definitive radiotherapy. We retrospectively reviewed our experience treating these
patients with radiotherapy (IMRT, 3-dimensional conformal radiotherapy [3DCRT], intraoperative radiotherapy [IORT], and external
beam radiation therapy [EBRT]). This report focuses on the pattern
of locoregional control, overall survival, and toxicity rates over the
study period. RESULTS: Median follow-up duration from diagnosis was 17 months
(range: < 2–441 mo). The 2-year estimates of overall survival and
locoregional control were 41% (95% confidence interval [CI], 32%–
50%) and 55% (95% CI, 44%–65%), respectively. The 5-year estimates
of overall survival and locoregional control for the entire patient population were 25% (95% CI, 17%–33%) and 49% (95% CI, 37%–60%),
respectively. The median overall survival for all patients was 18.3
months (range: 2–441 mo). With respect to treatment type, the median overall survival with EBRT was 13.8 months, 20.1 months for
3DCRT, and 37.8 months for IMRT (log-rank test: P = .04). Median
overall survival estimates by decade were not statistically significantly
different: 10.5 months for 1960–1969, 11.3 months for 1970–1979, 18.2
months for 1980–1989, 17.0 months for 1990–1999, and 37.8 months
for 2000–2010 (P = .22). There was a trend for improved locoregional
control comparing post-1980 treatment to pre-1980 treatment (P =
.09) but not for overall survival (P = .52). Treatment with chemotherapy was increasingly more common over the 5 decades studied (P <
.001) but did not impact locoregional or survival control (P = .69).
Having surgery did not impact overall survival (P = .28) but improved
locoregional control, resulting in 2-year and 5-year estimates of 66% vs
48% and 60% vs 41%, respectively (P = .045). The frequency of grade
≥ 3 mucositis decreased over time by decade (P = .01), whereas dysphagia did not. Data on xerostomia were not consistently recorded. CONCLUSIONS: With similar 10-year follow-up, there is a trend for
improved locoregional control if treated as of 1980. Our data suggest
that overall survival is longer for patients treated with IMRT. Our
data also suggest that toxicity from mucositis has declined over time.
The current study lends further support to the body of evidence
suggesting that in contrast to squamous cell carcinoma of the larynx, overall survival is improving for patients with squamous cell
carcinoma of the hypopharynx. (S006) Impact of Delays to Adjuvant Radiation Therapy
on Survival in Squamous Cell Carcinoma of the Oral
Cavity and Oropharynx Erik Liederbach, BS, Carol M. Lewis, MD, MPH, Chi-Hsiung Wang,
PhD, Arif Shaikh, MD, Mihir K. Bhayani, MD; Department of Surgery,
Center for Biomedical Research Informatics, Department of Radiation
Oncology, Department of Head and Neck Surgery, NorthShore University
HealthSystem; Department of Head and Neck Surgery, UT MD Anderson
Cancer Center
INTRODUCTION: Few studies have analyzed how treatment delays
to postoperative radiation therapy (RT) for oropharynx and oral
cavity squamous cell carcinoma (OSCC) affect overall survival (OS).
This study investigates time intervals from surgery to RT using the
National Cancer Data Base (NCDB).
METHODS: Utilizing the NCDB, we selected 14,058 stage I–IV
OSCC patients (4,786 oropharynx, 9,272 oral cavity) treated with
surgery and RT from 1998 to 2011. Patients who received neoadjuvant radiation or chemotherapy, adjuvant chemotherapy, and biopsy alone were excluded. Analysis of Variance (ANOVA) and Cox
proportional hazard models were utilized. Patients were categorized
into four delay groups based on their time from surgery to RT initiation (group 1: ≤ 30 d, group 2: 31–60 d, group 3: 61–90 d, and
group 4: > 90 d).
RESULTS: The median age was 59 years (range: 18–90 yr), and
9,570 (68.1%) of patients were male. Half of the patients (51.2%)
were treated at academic/research facilities. The overall median
time from surgery to initiation of adjuvant RT increased from 42
days in 1998 to 52 days in 2011 (P < .001). In 2010–2011, stage I
patients on average received RT 11 days earlier than stage IV
patients (41 d vs 52 d; P = .007), and patients with no insurance
waited 6 days longer compared to patients with private insurance
(55 d vs 49 d; P < .001). Patients treated at academic/research hospitals experienced longer delays compared to patients treated at
community hospitals (51 d vs 44 d; P = .028), and those treated in
the Middle Atlantic region waited the longest for RT (57 d) compared to the West South Central region (42 d; P < .001). There
were no significant delays identified among age groups, races, and
genders. Between 1998 and 2006, there were 9,677 (68.8%) patients
available for survival analysis, who had a median follow-up of 3.7
years (range: 1–13 yr). The unadjusted 5-year OS rates for each
group were 53.0% for group 1, 48.4% for group 2, 44.3% for group
3, and 36.0% for group 4 (P < .001). After adjusting for patient,
facility, and tumor factors, survival was significantly reduced in
group 3 (hazard ratio [HR] = 1.17; 95% confidence interval [CI],
1.06–1.29; P < .001) and group 4 (HR = 1.35; 95% CI; 1.19–1.54; P
< .001) compared to group 1. Patients who started RT in group 2
had equivalent survival to group 1.
CONCLUSIONS: Delays to adjuvant RT > 60 days increased mortality by 17% to 35% compared to patients treated earlier. Current
efforts should be focused on timely delivery of care, and further
investigation into factors associated with delays is necessary.
(S007) Intensity of Follow-Up After Radiotherapy for
HPV-Positive Oropharyngeal Cancer Jessica M. Frakes, MD, Stephanie Demetriou, BS, Tobin Strom, MD,
Jeffrey Russell, MD, PhD, Julie A. Kish, MD, Judith McCaffrey, MD,
Kristen Otto, Tapan Padhya, MD, Andy Trotti, MD, Jimmy J. Caudell,
MD, PhD; Moffitt Cancer Center; Florida Atlantic University
3
PURPOSE AND OBJECTIVES: According to the American Cancer
Society, human papilloma virus-positive (HPV+) oropharynx cancer is an epidemic. Fortunately, outcomes for these patients with
radiotherapy +/− chemotherapy are excellent. We reviewed our
institutional experience with HPV+ oropharynx cancer to determine the time to recurrence or to grade ≥ 3 toxicities to better define
an optimal follow-up schedule.
MATERIALS AND METHODS: An institutional database of patients
with head and neck cancer seen between 2006–2014 was queried,
and 232 patients with a biopsy-proven diagnosis of nonmetastatic
HPV+ oropharynx squamous cell carcinoma were identified with at
least 6 months of follow-up. Charts were reviewed to capture
patients’ tumor, treatment, toxicity, and outcome information.
Recommended follow-up was every 3 months in the first year, every
4 months in Year 2, and every 6 months in Years 3–5. Locoregional
control (LRC), distant control (DC), and overall survival (OS) were
calculated according to the Kaplan-Meier (KM) method from the
end of treatment.
RESULTS: Median follow-up of all patients was 33 months (range:
6–99 mo). Based on Radiation Therapy Oncology Group [RTOG]
0129 risk stratification, 162 patients (70%) were low-risk and 70
(30%) were intermediate-risk. Concurrent systemic therapy was
utilized in 85% of patients (n = 196). Three-year LRC, DC, and OS
rates were 94%, 91%, and 91%, respectively. Late grade ≥ 3 toxicity
occurred in 9% (n = 21) of patients. There were a total of 19 grade 3
toxicities (most commonly feeding tube) and 2 grade 4 toxicities
(tracheostomy), with resolution in 15 patients and 1 patient, respectively, at time of last follow-up. Overall, local, regional, or distant
relapse or grade ≥ 3 toxicity occurred in 27 patients (68% of all
events) within the first 6 months. Subsequently, there were very few
events at each time point over 48 months (< 2% at each time point).
As expected, recurrence or toxicity events were more common in
the intermediate-risk group, while the time to an event was most
likely to occur within the first 6 months after therapy.
CONCLUSIONS: Following radiotherapy +/− chemotherapy for
HPV+ oropharynx cancer, there is a low risk of disease recurrence
or late grade ≥ 3 toxicity. As most events occur within 6 months of
treatment completion, it may be reasonable to reduce the intensity
of follow-up appointments to an every-6-month basis beyond this
window.
(S008) The Impact of HPV, HIV, and Smoking on
Oncologic and Functional Outcomes in Patients With
Head and Neck Cancer Waleed F. Mourad, Kenneth S. Hu, Catherine Concert, Daniel Shasha,
Louis B. Harrison; Beth Israel Medical Center
OBJECTIVES: To report the clinical outcomes and the impact of
HPV, HIV, and smoking on patients with head and neck cancer
(HNC).
MATERIALS AND METHODS: This is a single-institution retrospective study of 105 HIV+ pts with HNC treated from 1998–2013. The
median age at radiation therapy (RT) and HIV diagnosis was 51
years (range: 32–72 yr) and 34 (range: 25–50 yr), respectively. HIV
4
duration was 11 years (range: 6–20 yr). A total of 22%, 27%, and
51% had stage I-II, III, and IV disease, respectively. A total of 37%
were treated with RT alone, while 63% received concurrent chemoradiation (CRT), and 50% of patients were on highly active antiretroviral therapy (HAART) during treatment. A total of 34 patients
had oropharyngeal squamous cell carcinoma (SCC) and metastases
of unknown primary origin, 50% of whom were HPV+. Median
doses of 70, 63, and 54 Gy were delivered at 1.8–2-Gy/fraction to
gross disease and high- and low-risk neck, respectively. Twelve
patients underwent neck dissection for N3 disease.
RESULTS: Acute skin desquamation and mucositis grade ≤ 2 and 3
rates were 70% and 30%, respectively. Rates of treatment breaks ≥ 10
and 5 days were 10% and 20%, respectively. One patient died from
induction chemotherapy (CT), 1 died several weeks post transoral
robotic surgery (TORS) for T2N1 SCC of the tonsil, 1 developed
grade 4 mucositis, and 1 developed osteoradionecrosis during CRT.
The median weight loss was 25 lbs (range: 6–40lbs). With a median
follow-up of 60 months (range: 12–140 mo), rates of late dysphagia
grades ≤ 2, 3, and 4 were 74%, 15%, and 11%, respectively. Rates of
late xerostomia grades ≤ 2 and 3 were 77% and 23%, respectively.
The median CD4 counts and viral loads before, during, and after
treatment were 370, 135, and 100 and 0, 160, and 260 cells/μL,
respectively. Seven patients developed second primary malignancy.
The 4-year locoregional control (LRC) and overall survival (OS)
rates were 65% and 50%, respectively. Chi-square test showed a significant relationship between LRC and both RT duration and CT, as
well as a relationship between lower CD4 counts and higher viral
load) (P = .001). Positive trends were observed between weight loss
≤ 10% and LRC and between absence of second malignancy and OS.
There was no significant relationship between HPV positivity,
smoking, or CT with either LRC or OS.
CONCLUSIONS: HIV+ patients with HNC have inferior oncologic
and functional outcomes compared to HIV− patients. HPV positivity and smoking did not have a statistically significant impact on
clinical outcomes. Innovative treatment modalities and approaches
with better efficacy and less morbidity need to be developed for this
growing patient population.
(S009) Radiation Therapy Improves Outcomes With
Desmoplastic Melanoma of the Head and Neck Tobin J. Strom, MD, Jimmy J. Caudell, MD, PhD, Jonathan S. Zager, MD,
C. Wayne Cruse, MD, Jane L. Messina, MD, Vernon K. Sondak, MD,
Louis B. Harrison, MD, Andy M. Trotti, MD; H. Lee Moffitt Cancer Center and Research Institute
BACKGROUND: Desmoplastic melanomas are considered to have a
high risk of local recurrence after resection alone, especially in the
head and neck. We hypothesized that adjuvant radiotherapy might
reduce the risk of local recurrence.
METHODS: A single-institution institutional review board (IRB)approved study was performed including 140 patients with desmoplastic melanoma without distant metastatic disease treated
from 1990–2010 with wide excision ± sentinel lymph node dissection ± regional lymph node dissection. Patient, tumor, and treatment characteristics were compared between the groups based on
receipt of adjuvant radiotherapy. Adjuvant radiotherapy was delivered to the primary tumor bed in all cases with a 2–4-cm margin
as feasible and to the draining lymphatics in a minority of cases (n
= 5). Patients were treated to a total dose of either 30 Gy in 5-Gy
fractions dosed twice per week (n = 37) or 50–68 Gy in 25–34 daily
fractions (n = 32). Adjuvant systemic therapy was delivered in 18
cases (interferon in 16 of 18 cases). The primary study outcome
was local control, and the secondary outcome was locoregional
control. Kaplan-Meier (KM) analysis and the log-rank test were
used to compare outcomes. A Cox hazards multivariate (MV)
model was created for the primary outcome.
RESULTS: Median follow-up was 47 months. Receipt of radiotherapy was associated with deeper tumors (median 5.4 mm vs 2.8 mm;
P < .001) and positive margins (28% vs 13%; P = .03), compared
with no radiotherapy. Nevertheless, adjuvant radiotherapy was associated with improved local control compared with patients who did
not receive it (4-yr KM estimate: 94% vs 74%; P = .02) and locoregional control (4-yr KM estimate: 86% vs 69%; P = .03). On Cox MV
analysis, radiotherapy was independently associated with improved
local control (hazard ratio [HR] = 0.17; 95% confidence interval
[CI], 0.06–0.51]; P = .002) and locoregional control (HR = 0.26; 95%
CI, 0.11–0.63; P = .003). Variables associated with local recurrence
on MV analysis included age > 70 years (HR = 4.1; 95% CI, 1.6–10.6;
P = .004) and positive margins (HR = 5.6; 95% CI, 2.1–15.1; P =
.001). Among patients with positive margins (n = 28), those treated
with radiation therapy had improved local control (4-yr KM estimate: 88% vs 18%; P = .01) compared with those not treated with
adjuvant radiation. Similarly, patients who had negative margins
also benefited from adjuvant radiation therapy (4-yr KM local control estimate: 96% vs 80%; P = .048). CONCLUSIONS: Radiotherapy improves both local and locoregional control in patients with desmoplastic melanoma of the head and
neck, regardless of margin status.
(S010) A Phase III Randomized Trial of MRI-Mapped
Dose-Escalated Salvage Radiotherapy Post-Prostatectomy: The MAPS Trial—Feasibility and Acute Toxicity
Amber Orman, MD, Alan Pollack, MD, PhD, Kelin Wang, PhD, Radka
Stoyanova, PhD, Elizabeth Bossart, PhD, Deukwoo Kwon, PhD, Matthew
Abramowitz, MD; University of Miami
PURPOSE AND OBJECTIVES: MAPS is the first phase III randomized trial of magnetic resonance imaging (MRI)-mapped dose-escalated salvage radiotherapy. In this planned feasibility analysis, we
relate dosimetry to acute toxicity in the setting of dose escalation
using a simultaneous incorporated hypofractionated boost (SIHB)
to MRI-identified lesions in the prostate bed.
MATERIALS AND METHODS: Two intensity-modulated radiothera-
py (IMRT) plans were generated for each patient treated on the
MAPS protocol, regardless of actual randomization arm: one for the
standard fraction radiotherapy (SFRT) arm and one for the SIHB
arm. In the SFRT arm, 68 Gy in 34 fractions was prescribed to ≥ 95%
of the planning target volume (PTV). In the SIHB arm, an additional 2.25 Gy daily SIHB was prescribed to the gross tumor volume
(GTV) (2.25 Gy daily, total dose of 76.5 Gy in 34 fractions). The trial
stipulates that no more than 35% and 55% of the rectum should
receive ≥ 65 Gy and ≥ 40 Gy, respectively, and that no more than
50% and 70% of the bladder minus the clinical target volume
(B-CTV) should receive ≥ 65 Gy and ≥ 40 Gy, respectively. Acute
toxicities were recorded for patients at designated times per protocol
according to the National Cancer Institute Common Terminology
Criteria for Adverse Events, version 4.0.
RESULTS: Data from the first 14 enrolled patients were reviewed to
ensure dosimetric adequacy of the protocol requirements. In all
plans, at least 95% of the PTV received 68 Gy, and at least 95% of the
GTV received 76.5 Gy. Dosimetric constraints were achieved for all
organs at risk (OARs) except B-CTV. Five cases had > 70% of the
bladder receiving ≥ 40 Gy in both plans, and one case had > 50% of
the bladder receiving ≥ 65 Gy in the SIHB plan only. The only difference between the SFRT and SIHB plans, per patient or overall,
was a higher percent volume of the PTV receiving 68 Gy in the
SIHB plans. In 13 patients for whom full data were available, the
highest toxicity recorded was grade 2 gastrointestinal toxicity: one
episode in each arm.
CONCLUSIONS: This study demonstrates that even though most
MRI-identified GTVs are located in close proximity to critical structures, dose escalation is achievable without exceeding rectal constraints in all cases, and bladder constraints in the majority of cases.
These variations are in cases with small bladders encompassed in
the CTV and are not associated with increased acute toxicity.
(S011) Hypofractionated vs Standard Fractionated
Proton Beam Therapy for Early-Stage Prostate Cancer:
Interim Results of a Randomized Prospective Trial William F. Hartsell, MD, Megan Dunn, PhD, Gary Larson, MD, Carlos
Vargas, MD; CDH Proton Center; Proton Collaborative Group; ProCure
Proton Center; Mayo Clinic
PURPOSE: After prostate cancer treatment, most adverse event (AE)
and quality of life (QoL) changes can be initially identified within
the first 2 years. The purpose of this interim analysis is to determine
if there are differences in terms of QoL, International Prostate
Symptom Score (IPSS), or AEs among prostate cancer patients
treated on a randomized prospective trial with either standard fractionation or hypofractionation.
MATERIALS AND METHODS: Eighty-two patients were randomized
to 38 Gy(relative biologic effectiveness [RBE]) in 5 treatments (n =
49) vs 79.2 Gy(RBE) in 44 treatments (n = 33). All patients had stage
I prostate cancer and were treated with proton therapy using fiducial
markers and daily image guidance.
RESULTS: Median follow-up for both groups was 18 months, with 33
patients reaching follow-up of 2 years or more. Patient characteristics
for both groups were similar, with most patients being T1c (84%) and
all having a Gleason score of 6 and a prostate-specific antigen (PSA)
level < 10 ng/mL (median, 5.6 ng/mL). Baseline median IPSS was 5
for the 5-fraction arm (range: 0–15), and median IPSS was also 5 for
the 44-fraction arm (range: 0–14). There was no difference between
the two groups with regard to Expanded Prostate Index Composite
(EPIC) urinary, bowel, or sexual function scores at 3, 6, 9, 12, 18, 24,
5
or 36 months. The only significant difference was the IPSS score at 12
months: 5 for the 44-fraction arm vs 8 for the 5-fraction arm (P = .03),
but there was no difference in the IPSS scores at the other time points.
No grade ≥ 3 AEs were seen in either arm.
CONCLUSIONS: Patients tolerated proton therapy in this randomized trial well, with excellent QoL scores, persistent low IPSS, and
no grade ≥ 3 AEs in either arm. Thus far, there is no apparent clinical difference in outcomes with hypofractionated proton beam
therapy compared to standard fractionation.
(S012) Trends in the Selection of Definitive Treatment for
Newly Diagnosed Prostate Cancer in Men < 60 Years Old Joseph Safdieh, MD, J. Rineer, MD, M. Shao, MD, E. Navo, MD, D.
Schreiber, MD; SUNY Downstate Medical Center; University of Florida
Health Cancer Center at Orlando; Department of Veteran Affairs, NY
Harbor Campus
INTRODUCTION: According to the National Comprehensive Cancer
Network (NCCN) Guidelines, alternatives to definitive treatment
include active surveillance for men with low-risk (LR) prostate cancer and a life expectancy ≥ 10 years, as well as androgen deprivation
alone for men with high-risk (HR) disease who are not candidates
for definitive therapy. In this study, we utilized the Surveillance,
Epidemiology, and End Results (SEER) Database to analyze the
trends for selection of definitive treatment in a young patient population (age < 60 years).
MATERIALS AND METHODS: We identified all men < 60 years old
who were diagnosed with nonmetastatic prostate adenocarcinoma
from 2010–2011 and had a follow-up time > 6 months. Detailed
clinical and pathologic factors were collected, including the T-stage,
Gleason scores, and prostate-specific antigen, and these data were
used to group men into NCCN risk groupings. Receipt of treatment
was categorized as no definitive treatment, local treatment (such as
cryotherapy or transurethral resection of the prostate [TURP]),
radical prostatectomy (RP), and radiation therapy (RT). Since
androgen deprivation is not recorded in the SEER database, these
men were included as having no definitive treatment. Descriptive
analyses were used to determine rates of treatment receipt.
Multivariate logistic regression was used to determine predictors for
selecting treatment other than definitive therapy.
RESULTS: There were a total of 16,630 men identified. Of these subjects, 7,281 (43.8%) had LR disease, 5,660 (34%) had intermediaterisk (IR) disease, and 3,689 (22.2%) had HR disease. The median age
at diagnosis was 55 years (interquartile range [IQR]: 52–58 yr). For
those with LR disease, 20.5% pursued no definitive treatment, 0.3%
pursued local treatment, 57.8% pursued RP, and 21.3% underwent
RT. For IR disease, 8.0% pursued no definitive treatment, 0.7%
underwent local treatment, 69.2% underwent RP, and 22.0%
received RT. For HR disease, 25.5% underwent no definitive treatment, 1.3% underwent local treatment, 51.5% received RP, and
21.8% received RT. On multivariate logistic regression, AfricanAmerican race (odds ratio [OR] = 0.76; 95% confidence interval
[CI], 0.68–0.85; P < .001), and the presence of HR disease (OR =
0.74; 95% CI, 0.67–0.81; P < .001) were associated with a decreased
likelihood of selecting definitive treatment.
6
CONCLUSION: In this young patient population, no definitive treatment was selected in 22.5% of men with LR disease. For those with
HR disease, 25.5% did not undergo active treatment, indicating that
these men appear to be receiving less aggressive therapy than recommended by NCCN guidelines. In addition, African-American
race is also associated with a decreased likelihood for receipt of
definitive therapy.
(S013) Heterogeneity Within the Prostate and
Risk-Adapting Dose-Volume Analysis With SBRT for
Prostate Cancer Zachary A. Seymour, MD, Li Zhang, PhD, Albert J. Chang, MD, I-Chow
J. Hsu, MD, Alexander R. Gottschalk, MD, PhD; Department of Radiation Oncology, Cancer Center, University of California, San Francisco
PURPOSE AND OBJECTIVES: To evaluate dose-volume relationships of genitourinary (GU) toxicity after stereotactic body radiotherapy (SBRT) for prostate cancer to determine optimal cut points
for dosimetric parameters based on prostatic volume.
MATERIALS AND METHODS: Fifty-one of 56 patients treated with
SBRT for prostate cancer had evaluable dose-volume histograms.
All patients were treated in a uniform manner, receiving a total dose
of 38 Gy in 4 fractions. Acute, late, and overall GU toxicities were
documented according to the Common Terminology Criteria for
Adverse Events version 4 (CTCAE v4). Dose volumes were assessed
via receiver operating characteristic (ROC) curves to determine
optimal cut points at 0.5-Gy dose-volume intervals, and probabilities of toxicity for each cut point were produced. Only dose volumes
with a sensitivity and specificity > 0.65 were considered for analysis
of GU grade 2+ toxicity.
RESULTS: The median age at treatment was 68 years, and median
prostate volume was 45.4 mL. The median prescription isodose line
was 68%. The median clinical follow-up was 35.49 months. Acute
and late grade 2+ GU toxicities occurred in 35.7% and 23.2%,
respectively, with only 2 grade 3 GU toxicities. Overall toxicity was
associated with baseline prostate volume (continuous, P = .006; hazard ratio [HR] = 1.06; 95% confidence interval [CI], 1.02–1.10) with
an overall risk of 39% for grade 2+ toxicity in patients with prostate
volumes > 45 mL (AUC 0.722, sensitivity 67%, specificity 71%). The
probability of late grade 2+ GU toxicity was associated with absolute
and normalized prostate volumes across doses from 46–50 Gy, suggestive of increasing late toxicity with intraprostatic heterogeneity.
Normalized V50 Gy of 9% was the strongest normalized prostate
volume associated with a 19% late grade 2+ GU toxicity rate (AUC
0.763, sensitivity 82%, specificity 68%). Urethra 42 Gy volume was
also associated with grade 2+ toxicity with an optimal cutoff of 2.1
mL (AUC 0.62, sensitivity 82%, specificity 70%, probability 19%).
No bladder volume cut points were strongly associated with late or
overall GU grade 2+ toxicity.
CONCLUSIONS: Greater intraprostatic heterogeneity was associated
with late grade 2+ GU toxicity. Given the high correlation of prostate volume with toxicity, SBRT dose parameters should be individualized and risk-adapted based on normalized prostate volumes,
including a V50 not to exceed 9% of the prostate. The urethra is an
important organ at risk, and the 42-Gy dose-volume should be lim-
ited to 2 mL, while bladder dose-volumes appear to be poor predictors of GU grade 2+ toxicity.
(S014) pN+ Prostate Cancer (CaP) Does Not Imply
Incurable Disease Jan Poleszcuk, PhD, Heiko Enderling, PhD, Peter Johnstone, MD, FACR;
Moffitt Cancer Center
OBJECTIVES: Mathematical modeling of cancer provides mechanisms not simply to predict tumor behavior based on cellular signatures but also to predict patient options based on population
dynamics. We have previously reported that populations with cancer die according to an inverse Gompertzian model. Further, we
have shown that “incurability” is associated with an inflection point
in the Gompertz curve and a nadir in the derivatives of these curves
over time. Before reaching this inflection, potential curative interventions may be applied; after this point, reproducible cure is
unlikely. Randomized data supporting optimal therapy for pN+
prostate cancer (CaP) patients are frankly nonexistent beyond recommending hormonal therapy. We sought to stratify curability of
this cadre of patients by assessing survival by degree of lymph node
(LN) positivity (%LN+).
METHODS: Overall or observed survival data in the CaP population
are of less utility than in other cancers because of frequent comorbid
diagnoses. Thus, national registry-based data were specifically used:
relative survival data were retrieved by year postdiagnosis and stratified by the number of positive LNs and by the number of LNs
evaluated postoperatively. Data were obtained from the public
access Surveillance, Epidemiology, and End Results (SEER) between
1988 and 2011. Observed survival was corrected for an age-, race-,
and gender-matched national sample. These data, obtained from a
national sample, may be presumed to include hormonal therapy in
the disease trajectory. Raw data were then converted to %LN+ and
modeled using inverse Gompertzian kinetics. Inflection points were
determined for %LN+ values less than 10%, between 10% and 25%,
between 25% and 50%, and over 50%.
RESULTS: Data were retrieved from 8,018 pN+ patients. The inflection point varies inversely with increasing %LN+. For patients with
less than 10% LN+, the inflection was almost 14 years postoperatively. Patients with 10% to 25% LN+ had an inflection point at
almost 10 years; for those with more than 50% LN+, the inflection
point was just over 4 years. The difference in time to inflection
between cadres was significant.
CONCLUSIONS: When corrected for comorbid conditions in this
patient cohort, CaP patients with < 10% %LN+ have almost 14 years
before their disease becomes incurable. Progressively larger %LN+
yields smaller windows of such time. Above 50% LN+, the inflection
point is only about 4 years. While better therapies for pN+ CaP must
be defined, this patient cadre is not homogenous and should be
stratified by %LN+ in future clinical trials.
(S015) Impact of Health Insurance Status on Prostate
Cancer Treatment Modality Selection in the United
States Trevor Bledsoe, MD, Henry Park, MD, MPH, Charles Rutter, MD, Sanjay
Aneja, MD, James Yu, MD, MHS; Department of Therapeutic Radiology,
Yale University School of Medicine
INTRODUCTION: A variety of treatment modalities are available for
the management of men with clinically localized prostate cancer in
the United States. In addition to clinical factors, treatment choice
may be influenced by a patient’s insurance status. We investigated
the influence of health insurance on prostate cancer treatment
modality selection in the United States.
METHODS: Men aged 18–65 years treated for localized prostate cancer from 2010–2011 were identified in the National Cancer Data
Base. Patients with no insurance or private insurance were included.
Treatment modalities included minimally invasive surgery alone
(MIS), open surgery alone, external beam radiotherapy alone
(EBRT), proton therapy alone, brachytherapy alone, hormone therapy alone, active surveillance, and combinations of treatments.
Demographic and clinical covariates included age, race, income,
education level, year of diagnosis, treatment facility type, D’Amico
risk classification, and Charlson/Deyo score. Chi-square and multivariable logistic regression analyses were used to evaluate the association of insurance status and other covariates with treatment
modality selection.
RESULTS: We identified 67,370 patients with either no insurance
(3.2%) or private insurance (96.8%). The greatest disparities in treatment modality by insurance status were observed among men
receiving MIS and EBRT. For patients with no insurance, 35.1%
received MIS and 25.6% received EBRT. For patients with private
insurance, 60.1% received MIS and 9.7% received EBRT. Insurance
status was the strongest predictor of receipt of both MIS and EBRT
on multivariable analysis. Lack of insurance was associated with
decreased utilization of MIS (odds ratio [OR] = 0.39; 95% confidence interval [CI], 0.36–0.43; P < .001) and increased utilization of
EBRT (OR = 2.56; 95% CI, 2.27–2.85; P < .001). CONCLUSIONS: Patients without insurance were less than half as
likely to receive MIS and more than twice as likely to receive EBRT
compared with patients with private insurance in our national
cohort. Our findings suggest that with expanding access to private
insurance under the Affordable Care Act, there may be significant
shifts in the selection of treatment modality for men with prostate
cancer in the United States.
(S016) Intermediate-Risk Prostate Cancer: A MedicareBased Cost Comparison of Five Radiotherapy Regimens Romaine C. Nichols, MD, Kathy McIntyre, Juana Gifford, Steve Ritz,
Stuart Klein, Curtis M. Bryan, MD, MPH, Randal H. Henderson,
MD, MBA, William M. Mendenhall, MD, Nancy P. Mendenhall, MD,
Bradford S. Hoppe, MD, MPH; Proton Therapy Institute, Department of
Radiation Oncology, University of Florida
BACKGROUND: Patients with intermediate-risk prostate cancer choosing radiotherapy may be treated with a number of regimens. The cur-
7
rent study compares the direct treatment cost for five therapeutic
options based on fiscal year 2014 Medicare-allowable reimbursements.
METHODS: Hypothetical charge sheets were generated along with the
expected Medicare-allowable reimbursements (based on global billing where applicable) for the following regimens: (1) image-guided
intensity-modulated radiotherapy (IGIMRT) to a dose of 78 Gy in 39
fractions with one field reduction (IGIMRT); (2) dose-escalated
IGIMRT to 84.60 Gy in 47 fractions with one field reduction
(MSKCC-IGIMRT); (3) IGIMRT to a dose of 45 Gy in 25 fractions
followed by a 90-seed I125 prostate implant (IGIMRT-BTX); (4)
image-guided proton therapy to a dose of 78 Gy(relative biologic
effectiveness [RBE]) in 39 fractions with one field reduction (SFPT);
and (5) image-guided hypofractionated proton therapy to a dose of
72.50 Gy(RBE) in 29 fractions with one field reduction (HFPT).
RESULTS: Based on fiscal year 2014 Medicare-allowable reimbursements, the direct cost, including professional fees, technical fees,
isotope costs, and facility fees, for each intervention is as follows:
IGIMRT, $25,204.12; MSKCC-IGIMRT, $29,130.76; IGIMRT-BTX,
$31,104.39; SFPT, $46,652.66; and HFPT, $34,977.54.
CONCLUSIONS: These data present a framework for evaluating the
cost-effectiveness of proton therapy as compared to competing
therapeutic options. Under current Medicare-allowable reimbursements, the cost of proton therapy relative to the cost of other therapeutic options is highly dependent on the number of radiotherapy
fractions delivered. The feasibility of delivering hypofractionated
proton therapy for patients with localized prostate cancer is being
investigated at a number of institutions, as well as within the framework of a multicenter protocol. Ultimately, the cost of proton therapy will need to be weighed against tumor control probabilities, as
well as the economic and quality of life benefits associated with
reduced normal tissue exposure.
motherapy, and 9.2% received adjuvant chemotherapy. Median
patient age was 64 years (range: 23–93 yr), and median follow-up
was 3.7 years. A total of 23 men experienced RR following lymphadenectomy. Among men who failed to respond to treatment, median time to RR was 4.5 months (interquartile range: 3.6–9.0 mo).
Three- and 5-year cumulative incidence rates of RR were 15.5% and
16.8%, respectively. On univariate analysis, pathologic T-stage at
penile surgery (P = .013), clinical nodal stage before lymphadenectomy (P < .001), the presence of extranodal extension (ENE) at
lymphadenectomy (P < .001), and involvement of > 3 nodes at
lymphadenectomy (P < .001) were associated with RR. The 3-year
RR rate was 44.3% in men with ENE and 4.0% in men without ENE.
For men with > 3 involved nodes, the 3-year RR rate was 49.0% vs
8.7% in men with < 3 involved nodes. The 3-year RR rate for men
with cN0, cN1, cN2, and cN3 disease was 6.4%, 15.0%, 10.5%, and
38.6%, respectively. On multivariate analysis, the presence of cN3
disease before lymphadenectomy (vs cN0; adjusted hazard ratio
[AHR] = 6.91; 95% confidence interval [CI], 1.23–38.8; P = .028), >
3 pathologically involved nodes (AHR = 10.92; 95% CI, 2.51–47.5;
P = .001), ENE (AHR = 77.89; 95% CI, 12.59–482.0; P < .001), and
pT4 disease at penile surgery (vs pT1; AHR = 50.15; 95% CI, 5.04–
499.6; P < .001) continued to be associated with RR. Conversely,
adjuvant chemotherapy was associated with reduced RR (AHR =
0.09; 95% CI, 0.01–0.59; P = .012). Median survival for men who
experienced RR was 11.4 months compared with 15 years for men
who did not develop RR.
CONCLUSION: The presence of cN3 disease, ENE, and > 3 lymph
nodes at lymphadenectomy and the presence of pT4 disease at
penile surgery were associated with increased risk of early RR, while
adjuvant chemotherapy decreased RR. Since RR portends a dismal
prognosis with few salvage options, men with these adverse factors
should be considered for adjuvant therapy, including radiation therapy, to reduce RR.
(S017) Factors Associated With Regional Recurrence
Following Lymphadenectomy for Penile Squamous Cell
Carcinoma (S018) Intensity-Modulated Radiation Therapy or
Conformal Radiation Therapy and Cardiopulmonary
Mortality Risk in the Elderly With Esophageal Cancer Jay Reddy, MD, PhD, Curtis A. Pettaway, MD, Lawrence Levy, MS, Lance
Pagliaro, MD, Pherose Tamboli, MD, Priya Rao, MD, Isuru Jayaratna,
MD, Karen Hoffman, MD, MPH; UT MD Anderson Cancer Center
Steven H. Lin, MD, PhD, Ning Zhang, PhD, Joy Godby, BS, Jingya Wang,
MD, Gary D. Marsh, BS, Zhongxing Liao, MD, Ritsuko Komaki, MD,
Linus Ho, MD, Wayne L. Hofstetter, MD, Stephen G. Swisher, MD,
Thomas A. Buchholz, MD, Linda S. Elting, PhD, Sharon H. Giordano,
MD; UT MD Anderson Cancer Center
PURPOSE: Factors associated with regional recurrence (RR) following lymphadenectomy for penile cancer were assessed to determine
which patients might benefit from adjuvant therapy.
METHODS: Men who underwent lymphadenectomy for penile
squamous cell carcinoma between 1990–2014 were identified from
an institutional database. Kaplan-Meier curves estimated time to RR
calculated from the date of lymphadenectomy. Cox proportional
hazards models evaluated the association between RR and patient
and tumor characteristics. Backward selection with a P value cutoff
of .05 selected covariates into the multivariate model.
RESULTS: A total of 153 men underwent lymphadenectomy and did
not receive adjuvant radiation therapy: 54.9% of patients underwent
inguinal lymphadenectomy, and 44.4% underwent inguinal and pelvic lymphadenectomy; 28.8% of patients received neoadjuvant che-
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PURPOSE: We performed a population-based assessment for the
all-cause and cardiopulmonary mortality risk in esophageal cancer
(EC) patients treated with chemotherapy and radiation, comparing
conventional radiotherapy (CRT) or advanced radiation modality
defined by the use of intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: We identified 2,578 patients aged over
65 years from the Surveillance, Epidemiology, and End Results
(SEER)/Texas Cancer Registry-Medicare databases who had nonmetastatic EC diagnosed between 2002 and 2009 (CRT = 2,265;
IMRT = 313). We defined radiation modality by delivery claims,
whether it was by conventional radiation therapy, which could
either have been two-dimensional (2D) or three-dimensional (3D)
(CRT: Healthcare Common Procedure Coding System [HCPCS]:
77401–77416) or by IMRT delivery (HCPCS: 77418, G0174) within
6 months of diagnosis. Patients in both cohorts were compared
using propensity score–based adjustment. Cause-specific and overall mortality rates were evaluated using Kaplan-Meier LIFETEST
and a multivariate (MVA) Cox proportional hazards model. RESULTS: Except for marital status and SEER region, both radiation
cohorts were well balanced for various patient, tumor, and treatment
characteristics, including the distribution of the use of IMRT vs
CRT in urban/metropolitan or rural areas. CRT was done primarily
by 3D delivery (98.9%). IMRT use increased from 2.6% in 2002 to
30% in 2009, while 3D use decreased from 97.4% in 2002 to 70% in
2009. In the unadjusted analysis, all-cause mortality, EC-specific
mortality, and cardiac mortality were significantly reduced in the
IMRT group (all: 52.4% vs 74.5%, P < .0001; EC: 40.3% vs 55.6%, P
< .0001; and cardiac: 1.6% vs 5.3%, P = .0043). However, no difference was seen in deaths from pulmonary (0.96% vs 1.55%; P = .419)
or other causes (9.6% vs 12.1%; P = .204). On propensity score–
adjusted MVA, IMRT was not associated with EC-specific mortality
(hazard ratio [HR] = 0.87; 95% confidence interval [CI], 0.69–1.06),
pulmonary (HR = 1.04; 95% CI, 0.29–3.79), or other-cause mortality (HR = 0.81; 95% CI, 0.54–1.22) but was significantly associated
with higher overall survival (HR = 0.83; 95% CI, 0.70–0.98) and
lower cardiac mortality (HR = 0.35; 95% CI, 0.14–0.88). Similar
associations were seen even after adjusting for physician experience,
the type of chemotherapy used, and sensitivity analysis removing
hybrid radiation claims. CONCLUSION: In this population-based analysis, IMRT use was
significantly associated with improved overall survival and reduced
cardiac mortality in patients with esophageal cancer.
(S019) Radiation-Induced Liver Disease Following Liver
SBRT for Primary Hepatic Malignancies: Analysis of a
Prospective Institutional Study Ashley Weiner, MD, PhD, Jeffrey Olsen, MD, Daniel Ma, MD, Pawel
Dyk, MD, Todd Dewees, PhD, Parag Parikh, MD; Washington University; Mayo Clinic
PURPOSE AND OBJECTIVES: Although primary liver tumors are
commonly treated by surgery, transplant, radiofrequency ablation,
or transarterial therapies, there is an increasing patient population
that is not suited to these treatments. Stereotactic body radiotherapy
(SBRT) allows precise delivery of hypofractionated radiation—a
strategy that is thought to minimize the risk of radiation-induced
liver disease (RILD) over conventionally fractionated radiation. The
objective of this study was to evaluate the feasibility, safety, and efficacy of SBRT in the treatment of inoperable hepatocellular cancer
(HCC) and intrahepatic cholangiocarcinoma (IHC).
MATERIALS AND METHODS: A total of 28 patients with inoperable
HCC or IHC and Child-Pugh score ≤ 8 were enrolled on a singleinstitution prospective protocol. A total of 32 lesions in 26 patients
were treated with a planned dose of 55 Gy in five fractions, which
was reduced to maintain the mean liver dose < 20 Gy or spare 700
cc of liver with doses < 20 Gy. Treatment was delivered via linear
accelerator with immobilization, daily imaging, and end-expiratory
gating on fiducial markers. Kaplan-Meier survival analysis was per
formed. Toxicities were graded by Common Terminology Criteria
for Adverse Events version 4 (CTCAE v4) criteria, and radiographic response to treatment was scored by European Association for the
Study of the Liver (EASL) guidelines.
RESULTS: The study cohort included 12 patients with HCC, 13
patients with IHC, and 1 patient with a biphenotypic tumor. Median
prescribed dose was 55 Gy (range: 40–55 Gy) in five fractions. Mean
tumor diameter was 5.3 cm (range: 1.6–12.3 cm), and mean PTV
volume was 342 cc (range: 54–964 cc). Median follow-up was 7.7
months with a median overall survival (OS) of 9.8 months. The 6and 12-month OS rates were 80% and 44%, respectively. On imaging 8 weeks posttreatment, complete radiographic response was
noted in four patients, while six patients had a partial treatment
response. Two grade 5 toxicities occurred during study follow-up.
One patient with cirrhosis and a renal transplant history who was
being treated with tacrolimus, a potentially hepatotoxic medication,
developed RILD, which progressed to hepatic failure and death.
Another patient with longstanding cirrhosis succumbed to a gastrointestinal bleed in the setting of RILD.
CONCLUSIONS: Primary hepatic malignancies that are not amenable to surgical resection portend a poor prognosis, despite available
treatment options. Though RILD is rare following SBRT, this study
demonstrates a risk, despite close adherence to standard dose and
volume constraints. Further analysis of this prospective study will
seek to elicit patient parameters that may increase susceptibility to
toxicities, such as RILD.
(S020) Predictors of Local-Regional Failure and the
Impact on Overall Survival in Patients With Resected
Exocrine Pancreatic Cancer Kenneth Merrell, MD, MS, Christopher Hallemeier, MD, William
Harmsen, MS, Fernando Quevedo, MD, Michael Kendrick, MD,
Michael Haddock, MD, Robert Miller, MD; Department of Radiation
Oncology, Division of Biomedical Statistics and Informatics, Department
of Medical Oncology, Department of General Surgery, Mayo Clinic
PURPOSE: Resection of exocrine pancreatic cancer is necessary for
cure, but most patients subsequently develop progressive disease. In
prospective trials, rates of local-regional failure (LRF) range from
20% to 40%. We evaluated our institutional experience to better
understand the risk factors for LRF and the impact on overall survival (OS).
METHODS: We reviewed 665 consecutive patients with nonmetastatic exocrine pancreatic carcinoma who underwent resection (R0
or R1) at our institution between March 1985 and January 2011 and
received adjuvant therapy. A total of 458 patients had adequate follow-up and imaging to determine LR control (LRC) rates. All
patients received adjuvant chemotherapy (n = 80, 17.5%) or chemoradiotherapy (CRT) (n = 378, 82.5%). Chemotherapy and CRT most
frequently consisted of six cycles of gemcitabine and 50.4 Gy in 28
fractions with concurrent 5-fluorouracil (5-FU), respectively. In
addition to CRT, 207 (45%) patients received additional chemotherapy. LRF was defined as tumor bed or regional node progression
with or without distant metastatic progression. When available,
CA19.9 values were used to validate radiographic findings. LRC and
9
OS were estimated using the Kaplan-Meier method. Univariate and
multivariate (MVA) analyses were performed using Cox proportional hazards regression models.
RESULTS: Median patient age was 64.5 years (range: 37–88 yr).
Median follow-up for living patients was 84 months (range: 6–300
mo). Tumor location was pancreas head (80%), body (5%), and tail
(8%) or unspecified (7%). Tumor grade was I (0.5%), II (11.5%), III
(76%), or IV (12%). T-stage was T1 (7%), T2 (20%), T3 (70.5%), or
T4 (2.5%). N stage was N0 (38%) or N1 (62%). Extent of resection
was R0 (84%) or R1 (16%). The overall crude incidence of LRF was
17% (n = 79). Three-year rates of LRC for patients with and without
RT were 81.6% vs 68.3%, respectively (P = .003; hazard ratio [HR] =
0.45; 95% confidence interval [CI], 0.28–0.76). On MVA, no radiation therapy (P = .0097; HR = 2.2; 95% CI, 1.22–3.79), elevated preoperative CA19.9 (P = .046; HR = 1.92 per 20 units; 95% CI, 1.02–
3.59), and positive nodes/total nodes ratio ≥ 0.2 (P = .059; HR =
1.61; 95% CI, 0.98–2.65) were associated with LRF. When used as a
time-dependent covariate for OS, LRF was associated with worse OS
(P < .0001; HR = 4.07; 95% CI, 3.2–5.2) compared with no LRF. CONCLUSIONS: In our analysis of 458 patients with resected pancreatic cancer and adjuvant therapy, elevated preoperative CA 19.9
and no adjuvant RT were associated with increased risk of LRF. LRF
was associated with poor OS. As such, RT should be considered as
an adjunctive LR treatment modality for patients undergoing pancreatic cancer resection.
(S021) The Role of Neoadjuvant Stereotactic Body
Radiation Therapy in Pancreatic Cancer tively. Fluorouracil, leucovorin, irinotecan, and oxaliplatin
(FOLFIRINOX)-based chemotherapy was administered to 61.5%
and 45.9% of SBRT and chemotherapy-alone patients, respectively.
The majority (61.5%) of SBRT patients were deemed unresectable,
while only 29.7% in the chemotherapy-alone group had LAPC.
Pancreaticoduodenectomy was performed in 66.7% of SBRT
patients compared with 75.7% of chemotherapy-alone patients.
Median time to surgery was 2.0 months (range: 0.1–10.5 mo) from
the end of SBRT.
The overall rate of margin-negative resection in patients who
received SBRT was 87.2%, with 86.7% in BRPC and 87.5% in LAPC.
In comparison, the overall margin-negative resection rate in chemotherapy-alone patients was 48.6% (34.3% in BRPC, 54.5% in LAPC).
Node-negative resections were achieved in 71.7% of patients who
received SBRT (60.0% in BRPC, 79.2% in LAPC) and in 45.9% of
patients who received chemotherapy alone (50.0% in BRPC, 36.4%
in LAPC). The pCR rate was 10.3% in the SBRT group (6.7% in
BRPC, 12.5% in LAPC) and 2.7% in the chemotherapy-alone group
(0% in BRPC, 9.1% in LAPC). The npCR rate was 23.1% in the
SBRT group (20.0% in BRPC, 25.0% in LAPC) and 5.4% in the
chemotherapy-alone group (7.7% in BRPC, 0% in LAPC).
CONCLUSIONS: Selected patients who are initially deemed unresectable may now undergo resection after receiving neoadjuvant
induction chemotherapy and SBRT. Furthermore, improved surgical outcomes are observed with neoadjuvant SBRT in comparison
with neoadjuvant chemotherapy alone. Longer follow-up is needed
to validate its impact on survival.
Lauren M. Rosati, BS, Jin He, MD, Shalini Moningi, BA, Amy HackerPrietz, PAC, Thomas A. Huebner, MD, Daniel A. Laheru, MD, John L.
Cameron, MD, Timothy M. Pawlik, MD, MPH, PhD, Matthew J. Weiss,
MD, Christopher L. Wolfgang, MD, Joseph M. Herman, MD, MSc; Johns
Hopkins University School of Medicine
(S022) Experimental Insight Into the Preferential
Cytotoxicity of Cancerous vs Noncancerous Cells of
Metformin
BACKGROUND: Recent prospective data demonstrate that stereotactic body radiation therapy (SBRT) is safe and effective in locally
advanced pancreatic cancer (LAPC); however, little is known
regarding the role of SBRT in the neoadjuvant setting. This study
compared the role of neoadjuvant chemotherapy with and without
SBRT in patients with borderline resectable pancreatic cancer
(BRPC) or LAPC.
PURPOSE AND OBJECTIVE: Metformin is known to produce direct
cancer cell cytotoxicity, inhibit tumor growth, radioprotect normal
tissues, and radiosensitize cancer cells. However, the underlying
mechanism behind the anticancer activity is not yet understood.
This study was designed to investigate the biochemical effect of metformin on cancerous and noncancerous cells under varying conditions from the perspective of reactive oxygen species (ROS).
METHODS: All patients who underwent surgical resection following
chemotherapy alone or induction chemotherapy followed by SBRT
(SBRT group) were retrospectively reviewed. Disease stage was
determined by multidisciplinary review. Chemotherapy regimens
were heterogeneous; the cumulative SBRT dose range was 25–33 Gy
in five fractions. Pathologic complete response (pCR) was defined
as no residual tumor, and near pCR (npCR) was defined as microscopic foci of single cells of adenocarcinoma scattered among an
area of dense fibrosis.
MATERIALS AND METHODS: A549 (lung cancer), MCF-7 (breast
cancer), and MCF-10A (normal breast) cell lines were maintained
in cell culture and exposed to 5 mM metformin for 4–6 hours in
environments in which oxygen and glucose concentrations varied.
The level of ROS production was measured using a standard dihydroethidium (DHE) fluorescence reagent and flow cytometric spectroscopy. Oxygen levels were maintained with atmospheric oxygen
or a mixture of carbon dioxide/nitrogen gas. Clonogenic and MTT
assays were used to assess cellular response to radiation therapy.
RESULTS: Among 76 resected patients with BRPC or LAPC, 37
received chemotherapy alone and 39 received SBRT. Median age
was 60.4 years (range: 44.2–83.6 yr) and 64.4 years (range: 39.2–83.2
yr) in the SBRT group and chemotherapy-alone group, respec-
RESULTS: Metformin consistently and significantly increased ROS
levels at least 2-fold in A549 and 3-fold in MCF-7 cell lines. ROS
levels in MCF-10A cells were only moderately affected. Hypoxic
A549 cells treated with metformin showed a 137% increase in ROS
10
Derek Isrow, MD, PhD, Karen Lapanowski, Andrew Kolozsvary, Stephen
Brown, PhD, Jae Ho Kim, MD, PhD; Henry Ford Hospital
levels over baseline hypoxic cells without metformin (165% at 6 hr).
Oxygenated A549 cells treated with metformin showed a 117% ROS
increase compared with control cells without metformin (139% at 6
hr). When A549 cells were placed in glucose-free medium (GFM)
and exposed to metformin, ROS levels were 203% greater than A549
cells in GFM without metformin. Hypoxic A549 cells in GFM with
metformin produced a ROS level 120% greater than cells in hypoxic GFM without metformin. Cellular response studies confirmed
the ROS results. Increased cytotoxicity to radiation in the presence
of metformin was observed with A549 cells by clonogenic assay and
with MCF-7 cells by MTT assay. In agreement with the ROS studies,
no increased radiosensitization or cytotoxicity was observed in
MCF-10A cells using metformin.
CONCLUSIONS: Metformin was demonstrated to increase ROS levels, cytotoxicity, and radiosensitization in A549 and MCF-7 cancer
cells under oxic, hypoxic, glucose-full, and glucose-free conditions.
Normal MCF-10A cells did not show increased toxicity with metformin. The preferential metformin-induced increase in ROS levels
found in cancer cells, particularly hypoxic cells, may provide some
explanation for the therapeutic benefit seen in diabetic patients taking metformin while undergoing cancer treatment. Further studies
are underway in the hope of translating these findings into clinical
practice.
(S023) Ultrasound Tissue Characterization of Breast Fibrosis Following Hypofractionated Breast Radiotherapy Xiaofeng Yang, Mylin Torres, MD, Simone Henry, Donna Mister, Tatiana
Han, Walter Curran, Tian Liu; Emory University
PURPOSE: Hypofractionation whole-breast radiotherapy (RT) following conservation surgery has been used in many institutions for
several decades. However, the hypofractionation regimen has not
been widely accepted in the United States. Criticism has focused on
concerns about late normal-tissue effects. The purpose of this study
is to evaluate breast fibrosis in patients receiving hypofractionated
RT using quantitative ultrasound tissue characterization.
MATERIALS AND METHODS: Twenty postlumpectomy women
were enrolled in a prospective, longitudinal ultrasound imaging
study to examine the development of RT-induced normal-tissue
toxicity. Each received simultaneous integrated boost (SIB) RT (40
Gy plus simultaneous cavity boost to 48 Gy in 15 fractions). A baseline ultrasound scan was performed 1 week prior to RT, plus one
scan during RT, followed by evaluation at the 1-year follow-up.
Patients were imaged with 10-MHz ultrasonography at the 12, 3, 6,
and 9 o’clock positions of the breast. To compensate for individual
variation, scans taken on the untreated contralateral breast served
as a control. Ultrasonography parameters, including skin thickness,
Pearson coefficient, and midband fit, were calculated to quantify
cutaneous and glandular tissue toxicity. Quantitative ultrasonography parameters were generated by normalizing to the corresponding contralateral breast. Ultrasonography findings were compared
with clinical assessments based on the Radiation Therapy Oncology
Group (RTOG) toxicity scheme.
RESULTS: Based on the ultrasonography measurements, 50% to
60% of patients developed mild to moderate late toxicity (fibrosis)
1-year post-RT. For the 20 patients, the average skin thickness ratios
were 1.23 prior to RT, 1.33 during RT, and 1.37 at the 1-year followup. Prior to RT, the diseased breast experienced 23% greater skin
thickening secondary to postsurgical changes. The midband fit
ratios were 1.12 prior to RT, 1.70 during RT, and 2.45 1-year postRT. The Pearson ratios were 0.92 prior to RT, 0.78 during RT, and
0.63 1-year post-RT. Increased skin thickness and midband fit values correlated with increased cutaneous toxicity assessed using
RTOG scores (P < .05). The ultrasonography findings were consistent with the clinical assessments: 60% developed RTOG grade 1
toxicity, and 10% developed grade 2 toxicity at 1 year.
CONCLUSIONS: This is the first prospective imaging study to objectively document normal-tissue toxicity in patients treated with
hypofractionation breast RT using ultrasonography tissue characterization. Contrary to the criticism, patients receiving hypofractionation RT recovered better and experienced less late toxicity at
the 1-year follow-up. With this noninvasive ultrasonography technology, physicians can objectively compare the late effects of hypofractionation with the standard regimen and gain a better understanding of treatment responses in individual patients. (S024) Impact of Pelvic Radiotherapy on Sexuality
Reported by Women Surviving Cancer James M. Metz, MD, Erin Davis, Carolyn Vachani, Margaret K.
Hampshire, Christine E. Hill-Kayser, MD; University of Pennsylvania
INTRODUCTION: Many women are cured of pelvic malignancies
through multimodality treatment. Some treatments, including radiation, are recognized to impact female sexual function in the long
term; however, patient perspectives on these outcomes are not well
understood, nor are contributions of other treatment forms. Here,
we describe patient-reported outcomes after pelvic radiation, as well
as radiation elsewhere and chemotherapy alone.
METHODS: Patient-reported data were gathered via convenience
sample frame from cancer survivors voluntarily using an internet
tool for the creation of survivorship care plans. The tool requires
entry of data regarding diagnosis, demographics, and treatments
and provides customized guidelines for future care. It is publically
available and free of charge, with > 300,000 total users since 2007.
During use of the tool, survivors are queried regarding their experience with late effects associated with specific treatments.
RESULTS: The tool was used by 7,258 female cancer survivors from
November 2012–October 2014. Overall, the group was 82%
Caucasian, with a median age of 51 years (range: 18–84 yr) and a
median time of 2.5 yr from diagnosis (range: < 1–38 yr). Of these
patients, 503 had received pelvic radiation as part of treatment for
gastrointestinal or gynecologic malignancies (37% vs 63%, respectively). Of the pelvic radiation group, 78% reported receiving external beam radiation (EBRT) with x-rays, 35% received brachytherapy
(55% in conjunction with EBRT and 45% alone), and 3% received
proton radiation. When the entire group was queried, “Have you
experienced sexual changes since completing treatment?” 42%
responded “yes,” 23% answered “no,” and 17% responded “I don’t
know.” The brachytherapy group was more likely to respond “yes”
(56%) than the EBRT-alone group (40%) (P < .05).
11
The pelvic radiation group was compared with patients receiving
radiation outside of the pelvis. Of this group, 34% responded “yes,”
32% responded “no,” and 34% responded “I don’t know” (P < .05
when compared with the pelvic radiation group). The pelvic radiation group was also compared with patients receiving chemotherapy
alone, with 38% responding “yes,” 29% responding “no,” and 33%
responding “I don’t know” (P < .05).
CONCLUSIONS: Reports of sexual changes in women after cancer
treatment are highest in patients receiving pelvic radiation, particularly brachytherapy. Rates of sexual changes are higher than expected in patients receiving radiation elsewhere and/or chemotherapy
alone. These findings support the need for both adequate patient
counseling prior to treatment and support for late-effect management afterwards.
(S025) Discovery and Validation of Predictive Factors
for Safety Incident Reports in Patients Receiving
Radiation Therapy: Comparative Results From a Large
Safety Variance Database Shereef M. Elnahal, MD, MBA, Amanda Blackford, SCM, Eric C. Ford,
PhD, Annette N. Souranis, Valerie Briner, Koren Smith, PhD, Todd R.
McNutt, PhD, Theodore L. Deweese, MD, Jean Wright, MD, Stephanie
A. Terezakis, MD; Johns Hopkins University School of Medicine; Department of Radiation Oncology, University of Washington; Department of
Radiation Oncology, Johns Hopkins Hospital
OBJECTIVES: Patient safety is a vital concern in radiotherapy, but
little is known about the factors that predict patients at risk for safety incidents. We aimed to: a) describe patients who have experienced safety incident reports; and b) compare them with a cohort
without events to identify predictive factors and build a nomogram
tool to identify patients at risk.
MATERIALS AND METHODS: We used our institution’s radiation
treatment safety incident reporting system to build a database of
patients who experienced events from January 2011–October 2014.
Patient and treatment-specific data were reviewed from our institution’s radiation management software program for a random selection of patients with events in our reporting system. A control group
of sequential patients in 2014 was generated for comparison.
Summary statistics, likelihood ratios, and mixed-effect logistic
regression models were used for group comparisons.
RESULTS: The safety incident group comprised 1050 events. Errors
in treatment planning (eg, incorrect planning target volume [PTV]
margins submitted) (35.2%) and documentation (eg, wrong patient
name denoted) (34.9%) were the most common incident types, followed by communication (17.5%) and treatment delivery (12.4%).
Several clinical and treatment-specific factors correlated with safety
reports. Incidents were much more frequently reported in minors
(age < 18 yr) than in adults (25.3% vs 5.4%; P < .001). Patients with
head and neck (16% vs 8%; P < .001) and breast (20% vs 15%; P =
.03) primaries were more frequently associated with an incident.
Larger tumors (19% vs 11% had T4 lesions; P = .02), a greater mean
number of fractions (24 vs 20; P = .02), and cases on protocol (9%
vs 5%; P = .005) or with intensity-modulated radiation therapy
(IMRT)/image-guided IMRT (IGMRT) (52% vs 43%; P = .001) were
12
associated with incident events. Of note, IMRT was used in 70.5%
of minors treated. Other independently associated factors were
found in patients with T4 tumors (19.5% protocol, 50.7% head and
neck, mean of 24 fractions). On multivariate analysis, dose per fraction, head and neck cases, pediatric patients, protocol enrollment,
and average pain score independently predicted for safety events.
CONCLUSIONS: We determined several patient and treatment-specific characteristics that predicted for treatment incident events.
Children were more susceptible to incident alerts, possibly related
to increased staff vigilance or more frequent use of complex modalities. Patients with head and neck tumors, greater number of fractions, treatment on protocol, and use of IMRT also predicted for
incidents. Independently predictive variables have been built into a
nomogram that will be validated in a prospective dataset, the results
of which will be available at the time of the meeting. (S026) A Novel Method for Detecting Serious Cardiac
Device Errors in Patients Receiving Radiotherapy Using
Daily Pulse Checks Jonathan D. Grant, MD, Anne Dougherty, MD, Karimzad Kaveh, MD,
Daniel R. Gomez, MD, Marc A. Rozner, PhD, MD; UT MD Anderson
Cancer Center
INTRODUCTION: Little consensus exists for the proper monitoring
of cardiac implantable electronic devices (CIEDs) in patients undergoing radiotherapy. We present data supporting a novel, easy, safe,
and cost-effective method for detecting serious CIED problems
arising during radiotherapy using daily heart rate (HR) monitoring.
MATERIALS AND METHODS: Since all CIEDs default to pacing at
60–72 beats per minute (bpm) without rate-response function
(RRF) upon detection of a serious error, we instituted the following
daily posttreatment pulse check protocol in 2010. Any patient who
can be safely paced at a lower set rate of 75 bpm with RRF undergoes
reprogramming at his preradiation CIED interrogation. Following
each fraction of radiotherapy, these patients rest for 5 minutes and
then undergo a pulse check. An HR of ≥ 74 bpm verifies the absence
of a serious error. Because paroxysmal ventricular contractions may
permit perfused pulses that register < 74 bpm, “tapping” on the
CIED ensues to simulate patient exercise. An HR increase verifies
the appropriate programming and the absence of a serious error. In
a patient with an HR ≤ 73 and nonresponse to the tapping maneuver, a serious error is suspected, and a CIED interrogation is performed. At the completion of radiotherapy, device interrogation is
performed for all patients, with return of the CIED to the appropriate settings.
RESULTS: Between February 2010 and October 2013, a total of 36
patients with CIEDs received treatment at the proton therapy center,
29 (81%) of whom were eligible for the pulse protocol. We found four
patients (14%) with five serious CIED errors, manifested as a device
parameter reset. A total of 845 fractions of radiotherapy were delivered in this cohort, giving an error rate per fraction of 0.6%. All affected patients were detected by a decrease in the measured HR of ≤ 73.
No additional resets were discovered on any other device at routine
posttreatment interrogation. No adverse events were experienced by
any patient as a result of the increased lower pace rate. In one patient
with HR < 74 bpm, the “tapping maneuver” confirmed the absence of
a reset and prevented an unnecessary device interrogation.
CONCLUSIONS: A novel method for monitoring CIEDs during
radiotherapy is presented, which we report as effective, easy, and
lacking adverse side effects. This simple technique is a cost-effective
alternative to frequent device interrogations during the course of
radiotherapy and allows for consistent daily monitoring.
(S027) Novel Mechanisms of Adaptive Resistance
in Head and Neck Cancer Vinita Takiar, MD, PhD, Jennifer B. Dennison, PhD, Shreya Mitra, PhD,
Dominic Ma, BS, Jack Phan, MD, PhD, Gordon B. Mills, MD, PhD; UT
MD Anderson Cancer Center
OBJECTIVE: Locoregional recurrence after definitive radiation therapy (XRT) for head and neck (H&N) cancer is a significant clinical
challenge, with many patients failing after combined doses > 100 Gy.
Although multimodality treatment is prescribed for many cancers,
such treatment algorithms are generally empiric, with no identified
molecular basis. The efficacy of XRT is limited by intrinsic and
acquired radioresistance. We hypothesize that resistance to XRT is,
at least in part, mediated by adaptive signaling events induced by the
XRT itself. Using signal transduction to better understand these
adaptive responses is therefore crucial to developing rational treatment combinations that increase the therapeutic efficacy of XRT.
MATERIALS AND METHODS: Two representative H&N cell lines
(FaDu and HN5) were grown in both two dimensions (2D) and
three dimensions (3D) (spheroids suspended in Matrigel). Based on
cell survival assays conducted in 2D culture, a dose of 4 Gy (~LD50)
was chosen for subsequent experiments. Cells in both 2D and 3D
were exposed to either 0 Gy or 4 Gy with a cobalt-60 source and
then subjected to high-throughput reverse phase protein analysis
(RPPA) to screen for differential protein expression in cells able to
survive radiation. As the expression of multiple energy-related
metabolites was increased, oxygen consumption rate (OCR), which
is a readout of aerobic respiration, was subsequently analyzed using
an extracellular flux analyzer. RESULTS: Both HN5 and FaDu cells formed intact monolayers in
2D and spheroids in 3D. Radiation of 4 Gy in one fraction resulted
in differential expression of multiple signaling pathways in both cell
lines, with significant upregulation of multiple components of the
mammalian target of rapamycin (mTOR) pathway (P < .05), including pACC, pAMPK, pAkt, and p70S6K—collectively suggesting
altered energy metabolism. Glutamine metabolism, regulated by the
mTOR pathway, serves as an anaplerotic and limiting reagent for
citric acid cycle progression and thus serves as a proof-of-concept
pathway. Using a glutaminase-specific inhibitor that prevents the
conversion of glutamine to glutamate, we report that the cellular
OCR was significantly reduced (P < .001) in the presence of glutamine. However, the OCR was unchanged in the presence of glucose
alone, suggesting that glutamine metabolism is indeed the driver of
aerobic respiration in these cells.
CONCLUSIONS: Targeted combinatorial therapy with XRT is neces-
sary to overcome adaptive radioresistance. RPPA is a powerful pro
teomic platform, suggesting alterations in energy metabolism following XRT that are targetable by inhibition of the enzyme glutaminase. Further in vivo experiments with glutaminase inhibition
and xenograft models to assess combinatorial efficacy with radiation are warranted.
(S028) Patient-Level DNA Damage and Repair
Pathway Profiles Are Prognostic After Prostatectomy
for High-Risk Prostate Cancer Joseph R. Evans, MD, PhD, Shuang Zhao, MSE, Scott A. Tomlins, MD,
PhD, Karen E. Knudsen, PhD, Eric A. Klein, MD, Robert B. Den, MD, R.
Jeffrey Karnes, MD, Elai Davivioni, PhD, Felix Y. Feng, MD; University
of Michigan; Thomas Jefferson University; Cleveland Clinic; Mayo Clinic;
GenomeDx Biosciences Inc.
PURPOSE/OBJECTIVES: A substantial number of patients who are
diagnosed with high-risk prostate cancer are at risk for metastatic
progression after primary treatment. Better biomarkers are needed
to identify patients who are at the highest risk so that therapy can be
intensified. MATERIALS AND METHODS: We developed a novel patient-level
DNA damage and repair (DDR) pathway profiling approach in a
cohort of 1,090 patients undergoing prostatectomy for high-risk
prostate cancer who had long follow-up (mean, 7–13 yr). Highdensity microarray gene expression data from prostatectomy samples were analyzed for DDR pathway enrichment with the gene set
enrichment analysis algorithm and clustered hierarchically. The
prognostic performance of pathway-based biomarkers for metastatic progression and overall survival (OS) was analyzed with univariate and multivariate logistic regression models. RESULTS: We found that there were distinct clusters of DDR pathway patterns within the cohort. DDR pathway enrichment correlated only weakly with the clinical variables age, Gleason score, and
PSA (Spearman’s rho ≤ 0.20) and correlated much more strongly
with AR pathway enrichment (Spearman’s rho up to 0.82). Many of
the individual pathways were significantly associated with increased
metastatic progression risk (odds ratio [OR] = 1.28–1.78) and worse
OS (OR = 1.51–2.23) on univariate and multivariate analysis, and a
composite DDR pathway biomarker showed improved prognostic
performance for metastatic progression risk (OR = 2.09 [1.33,
3.28]). Interestingly, this prognostic significance was restricted to
patients aged < 70 years. CONCLUSIONS: Patient-level DDR pathway profiling revealed distinct clusters. Individual DDR pathways and a composite biomarker
showed strong prognostic performance with the long-term outcomes
of metastatic progression and OS, which may be useful for risk stratification of high-risk prostate cancer patients aged < 70 years.
(S029) Evaluating the Role of a 21-Gene Expression
Assay in Directing Adjuvant Radiotherapy Decisions
for Elderly Women With Early-Stage Breast Cancer Charles E. Rutter, MD, Nataniel H. Lester-Coll, MD, Suzanne B. Evans,
MD, MPH; Department of Therapeutic Radiology, Yale University School
of Medicine
13
Objective: Adjuvant breast radiotherapy (RT) after breast-conserving surgery (BCS) in elderly women with early-stage breast cancer (ESBC) confers a local control benefit but no improvement in
overall survival. Hence, the role of RT in this population is uncertain. In the separate context of adjuvant chemotherapy recommendations for node-negative ESBC, gene expression testing has allowed
risk-adapted decision making and has had a marked impact on
clinical practice. We sought to determine the potential role and costeffectiveness of gene expression testing in directing adjuvant RT
decisions for elderly ESBC patients, given a published relationship
of Oncotype DX (ODX) results with local-regional recurrence risk.
METHODS: The distribution of ODX recurrence scores (RSs) among
elderly women (aged ≥ 70 yr) with estrogen receptor–positive ESBC
(pT1N0M0) post-BCS was defined within the National Cancer Data
Base (NCDB), using standard definitions of low (< 18), intermediate
(18–30), and high risk (> 30). Next, a decision tree was constructed
to determine the overall cost-effectiveness of ODX in directing RT
recommendations. Local-regional recurrence estimates at 10 years
were extrapolated from the literature and assumed to be 1%, 3%,
and 5% in patients with low, intermediate, and high RSs, respectively, following BCS, RT, and 5 years of tamoxifen. Rates of adjuvant
radiotherapy utilization for each RS stratum were based upon published patterns of RS-guided adjuvant chemotherapy utilization.
RESULTS: We identified 2,564 elderly ESBC patients treated between
2007 and 2011 within the NCDB with ODX RS results. Median age
and tumor size were 73 years (range: 70–90 yr) and 1.2 cm (range:
0.1–2 cm), respectively. Median RS was 15 (standard deviation [SD]
= 8.3). RS was low, intermediate, and high in 69.2%, 28.3%, and
2.5% of patients, respectively. Neither age nor tumor size was associated with RS. ODX-directed adjuvant radiotherapy recommendations resulted in a net savings of $1,163.05 per patient and a utility
decrease of 0.024 quality-adjusted life years (QALYs) relative to current clinical practice, yielding an incremental cost-effectiveness
ratio for ODX-directed adjuvant radiotherapy of $47,920.78/QALY.
CONCLUSIONS: We observed a wide range of RSs among elderly
ESBC patients in the NCDB. Further research is needed to determine if gene expression assays are capable of risk-stratifying within
this population, as a means for directing adjuvant RT recommendations after BCS. Should this be proven, our findings would suggest
that ODX-directed decision-making is theoretically cost-effective at
a conservative willingness-to-pay threshold of $50,000/QALY.
varying results, with some showing equivalence and others favoring
M. Outcomes for BCT have improved significantly over time. The
most appropriate comparison for BCT and M should reflect treatment techniques from the modern era. We hypothesize that in the
modern treatment era, BCT and M have equivalent outcomes.
METHODS: Breast cancers diagnosed between 1975 and 2012 in
women aged ≤ 40 years were collected from our institutional tumor
registry. Four cohorts were then created based on year of diagnosis
and treatment approach: BCT before 2000, BCT during or after
2000, M before 2000, and M during or after 2000. Vital status and
cause of death were obtained from the government cancer registry.
Kaplan-Meier survival estimates were used to analyze the primary
outcome (freedom from locoregional recurrence [FFLR]) and secondary outcomes (overall survival [OS] and relapse-free survival
[RFS]).
RESULTS: A total of 427 BCT candidates were identified from our
institutional tumor registry. Among those who received BCT, OS
and RFS were similar for those diagnosed before and after 2000.
FFLR, however, was significantly improved after 2000. FFLR at 10
years was 78.8% vs 95.4% for BCT before and after 2000, respectively (P = .03). Among those who received M, OS (P = .03) and RFS
(P < .0001) were significantly improved with diagnosis after 2000.
FFLR at 10 years was 85.6% vs 93.1% for M before and after 2000,
respectively (P = .08). When comparing BCT and M after 2000,
FFLR, RFS, and OS were all similar. FFLR at 10 years was 95.4% vs
93.1% for BCT and M, respectively (P = .75). When comparing BCT
and M before 2000, OS and RFS rates were similar.
CONCLUSIONS: Outcomes for women with breast cancer aged ≤ 40
years undergoing BCT and M have improved significantly over
time, likely reflecting the advent of improved local and systemic
therapies. In addition, for women treated after 2000, BCT appears
to be safe and equivalent to M at 10 years in terms of FFLR, OS, and
RFS.
(S031) Dosimetric Analysis of Left-Sided Breast Cancer
Treatment With Tomotherapy IMRT, IMRT, VMAT, and
3D-CRT Twisha Chakravarty, MD, Eugene C. Endres, Brent Parker, PhD, DABR,
Sandra Hatch, MD; University of Texas Medical Branch
Jonathan Frandsen, MD, David Ly, MD, MPA, Gita Suneja, MD, MPH,
Cindy Matsen, MD, Matthew Poppe, MD; Department of Radiation Oncology, Department of General Surgery, Huntsman Cancer Hospital, University of Utah School of Medicine
OBJECTIVES: Previous studies have demonstrated that the risk of
ischemic heart disease is increased as a result of exposure to ionizing
radiation in women treated for breast cancer. Alternative radiation
techniques, such as intensity-modulated radiation therapy (IMRT),
volumetric-modulated arc therapy (VMAT), and TomoTherapy
IMRT, have been shown to improve dosimetric parameters of the
heart and substructures. However, these techniques have not been
compared with each other to potentially guide treatment decisions.
INTRODUCTION: Women aged < 40 years with breast cancer have
worse outcomes compared with older women. Mastectomy (M) is
often recommended as primary therapy, even for women with earlystage disease, because young women have been underrepresented in
the landmark trials showing equivalence of breast conservation therapy (BCT) and M. Retrospective series comparing BCT and M show
METHODS: Treatment plans from 10 patients treated to the whole
breast for left-sided breast cancer in 2014 were collected. Treatment
plans using TomoTherapy IMRT, IMRT, VMAT, and three-dimensional (3D) conformal radiation therapy with TomoDirect and
opposed tangents were generated for each patient. Dosimetric
parameters for the heart, left ventricle, and left anterior descending
(S030) Breast Conservation in Young Women in the
Modern Era 14
artery (LAD), including V2, V5, V10, Dmax, and mean doses, were
collected and analyzed using paired t-test and analysis of variance
(ANOVA).
RESULTS: For V2 of the LAD, no statistically significant difference
was found between TomoTherapy IMRT and 3D conformal plans
(67.2% vs 70.5% vs 75.0%; P = .49); however, TomoTherapy IMRT
plans had significantly reduced V5 of the LAD when compared with
3D conformal plans, as well as IMRT and VMAT (2.0% vs range:
12.0–49.0%; P < .01). With regard to the heart and left ventricle, the
V2 was significantly lower for 3D conformal plans vs TomoTherapy
IMRT, VMAT, and IMRT (P < .01). This difference was maintained
for V5 for the heart but not for the left ventricle. Across all three
cardiac parameters, the average Dmax was significantly lower with
TomoTherapy IMRT plans when compared with all other planning
techniques (P < .01). CONCLUSIONS: Our analysis of this single-institution population of
women with left-sided breast cancer treated to the whole breast
demonstrates that differing radiation treatment techniques have statistically significant impacts on dosimetric parameters of the heart,
left ventricle, and LAD. TomoTherapy IMRT was shown to be superior for reducing low-dose radiation to the LAD and maximum dose
to all cardiac structures, particularly when compared with VMAT
and IMRT. No significant difference was demonstrated in low-dose
radiation exposure from treatment with TomoDirect vs opposed
tangents. These results provide insight into treatment differences
that may help guide clinical practice in the future, with an emphasis
on reducing long-term patient toxicity. (S032) Complications of Contralateral Prophylactic
Mastectomy With Tissue Expander Reconstruction and
Potential Impact on Adjuvant Oncologic Therapy Rahul D. Tendulkar, MD, Neil M. Woody, MD, Mihir Naik, DO,
Chandana A. Reddy, MS, Paul Durand, MD, Adekunle Elegbede, Eliana
Duraes, Stephen R. Grobmyer, MD, Joseph P. Crowe, MD, Risal Djohan,
MD; Cleveland Clinic
PURPOSE: One concern of contralateral prophylactic mastectomy
(CPM) is that a complication may delay adjuvant chemotherapy or
radiotherapy for breast cancer. We report acute (< 6 mo), delayed (>
6 mo), and total complication rates in patients undergoing synchronous bilateral mastectomies and tissue expander reconstruction
(TER), comparing complications between the ipsilateral (therapeutic) side and the contralateral (prophylactic) side within a perfectly
matched cohort.
METHODS: We conducted a retrospective review of breast cancer
patients treated at Cleveland Clinic from 2000–2007, and 88 women
undergoing synchronous bilateral mastectomies with TER for unilateral invasive breast cancer were identified. Complications were
defined as hematoma or seroma requiring reoperation, blood transfusion, capsular contracture (Baker grade III–IV), wound infection
requiring intravenous (IV) antibiotics or implant removal, wound
dehiscence, implant leak, and extrusion. The timing and laterality of
complications were determined to compare the therapeutic and prophylactic sides.
RESULTS: The median age was 43 years (range: 23–63 yr), and the
median follow-up was 6.1 years. Overall, 64 patients (73%) were
premenopausal, 39 (44%) were lymph node-positive, 18 (20%)
received preoperative chemotherapy, 57 (65%) received postoperative chemotherapy, and 24 (28%) received postoperative radiation
therapy to the ipsilateral side. Twelve patients (14%) had received
prior breast radiotherapy and underwent mastectomy for recurrence. Total complications on the therapeutic side were more common than on the prophylactic side, including wound dehiscence
(4% vs 1%; P = .17), capsular contracture (13% vs 5%; P = .06),
implant extrusion (10% vs 2%; P = .03), wound infection (20% vs
9%; P = .04), any complication (38% vs 25%; P = .08), and reoperation for a complication (34% vs 21%; P = .048). On the therapeutic
side, 23 of 36 (64%) radiated TER patients experienced a complication compared with 10 of 52 (19%) nonirradiated patients (P <
.0001). Delayed complications were more common on the therapeutic side than on the prophylactic side (24% vs 13%; P = .04), but
acute complication rates were similar (14% vs 13%, respectively; P
= .8). Among 11 patients with an acute complication of a CPM,
receipt of postoperative chemotherapy or radiotherapy was actually
delayed by a complication in 2 of 63 (3%) patients who received
adjuvant treatment.
CONCLUSIONS: CPM with TER resulted in a complication in 25%
of patients, half of which occurred within 6 months of surgery.
However, adjuvant chemotherapy or radiotherapy was delayed by
acute complications in only 3% after CPM. Delayed complication
rates were higher on the therapeutic side, possibly due to effects of
radiotherapy. These data may better inform patients considering
bilateral mastectomies with TER.
(S033) Predictive Capacity of Three Comorbidity
Indices in Estimating Survival Endpoints in Women
With Early-Stage Endometrial Carcinoma Sean Vance, MD, Meredith Mahan, Mohamed Elshaikh, MD; Henry
Ford Hospital
PURPOSE/OBJECTIVES: The negative impact of medical comorbidity on survival endpoints in women with endometrial carcinoma
(EC) is well known. Few validated comorbidity indices are available
for clinical use—eg, the Charlson Comorbidity Index (CCI), ageadjusted Charlson Comorbidity Index (AACCI), and Adult
Comorbidity Evaluation-27 (ACE-27). The study goal is to evaluate
which index correlates best with survival endpoints in women with
early-stage EC.
MATERIALS AND METHODS: For this institutional review board
(IRB)-approved study, our prospectively maintained database of
1,920 women with endometrial cancer was reviewed. We identified
1,132 women with endometrioid carcinoma International
Federation of Gynecology and Obstetrics (FIGO) stages I–II who
underwent hysterectomy from 1987–2011. The three comorbidity
indices at the time of hysterectomy were retrospectively calculated
by physician chart review. Univariate and multivariate modeling
with Cox regression analysis was used to determine the significant
predictors of survival endpoints. Kaplan-Meier and log-rank test
methods were used to evaluate survival outcomes.
15
RESULTS: After a median follow-up of 60 months, 262 deaths were
recorded (42 from EC [16%] and 220 [84%] from other causes). For
each of the studied comorbidity indices, the highest scores correlated significantly with poorer overall survival (OS). The hazard
ratio of death from any cause was 3.92 (95% confidence interval
[CI], 2.95–5.20) for AACCI, 2.25 (95% CI, 1.73–2.94) for CCI, and
1.57 (95% CI, 1.23–2.01) for ACE-27. Lymphovascular space
involvement, tumor grade, lower uterine segment involvement, and
AACCI were independent predictors of OS. None of the three
comorbidity indices was significantly predictive of disease-specific
or recurrence-free survival.
ropathy, 4/105 (3.8%) metabolic, and 1/105 (0.95%) venous thromboembolism. Dose reduction occurred in 6/115 cycles (5.2%), and
dose delay occurred in 12/115 cycles (10.4%). Since the study onset,
1 of 21 pts had a recurrence (lung) and died of disease.
CONCLUSIONS: While all three comorbidity indices correlated significantly with OS in women with early-stage EC, AACCI was the
only independent predictor of OS and should be considered for
evaluating comorbidity in future endometrial cancer patients. (S035) Cervical Cancer Outcome Prediction to HighDose-Rate Brachytherapy Using Quantitative Magnetic
Resonance Imaging Analysis of Tumor Response to
External Beam Radiotherapy (S034) Pilot Phase II Trial of “Sandwich” Radiation and
Combination Carboplatin and Paclitaxel Chemotherapy
in Patients With High-Risk Endometrial Cancer Lori Spoozak, MD, MHS, Divya Gupta, MD, Laura Reimers, MPH,
Jennifer Jorgensen, MD, Rafi Kabarriti, MD, Keyur Mehta, MD, Gary
Goldberg, MD, Mark Einstein, MD, MS, Dennis Yi-Shin Kuo, MD; Albert Einstein College of Medicine; Weill Cornell Medical College
OBJECTIVES: We sought to determine the toxicity, tolerability,
and outcome of radiation therapy (RT) sandwiched between
combination chemotherapy in patients (pts) with high-risk endometrial cancer.
CONCLUSIONS: Sandwich chemotherapy and radiation therapy is a
tolerable treatment modality for patients with high-risk endometrial cancer. Rates of hematologic toxicities are acceptable, and nonhematologic toxicities are uncommon. Further enrollment of
patients is underway to determine efficacy.
Beant S. Gill, MD, David Minkoff, BA, Hayeon Kim, MS, DABR,
Christopher Houser, MS, Sushil Beriwal, MD; Magee-Womens Hospital,
University of Pittsburgh Medical Center
PURPOSE: Image-guided brachytherapy (IGBT) has been shown to
improve outcomes for cervical cancer. Integration of magnetic resonance imaging (MRI) allows visualization of residual disease. In
order to assess tumor regression and outcomes, a volumetric analysis was conducted among patients treated with MRI-based IGBT.
METHODS: High-risk endometrial cancer was defined as surgically
staged endometrioid adenocarcinoma, IA with grade (G) 3 tumor and
with lymphovascular space involvement, IB with G2 or 3 tumor, and
stage II–IV disease, any grade. Treatment involved paclitaxel (T) (175
mg/m2) and carboplatin (C) (area under the concentration-time
curve [AUC] = 6.0 or 6.5) every 21 days × 3 doses, followed by pelvic
external beam radiation therapy (45 Gy) and brachytherapy (15 Gy).
Per protocol, brachytherapy only (25 Gy) was administered to pts with
stage IA G3 and IB G2 disease. Three additional cycles of T/C (AUC
= 5) were administered after RT. Toxicity was graded by Common
Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).
Analysis of toxicities was performed on all evaluable pts.
METHODS: Consecutive patients with International Federation of
Gynecology and Obstetrics (FIGO) stage IB1–IVA cervical cancer
receiving definitive chemoradiation from 2007–2013 were identified. Patients were excluded if they were undergoing perineal template-based interstitial brachytherapy or if MRI was not completed
prior to therapy and at first brachytherapy application. All patients
were treated using a ring and tandem with or without interstitial
needles. High-dose-rate brachytherapy was delivered in five onceor twice-weekly fractions of 5–6 Gy/fraction. Optimization was
completed to meet the following cumulative equivalent 2-Gy doses
(EQD2): high-risk clinical target volume (HRCTV) 75–85 Gy and 2
cc of rectum ≤ 70 Gy, sigmoid ≤ 70 Gy, and bladder ≤ 85 Gy.
T2-weighted imaging using 1.5-T MRI was completed following
brachytherapy applicator insertion. Gross tumor volumes (GTVs)
were retrospectively contoured and defined: GTV prior to therapy
(GTVPre-EBRT), GTV at first application (GTVIGBT), and percentage
residual GTV at first application (GTV%Residual).
RESULTS: A total of 21 pts were enrolled between 2008–2014. The
median age was 62 years (range: 48–74 yr): 66.7% (14/21) pts had
stage I/II disease, while the remaining 33.3% (7/21) had stage IIIC
disease; 42.9% (9/21) had International Federation of Gynecology
and Obstetrics (FIGO) G1 disease, and 23.8% (5/21) and 33.3%
(7/21) had G2 and 3 disease, respectively; 66.7% (14/21) pts completed the treatment per protocol; and 76.2% (16/21) pts completed
six cycles of chemotherapy. One pt refused chemotherapy after
enrollment, and four pts could not complete chemotherapy due to
hematologic toxicities. Of 115 evaluable chemotherapy cycles, the
G3 or 4 combined hematologic toxicity events were as follows:
33/115 cycles (28.7%) neutropenia, 9/115 cycles (7.8%) thrombocytopenia, and 10/115 cycles (8.7%) anemia. Of 105 evaluable chemotherapy cycles, the G3 or 4 combined nonhematologic events were
as follows: 2/105 cycles (1.9%) infection, 1/105 cycles (0.95%) neu-
RESULTS: Eighty-four patients were identified. The majority had
FIGO stage IIB disease (57.1%) and squamous histology (82.1%) and
received median external beam and brachytherapy doses of 45.0 Gy
and 27.5 Gy, respectively. With a 20.8-month (range: 3–74 mo) median follow-up, the 2-year Kaplan-Meier estimates of local control (LC),
disease-free survival (DFS), and overall survival (OS) were 91.3%,
79.8%, and 85.0%, respectively. Median GTVPre-EBRT, GTVIGBT, and
GTV%Residual values were 31.9 cc (range: 2.6–171.3 cc), 3.5 cc (range:
0.0–36.6 cc), and 9.7% (range: 0.0%–67.3%). Multivariate Cox regression revealed adenocarcinoma (hazard ratio [HR] = 5.76; P = .03) and
GTVIGBT (HR = 1.17; P < .01) as predictors for local failure.
Additionally, GTVIGBT was associated with any disease recurrence
(HR = 1.17; P < .01) and overall mortality (HR = 1.20; P < .01).
GTVIGBT > 7.5 cc was associated with inferior 2-year LC (75.0% vs
96.6%; P < .01), DFS (42.6% vs 91.6%; P < .01), and OS (65.2% vs
16
91.5%; P < .01). No difference in mean HRCTV D90 EQD2 was seen
between these groups (83.2±2.2 Gy vs 83.5±2.7 Gy; P = .61).
CONCLUSION: Aside from the known benefits of IGBT, MRI-based
planning allows for assessment of tumor regression and prognosticates patients, as shown in the present study. If these findings are
replicated in prospective trials, alternative methods, such as dose
escalation and surgical salvage, should be considered to offset poor
prognoses.
(S036) Circulating Tumor DNA and Implications for
Clinical Decision-Making in Stage I NSCLC Julie Koenig, Ben Durkee, Erqi Pollom, Iris Gibbs, Max Diehn; Stanford
University School of Medicine; Department of Radiation Oncology, Stanford University Medical Center; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
BACKGROUND: A nontrivial fraction of stage I non–small-cell lung
cancer (NSCLC) is occult metastatic disease [Rusch, JCO 2011].
These patients have worse disease-free survival and overall survival
(OS) [Rusch, JCO 2011]. The phase III Cancer and Leukemia Group
B (CALGB) 9633 trial found a small benefit for adjuvant chemotherapy in stage I patients with high-risk disease based on size criterion [Strauss, JCO 2008]. However, the authors could not reproducibly identify these high-risk patients [Strauss, JCO 2008].
Circulating tumor DNA (ctDNA) is highly predictive of residual
disease after definitive therapy [Newman, Nat Med 2014]. We
hypothesize that ctDNA could identify high-risk patients with stage
I NSCLC who could benefit from early systemic therapy.
METHODS: We created a Bayesian model to simulate posterior
probabilities after screening for occult metastatic disease by ctDNA.
We used prevalence data from the American College of Surgeons
Oncology Group (ACOSOG) Z0040 trial, and recently published
receiver operating characteristics for ctDNA [Newman, Nat Med
2014].
Next, we built a two-state Markov model, with the assumption that
occult micrometastases conferred worse survival (hazard ratio [HR]
= 1.82), based on ACOSOG. Patients receiving chemotherapy were
assigned a survival benefit (HR = 0.69, high risk) and detriment
(HR = 1.12, low risk) by extrapolation from Cancer and Leukemia
Group B (CALGB) trial 9633. The model was run with no patient
receiving chemotherapy and rerun with patients who had detectable
ctDNA receiving adjuvant chemotherapy.
high-risk patients could benefit from systemic therapy. There are
limitations to this study: a model does not substitute for a clinical
trial. We did not do a sensitivity analysis. Our time horizon (3 yr) is
short. We assumed that our high-risk patients (defined by ctDNA)
would derive the same benefit as high-risk patients in the CALGB
trial (defined by size). To support this, the data show that ctDNA
levels correlate with tumor volume [Newman, Nat Med 2014]. We
assumed that occult micrometastases and ctDNA had clinical significance, which is supported in published literature.
(S037) Phenotypic Diversity Measured in PET/CT
Scans Predicts Overall Survival in Early-Stage Lung
Adenocarcinoma Jennifer S. Chang, Viola Walther, Natalie Lui, Aleah F. Caulin, David
Jablons, Carlo Maley, Trevor Graham, Sue S. Yom; University of California, San Francisco; Barts Cancer Institute, Queen Mary University of
London
BACKGROUND: Although most patients with early-stage lung adenocarcinoma have favorable outcomes, stratification of a high-risk subset may facilitate clinical decision making on therapy and surveillance. The degree of within-tumor heterogeneity may be a prognostic
biomarker, as more diverse tumors are more likely to contain a subpopulation that is adapted to a new selective pressure (eg, radiotherapy), whereas homogeneous tumors are less likely to harbor a resistant
subclone. We recently found that within-tumor genetic heterogeneity
predicts overall survival (OS) in patients with early-stage lung adenocarcinoma. Here, we investigated whether quantification of withintumor phenotypic diversity, measured by 18-fluorodeoxyglucosepositron emission tomography (FDG-PET) and computed tomography (CT) imaging, was also a predictor of OS.
METHODS: Genetic analysis had previously been performed on 58
patients initially diagnosed with stage I/II lung adenocarcinoma,
treated with surgery and no neoadjuvant therapy. We obtained the
presurgery PET and CT scans. The primary lung lesion was contoured on PET and CT scans using the software program MIM 5.6.
Phenotypic diversity was then quantified using the Moran I statistic,
which describes spatial autocorrelation. The prognostic value of the
Moran I coefficient was assessed using Cox proportional hazards
(CPH) models and Kaplan-Meier curves. Statistical analyses were
performed in R.
RESULTS: The 3-year OS rate was 71% and 73% for high- and lowrisk patients, respectively, with a total payoff of 2.56 life-years. These
modeled estimates correlate well with CALGB data. The positive
likelihood ratio for ctDNA was 10.0. After screening for ctDNA, the
posterior probability of occult disease for a positive test improved to
67.0%, from a baseline prevalence of 16.9%. Treating high-risk
patients with adjuvant chemotherapy improved survival to 79%.
The number needed to treat was 12.5.
RESULTS: Tumors were contoured on 46 CT and 32 PET
scans. Differences in phenotypic diversity were identified across the
cohort for both PET and CT images. Patients in the upper quartile
of Moran I values (phenotypic diversity) had significantly shorter
survival using PET scans (log-ranked: P = .02; CPH: P = .08; hazard
ratio [HR] = 2.72; 95% confidence interval [CI], 0.88–8.39), and the
upper quartile was borderline significant for CT scans (log-ranked:
P = .051; CPH: P = .061; HR = 2.83; 95% CI, 0.95–8.45). There was
a weak rank correlation between Moran’s I statistic and genetic
diversity for both PET (P = .85) and CT (P = .21). Moran I and
genetic diversity were significant predictors for overall survival
using PET scans (Moran I: P = .045; genetic diversity: P = .032).
CONCLUSION: Our model suggests that ctDNA could improve
clinical decision-making for stage I NSCLC. Prospectively identified
CONCLUSIONS: These results suggest that within-tumor phenotypic diversity, as quantified in PET-CT scans, can predict OS in
17
patients with early-stage lung adenocarcinoma. Quantification of
within-tumor heterogeneity in this routine clinical imaging may
provide a noninvasive method for identifying a high-risk subset of
patients with early-stage non–small-cell lung cancer.
(S038) Pulmonary Dose-Volume Predictors of Radiation
Pneumonitis Following Stereotactic Body Radiation
Therapy Eileen M. Harder, BS, Henry S. Park, MD, MPH, Zhe Chen, PhD,
FAAPM, Roy H. Decker, MD, PhD; Department of Therapeutic Radiology, Yale University School of Medicine
PURPOSE: Radiation pneumonitis (RP) can be a significant risk
after stereotactic body radiation therapy (SBRT). The purpose of
this study was to identify clinical and dosimetric predictors of symptomatic (grade ≥ 2) RP following pulmonary SBRT. MATERIALS AND METHODS: Patients with ≥ 3 months of follow-up
who received SBRT for primary lung cancer were selected from an
institutional database. RP was determined retrospectively from all
available records, including those from appointments with radiation
oncology, pulmonology, and medical oncology and hospitalizations.
RP was scored per Common Terminology Criteria for Adverse
Events version 4.0 (CTCAE v4.0). Normal lung volume was defined
as total lung volume minus gross tumor volume (GTV) on the planning computed tomography (CT). Pulmonary Dmax (maximum
point dose), mean lung dose (MLD), and Vx (volume of lung receiving ≥ x Gy) in 5-Gy increments were collected. Univariate analyses
were performed with the chi-square or Student’s t-test. Dosimetric
predictors of RP were identified using multivariate logistic regression with a manual forward stepwise selection technique.
RESULTS: A total of 264 patients were included (median follow-up
29.4 mo). Median prescription dose was 54 Gy (range: 40–60 Gy).
Patient characteristics were as follows: 27 (10.2%) had multifocal
disease, 58 (22.0%) had T-stage ≥ 2, 26 (9.8%) had prior lung radiotherapy (4.2% with SBRT), and 72 (27.3%) had prior lung resection.
Grade ≥ 2 RP occurred in 61 patients (23.1%) with a median onset
time of 1.8 months (range: 0.1–16.2 mo). Grade ≥ 3 RP occurred in
23 patients (8.7%). Lung V5, V10, V15, V20, V25, V30, V35, V40,
V45, and MLD were significantly associated with grade ≥ 2 RP on
univariate analysis (P < .05), but no correlation was seen with lung
V50, lung Dmax, age, gender, Eastern Cooperative Oncology Group
(ECOG) performance status, cigarette use, T stage, location (central/peripheral), lobe (upper/lower) synchronicity, prescribed BED,
GTV, ITV, PTV, pretreatment pulmonary comorbidity, or any heart
dosimetric volume. Among these significant factors, lung V10 was
the strongest predictor of RP on multivariate analysis (P = .006). The
median lung V10 was 10.9 Gy. Symptomatic RP was present in
18.9% of patients receiving lung V10 < 10.9 Gy, compared with
27.3% with lung V10 ≥ 10.9 Gy. CONCLUSIONS: Symptomatic RP occurred in 23.1% of our patients
treated with SBRT. Lung V10 was the strongest predictor of grade ≥ 2
RP on multivariate logistic regression, associated with a 30% decrease
in risk for patients with V10 < 10.9 Gy compared with ≥ 10.9 Gy.
Further research is needed to validate these findings and the importance of lung V10 in predicting symptomatic RP following SBRT.
18
(S039) High-Resolution 4D Ventilation and Perfusion
PET/CT Facilitates Functionally Adapted IntensityModulated Radiation Therapy (IMRT) in Lung Cancer David Ball, MD; Peter MacCallum Cancer Centre
PURPOSE: To assess the utility of functional lung avoidance using
intensity-modulated radiation therapy (IMRT) informed by fourdimensional ventilation/perfusion positron emission tomography/
computed tompgraphy (4D-V/Q PET/CT) in patients with non–
small-cell lung cancer (NSCLC).
MATERIALS AND METHODS: In a prospective clinical trial, patients
underwent 4D-V/Q PET/CT scanning before 60 Gy of definitive
chemoradiation. Both “highly perfused” (HPLung) and “highly ventilated” (HVLung) lung volumes were delineated using a visually
adapted 70th percentile standardized uptake value (SUV) threshold
method. The HVLung was universally smaller than HPLung; so, a
“ventilated lung volume” (VLung) was created to approximate the
HPLung using a 50th percentile SUV threshold. For each patient,
four IMRT plans were created, optimized to the anatomical lung,
HPLung, VLung, and HPLung volumes. IMRT that was optimized
to the anatomical lung was compared with functionally adapted
IMRT using functional lung volumetrics, including mean lung dose
(MLD), V5, V10, V20, V30, V40, V50, and V60 parameters. Plan
quality was assessed by dose to 95% and 5% of planning target volume (PTV) (D95 and D5), conformity index (CI), and heterogeneity index (HI).
RESULTS: The study cohort consisted of 20 patients with 80 IMRT
plans. The mean (+/– SD) lung volume for the HPLung and VLung
was similar at 1,876 cc (+/– 677 cc) and 1,904 cc (+/– 505 cc),
respectively, while HVLung was smaller at 932 cc (+/– 258 cc). Plans
that were optimized to HPLung resulted in a significant reduction
of functional MLD by a mean of 13.0% (1.7 Gy; P = .02). Functional
V5, V10, and V20 were improved by 13.2%, 7.3%, and 3.8%, respectively (P < .04). There was no sparing of dose to functional lung
when adapting to VLung or HVLung. Plan quality was highly consistent with a mean PTV D95 and D5, ranging from 60.8–61.0 Gy
and 63.4–64.5 Gy, respectively, and with mean CI and HI ranging
from 1.11–1.17 and 0.94–0.95, respectively.
CONCLUSIONS: IMRT plans that were adapted to perfused but not
ventilated lung on 4D-V/Q PET/CT allowed for reduced dose to the
functional lung while maintaining consistent plan quality.
(S040) Has Severe Acute Esophagitis Been Reduced by
21st Century Treatment Modalities Among
Patients With Limited-Stage Small-Cell Lung Cancer? Ritsuko Komaki, MD, Pamela K. Allen, PhD, Xiong Wei, Emma B. Holliday, MD, Brett Carter, MD, Stephen D. Bilton, CMD, James D. Cox, MD;
UT MD Anderson Cancer Center
PURPOSE: Severe acute esophagitis (grade 3–5) is a limiting factor
when twice-daily radiation treatment (RT) with concurrent chemotherapy (CChRT) is applied. The previous Intergroup study (IG
0096) has shown a significant 27 % rate of severe acute esophagitis
with twice-daily RT compared to an 11 % esophagitis rate with daily
RT and concurrent etoposide and cisplatin (EP) among patients
with limited-stage small-cell lung cancer (SCLC) (P < .01), although
twice-daily treatment significantly improved 5-year overall survival
(OS). Neither intensity-modulated radiation therapy (IMRT) nor
three-dimensional conformal radiotherapy (3D-CRT) was used for
the IG 0069 study. We investigated if IMRT has reduced severe acute
esophagitis with concurrent EP in our institution.
METHODS: We identified 577 patients with limited-stage SCLC
treated at a single institution from 1986–2009 with definitive
CChRT to a total dose of at least 45 Gy. Candidate variables included tumor size, year of diagnosis, gender, age, Karnofsky performance status (KPS), ethnicity, radiation dose, cycles of induction
chemotherapy, use of IMRT, and once- vs twice-daily fractionation.
Tumor measurement used the biggest dimension of the primary or
regional node. The chi-square test was used for between-group
comparisons for categorical variables, and the median test was used
for between-group comparisons for continuous variables. KaplanMeier estimates were constructed for OS, disease-free survival
(DFS), local recurrence–free survival (LRFS), and distant metastasis–free survival (DMFS). Analysis was performed using logistic
regression analysis with severe acute esophagitis as the primary endpoint.
RESULTS: Of the 577 patients included in this analysis, 520 patients
had tumor size data available. Patients with severe esophagitis were
treated with immediate CChRT (n = 99 [95%] vs n = 5 [5%]; P <
.001), more likely to have a KPS score < 90 (n = 50 [48%] vs n = 45
[43%]; P = .008), treated with radiation therapy twice daily (n = 66
[63%] vs n = 34 [33%]; P = .01), had been treated since 2000 (n = 47
[55%] vs n = 47 [45%]; P = .02), and had tumors ≥ 5 cm (n = 66
[63%] vs n = 34 [33%]; P = .01) All other patient, tumor, and treatment characteristics were not significantly different between the
groups. For the entire cohort, Kaplan-Meier estimates showed
severe esophagitis to be associated with reduced local-regional failure–free survival (5-year survival 39.3% vs 53.2%; P = .027). Logistic
regression analysis found immediate CChRT (odds ratio [OR] =
2.39; P = .001) and tumor size ≥ 5 cm (OR = 1.66; P = .024) to be
associated with severe esophagitis.
CONCLUSIONS: Patients with tumors ≥ 5 cm, receiving immediate
CChRT or twice-daily RT, and having local-regional failure experienced significantly higher rates of severe acute esophagitis. IMRT
did not reduce acute severe esophagitis.
(S041) The Role of Chemoradiation in Elderly
Limited-Stage Small-Cell Lung Cancer Patients Christopher D. Corso, MD, PhD, Charles E. Rutter, MD, Henry S. Park,
MD, MPH, Nataniel Lester-Coll, MD, Roy H. Decker, MD, PhD; Department of Therapeutic Radiology, Yale University School of Medicine
INTRODUCTION: Small-cell lung cancer (SCLC) in elderly patients is
a frequent problem, with prior studies suggesting that 40% to 55% of
patients with limited stage SCLC (LS-SCLC) are aged 70 years or
older. A meta-analysis examining the role of thoracic radiotherapy
(RT) in LS-SCLC suggested that there is no clear benefit to combined
modality therapy over chemotherapy alone in patients aged over 70
years. In this retrospective study, we sought to investigate outcomes
for elderly patients treated with chemotherapy alone vs chemotherapy
(chemo)-RT in the modern era using a national database.
METHODS: We identified elderly patients (age ≥ 70 yr) diagnosed
with LS-SCLC (cT1-T4, cN0-N3, cM0) in the National Cancer Data
Base from 1998–2006. Patients treated with surgery or RT initiated
> 30 days before or > 270 days after chemotherapy were excluded.
Patients were stratified as receiving chemotherapy alone vus chemoRT. The group receiving chemo-RT was further subdivided into
concurrent vs sequential treatment. Concurrent therapy was defined
as those starting RT 30 days before to 90 days after chemotherapy
began. Overall survival (OS) from the start of treatment was compared between groups using log-rank analysis. Conditional survival
analysis was performed for patients who were alive 6 months after
the initiation of treatment.
RESULTS: We identified 20,836 patients who met the inclusion criteria; 47.9% received chemo alone, and 52.1% received chemo-RT.
The median RT dose was 55.8 Gy. OS was significantly higher in the
chemo-RT group when compared with patients who received
chemo alone (median OS 20.0 mo vs 10.7 mo; log-rank P < .001).
This survival benefit was observed in elderly patients with no
comorbid illness and in those with multiple comorbidities. Analysis
of the treatment sequence revealed a significant difference between
concurrent vs sequential therapy by log-rank analysis (P < .037).
The Kaplan-Meier curves crossed at approximately 18 months, suggesting that there is initially improved OS with sequential therapy,
but long-term survival is improved with chemo-RT. Conditional
survival analysis showed that patients who were alive 6 months after
diagnosis had a significant survival benefit with concurrent chemoRT over sequential therapy (2-yr OS 35% vs 27%; log-rank P < .001).
CONCLUSION: With modern treatment, there appears to be a significant benefit to the use of combined modality therapy in elderly
patients with LS-SCLC, even in those with medical comorbidities.
For patients who would be expected to tolerate the acute effects of
concurrent chemo-RT, there appears to be a significant long-term
survival benefit over sequential therapy.
(S042) Factors Influencing Brain Recurrence After PCI
Among Patients With Limited Small-Cell Lung Cancer Emma B. Holliday, Pamela K. Allen, Brett Carter, Xiong Wei, Stephen D.
Bilton, Ritsuko Komaki; UT MD Anderson Cancer Center
PURPOSE: The brain is the most common site of distant failure for
patients with small-cell lung cancer (SCLC) after complete response
(CR) to treatment. Prophylactic cranial irradiation (PCI) was established as the standard of care for limited-stage disease after definitive chemoradiation (CRT). PCI confers an overall survival (OS)
advantage but is not without toxicity. Therefore, we sought to identify a low-risk population for whom PCI may not be necessary. We
hypothesized that patients with small tumor size may be at lower
risk for brain failure, even in the absence of PCI.
METHODS: We identified 577 patients with limited-stage SCLC who
were treated with definitive CRT at a single institution from 1986–
2009 to a dose ≥ 45 Gy. The chi-square test was used for betweengroup comparisons for categorical variables, and the median test
was used for between-group comparisons for continuous variables.
19
Kaplan-Meier estimates were constructed for brain metastasis–free
survival (BMFS) and OS. Analysis was performed using competing
risk regression with BMFS as the primary endpoint. Factors identified as significantly associated with improved BMFS were entered
into the multivariate model, and log-rank test was performed.
Tumor size was recorded as the largest dimension of the primary
parenchymal tumor or the largest regional node, if the primary
tumor could not be visualized.
RESULTS: Of the 577 patients identified, 307 (53.2%) received PCI.
Patients who did not receive PCI were older (median age 64 years
[range: 27–95 yr] vs 61 years [range: 31–79 yr]; P = .021) and had a
higher rate of those with Karnofsky performance status (KPS) score
< 80 (n = 49 [18.1%] vs n = 24 [7.8%]; P < .001). Fifty-four (17.6%)
patients who received PCI and 71 (26.3%) patients who did not
receive PCI ultimately developed brain metastases. Tumor size was
available for 520 patients. Among patients who received PCI, those
with tumor size ≥ 5 cm trended towards increased brain failure (n =
21 [13.5%] vs n = 25 [22.3%]; P = .058). On multivariate competing
risk analysis with other distant metastases DM as the competing
risk, those with a tumor ≥ 5 cm were 50% more likely to develop
brain failure (P = .035). For patients who received PCI, tumor size
was still significantly associated with increased brain failure (subdistribution hazard ratio [SHR] = 1.79; 95% confidence interval [CI],
1.01–3.18; P = .048). For patients who did not receive PCI, tumor
size was not associated with increased brain failure. There was no
difference in OS based on tumor size.
CONCLUSIONS: Tumor size appears to be a significant prognostic
factor for brain recurrence in patients with limited-stage SCLC after
PCI. Further investigation is warranted to in order to best individualize treatment for limited-stage SCLC patients with large tumors.
(S043) Changes in Quality of Life After Radiation
Therapy for Localized Prostate Cancer After Dissemination of Intensity-Modulated Radiation Therapy Elyn H. Wang, Shiyi Wang, Pamela Soulos, Ronald Chen, Cary P. Gross,
James B. Yu; Yale University School of Medicine; University of North Carolina School of Medicine
PURPOSE: Although intensity-modulated radiation therapy (IMRT)
has replaced three-dimensional conformal radiotherapy (3D-CRT)
to become the dominant form of external beam radiation therapy
(EBRT) for prostate cancer, it is unclear whether this change in practice has been associated with improved patient outcomes. To estimate the impact of IMRT on health-related quality of life (HRQOL),
we examined the HRQOL of elderly patients who had undergone
EBRT during two eras: 1998–2001, when 3D-CRT was the standard
of care for EBRT, and 2006–2009, when IMRT became the dominant form of EBRT. METHODS: The Surveillance, Epidemiology, and End Results
(SEER)-Medicare Health Outcomes Survey was used to obtain
HRQOL measurements of Medicare beneficiaries who had received
external beam radiotherapy for nonmetastatic prostate cancer and
control subjects without cancer.
Control subjects during each era were matched 10:1 by use of pro20
pensity scores estimated from demographics and comorbid medical
conditions. A total of 90 patients during the early era and 75 patients
during the late era had eligible surveys both before and after treatment. Descriptive statistics and random effects linear regression were
used to compare HRQOL between cancer patients and matched controls during the two eras. Area under the curve (AUC) was calculated to determine quality-adjusted life-years (QALYs) gained.
RESULTS: During the first 2 years after treatment, patients who were
treated in the late era had 0.19 more QALYs compared with patients
treated in the early era, relative to matched noncancer controls.
Additionally, health utility and mental component scores at followup among cases during the early era declined significantly compared with controls, whereas they were similar between cases treated in the late era and their controls (P = .02 for difference in change
in health utility and mental component scores between cases and
controls during early vs late era).
CONCLUSIONS: External beam radiotherapy during an era after
IMRT has become widespread is associated with improved HRQOL
measures among prostate cancer patients compared with the era
prior to IMRT dissemination.
(S044) Patient-Reported Quality of Life After
Stereotactic Body Radiotherapy (SBRT), IntensityModulated Radiotherapy (IMRT), and Brachytherapy Joseph R. Evans, MD, PhD, Shuang Zhao, MSE, Stephanie Daignault,
MS, Martin G. Sanda, MD, Jeff Michalski, MD, Howard M. Sandler,
MD, Deborah A. Kuban, MD, Jay Ciezki, MD, Irving D. Kaplan, MD,
Anthony L. Zietman, MD, Larry Hembroff, PhD, Felix Y. Feng, MD, Simeng Suy, PhD, Ted A. Skolarus, MD, P. William McLaughlin, MD, John
T. Wei, MD, Rodney L. Dunn, MS, Steven E. Finkelstein, MD, Constantine A. Mantz, MD, Sean P. Collins, MD, PhD, Daniel A. Hamstra, MD,
PhD; University of Michigan; Emory University; Washington University;
Cedars-Sinai Medical Center; UT MD Anderson Cancer Center; Cleveland Clinic; Beth Israel Deaconess Medical Center; Massachusetts General
Hospital; Michigan State University; Georgetown University; University of
Michigan; VA Ann Arbor Healthcare System; 21st Century Oncology
background: Stereotactic body radiotherapy (SBRT) is gaining
popularity as a radiotherapy option for localized prostate cancer that
is less invasive than brachytherapy and less costly and time-intensive
than intensity-modulated radiotherapy (IMRT). However, there are
ongoing concerns about excess toxicity after SBRT compared with
other radiotherapy options.
METHODS: We conducted a multi-institutional pooled cohort analysis of patient-reported quality of life (QoL) using the Expanded
Prostate Cancer Index (EPIC-26) survey collected serially from
baseline to 2 years. Men were treated with IMRT, brachytherapy, or
SBRT at multiple institutions. Mean EPIC symptom domain scores
were evaluated, as was the proportion of patients with a minimal
clinically detectable difference (MCD) in each domain. Multivariate
analyses were used to determine the independence and association
of standard clinical variables and treatment type with domain
scores at 2 years. Sensitivity analysis was performed for 12-Item
Short Form Health Survey (SF-12) data, as a minor proportion of
the SBRT patients were missing SF-12 data, and for year of IMRT
treatment, as we suspected that IMRT technique may have evolved
over time, which would be expected to decrease toxicity and reduce
the impact on QoL.
RESULTS: Data were analyzed from 803 patients at baseline and
from 645 patients at 2 years. Mean declines at 2 years across all
patients were −1.9, −4.8, −4.9, and −13.3 points for the urinary
obstructive, urinary incontinence, bowel, and sexual symptom
domains, respectively. Based upon MCD, 29%, 20%, and 28% of all
patients had detectable differences in urinary, bowel, and sexual
domains, respectively, at 2 years. On multivariate analysis, brachytherapy had worse urinary irritation (−6.8 [−9.9, −3.6] points vs
IMRT, P < .0001; −5.8 points [−9, −2.5] vs SBRT, P < .0001), but
there were no differences in the bowel (P = .48), urinary incontinence (P = .21), or sexual domains (P = .18). QoL after SBRT was
similar to IMRT for the urinary (P = .55, obstruction; P = .74, incontinence) and sexual domains (P = .57) but was associated with better
bowel score (+6.7 [3.2, 10] vs IMRT, P < .0002; +5.5 [2.2, 8.8] vs
brachytherapy, P = .001). We observed a positive association
between SF-12 Mental and Physical component scores and 2-year
domain scores for nearly all domains. Sensitivity analyses demonstrated a minimal effect of missing SF-12 data and no changes in
2-year domain scores with year of IMRT treatment.
CONCLUSIONS: There were slightly smaller declines in bowel QoL
after SBRT and slightly larger declines in urinary QoL after brachytherapy. While QoL after SBRT, IMRT, or brachytherapy is largely
similar and supports SBRT as a reasonable radiotherapy option for
localized prostate cancer, a randomized comparison is needed for
the strongest evidence.
(S045) Equivalent Survival With Breast-Conserving
Therapy and Mastectomy in Young Women Under the
Age of 40 With Early-Stage Breast Cancer: A National
Registry-Based Stage-by-Stage Comparison Jason C. Ye, MD, Weisi Yan, MD, PhD, Paul Christos, DrPH, MS,
Dattatreyudu Nori, MD, MBBS, Akkamma Ravi, MD, MBBS; Department of Radiation Oncology, New York Presbyterian Hospital/Weill
Cornell Medical College; Department of Radiation Oncology, New York
Hospital Queens/Weill Cornell Medical College; Division of Biostatistics
& Epidemiology, Department of Public Health, Weill Cornell Medical
College
PURPOSE: Studies have shown that young patients with early-stage
breast cancer (BC) are increasingly getting mastectomy instead of
breast-conserving therapy (BCT) despite the lack of clear survival
evidence in this approach. We examined the difference between
outcomes in young women (aged < 40 yr) treated with BCT vs
mastectomy.
METHODS: The Surveillance, Epidemiology, and End Results
(SEER) database was queried for women aged < 40 years and diagnosed with stage I or II invasive BC treated with surgery from 1998–
2003. Breast cancer–specific survival (BCSS) and overall survival
(OS) were evaluated by Kaplan-Meier survival analysis, and the logrank test was used to compare survival between treatment categories
of interest. Multivariable Cox regression model analysis was performed to estimate the predictors of BCSS.
RESULTS: Of the 7,665 women identified, 3,249 (42%) received
BCT, while 2,627 (34%) patients had mastectomy and no radiation.
There were also 994 (14%) patients who had lumpectomy but no
radiation, and 795 (10%) were treated with mastectomy plus radiation. On multivariate analysis, higher stage, estrogen receptor–negative status, and mastectomy plus radiation were found to have a
higher risk of BC mortality. When separated by stage, with a median
follow-up of 111 months (based on living patients), the BCT and
mastectomy-only groups showed no statistically significant difference in BCSS or OS. There was also no difference in non-BC mortality in any-stage disease between the two treatment groups. The
group aged 35–39 years (66% of total) was associated with better
10-year BCSS (88%) and OS (86.1%) compared with patients aged
20–34 years (34% of total), who had 10-year BCSS and OS rates of
84.1% and 82.3%, respectively (P < .001 for both BCSS and OS).
When patients of each age group were further subdivided into stages I, IIA, and IIB, there was no statistically significant difference in
BCSS or OS between the BCT and mastectomy groups for any stage
for those aged 35–39 years or for stages I and IIA in the 20–34-yearold age group. However, in patients aged 20–34 years with stage IIB
disease only, the mastectomy-only group (n = 183) had significantly inferior 10-year BCSS (64% vs 79%; P = .004) and OS (61% vs
77%; P = .002) compared with the BCT group (n = 183).
CONCLUSION: Our study suggests that while young age may be a
poor prognostic factor for breast cancer, there is no evidence that
these patients have better outcomes with mastectomy over BCT,
supporting the continued use of BCT.
(S046) Prognosis for Patients With Metastatic Breast
Cancer Who Achieve ‘No-Evidence-of-Disease’ Status
After Systemic or Local Therapy Andrew J. Bishop, Joe Ensor, Stacy L. Moulder, Simona F. Shaitelman,
Mark A. Edson, Gary J. Whitman, Sandra Bishnoi, Karen E. Hoffman,
Michael C. Stauder, Vicente Valero, Thomas A. Buchholz, Naoto T. Ueno,
Gildy Babiera, Wendy A. Woodward; UT MD Anderson Cancer Center; Rice University
PURPOSE/OBJECTIVES: Newer systemic therapy regimens are
more commonly associated with complete or near-complete radiographic response in patients with metastatic breast cancer (MBC).
We investigated outcomes for patients with MBC with no evidence
of disease (NED) after treatment and identified factors that were
predictive of outcome once NED status was achieved.
MATERIALS AND METHODS: We reviewed 570 patients with MBC
consecutively treated between January 2003 and December 2005.
NED was defined as a complete metabolic response by positron
emission tomography (PET) and/or sclerotic healing of bone metastases on computed tomography (CT) or magnetic resonance imaging (MRI). Median follow-up was 27 months (range: 0–134 mo) for
all patients and 100 months (range: 14–134 mo) for NED patients.
The Kaplan-Meier method estimated overall survival (OS) and
progression-free survival (PFS); log-rank tests assessed for equality
among groups. Cox proportional hazard models were used.
Estimated hazard ratios (HRs) are reported. RESULTS: The 3- and 5-year OS rates for the entire group were 44%
21
and 24% compared with 96% and 78%, respectively, for the NED
subset (n = 90, 16%). Patients who attained NED status had a longer
median survival (112 vs 24 months; P < .001), which correlated
strongly with survival on multivariate analysis (P < .001; HR = 0.15).
Several other factors were also associated with more favorable survival on multivariate analysis, including presenting with de novo
MBC (P < .001; HR = 0.60) and distant metastases involving only
bone (P < .001; HR = 0.52) or only lung (P < .001; HR = 0.47).
Patients who developed NED were more likely to have a normal
body mass index (BMI) (P < .001), have either estrogen receptor
(ER)+ or human epidermal growth factor receptor 2 (HER2)+
tumors (P < .001), have single sites of metastasis (P < .001), and
present with de novo MBC (P = .04) when compared with the nonNED group. For patients with NED, the 3- and 5-year PFS rates
(after NED) were 54% and 38%, respectively, with a median NED
duration of 41 months (range: 0–115 mo). The only characteristics
associated with PFS after NED were receptor status (HER2+ 58 mo
vs ER+ 35 mo vs TNBC 13 mo; P = .02), inflammatory breast cancer
at presentation (28 mo vs 45 mo; P = .02), and trastuzumab use (73
mo vs 31 mo; P = .02). Of the 63 patients who had disease progression, 20 achieved a second NED status. Ultimately, 31 patients (34%)
with NED remained in remission at last follow-up. CONCLUSIONS: Achieving NED status correlates strongly with outcome in MBC, making this a potentially valuable short-term clinical
trial endpoint akin to pathologic complete response. MBC patients
who attain NED have prolonged survival, with perhaps up to onethird achieving complete remission.
(S047) Radiotherapy vs Chemotherapy Effects on Neuronal Architecture and Spine Density in the Hippocampus Nevine Hanna, MD, MPH, Munjal Acharya, PhD, Charles Limoli, PhD;
University of California, Irvine
PURPOSE: Studies have shown that cognitive function is compromised by both radiation treatment (RT) and the use of chemotherapy (ie, the “chemobrain” phenomenon). Given that advancements
in diagnosis, beam delivery, and drug treatments have extended
long-term cancer survivorship, it has become increasingly critical to
address the extent and persistence of, and neurobiological mechanisms underlying, cognitive dysfunction associated with cancer
treatments. Through immunofluorescence studies in mice, our lab
previously established that irradiation elicits significant reductions
in neuronal morphology. In the present study, we examine the consistency of the effects of radiation or chronic cyclophosphamide
(CYP) treatment, a commonly prescribed chemotherapeutic agent,
on animal behavior and neuronal morphology via different staining
techniques.
METHODS: Adult athymic nude rats were treated with 9 Gy of
x-rays every other day to a total of 27 Gy (biologically effective
dose [BED] = 108 Gy) or with CYP (100 mg/kg) once weekly for
4 weeks and compared with sham-irradiated or saline controls,
respectively. At 1 month posttreatment, animals were administered hippocampus- and cortex-dependent cognitive tasks, including novel place recognition (NPR) and a temporal order (TO) task.
Following cognitive testing, immunohistochemical staining was
used to trace immature (doublecortin, DCX+) and mature (Golgi-
22
Cox–impregnated) neurons in the brain for an assessment of neuronal morphology in the CA1 region. Spine density was also
counted to delineate the number of long/thin, mushroom, and
stubby spines in the same region.
RESULTS: Both irradiated and CYP-treated rats showed significant
decrements in learning and memory when assessed on both the
NPR and TO tasks. CYP-treated animals were impaired in hippocampus-dependent place recognition memory and cortex-dependent recency memory compared with controls. Quantification of
ultrastructural parameters of neurons in the hippocampus using
Neurolucida software indicated compromised dendritic morphology in the immature (DCX+) and mature (Golgi-Cox) neurons in
the CA1 hippocampal region. Chronic CYP treatment (n = 20) led
to significant reductions in the apical dendritic volume (P =
.0033), basal total dendritic length (P = .0161), endings (P =
.0352), volume (P = .0004), and complexity (including branching
and three-dimensional morphology; P = .01) compared with
sham. Early analysis (n = 5) is also showing similar significance in
the irradiated cohort. With regard to spine density, overall group
effects were found for altered numbers of long/thin (P = .0079),
mushroom (P = .0048), and stubby (P = .006) spine types in the
CA1 region.
CONCLUSIONS: Exposure to chemotherapy or RT disrupts the formation and establishment of proper synaptic connections by causing significant alterations in neuronal structure that compromise
neurotransmission and cognition.
(S048) Identification of Excellent and Poor Prognostic
Groups After Stereotactic Radiosurgery for Spinal Metastasis: Secondary Analyses of Mature Prospective Trials Chad Tang, Kenneth Hess, Andrew Bishop, Hubert Pan, Eva Christiansen, Nizar Tannir, Behrang Amini, Claudio Tatsui, Lawrence Rhines, Paul
Brown, Amol Ghia; UT MD Anderson Cancer Center
BACKGROUND /PURPOSE: There is uncertainty in the prognosis of
patients following treatment of spinal metastases. To stratify patients
between poor and excellent predicted survival after stereotactic
spine radiosurgery (SSRS), we created a Cox proportional hazards
regression model.
PATIENTS AND METHODS: Patients who were enrolled (between
2002 and 2011) in two prospective trials investigating SSRS for spinal metastasis were analyzed. To ensure mature survival data, living
patients with < 3 years of follow-up were excluded. A multivariate
Cox regression model was utilized to create a survival model via
backward selection at P < .05. Pretreatment variables included race,
sex, age, performance status, tumor histology, extent of vertebrae
involvement, prior therapy at SSRS site, disease burden, and timing
of diagnosis and treatment. Four prognostic groups were generated
based on the model-derived prognostic index (PI).
To assess whether pretreatment symptoms were associated with survival and survival model predictions, patients were prospectively
queried for their pretreatment symptoms via the MD Anderson
Symptom Inventory (MDASI) and Brief Pain Index (BPI).
RESULTS: A total of 206 patients were included in this analysis.
Median follow-up time was 70 months (range: 37–133 mo) among
all living patients (n = 40). Seven variables were selected in the prediction model: female sex (hazard ratio [HR] = 0.7; P = .04),
Karnofsky performance status (KPS) (HR = 0.7 per 10% increase; P
= .005), prior surgery at the SSRS site (HR = 0.6; P = .005), prior
radiation at the SSRS site (HR = 1.7; P = .003), SSRS site as the only
site of disease (HR = 0.5; P < .001), number of organ systems
involved (HR = 1.4 per involved system; P < .001), and time between
initial diagnosis and spine metastasis after variable normalization
(HR = 0.6 per log10[time in months+5]; HR = 0.01). The c-index of
the stratified and unstratified model was 0.68 and 0.70, respectively.
The median survival time among all patients included in the analysis was 25.5 months and was significantly different among prognostic groups (Group 1 [excellent prognosis]: not reached, Group 2:
32.6 mo, Group 3: 19.7 mo, Group 4 [poor prognosis]: 8.2 mo; P <
.001). Patients within the excellent prognosis group exhibited a
Kaplan-Meier estimated 10-year survival rate of 71%. Furthermore,
all pretreatment symptom metrics were predictive of overall survival and correlated with the model-derived PI (all P ≤ .01).
0.33–65.2 mo), with 12- and 18-month OS rates of 56.6% and 44.3%,
respectively. On univariate analysis, inferior survival was associated
with lower Karnofsky performance status (KPS) score (P = .038),
presence of extracranial metastases at iSRS (P = .003), new metastases at the time of rSRS (P = .027), having rSRS < 9 months from iSRS
(P = .019), and melanoma histology (P = .015). For all metastases
from rSRS, the 12- and 18-month LC rates were 77.5% and 71.6%,
respectively. Univariate analysis for local failure showed no significant association. Regarding DBF, the 12- and 18-month estimates
were 52.8% and 62.9%, respectively. Univariate analysis for DBF was
significant for melanoma (P < .01) and persistent systemic disease
at rSRS (P = .012). Multivariate analysis showed a significant association for DBF with melanoma (hazard ratio [HR] = 22.34; P value
< .00), presence of extracranial disease at rSRS (HR = 2.89; P = .07),
and having at least one new brain metastasis at rSRS (HR = 3.32; P
= .03), with an overall model P value < .00. Twelve patients (11.1%)
had grade 3 radiation toxicities following rSRS at a median time of
4.0 months (range: 1.2–10.6 mo). The grade 3 toxicities consisted of
radiation necrosis (10), seizure (3), headache (3), and an optic nerve
disorder. No grade 4 or 5 toxicities were seen. Neither a dose nor
volume relationship with toxicity was observed.
CONCLUSIONS: We present a survival prediction model that has
identified patient subgroups with poor (Group 4) to excellent
(Group 1) prognoses. In addition, pretreatment symptoms were
predictive of survival and correlated with the prediction of the
model. If validated, we believe that this model, possibly in conjunction with patient symptoms, may aid in determining optimal treatment strategies.
CONCLUSIONS: Repeat SRS represents a potential salvage therapy
for patients with locally recurrent brain metastases, providing additional tumor control with acceptable toxicity, even in the setting of
prior SRS, surgical resection, and/or WBRT. Repeat SRS may also be
reasonable to use to either avoid or delay the treatment of WBRT.
(S049) Salvage Stereotactic Radiosurgery for Locally
Recurrent Brain Metastases Treated Previously With
Stereotactic Radiosurgery Ben Y. Durkee, MD, PhD, Joseph Sanford, MD, Anna Oh, PhD, Daniel
Slate, BS, Brandon Turner, BS, Erqi L. Pollom, MD, Iris C. Gibbs, MD,
Scott G. Soltys, MD; Department of Radiation, Department of Radiation Oncology, Stanford University; Department of Nursing, University of
California, San Francisco; Stanford University Graduate School of Business; Stanford University School of Medicine
Douglas E. Holt, BS, Beant S. Gill, MD, David A. Clump, MD, PhD,
Steven A. Burton, MD, John C. Flickinger, MD, Jonathan A. Engh, MD,
Nduka Amankulor, MD, PhD, Dwight E. Heron, MD; University of Pittsburgh Medical Center
PURPOSE AND OBJECTIVES: Patients with local recurrence of
brain metastases following prior stereotactic radiosurgery (SRS) can
be challenging to manage. Given the concerns of neurotoxicity with
whole-brain radiotherapy (WBRT), we evaluated the efficacy of
repeat SRS (rSRS) for patients with locally recurrent brain metastases after initial SRS (iSRS).
MATERIALS AND METHODS: A retrospective review from 2004 to
2014 identified 108 patients (133 lesions) who received rSRS due to
locally recurrent brain metastases after iSRS. Among these patients,
19.4% had WBRT prior to rSRS, with 40.6% of the lesions previously treated with surgical resection. Kaplan-Meier estimates were
calculated from rSRS for overall survival (OS), local control (LC),
and distant brain failure (DBF), as well as radiation-related toxicity.
Cox proportional hazards modeling was conducted to establish predictive factors for OS, LC, DBF, and toxicity (P < .05) from the time
of rSRS.
RESULTS: With a median follow-up time of 12.0 months (range:
0.03–65.7 mo) from rSRS, the median OS was 14.2 months (range:
(S050) Cost-Effectiveness of Neurocognitive
Preservation for Whole-Brain Radiotherapy BACKGROUND: Whole-brain radiotherapy (WBRT) is the standard
of care for nonsurgical intracranial metastatic disease. Patients
receiving WBRT are at risk for neurocognitive degeneration, which
is weighed against the neurocognitive detriment of tumor progression. Recent results from RTOG 0614 and RTOG 0933 have shown
cognitive benefit with memantine (WBRT+M) or hippocampal
avoidance (HA-WBRT) [Li, JCO 2007; Brown, Neuro Onc 2013;
Gondi, JCO 2014].
Neurocognitive compromise is associated with lower quality of life
(QoL). Utility scores for these health states are well described and
reproducible. The cost of these cognitive preservation strategies
must be weighed against the gains in QoL during the patients’ final
months.
METHODS: We created a decision tree with an integrated three-state
Markov model. Treatment strategies included best supportive care
(BSC), WBRT, WBRT+M, and HA-WBRT. Health states were cognitively intact, cognitively impaired, and dead. Cycle-specific probabilities for cognitive states were derived from PCI-P120-9801,
RTOG 0614, and RTOG 0933. Survival data were derived from
23
recursive partitioning analysis (RPA) of three RTOG trials [Gaspar,
IJROBP 1997].
Utility scores for the base case of a patient with metastatic cancer
were derived from the available literature. The effect of cognitive
detriment was extrapolated from patients with mild dementia, who
scored similarly on a Hopkins Verbal Learning Test. The model was
run using each RPA class (I/II/III) as the base case scenario.
The analysis was done from a societal perspective, with a single
payer system. Threshold for cost-effectiveness was set at a willingness to pay (WTP) of $100,000 per quality-adjusted life-year
(QALY). Costs were derived from the Medicare Physician Fee
Schedule. We performed multiway sensitivity analyses to address
uncertainties in cost, utility scores, efficacy of intervention, life
expectancy, and distribution of baseline cognitive states.
RESULTS: BSC is the dominant strategy for the base case scenario.
No strategy for neurocognitive preservation is cost-effective at a
WTP of $100,000/QALY. Neurocognitive-preservation strategies
become cost-effective in the theoretical cohort of patients with perfect baseline cognition and long expected survival (> 14 mo for base
case distribution; > 10 mo for perfect baseline cognition). The
model was sensitive to assumptions about the initial distribution of
patients’ cognitive states and cost. It was minimally sensitive to utility scores and efficacy of the intervention.
CONCLUSION: Neurocognitive-preservation strategies for WBRT
are not cost-effective from a societal perspective, though they may
be effective for patients who are cognitively intact at baseline and
have a long expected survival.
(S051) The Role of Temozolomide in the Treatment
of Low-Grade Glioma Emi J. Yoshida, MD, Alicia Ortega, BA, Chirag G. Patil, MD, MS, Stephen
L. Shiao, MD, PhD; Cedars-Sinai Medical Center
BACKGROUND/OBJECTIVE: World Health Organization (WHO)
grade II gliomas are relatively slow-growing brain tumors, with 5-year
progression-free survival rates ranging widely, from 13% to 70%. A
subset of these tumors will transform into high-grade aggressive cancers with dismal prognoses. A number of phase II trials have demonstrated a role for well-tolerated temozolomide in the prevention of
tumor progression and malignant transformation, despite a lack of
impact on survival. The institutional paradigm at Cedars-Sinai
Medical Center is to manage low-grade gliomas with single-agent
temozolomide and to reserve radiotherapy for progression. The aim
of this study is to report the preliminary results of our experience with
temozolomide in the management of low-grade glioma.
MATERIALS AND METHODS: The records of 234 patients diagnosed
with WHO grade II glioma at Cedars-Sinai Medical Center from
January 1991 to April 2014 were reviewed. Median age was 47.5
years (range: 39.0–60.0 yr). Ninety-four (40.2%) patients were treated with temozolomide +/− radiotherapy after surgery. Surgery
included biopsy (75 patients, 33.8%), subtotal resection (56 patients,
25.2%), and gross total resection (91 patients, 40.9%). Median follow-up time was 51.0 months (range: 25.0–84.4 mo). Statistical
24
analysis controlled for tumor histology, tumor size, extent of resection, and patient age. P values < .05 were considered statistically
significant.
RESULTS: Of the 234 patients analyzed, 211 patients recurred or
progressed (90.2%). Average time to progression was 42.7 months
among patients treated with temozolomide +/− radiotherapy
compared with 46.5 months among patients who did not receive
temozolomide (P = .35). Five-year progression-free survival (PFS)
was 20.7% in those who received temozolomide +/− radiotherapy
compared with 29.5% among those who were observed +/− radiotherapy.
CONCLUSION: Temozolomide has become widely used as a
primary intervention for low-grade glioma in the past decade. Our
preliminary results suggest that the use of temozolomide in the
management of low-grade glioma is neither deleterious nor beneficial in terms of PFS. In comparison with the PFS reported by the
European Organisation for Research and Treatment of Cancer
(EORTC) 22844/22845 and Radiation Therapy Oncology Group
(RTOG) 9802 trials, our PFS is markedly worse. This finding is
likely attributable to the high median age of our patient population, which is noticeably older and thus assumed to have a poorer
prognosis. Ongoing studies are investigating the impact of temozolomide on time to radiotherapy and examining survival outcomes after concurrent temozolomide and radiotherapy. (S052) Inverse Optimization for Correlating 4DCT
Ventilation Imaging and Radiation Dose Edward Castillo, PhD, Richard Castillo, PhD, Thomas Guerrero, MD,
PhD; Beaumont Health System; UT Medical Branch
PURPOSE: Four-dimensional computed tomography (4DCT) ventilation imaging is an emerging modality with utility in thoracic
radiotherapy treatment planning. Though recent studies have demonstrated its potential for quantifying the functional response of
lung tissue to irradiation, ventilation image analysis is challenging
and difficult to reproduce because of issues such as spatial inaccuracies in the required deformable image registration (DIR), cine mode
phase-binning artifacts, and variations in the patient’s breathing. In
order to address these issues, we have developed a numerical method for computing 4DCT ventilation images that correlate perfectly
with a given radiation dose distribution or dose-response model
while maintaining high-spatial accuracy in the corresponding DIR
solution.
METHODS: Ventilation images are defined by a DIR spatial transformation that maps the position of inhale lung voxels to their corresponding position at exhale (or vice versa). A voxel’s volume
change under the transformation, described mathematically by the
Jacobian matrix, is the intensity value of the ventilation image and
quantifies the air exchanged. Given an initial DIR estimate and a
target ventilation image, we define an optimization problem
describing the spatial transformation closest to our initial estimate
(according to the L2-norm), with Jacobian values equal to those in
the target ventilation image.
RESULTS: The inhale/exhale phases of a treatment-planning 4DCT
for a patient with non–small-cell lung cancer were registered using
a previously reported DIR method. The spatial accuracy of the DIR
solution, given as the average (standard deviation) millimeter error
with respect to 417 expert-determined landmark points, was 1.03
(1.01) mm. The radiation dose distribution image was used to generate a target ventilation image using a linear dose-response model
applied to the original ventilation image. Our numerical method
was then applied to the initial DIR solution to produce a spatial
transformation and corresponding ventilation image that matched
the target ventilation image within 1e-2.The average millimeter
error for the new transformation was 1.11 (1.10).
CONCLUSION: A numerical method for computing a DIR transformation according to a target ventilation image was used to generate
a ventilation image that correlates precisely with the dose distribution while maintaining high DIR spatial accuracy. Thus, by employing this approach, the focus of future CT ventilation studies that are
designed to assess radiation dose response is reduced to assessing
the physical feasibility of the DIR transformation that generates the
ventilation image predicted by the dose-response model. (S053) Nodal Surveillance With Diffusion-Weighted
MRI After Definitive (Chemo) Radiotherapy for
HPV-Predominant Squamous Cell Cancers of the
Oropharynx and Unknown Primary Yao Yu, MD, Marc Mabray, MD, William Silveira, MD, PhD, Peter Y.
Shen, MD, PhD, William Ryan, MD, Alina Uzelac, DO, Sue S. Yom; University of California, San Francisco
BACKGROUND: Diffusion-weighted MRI has been proposed as a
method to differentiate treatment effect from persistent or recurrent
nodal disease after definitive treatment with radiotherapy.
METHODS: Records and imaging were reviewed for 70 patients
treated with definitive radiotherapy with or without chemotherapy
for squamous cell carcinomas of the oropharynx or p16-positive
unknown primary of the head and neck. A total of 40 patients were
available for analysis. Surveillance imaging with magnetic resonance
imaging (MRI) was obtained 6–8 weeks after treatment, followed by
positron emission tomography/computed tomography (PET/CT) at
12 weeks after treatment. Apparent diffusion coefficient (ADC) values were calculated for each node and for each hemineck. PET/CT
results and ADC values were correlated with regional control at 6
months based on histopathology and clinical follow-up.
RESULTS: The mean ADC was significantly lower for lymph nodes
corresponding with recurrent disease compared with control at 6
months (1,301 μm2/s vs 2,049 μm2/s; P = .04). Using receiver operating characteristic (ROC) analysis, an optimal threshold of 1,600 μm2/s
was identified; lymph nodes with ADC values below this threshold
were found to be at higher risk for recurrent disease. Sensitivity and
specificity were 100% and 84%, respectively, with positive and negative predictive values of 41% and 100%, respectively. When analyzed
by hemineck, the sensitivity and specificity were 100% and 85%,
respectively. PET/CT at 12 weeks yielded a sensitivity and specificity
of 100% and 85%, respectively. On Kaplan-Meier analysis, ADC was
predictive of nodal progression-free survival (P = .00023).
CONCLUSION: Early surveillance imaging with diffusion-weighted
MRI at 6–8 weeks following definitive treatment with radiotherapy
is feasible and may be predictive of early nodal failure. Further validation in a prospective cohort is warranted. (S054) Long-Term Survival and Racial Differences in
Pediatric Hodgkin Lymphoma Patients From the State
of Florida: Three Decades of Experience Hanmanth Neboori, MD, William Grubb, BS, Hua Li, PhD, MD, Joseph
Panoff; University of Miami/Jackson Health System
PURPOSE/METHODS: Hodgkin lymphoma (HL) represents 9% of
all pediatric malignancies in the United States. Data are conflicting
with regard to racial/ethnic survival differences. We sought to investigate overall survival (OS) differences in a large cohort of racially
and ethnically diverse patients with 30 years of follow-up in the state
of Florida.
METHODS: The Florida Cancer Database System was used to retrospectively assess the long-term outcomes of 1,778 pediatric patients
(age range: 1 mo–21 yr) diagnosed with HL between 1981 and 2010.
Log-rank test and Cox univariate and multivariate regression analysis were used to identify predictors of OS.
RESULTS: Median age at diagnosis was 1.7 years (range: 0.1–21 mo).
Males and females were equally represented (50.5% vs 49.5%). The
database consisted of 68% white, 13% African American (AA), 18%
Hispanic, and 2% unknown. The breakdown of diagnosis by decade
was as follows: 27% from 1981–1990; 31% from 1991–2000; and
42% from 2000–2010. There were 16% of patients diagnosed as
stage I, 42% diagnosed as stage II, 31% diagnosed as stages III and
IV, and 11% unknown. Nodular sclerosing was diagnosed in 69% of
patients, mixed cellularity was diagnosed in 13%, lymphocyte-rich
disease was diagnosed in 4%, lymphocyte-depleted (LD) disease
was diagnosed in 2%, and nodular lymphocyte-predominant HL
(NLPHL) was diagnosed in 2%. Radiation was administered in 43%
of patients, and chemotherapy was given to 73% of patients. Median
survival of the entire cohort at the time of last follow-up was 23.8
years. The 5-year OS rate was 84.2%. Men had worse OS than
women at 25 years (36% vs 58%; P < .0001). AA patients had worse
OS than white and Hispanic patients at 25 years (33% vs 49.2% vs
44.7%, respectively; P = .0005), and this finding persisted after controlling for decade of treatment (P < .001). There was no difference
in OS between whites and Hispanics. There were no OS differences
regarding decade of treatment, chemotherapy, or age at diagnosis.
Patients who had radiation therapy had better OS (hazard ratio
[HR] = 1.49; P = .0025). Additionally, patients with the LD subtype
had worse OS (HR = 3.85; P = .01).
CONCLUSION: This is the largest retrospective review with the longest outcome to specifically evaluate pediatric Hodgkin lymphoma
patients. Furthermore, this is the first analysis to find that AA
patients have inferior OS when compared with whites and
Hispanics. These differences remained significant over the course of
30 years, indicating that modern treatment modalities have not
improved this racial disparity.
25
SCIENTIFIC POSTERS*
(P001) Disparities in the Local Management of
Breast Cancer in the United States According to
Health Insurance Status Thomas M. Churilla, MD, Brian Egleston, PhD, Joshua Meyer, MD,
Yanqun Dong, MD, PhD, Penny Anderson, MD; Fox Chase Cancer
Center
INTRODUCTION: Various studies have suggested disparities in
breast cancer care due to inadequate health insurance coverage.
The purpose of our study was to test for associations between
patient insurance status and the presentation and local therapy patterns among a large, nationally representative cohort of patients
with localized breast cancer.
METHODS: We queried the National Cancer Institute (NCI)
Survival, Epidemiology, and End Results (SEER) database for
breast cancer cases diagnosed from 2007–2011 in women aged
18–64 years, limited to ductal or lobular histology, nonmetastatic
stage, and treated with mastectomy or lumpectomy. Patients ≥ 65
years were excluded based on their eligibility for Medicare. We
characterized clinical and demographic variables according to
insurance status (insured vs Medicaid vs uninsured). We tested for
associations between patient insurance status and choice of definitive surgical procedure (mastectomy vs breast-conserving surgery),
omission of radiation therapy (RT) following breast-conserving
surgery, and administration of postmastectomy RT (PMRT). We
calculated odds ratios (ORs), performed Pearson’s chi-square test
for univariable analysis, and used multiple logistic regression analysis to adjust for clinical and demographic covariates.
RESULTS: A total of 129,565 patients with localized breast cancer
were analyzed. The health insurance statuses included insured
(84.5%), Medicaid (11.5%), uninsured (2.1%), and unknown
(1.9%). Patients with Medicaid or uninsured status were more
likely to present with large, node-positive tumors and be black or
unmarried and reside in low-income counties. The breast-conserving surgery rate was 51.3% among all patients and varied according
to insurance status: insured (52.2%), uninsured (47.7%), and
Medicaid (45.2%) (P < .001). Medicaid insurance status remained
significantly associated with receipt of mastectomy in the multivariable analysis (OR =1.07; 95% confidence interval [CI], 1.03–
1.11; P < .001). Radiation therapy was more frequently omitted
after breast-conserving surgery in both Medicaid (OR = 1.14; 95%
CI, 1.07–1.21) and uninsured (OR = 1.29; 95% CI, 1.14–1.47)
patients in the multivariable analysis (P < .001 for both). PMRT was
more frequently administered among Medicaid and uninsured
patients; however, only Medicaid status remained significantly
associated with PMRT in the multivariable analysis (OR = 1.10;
95% CI, 1.04–1.18; P = .002).
CONCLUSION: Patients with inadequate health insurance were
more likely to receive mastectomy, omit RT following breast-conserving surgery, and receive PMRT. Differences in clinical presen*Scientific posters P001 through P014 have been designated by the
American Radium Society as Posters of Distinction.
26
tation and demographics according to insurance status incompletely explain the variation in therapy. Further study is needed to validate and address these disparities and to evaluate the impact of
health insurance legislative efforts in localized breast cancer.
(P002) Predictors of CNS Disease in Metastatic
Melanoma: Desmoplastic Subtype Associated With
Higher Risk Gary B. Deutsch, MD, MPH, Samuel Yost, BA, Mariel B. Deutsch,
MD, Ji Hey Lee, PhD, Leland Foshag, MD, Garni Barkhoudarian, MD,
Daniel F. Kelly, MD, Mark B. Faries, MD; John Wayne Cancer Institute
at Providence Saint John’s Health Center; David Geffen School of Medicine at UCLA and West Los Angeles VA Healthcare System
INTRODUCTION: Brain metastases are a major cause of mortality
in metastatic melanoma. Histologic subtype—specifically, the desmoplastic subtype and its propensity for neurotropism—has not
been well studied as a predictor of central nervous system (CNS)
disease. We report the largest series of brain metastases in order to
better define the clinicopathologic risk factors and help guide management and surveillance. METHODS: A prospective institutional melanoma database was
used to identify patients diagnosed with metastatic melanoma
between 1971 and 2013. Patient age and sex; primary tumor location, thickness, ulceration, and histology; and types of recurrence
and treatment were analyzed. Primary endpoints were development of brain metastases and 2-year brain metastases–free survival (BMFS). The secondary endpoint was overall survival (OS)
from the date of stage IV diagnosis. RESULTS: Among 3,756 patients with metastatic melanoma, 711
(18.9%) developed brain metastases. Histology was available for
2,132 patients, 397 (18.6%) of whom developed brain metastases
(32 [8.1%] brain only, 38 [9.6%] brain as the first site of stage IV
disease). Head and neck (H&N) location (P = .01), presence of
ulceration (P = .04), and desmoplastic variant (P = .04) were associated with a higher risk of CNS disease. Multivariable analysis identified presence of ulceration (hazard ratio [HR] = 1.49; P < .01),
primary location (upper extremity vs H&N: HR = 0.55, P < .01;
lower extremity vs H&N: HR = 0.63, P = .01; mucosal vs H&N: HR
= 0.42, P = .04; ocular vs H&N: HR = 0.29, P = .04), and histologic
subtype (desmoplastic vs superficial spreading; HR = 2.38; P = .01)
as independent predictors of 2-year BMFS. Improved 2-year OS
was seen with female sex, younger age, upper extremity location,
lack of ulceration, and ipilimumab therapy. Of the 25 patients diagnosed with desmoplastic melanoma, 9 (36%) were found to have
brain metastases, all within the first year after the diagnosis of
another systemic disease. Thick lesions (> 4 mm) of the H&N
region were at greatest risk. CONCLUSIONS: Desmoplastic histologic subtype is a strong predictor of brain metastasis development and decreased 2-year BMFS in
patients with metastatic melanoma. Patients with desmoplastic
melanoma, particularly thick lesions involving the H&N, should be
imaged frequently during the first year after the diagnosis of stage
IV disease.
(P003) Identification of Somatic Mutations Using Fine
Needle Aspiration: Correlation With Clinical Outcomes
in Patients With Locally Advanced Pancreatic Cancer Arti Parekh, Lauren M. Rosati, Vicente Valero III, Matthew J. Weiss,
Ryan K. Assadi, Daniel A. Laheru, Christopher L. Wolfgang, Christine
A. Iacobuzio-Donahue, Joseph M. Herman; Johns Hopkins Hospital
PURPOSE/OBJECTIVE: Historically used to biopsy tumors that
raise suspicion for pancreatic cancer, fine needle aspirates (FNAs)
can also be obtained at the time of fiducial placement to perform
molecular studies. We present an exploratory analysis of genomic
sequencing data from patients who received stereotactic body radiation (SBRT) for locally advanced pancreatic cancer (LAPC). The
purpose of this study was to identify somatic mutations associated
with clinical outcomes and survival.
MATERIALS AND METHODS: FNAs from 15 patients undergoing
SBRT for LAPC were sequenced for 409 known cancer genes. All
FNAs were obtained prior to the delivery of 25–33 Gy SBRT in five
fractions. Induction gemcitabine was administered to all patients,
and the majority (93%) of patients received maintenance gemcitabine following a 1-week break from SBRT. Kaplan-Meier survival analysis was used to evaluate the association between gene
variants and treatment response to SBRT.
RESULTS: Median follow-up time was 13.6 months (range: 2.4–26.2
mo). Median age was 66.3 years, and 66.7% of patients had pancreatic head tumors. Fourteen (93%) patients had disease progression,
with 14.3% initially experiencing local progression alone, 71.4%
experiencing distant progression alone, and 14.3% experiencing
synchronous local and distant progression. Median overall survival was 16.7 months (95% confidence interval [CI], 11.6–21.7
mo), and the 1-year and 2-year survival rates were 63.4% and
22.6%, respectively. Advanced age (≥ 65 yr) was associated with
inferior survival (10.8 vs 21.1 mo; P = .048). Patients who first
experienced local failure alone had inferior survival compared with
those who experienced distant failure only (6.9 vs 16.7 mo; P = .01).
At least two patients in this cohort expressed mutations in the following genes: KRAS, CDKN2A, TP53, SMAD4, TRIM33, ARID1A,
GRM8, and NOTCH. No specific correlations were observed
between most driver mutations known in pancreatic cancer
(CDKN2A, TP53, SMAD4) and overall survival. Interestingly,
improved survival was observed in patients harboring KRAS mutations compared with those with the wild-type variant (17.9 vs 8.5
mo; P = .015). One patient (6.7%) had an ATM mutation and survived 19.2 months.
CONCLUSIONS: This is the first study to demonstrate the feasibility of genomic sequencing of FNAs from pancreatic tumors. We
have been able to successfully identify unique genetic signatures in
patients with LAPC; however, the small sample size limits our ability to identify generalizable patterns. With this exploratory analysis,
we propose that routine FNA sequencing, as well as additional
molecular studies, such as immunohistochemistry, of larger cohorts
may allow for identification of unique patterns that guide individualized selection of patients for SBRT.
(P004) A Retrospective Study to Assess Disparities in
the Utilization of Intensity-Modulated Radiotherapy
(IMRT) and Proton Therapy (PT) in the Treatment of
Prostate Cancer (PCa) Kristina L. Demas, MD, Neha Vapiwala, MD, Stefan Both, PhD,
Curtiland Deville, MD; University of Pennsylvania
BACKGROUND: Despite its increase in use, proton therapy (PT) is a
relatively limited resource. The purpose of this study was to examine
clinical and demographic differences in intensity-modulated radiotherapy (IMRT) and PT utilization for prostate cancer (PCa).
METHODS: All patients with low- and intermediate-risk PCa (n =
350) undergoing definitive RT (2.5 Gy × 28 fractions or 1.8 Gy ×44
fractions) between 2010–2012 at a single institution were divided
into IMRT (n = 58) and PT (n = 292) comparison groups.
Pretreatment characteristics, including age, race, socioeconomic
status (SES) (low vs high, defined as geocoded census tract 20%
below or above poverty level, respectively), prostate-specific antigen (PSA), clinical tumor stage, Gleason score, risk group, prostate
volume, and patient-reported outcomes, were retrospectively collected. Chi-square and independent sample t-tests were used for
analyses.
RESULTS: Of PT patients, 228 (78%), 51 (18%), 4 (1%), and 9 (3%)
were white, black, Asian, or other, respectively; 256 patients (88%)
had high SES, and 36 (12%) had low SES. Mean age, distance from
center, PSA level, prostate volume, International Prostate Symptom
Score (IPSS), and International Index of Erectile Function (IIEF) in
the PT group were 65 ± 7.1 years, 86 ± 190 miles, 5.6 ± 2.9 ng/mL, 41
± 18 cc, 8 ± 6, and 19 ± 6, respectively; 142 (49%) patients were lowrisk, and 150 (51%) were intermediate-risk. A total of 236 (81%), 46
(16%), and 10 (3%) PT patients were T1c, T2a, and T2b, respectively;
154 (53%) and 138 (47%) patients were Gleason 6 and 7.
In the IMRT group (n = 58), 28 (48%), 24 (42%), 3 (5%), and 3 (5%)
patients were white, black, Asian, or other, respectively; 40 (69%)
patients had higher SES, and 18 (31%) had low SES. Mean age,
distance, PSA, prostate volume, IPSS, and IIEF were 69 ± 8.6, 16 ±
18 miles, 7.4 ± 4.5 ng/mL, 54 ± 40 cc, 8 ± 7, and 14 ± 8, respectively; 142 (49%) were low-risk, and 150 (51%) were intermediaterisk patients. A total of 236 (81%), 46 (16%), and 10 (3%) IMRT
patients were T1c, T2a, and T2b, respectively; 154 (53%) and 138
(47%) patients were Gleason 6 and 7.
The cohorts varied in average age (P = .0005), race (P < .0001), SES
status (P = .0007), and average miles traveled to the facility (P =
.0054)—ie, IMRT patients were older, resided closer, and consisted
of more black and low-SES patients. Baseline PSA (P = .0001),
Gleason score (P = .0244), prostate volume (P = .0040), and IIEF (P
< .001) were significantly increased for IMRT, while risk group, T
stage, and IPSS were not (P > .05 for all). Therapeutically, IMRT
patients were less likely to receive hypofractionated therapy (P <
.0001) and more likely to receive androgen deprivation therapy (P
= .0006).
CONCLUSION: Disparities exist in PT utilization compared with
IMRT by age, race, and SES and merit further investigation.
27
(P005) Ultrasensitive PSA Identifies Patients With
Organ-Confined Prostate Cancer Requiring Postop
Radiotherapy Jung Julie Kang, MD, PhD, Robert Reiter, MD, Patrick Kupelian, MD,
Michael Steinberg, MD, Christopher R. King, PhD, MD; Department of
Radiation Oncology, Department of Urology, UCLA
PURPOSE/OBJECTIVES: Randomized controlled trials have shown
that adjuvant radiotherapy (RT) after radical prostatectomy (RP)
improves biochemical relapse-free and overall survival in patients
with extracapsular disease. However, even patients with organconfined disease are at risk for failure. This study analyzes postoperative (postop) ultrasensitive prostate-specific antigen (uPSA) in
the surveillance of these patients.
MATERIALS AND METHODS: From 1991–2013, 146 patients with
pT2N0 disease who were referred for a rise in PSA after RP were
identified: 85 were margin-positive (m+), and 61 were margin-negative (m−). Surgical approach (open vs robotic), initial PSA (iPSA),
Gleason grade, margin status, and postop uPSA were covariates for
analysis. Median first postop PSA and follow-up were 3 and 38
months, respectively. The uPSA threshold was 0.01 ng/mL.
Benign uPSA patterns occurred from 0.01–0.02 ng/mL; thus, ≥
0.03 ng/mL was defined as uPSA failure. True (conventional) biochemical relapse (tBCR) was defined as PSA ≥ 0.2 ng/mL. Patients
were censored at last follow-up or adjuvant therapy. Kaplan-Meier
and Cox multivariate analyses were used to compare tBCR rates.
RESULTS: Median time to tBCR for the entire cohort was 50
months. The m+ patients revealed a more indolent course than
m− patients (median time to relapse: 86 mo for m+ vs 33 mo for
m−; P = .0003). No differences in Gleason grade or iPSA between
m+ and m− patients were seen. On multivariate analysis (MVA), only first postop uPSA ≥ 0.03 ng/
mL (hazard ratio [HR] = 4.1; P < .001) and margin status (m−: HR
= 5.6; P = .0315) independently predicted for time to tBCR.
First postop uPSA ≥ 0.03 ng/mL discerned tBCR with much greater sensitivity than undetectable first conventional PSA < 0.2 ng/mL
(44% vs 19%). First postop uPSA < 0.03 ng/mL vs. ≥ 0.03 ng/mL
predicted median tBCR at 61 vs 10 months (P = .0003). Any postop
uPSA ≥ 0.03 ng/mL captured all failures missed by analyzing only
the first postop value (100% sensitivity).
Using uPSA ≥ 0.03 ng/mL to identify relapse yields a substantial
(33 mo) lead time advantage over waiting until conventional
relapse at PSA ≥ 0.2 ng/mL (median 17 vs 50 mo in favor of uPSA
≥ 0.03 ng/mL).
CONCLUSIONS: Only first postop uPSA ≥ 0.03 ng/mL and margin
status independently predicted biochemical relapse for organ-confined prostate cancer. The m− patients exhibited much earlier failures, suggesting greater biologic aggressiveness.
Biochemical failure can be called at uPSA ≥ 0.03 ng/mL with excellent sensitivity, and adopting it offers an impressive lead time advantage over the conventional failure definition (PSA ≥ 0.2 ng/mL).
28
Integrating uPSA into the immediate and continued frequent surveillance of RP patients with organ-confined cancer will improve
postop RT outcomes by identifying failures sooner and promoting
an early salvage strategy.
(P006) The Role of Sequential Imaging in Cervical
Cancer Management A. MacDonald, C. Tung, M. Bonnen, M.Y. Williams-Brown, C.R.
Diaz-Arrastia, M. Ludwig, M.L. Anderson; UT Health Science Center at
Houston; Baylor College of Medicine
OBJECTIVES: In the absence of International Federation of
Gynecology and Obstetrics (FIGO) guidelines, optimal imaging of
women diagnosed with cervical cancer in settings where multiple
modalities are available for treatment planning remains unclear.
The purpose of this study was to determine whether sequential
imaging by contrast-enhanced computed tomography (CT),
18-fluoro-deoxyglucose positron emission tomography (FDGPET)-CT, and/or magnetic resonance imaging (MRI) enhances
radiation treatment planning for women with cervical cancer.
METHODS: After obtaining institutional review board (IRB)
approval, all women diagnosed with cervical cancer who were eligible for definitive chemoradiation (FIGO stages IB1–IVA) in a
regional safety-net health system between July 2012 and August
2014 were identified. Clinical demographics and treatment plans
were reviewed and abstracted so that the impact of imaging modalities could be compared. RESULTS: A total of 93 women (mean age: 51.0 ± 13.2 yr) with IB1
(n = 3, 3.2%), IB2 (n = 16, 17.2%), IIA (n = 11, 11.8%), IIB (n = 33;
35.4%), IIIA (n = 5, 5.3%), IIIB (n = 22; 23.7%), and IVA (n = 3;
3.2%) disease were identified. Histologies included squamous cell
(n = 78, 83.8%), adenosquamous (n = 2, 2.1%), poorly differentiated (n = 3, 3.2%), small cell (n = 1, 1.1%), and adenocarcinomas
(n = 9, 9.6%). Pretreatment, 48 women underwent contrastenhanced CT (abdomen/pelvis and/or chest) alone, 28 received CT
followed by PET, 6 received PET and MRI, 4 received CT and MRI,
1 received PET only, and 6 underwent all three tests. For the 34
women who had CT followed by PET, no anatomic findings were
identified by CT that were not also detected by PET. In contrast,
PET identified lesions that were not seen in anatomic fields evaluated by CT in eight women. PET resulted in radiation treatment
modifications for 22 (65%) of these women. Of the 12 patients who
received PET and MRI, treatment was modified in response to PET
but not MRI for 8 (67%). Treatment modifications due to PET
included nodal boost (n = 20, 67%), extension of irradiated field (n
= 8, 26%), or both (n = 2, 7%).
CONCLUSIONS: Despite uncertainty regarding the anatomic
resolution of PET, sequential use of contrast-enhanced CT, PETCT, and/or MRI had no impact on treatment planning that was not
accomplished by the use of PET alone. Future work should focus
on determining the optimal pretreatment imaging for women with
cervical cancer and developing guidelines to optimize outcomes
while minimizing cost and radiation exposure.
(P007) Pooled Analysis of Locoregional Relapse After
Minimally Invasive Surgery Alone for Intermediateor High-Risk HPV+ Oropharyngeal Squamous Cell
Carcinoma Ryan K. Funk, MD, David G. Stoddard, MD, Kanograt Tangsriwong,
MD, Michael G. Keeney, MD, Qihui Zhai, MD, Eneida F. Vencio, DDS,
Alexander Lin, MD, Joaquin J. Garcia, MD, Eric J. Moore, MD, Robert
L. Foote, MD, Katharine A. Price, MD, Daniel J. Ma, MD; Department
of Radiation Oncology, Department of Otolaryngology, Department
of Laboratory Medicine and Pathology, Division of Medical Oncology,
Mayo Clinic; Department of Radiation Oncology, University of Pennsylvania; Department of Laboratory Medicine and Pathology, Mayo Clinic,
Jacksonville, FL; Department of Oral Pathology, School of Dentistry, Federal University Goiás
PURPOSE/OBJECTIVES: Traditional risk factors predicting locoregional relapse (LRR) following surgery for head and neck squamous cell carcinomas were identified in the pre–human papillomavirus (HPV) era. Patients with HPV-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) present at younger age and
have an approximately 50% reduction in death when compared
with their HPV− counterparts. Minimally invasive surgery (MIS)
(eg, transoral robotic surgery [TORS] and transoral laser microsurgery [TLM]) allows for improved intraoperative assessment of the
tumor. It is unknown if traditional risk factors fully apply to the
HPV+ population that undergoes MIS. We examined whether traditional indications for adjuvant radiation therapy (RT) (perineural
invasion [PNI], angiolymphatic invasion [ALI], T3–4, or N2a–b)
or adjuvant chemoradiation therapy (CRT) (extracapsular extension [ECE] or positive margins) also predict for LRR in patients
with HPV+ OPSCC who undergo MIS alone.
MATERIALS AND METHODS: After institutional review board (IRB)
approval, the medical records of patients treated with TORS (two
institutions) or TLM (one institution) for OPSCC were reviewed to
identify patients with HPV+ tumors who had indications for adjuvant therapy but did not receive adjuvant therapy. HPV status was
confirmed by p16 immunohistochemistry. Individual data from all
three institutions were pooled into a single database for analysis.
RESULTS: A total of 43 patients with HPV+ base of tongue (n = 16)
or tonsil (n = 27) OPSCC with a median age of 60 years (range:
37–81 yr) who did not receive adjuvant therapy despite the presence of intermediate- or high-risk features were identified.
Seventeen of 43 patients had a smoking history > 10 pack-years.
Fourteen patients had ECE as an indication for CRT. Margins were
close in all patients due to the nature of MIS, but the final margins
were all negative. Intermediate-risk features were ALI (n = 4), PNI
(n = 3), T3 (n = 6), N2a (n = 13), and N2b (n = 6). Three patients
had two intermediate risk factors. Median follow-up after surgery
was 30.1 months (range: 3.1–161.7 mo). Eleven of 47 (26%) patients
developed LRR at a median of 5.7 months (range: 2.9–39.2 mo).
Kaplan-Meier estimate of 2-year relapse-free survival was lower for
patients with ECE vs patients with intermediate-risk factors only
(43% vs 88%, respectively; P = .02). LRR was detected locally (n =
3, base of tongue), locally and in ipsilateral regional lymph nodes
(ILNs) (n = 1), in ILNs alone (n = 4), in contralateral regional LNs
(n = 2), or in bilateral neck nodes (n = 1).
CONCLUSION: In the HPV+ population, ECE remains a significant
risk factor for LRR without adjuvant therapy after MIS. Patients
with intermediate-risk disease after MIS have moderate rates
of LRR.
(P008) Pretreatment FDG Uptake of Nontarget Lung
Tissue Correlates With Symptomatic Pneumonitis
Following Stereotactic Ablative Radiotherapy (SABR) Aadel A. Chaudhuri, MD, PhD, Michael S. Binkley, BA, Justin N. Carter,
BA, Maximilian Diehn, MD, PhD, Billy W. Loo, MD, PhD; Stanford
University School of Medicine
INTRODUCTION: Radiation pneumonitis (RP) is the most common
toxicity associated with radiation therapy to the lung. It can be
debilitating and even life-threatening, especially since many
patients with lung malignancies have other pulmonary comorbidities. Here, we report our institution’s experience in using pretreatment positron emission tomography-computed tomography (PETCT) to calculate baseline nontarget lung fluorodeoxyglucose (FDG)
avidity, which we have found to be significantly associated with
symptomatic RP following stereotactic ablative radiotherapy
(SABR).
METHODS: We retrospectively reviewed outcomes in 73 patients
with lung tumors treated with SABR. All patients underwent whole
body PET-CT and four-dimensional (4D) chest CT simulation
scan within 2 weeks prior to treatment. Gross tumor volume
(GTV) was contoured on axial CT slices using lung windows.
Respiration-induced motion was assessed by 4D CT, used to design
the internal target volume (ITV), and a 0.5-cm margin was added
to form the planning target volume (PTV). Total lung minus PTV
and ipsilateral lung minus PTV were contoured using lung windows. All contouring was done using Varian Eclipse and MIM software. We used the simulation PET-CT scans to calculate the standard uptake value (SUV) at the 85th (SUV85), 90th (SUV90), and
95th (SUV95) percentiles and mean SUV for total lung minus PTV
and ipsilateral lung minus PTV using MIM and compared these
values between patients who experienced symptomatic RP and
those who did not. All strata were compared using Student’s t-test
and Cox regression for univariate and multivariate analyses.
RESULTS: Median follow-up time was 15 months (range: 4–45 mo).
A total of 70 patients (95.9%) were treated for T1 to T3 non–smallcell lung cancer, while 3 (4.1%) were treated for oligometastatic
disease from non-lung primary cancers. Sixty-six patients (90.4%)
were treated for one lung tumor, and seven patients (9.6%) were
treated for two lung tumors. Sixteen patients (21.9%) experienced
grade ≥ 2 RP, 3 of whom experienced grade ≥ 3 RP. Median time to
pneumonitis was 4.95 months (range: 2.5–24 mo). Analysis of
simulation PET-CT scans from all patients revealed that those who
experienced grade ≥ 2 RP had significantly higher total lung minus
PTV SUV85 (P = .0005), SUV90 (P = .0014), and SUV95 (P =
.0078) than those with no symptomatic pneumonitis. We saw similar results when we analyzed ipsilateral lung minus PTV, with significantly higher baseline SUV85 (P = .0021), SUV90 (P = .0036),
SUV95 (P = .0108), and mean SUV (P = .0012) in patients who
experienced grade ≥ 2 RP. A significant association was observed
between grade ≥ 2 RP and total lung minus PTV SUV85 on uniARS PROCEEDINGS 2015
29
variate (hazard ratio [HR] = 28.9; 95% confidence interval [CI],
3.66–216.61; P =.001) and multivariate (HR = 25.22; 95% CI, 3.3–
192.94; P =.002) analysis.
CONCLUSION: Patients with higher nontarget lung FDG avidity
appear to be at greater risk for radiation pneumonitis following SABR.
(P009) Monte Carlo Dosimetry Evaluation of Lung
Stereotactic Body Radiosurgery Colbert A. Parker, BS, Roger Ove, MD, PhD, Madhu B. Chilikuri, PhD,
Suzanne M. Russo, MD; University of South Alabama School of Medicine; Mitchell Cancer Institute
BACKGROUND: Promising results have been obtained using stereotactic body radiosurgery (SBRT) for early-stage lung cancer. The
calculation of dose in pulmonary parenchyma can be inaccurate. MATERIALS AND METHODS: We retrospectively analyzed 47 cases
treated over a 2-year period with CyberKnife SBRT, planned with
the standard pencil beam (PB) algorithm. Cases were a mixture of
early-stage lung cancer and oligometastatic cases. The median prescribed dose was 50 Gy in four or five fractions. We compared the
planned dose with the dose actually delivered, as estimated with
Monte Carlo (MC) dosimetry to the 1% level. We correlated the
dosimetric deficiencies with recurrences, using deformable registration to determine the dose delivered to the site of recurrence.
RESULTS: With a median follow-up of 2 years, the local control at
1 year was 90%, declining to 70% at 2 years. The total number of
local recurrences was 10, and 8 of these patients died with progressive disease. Two recurrences occurred synchronously with metastases, and two recurrences were in palliative cases treated to lower
doses with tight margins, and disease was never cleared locally. MC
calculations showed that the mean dose delivered to the planning
target volume (PTV), averaged over all cases, was 7% lower than
planned. Most cases were planned with an expansion on the PTV
(PTVmicro = GTV + 8-mm expansion in lung + 3 mm), representing a region at risk for microscopic extension, and were intended to
receive a minimum dose of 80% of the prescription dose. MC calculations showed that the minimum dose to this structure, averaged over all cases, was 47% lower than the intended dose. For cases
that recurred, the mean dose to the PTVmicro was 8% lower than
intended, while it was only 2% lower for those whose disease was
controlled. There were no other significant differences in target
coverage between patients with local control and local recurrence.
The PB algorithm and MC estimates for pulmonary exposure were
assessed, recording the V5, V10, and V20 for the ipsilateral and
total lung volumes. These estimates roughly agreed for the two
algorithms, with the MC results almost universally lower than PB
by an absolute difference of 1% to 3% on average.
CONCLUSIONS: Without the use of MC planning, target structures
were substantially underdosed. Local failures were associated with
PTVmicro undercoverage, which suggests that delivering a therapeutic dose to this expanded microscopic disease target volume is
beneficial. MC dosimetry is preferable for lung SBRT, while the PB
algorithm is adequate for predicting pulmonary toxicity.
30
(P010) Stereotactic Body Radiotherapy for Treatment
of Adrenal Gland Metastasis: Toxicity, Outcomes, and
Patterns of Failure
William W. Chance, MD, Quynh-Nhu Nguyen, MD, Reza J. Mehran,
MD, James W. Welsh, MD, Daniel R. Gomez, MD, Peter A. Balter, PhD,
Ritsuko Komaki, MD, Zhongxing Liao, MD, Joe Y. Chang, MD, PhD; UT
MD Anderson Cancer Center
PURPOSE: A single-institution, retrospective review of toxicity,
patterns of failure, and outcomes in patients undergoing stereotactic body radiotherapy (SBRT) for metastasis to the adrenal gland.
MATERIALS AND METHODS: From 2009–2014, a total of 36
patients with 40 adrenal metastases were treated with SBRT. The
median age of the patient population was 63.7 years (range: 50–77
yr). Primary sites included lung (n = 31), ovary (n = 2), bladder (n
= 1), esophagus (n = 1), and melanoma (n = 1). A total of 32
patients received treatment to a single adrenal gland, while 4
patients received treatment to the bilateral adrenal glands. The prescription dose to the target was 60 Gy in 10 fractions (n = 25), 50
Gy in 10 fractions (n = 10), 50 Gy in 4 fractions (n = 4), or other (n
= 4). Failures within the prescribed high-dose irradiated region
were considered local failures. New or progressive distant metastases outside of the treated adrenal gland were considered distant
failures. After review of the radiation treatment plan, local failures
were characterized as in-field (epicenter within the 100% isodose
line) or marginal (between the 50% and 100% isodose lines).
RESULTS: Median follow-up was 12.6 months after radiation treatment (range: 1.4–37.1 mo). Six patients developed grade 1 gastrointestinal toxicity. Two patients who were treated to the bilateral
adrenal glands developed grade 2 adrenal insufficiency. There was
no grade 3 or 4 toxicity observed. Median overall survival after
treatment was 19.5 months. The 1- and 2-year overall survival rates
were 67% and 55%, respectively. The 1-year freedom from local
failure was 87%. The median time to local failure was not reached.
The 1-year freedom from disease progression was 25% (median
time to progression, 5.9 mo). The 1-year freedom from distant failure was 33% (median time to distant failure, 6.0 mo). There were
six in-field local failures and one marginal failure observed.
CONCLUSION: SBRT is an effective treatment modality, achieving
excellent local control with minimal toxicity for patients with
adrenal metastases. The development of progressive distant metastasis is the predominant pattern of failure affecting patients’ survival outcomes. (P011) Stereotactic Radiosurgery and BRAF Inhibitor
Therapy for Melanoma Brain Metastases Is Associated
With Increased Risk for Radiation Necrosis. Kirtesh Patel, MD, Roshan Prabhu, MD, Mohammad K. Khan,
MD; Winship Cancer Institute, Emory University; Levine Cancer Institute, Carolinas Medical Center
INTRODUCTION: Melanoma is an aggressive malignancy with a
deplorable penchant for spreading to the brain. BRAF inhibitors, as
single agents, have demonstrated intracranial efficacy. The 2015
National Comprehensive Cancer Network (NCCN) guidelines
have raised concerns about increased toxicity when BRAF inhibitors are combined with radiotherapy, based on limited case reports.
Thus, we investigate the safety and efficacy of stereotactic radiosurgery (SRS) and BRAF inhibitors for melanoma brain metastases
patients.
METHODS: We reviewed melanoma patients with newly diagnosed
brain metastases from 2005–2012. Radiation necrosis was compared by Fisher’s exact test; local control, intracranial control, and
overall survival were estimated by the Kaplan-Meier method.
RESULTS: A total of 72 patients received SRS, with 12 (16.7%) also
receiving BRAF inhibitor therapy. BRAF inhibitor patients were
similar to SRS-alone patients, except for having a higher percentage
of RPA class 3 patients (25.0% vs 0.0%; P = .0030) and lower rates of
solitary metastases (25.0% vs 55.0%; P = .034). No significant differences between radiation therapy total dose and dose per fraction,
gross tumor volume (GTV), prescription isodose line, or conformality index were identified. Rates of all grades of radiation necrosis
were statistically higher in the BRAF cohorts (58.3 vs 26.7%;
P = .044); furthermore, symptomatic radiation necrosis was also
more frequent in the BRAF inhibitor group (41.7% vs 15.0%;
P = .048). One-year local control (83.5% vs 83.5%, P = .835) and
intracranial control were similar between cohorts (30.3% vs 26.3%;
P = .395). One-year overall survival was higher in the BRAF inhibitor group but not statistically significant (72.7% vs 38.1%;
P = .172).
CONCLUSION: Rates of symptomatic radiation necrosis appear to
be higher for the BRAF inhibitor therapy group. Prospective studies investigating BRAF inhibitor therapy and SRS for melanoma
brain metastases should consider incorporating methods to
decrease potential radiation necrosis, including fractionating
radiosurgery.
(P012) Characteristics of Mentorship During Radiation
Oncology Residency Gurleen Dhami, MD, Wendy Gao, MD, Michael Gensheimer, MD,
Andrew D. Trister, MD, PhD, Gabrielle M. Kane, MD, Jing Zeng, MD;
University of Washington Medical Center
PURPOSE: The mentor-mentee relationship is crucial during residency training to foster professional and personal growth. Multiple
surveys in other residency specialties have identified the mentorship’s role in professional development and career satisfaction. This
national survey of radiation oncology residents was conducted
to identify key characteristics of resident mentorship to identify
areas for improvement. MATERIALS AND METHODS: An anonymous questionnaire was
sent to all radiation oncology residents/recent graduates at
Accreditation Council for Graduate Medical Education (ACGME)accredited residency programs, identified per the Association of
Residents in Radiation Oncology (ARRO) member directory.
Questions assessed demographics, prevalence of formal mentorship program, opinions about the value of mentorship, and details
of the relationship. Responses were scored on a 5-point ordinal
Likert scale. RESULTS: Out of 596 survey invitations, 157 residents responded
(25%). Just over half of respondents had a current mentor
(53%). The majority found their mentors early in training, with
49% identified during postgraduate year (PGY)-2, 28% establishing relationships during medical school, and only 14% during
PGYs 3,4, and 5. Mentors were most commonly selected from faculty members whom the residents knew (64%). They were also
identified by contacting faculty members with similar interests (33%) and by recommendations from others (29%). Most
mentors were chosen from the junior faculty (29%) but also
included senior faculty members (19%), radiation oncologists at
another academic center (18%), other faculty members at the same
institution (10%), program directors (11%), department chairs
(6%), and others (7%).
Residents often had more than one active mentor, with most having
two to three active mentors (68%), while 26% had one mentor, and
6% had more than active mentors. Frequent and regular meetings
were a common feature of the mentor-mentee relationship, with
28% meeting more than once per week, 30% meeting once per
week, and 30% meeting once per month. Only 13% of residents met
twice per year or less with their mentors. The most valued trait that
was desired from a mentor was approachability (90%). Other
desired traits included availability (82%), ability to provide opportunities (77%), and a clinical role model (68%). The majority of
residents found mentorship helpful for career development (83%),
research (75%), lifestyle/personal advice (71%), networking
(46%), and coping with residency (46%).
CONCLUSION: Almost half of current radiation oncology residents
do not have a mentor. Of those with mentors, most established
relationships early in their training, during PGY-2 or prior.
Therefore, it is imperative to intervene early in the training process
to produce successful mentorship experiences. Many residents
require more than one active mentor, which enables multiple goals
to be met, such as career development, increasing one’s research
portfolio, networking, and coping with residency. (P013) Perioperative Mortality in Nonelderly Adult
Patients With Cancer: A Population-Based Study
Evaluating Healthcare Disparities in the United States
According to Insurance Status Arya Amini, Norman Yeh, Bernard Jones, Yevgeniy Vinogradskiy,
Edward Bedrick, Chad G. Rusthoven, Ava Amini, William T. Purcell,
Brian D. Kavanagh, Sana D. Karam, Christine M. Fisher; University of
Colorado; Northwestern University
PURPOSE: Cancer survival is known to vary based on socioeconomic factors, including insurance status. The purpose of this
study was to evaluate predictors for perioperative mortality (death
within 30 d of cancer-directed surgery) for the 15 most common
surgically treated cancers in the United States.
PATIENT AND METHODS: The Surveillance, Epidemiology, and
End Results (SEER) database was examined for the 15 most common surgically resected cancers. The database was queried from
2007 to 2011, with a total of 506,722 patients included in the analysis. Binomial logistic regression was used to assess the effect of
31
patient and tumor characteristics on perioperative mortality under
multivariable analysis.
RESULTS: The insurance status for all patients was as follows: non-
Medicaid insurance (83%), any Medicaid (10%), uninsured (4%),
and unknown (3%). Under univariable analysis, predictors for perioperative mortality included Medicaid or uninsured status (P <
.001), older age (≥ 60 yr) (P = .015), nonwhite race (P < .001), being
unmarried (P < .001), urban and rural residence (vs metropolitan)
(P = .002), higher percent of county below the federal poverty level
(P < .001), and lower median household income (P < .001).
Perioperative mortality was also associated with more advanced
disease, including higher tumor stage (P < .001) and metastasis (P
< .001). After adjusting for age, race, sex, marital status, residence
(urban or rural), extent of disease (in situ, local, regional, distant),
and percentage of county below federal poverty level, patients with
either Medicaid insurance (odds ratio [OR] = 1.22; 95% confidence
interval [CI], 1.15–1.29; P < .001) or uninsured status (OR = 1.75;
95% CI, 1.61–1.87; P < .001) were more likely to die within 30 days
of surgery compared with patients with non-Medicaid insurance.
Additional statistically significant predictors for perioperative mortality under multivariable analysis included rural residence (OR =
1.07), race—including being African-American (OR = 1.07),
Hispanic, (OR = 1.27), and Asian or Pacific Islander (OR = 1.19)—
and being unmarried (OR = 1.08). CONCLUSION: In the largest reported analysis of perioperative
mortality evaluating the 15 most common surgically treated malignancies, those with Medicaid coverage or without insurance were
more likely to die within 30 days of surgery. (P014) Absence of Infection From Injection of a Rectal
Spacer Into the Anterior Perirectal Fat Space Jekwon Yeh, MD, Justin Ren, Kenneth Tokita, MD, John Ravera, MD;
Cancer Center of Irvine
OBJECTIVE/PURPOSE: There is now increasing literature to support the use of a rectal spacer to decrease rectal side effects during
radiation for prostate cancer. A rectal spacer (polyethylene glycol
hydrogel) is usually placed via transperineal injection behind
Denonvillier’s fascia to enhance the separation between the prostate and rectum. This causes a decrease in radiation dose to the
rectum. Occasionally, the needle can penetrate the rectal wall, and
the spacer material is accidently injected into the rectal lumen. This
study aims to evaluate the rate of infection from rectal spacer placement and in patients who experienced rectal wall penetration with
the rectal spacer applicator needle. MATERIALS AND METHODS: From January 2010 to May 2014, a
total of 370 patients had a rectal spacer placed via transperineal
injection. Patients were instructed to perform an enema the night
before and immediately prior to the surgery. The perineum was
also sterilized with Betadine prior to the procedure. Patients also
took ciprofloxacin 500 mg bid for 10 days, starting the day prior to
the procedure. Patients also received gentamicin 80 mg and cefazolin 1 gram intraoperatively. Afterwards, a computed tomography
(CT) scan and magnetic resonance imaging (MRI) were performed
on all patients to confirm placement of the rectal spacer and for
32
external beam radiation planning.
RESULTS: Out of 370 patients who received the hydrogel spacer, no
patient developed a rectal infection. A total of 18 (5%) patients had
known rectal penetration seen on imaging or clinically. None of
these patients experienced any rectal infections.
CONCLUSIONS: With proper preparation and antibiotics, placement of the rectal spacer into the anterior perirectal fat is extremely safe, without any risk of infection, in our series. Also, infections
were not found in patients who had rectal wall penetration with the
rectal spacer applicator needle.
(P015) Radiation Biological Responses of MRI-Linac vs
Linac in Human Head and Neck and Lung Cancer Cells Li Wang, Marco van Vulpen, Zhifei Wen, Stan Hoogcarspel, David P.
Molkentine, Jan Kok, Steven Hsesheng Lin, R. Broekhuizen, Kie-kian
Ang, A.N. Bovenschen, Bas Raaymakers, Steven Jay Frank; UT MD Anderson Cancer Center; University of Utrecht Medical Center
OBJECTIVE: The MRI-Linac (MRL) is a novel radiotherapy technology designed to enable high cure rates with low toxicity and
treatment response monitoring. However, the biological influence
on radioresponses of human solid tumors within the 1.5-T magnetic field (MF) generated by MRL is unknown. Our hypothesis is
that the 1.5-T MF has no influence on cell viability or radiation
effects.
METHODS: Two non–small-cell lung carcinoma (NSCLC) lines
(H460 and H1299) and two head and neck squamous cell carcinoma (HNSCC) lines (HN-5 and UMSCC-47) were used. The
influences of a 1.5-T MF on in vitro cell viability and on cellular
radioresponses were determined by cell plate efficiency (PE) and by
clonogenic cell survival assay (CSA) after exposing the cells to
graded single doses or fractionated 6 MV radiation using Linac
(100 MU/min) or MRL (134 MU/min), respectively. The experiments were performed with cell flasks placed inside a 37°C water
bath with an optimized radiation dose distribution. The radiation
output of Linac and the MRL was measured with a corrected chamber. The physical dose received by the cells was verified using radiation detectors. The results were analyzed by t-test.
RESULTS: Our results supported a very strong trend that MF, as a
single factor, had no influence on cell viability. No significant PE
change occurred after single exposure or multiple exposures to MF
compared with the Linac environment for the four cell lines (12 of
16 experiments; all P > .05) except for one experiment with the
H460 cells (borderline; P = .044) and three experiments
with UMSCC-47 cells. Similarly, single exposure or multiple exposures to MF had no influence on cell radioresponse (all P > .05).
When the cells were exposed to MRL or Linac treatment for up to
four times, no significant changes were observed for the D0s for
with MF vs without MF (all P > .05).
CONCLUSIONS: The 1.5-T MF generated by MRL had no effect on
the viability or radioresponses of NSCLC or HNSCC cell lines in
vitro. These results suggest that MRL, as a novel cancer treatment
technology, has the potential not to influence the radiotherapy out-
come of patients. Considering the complicated in vivo microenvironment, further in vivo study is warranted.
(P016) The Cell Cycle Inhibitor P21 Regulates
Langerhans Cell Radiation Resistance and Promotes
T Regulatory Cell Induction Upon Exposure to
Radiotherapy Jeremy G. Price, Juliana Idoyaga, Brandon Hogstad, Helene Salmon,
Marylene Leboeuf, Miriam Merad; Icahn School of Medicine at Mount
Sinai; Stanford University
Several studies have revealed that exposure to ionizing irradiation
(IR) may lead to increased accumulation of tumor-infiltrating T
regulatory cells (Tregs), which in turn promotes tumor resistance
to radiation therapy. Here, we questioned the contribution of tissue-resident antigen-presenting cells (APCs) to the induction of
Tregs upon exposure to IR. Specifically, we focused on Langerhans
cells (LCs), the resident APCs of the epidermis, because of their
unique ability to resist depletion by high-dose IR. Therefore, LC IR
resistance may inform us of the underlying IR resistance mechanisms utilized by other progenitor cells. However, a comprehensive
study of the molecular and cellular mechanisms conferring LC IR
resistance has never been undertaken.
We found that LCs do not undergo apoptosis following IR as do
other dendritic cell (DC) subsets but instead persist and migrate
to skin-draining lymph nodes. Subsequent analysis in migrationdeficient CCR7−/− mice revealed a constant number of epidermal
LCs, indicating that changes in LC number following IR are due
solely to migration and not to cell death. Moreover, we show for
the first time that LCs are resistant to the formation of DNA damage, as measured by induction of H2AX foci and COMET assay. In
contrast, other members of the myeloid lineage, notably lymphoid
tissue-resident DCs, are exquisitely sensitive to IR-induced DNA
damage. In addition, both steady-state and postlethal IR LCs
express a unique repertoire of prosurvival and stress-related proteins and diminished levels of proapoptotic molecules by microarray analysis. Additionally, we found that the cell cycle regulator
p21 is overexpressed in LCs at rest and that in contrast to WT LCs,
p21−/− LCs undergo apoptosis, accumulate significant DNA damage, and fail to experience cell cycle arrest following IR. Strikingly,
upon skin exposure to IR, WT LCs lead to significant expansion
of Treg, whereas p21−/− LCs fail to do so. In a cutaneous tumor
model, we show that p21−/− LCs cannot promote tumor-infiltrating Tregs and correlate with smaller tumor volumes.
Moving forward, these data suggest a novel means by which targeting LC IR resistance can be used to increase the response to radiotherapy of cutaneous tumors. LCs uniquely express an IR resistance
module of genes that permits them to persist and repopulate the
epidermal niche following IR. Future analyses will seek to elaborate
the functional implications of LCs and IR-sensitive DC IR-exposure
as it relates to the priming and development of graft-versus-host
disease (GVHD) and local antitumor immunity following radiation
therapy.
(P017) Dosimetric Evaluation of Respiratory-Gated
Radiotherapy for Left-Sided Breast Cancer Veronica Finnegan, MD, Varun Chowdhry, MD, Weidong Li, PhD,
Katrina Stellingworth, CMD, Jeffrey Bogart, MD, Anna Shapiro,
MD; SUNY Upstate; Massachusetts General Hospital
PURPOSE/OBJECTIVES: Adjuvant radiotherapy is associated with
improvements in local control and survival in patients with breast
cancer. As oncological outcomes have improved, there is a greater
importance in preventing long-term toxicity from treatment.
Technological advancements in radiotherapy delivery have the
potential to allow better coverage of complex targets while reducing
doses to normal structures. The use of four-dimensional computed
tomography (4DCT) and respiratory gating has increased in clinical practice, but there is limited information regarding the utility of
respiratory gating in breast cancer. The purpose of the study is to
assess the dosimetric benefits of respiratory gating for patients
receiving radiotherapy for left-sided breast cancer.
PATIENTS/METHODS: A total of 38 women with left-sided breast
cancer were treated with respiratory gating between 2009 and 2013.
All patients underwent 4DCT simulation using the Varian RealTime Position Management respiratory gating system. The determination to use respiratory gating was at the discretion of the treating physician. For this study, maximum intensity projection (MIP)
image sets containing images from all phases were also created. The
original plans were copied to both the gated MIP and the all-phase
MIP sets for dosimetric evaluations. Dose-volume histograms were
calculated and compared. Doses to predefined heart and lung
parameters were compared on two plans for each patient. Cardiac
and pulmonary doses were compared for each patient using a twosided paired difference test (t-test).
RESULTS: The use of respiratory gating resulted in statistically significant dose reductions to the heart on nearly all parameters evaluated. Mean whole heart dose was 368 cGy with gating and 389
cGy without gating (P < .001). V5 heart was 77% with gating and
84% without gating (P < .001). Max left anterior descending (LAD)
dose was 3,990 cGy with gating and 4,264 cGy without gating (P =
.009), and mean left ventricular dose was 511 cGy with gating and
549 cGy without gating (P < .001). There were trends toward a
reduction of mean LAD dose (2,298 cGy with gating and 2,569 cGy
without gating; P = .059) and max left ventricular dose (4,021 cGy
with gating and 4,183 cGy without gating; P = .067). Statistically
significant differences were not noted in any of the lung parameters
tested (V5, V20, or V40).
CONCLUSION: The use of respiratory gating has resulted in small but
statistically significant reductions in heart dose. Further studies are
needed to understand the clinical implications of these differences.
(P018) Accelerated Partial Breast Radiotherapy
Using VMAT—A Preliminary Dosimetric Comparison
to Single-Entry Brachytherapy Yucel Saglam, Yasemin Bolukbasi, Steve Kirsner, Vildan Alpan, Duygu
Sezen, Ugur Selek; American Hospital, MD Anderson Radiation Treatment Center, Istanbul; Department of Radiation Oncology, UT MD Anderson Cancer Center; Department of Radiation Oncology, Koc University
33
PURPOSE: To compare the dosimetric aspects of accelerated partial
breast irradiation (APBI) with a single-entry brachytherapy device,
strut-adjusted volumetric (SAVI), and external APBI using volumetric arc therapy (VMAT), with the intent of investigating the
feasibility of using VMAT for the delivery of APBI treatments.
MATERIALS AND METHODS: Five left breast cancer patients who
were planned and treated with SAVI at MD Anderson Cancer
Center in Istanbul at American Hospital were randomly and retrospectively chosen from a database for this preliminary study. All
patients were staged with T1N0M0 invasive breast cancer after partial mastectomy and sentinel lymph node dissection. The age of the
patients ranged from 50 to 82 years. None of the patients received
chemotherapy. The average cavity size was 12.6 mm (range: 2.2–18
mm), and all patients had invasive ductal carcinoma.
The plans and their contours were sent from the Oncentra
Treatment Planning System to the Philips Pinnacle treatment planning system for replanning. VMAT APBI treatment plans were run
on these same patients using the same contours delineated in the
Oncentra planning system. The target volumes and planning
parameters were set according to the National Surgical Adjuvant
Breast and Bowel Project (NSABP)-39 protocol for external beam
APBI, with a prescription dose of 38.5 Gy in 10 fractions.
Dosimetric criteria on the heart and ipsilateral lung were used to
compare the two techniques. Paired two-tailed Student’s t-test was
performed to assess the differences in lung mean dose, heart mean
dose, V20, V10, and V5 (%).
RESULTS: Even VMAT resulted in a decreased low-dose volume of
the lung (V5: 0.1% vs 12.2%; P = .03); mean dose (204.1 cGy vs
287.2 cGy; P = .08), and V10 (0.02% vs 2.83%; P = .132) and V20
(0.001% vs 4.540%; P = .063) percentages of the lung were found to
be similar. The difference in heart mean dose (243.6 cGy vs 342.8
cGy; P = .022) was influenced by the significant difference of heart
V5 (0.083% vs 21.4%; P = .004), but the V20 (0.0001% vs 0.126%;
P = .374) and V10 (0.008% vs 3.448%; P = .104) values of the heart
were found to be comparable between the two techniques.
CONCLUSION: VMAT planning for the delivery of APBI in this preliminary dosimetric evaluation has been shown to be a viable option
for APBI. VMAT planning gives acceptable lung and heart doses
and appears to deliver lower doses to the heart and ipsilateral lung
than APBI delivered with the single-entry SAVI applicator.
(P019) Predictors of Outcomes in Breast Cancer Patients
With Oligometastases with oligometastases tend to fare better than patients with oligometastases from other primary sites. However, no studies have
examined predictors of outcomes in patients with oligometastatic
breast cancer.
MATERIALS AND METHODS: We identified 380 patients treated at
our institution with SBRT or SRS from 2010–2014. We retrospectively reviewed the records of 62 patients with metastatic breast
cancer. We defined oligometastases as metastases at ≤ 5 distinct
clinical sites. Oligometastases were determined by imaging and
clinical documentation. Kaplan-Meier curves were used to determine survival after metastasis. A Cox proportional hazards model
was used to assess the effect of patient, tumor, and treatment characteristics as predictors of survival after metastases.
RESULTS: There were 30 patients with oligometastases and 32
patients with non-oligometastases. A total of 60% of patients had
initial stage I, II, or III disease, while 40% had stage IV. The tumor
was estrogen receptor (ER)-positive, progesterone receptor (PR)positive, and human epidermal growth factor type 2 (HER2)positive in 63%, 46%, and 20% of oligometastatic patients and in
66.7%, 57%, and 28% of nonoligometastatic patients, respectively.
Triple-negative disease was noted in 27% of patients in both arms.
Further, 95% received chemotherapy and about 60% received hormonal therapy in both groups. The 5-year survival rate after metastases was 79.6% for oligometastatic vs 45.7% for nonoligometastatic patients. Univariate models showed that the predictors of
inferior survival after metastases included: absence of oligometastases (hazard ratio [HR] = 3.39; 95% confidence interval [CI],
1.28–9.19; P = .016), HER2-negative status (HR = 12.42; 95% CI,
1.63–94.56; P = .015), and triple-negative status (HR = 3.61; 95%
CI, 1.43–9.07; P = .006). On bivariate analyses, absence of oligometastases remained a significant predictor of worse survival after
metastasis: absence of oligometastases (HR = 6.07; 95% CI, 1.56–
23.710; P = .009) adjusted for HER2-positive status (HR = 17.55;
95% CI, 2.13–144.84; P = .008) in model 1 and absence of oligometastases (HR = 5.31; 95% CI, 1.54–18.31; P = .008) adjusted for
triple-negative status (HR =3.65; 95% CI, 1.43–9.29; P = .007) in
model 2.
CONCLUSION: Our study showed that oligometastatic breast cancer patients have improved 5-year survival after metastases compared with non-oligometastatic patients. In patients with oligometastases and HER2-positive disease or without triple-negative disease, survival after metastases was superior. Further studies are
needed to identify a favorable subset of patients with oligometastases who would benefit from aggressive therapy.
Shefali Gajjar, MD, Arthy Yoga, MD, Isildinha M. Reis, PhD, Youssef
Zeidan, MD, PhD, Cristiane Takita, MD; Department of Radiation
Oncology, Department of Epidemiology & Public Health, University of
Miami/Sylvester Comprehensive Cancer Center; Department of Surgery,
University of Miami
(P020) 3D Conformal External Beam Radiation Therapy
May Result in Lower Heart Dose and Risk of RadiationInduced Major Coronary Events Compared With
Multicatheter Balloon High-Dose-Rate Brachytherapy
for Left-Sided Breast Cancer Patients BACKGROUND: Oligometastases are hypothesized to represent a
potentially curable disease. With the emergence of stereotactic
body radiotherapy (SBRT) and stereotactic radiosurgery (SRS),
additional treatment options have been presented to patients with
limited metastases. Studies have shown that breast cancer patients
Jason C. Ye, MD, Brittney Wilson, BS, CMD, Igor Shuryak, MD,
Jenghwa Chang, PhD, Samuel Trichter, MSc, David Brenner, MD, DSc,
Dattatreyudu Nori, MD, John Ng, MD; Department of Radiation Oncology, Weill Cornell Medical College; Center for Radiologic Research,
Columbia University Medical Center
34
PURPOSE: To determine and compare the heart dose and potential
increased risks in long-term cardiac toxicity from three-dimensional conformal external beam radiation therapy (3DCRT) and
multicatheter balloon high-dose-rate (HDR) brachytherapy treatments for left-sided breast cancer patients.
METHODS: Fifteen consecutive patients who were treated with balloon HDR (3,400 cGy in 10 fractions, twice daily) after lumpectomy
for left-sided breast cancer between 2011 and 2014 were included in
this study. Target volumes drawn for HDR brachytherapy. Left
breast, heart, and left anterior descending artery (LAD) were contoured by a physician in the brachytherapy treatment planning system and independently confirmed by another physician. 3DCRT
plans (5,040 cGy in 28 fractions using opposed tangential beams)
were developed using the same computed tomography (CT) scans
and contours by the same team by transferring the image and structure sets to the external beam planning system. Appropriate target
coverage, dose distribution, and dose homogeneity (± 7%) were
confirmed independently. Cardiac blocks were allowed, as long as
they did not significantly affect the breast and lumpectomy cavity
coverage. The radiation doses to the heart and LAD using 3DCRT
and HDR techniques were recorded. The risk of long-term additional cardiac toxicity was estimated by calculating the 10-year
radiation-induced estimated actual risk (EAR) for major coronary
events using a previously published cardiac risk model.
RESULTS: The 15 women (median age: 65 yr, range: 59–86 yr) all
had early-stage localized disease that fit the American Society for
Radiation Oncology (ASTRO) guidelines for accelerated partial
breast irradiation. Average of the mean heat doses (MHDs) delivered using HDR was 251.6 cGy (range: 137–427 cGy), while the
average MHD that they would have received using 3DCRT was
128.99 cGy (range: 90–236.4 cGy) (Student’s t-test: P < .001). The
mean dose to the LAD was not statistically significant (551 cGy for
HDR vs 814 cGy for 3DCRT; P = .11 by Student’s t-test). After
factoring in MHD, age, smoking status, history of hyperlipidemia,
hypertension, and diabetic history, the mean 10-year radiationinduced EAR for 3DCRT and HDR for the 15 women was 0.51%
(range: 0.17%–1.51%) and 1.01% (range: 0.31%–3.5%), respectively (Student’s t-test: P = .0064).
CONCLUSIONS: Both 3DCRT and balloon HDR can achieve relatively low MHDs and result in minimal increases in the risk of
additional major coronary events. In certain cases, compared with
HDR brachytherapy, 3DCRT may result in lower MHDs and a
lower risk of long-term cardiac toxicity.
(P021) Improving Clinical Documentation and
Prospectively Populating a Research Database
Through an Electronic Data Capture System for
Routine Clinical Care Hubert Y. Pan, MD, Timothy J. Edwards, BS, David P. Giragosian,
PsyD, Emma B. Holliday, MD, Cameron W. Swanick, MD, Geoffrey V.
Martin, MD, Karen E. Hoffman, MD, Simona F. Shaitelman, MD,
Wendy A. Woodward, MD, PhD, Benjamin D. Smith, MD; UT MD Anderson Cancer Center
INTRODUCTION: With the current emphasis on value-based health
care, there is increased importance of quantifying value and reducing cost. Electronic health records (EHRs) are being adopted at an
increasing rate but often capture information as unstructured text,
requiring time-consuming retrospective reviews to extract outcomes data. Electronic data capture (EDC) using case report forms
is commonly used to collect structured data for clinical trials. We
implemented a web-based EDC system for routine clinical care and
describe our experience piloting the system for our breast radiation
therapy (RT) service.
METHODS: Our institution uses dictation and transcription for
clinical documentation stored in an in-house–developed EHR. A
separate RT-specific system contains RT prescriptions, schedules,
and treatment records. The implemented EDC serves as an intermediary between these two systems. Providers specify patient,
tumor, and treatment characteristics through the EDC using structured data fields. These fields are merged with relevant data extracted from the RT system to generate template-based notes in the
EHR for simulation, treatment planning, quality assurance (QA),
weekly on-treatment visits (OTVs), and treatment summaries.
Dictation and EDC times are reported as means and compared
using t-tests.
RESULTS: The EDC had been used by 21 providers and generated
850 notes for 127 patients during the most recent month. A consult
form collecting tumor and treatment details was completed in the
EDC as an initial additional step, requiring 2.5 minutes. This form
generated a patient identifier used in all subsequent notes.
Simulation notes, treatment planning notes, and treatment summaries were all completed more quickly using the EDC as compared
with dictation (P < .001). QA notes recording the results of weekly
treatment plan reviews were completed in real time during the conference (2.1 min with dictation). OTV notes were often completed
during the patient encounter using a tablet (1.8 min with dictation).
The total documentation time for a typical course of breast RT was
5.4 minutes with EDC and 22.1 minutes with dictation.
CONCLUSION: We implemented an EDC system for routine clinical use in our breast RT service that resulted in significant time
savings for clinical documentation and a prospective population of
a database for future outcomes research. Additional follow-up is
needed to determine how easily this system can be generalized to
other RT disease sites and practices.
(P022) Proton Therapy on an Incline Beam Line: Acute
Toxicity Outcomes in Locally Advanced Breast Cancer
Patients Lisa A. McGee, MD, Molly McGue, Megan Dunn, PhD, Stacey Schmidt,
Darren Kaplan, Mark Pankuch, William Hartsell, MD; CDH Proton
Center; Proton Collaborative Group
background: Adjuvant radiotherapy for locally advanced breast
cancer (LABC) is known to reduce local recurrence. Proton therapy can be used to improve the therapeutic ratio by sparing the dose
to adjacent nontargeted tissues, including the heart and lung, in
breast cancer patients requiring treatment of comprehensive
regional lymphatics, including the internal mammary lymph nodes
(IMNs). This retrospective series evaluates the acute toxicity outARS PROCEEDINGS 2015
35
comes for LABC patients treated with uniform scanning (US) proton therapy (PT) on an incline beam line (IBL).
METHODS: From September 2011 to May 2014, a total of 35
patients with LABC received adjuvant US PT targeting either the
chest wall (n = 25) or intact breast (n = 10) plus comprehensive
regional lymphatics, including the IMNs. Patients were treated on
the IBL with one of the following techniques: superior and inferior
anterior superior oblique (ASO) fields alternated every other day
with a superior and inferior en face anterior oblique (AO) field (n
= 12), all 4 fields daily (n = 22), or a superior and inferior en face
AO field only (n = 1). Patients were simulated in a supine position,
immobilized in an alpha cradle with the thorax rotated 30 degrees
to approximate an en face angle achieved with the AO fields.
Toxicity was prospectively assessed using Common Terminology
Criteria for Adverse Events version 4.0 (CTCAE v4.0) weekly during treatment and at 4 weeks following treatment completion.
Outcomes: Median follow-up was 3 months. A total of 34 women
and 1 man were treated with adjuvant US PT for stage I (n = 1), II
(n = 7), III (n = 27) LABC; 20 were left-sided, 12 were right-sided,
and 3 were bilateral. Of the 25 postmastectomy patients, 14 were
reconstructed. Initial fields were planned to 50.4 cobalt gray equivalent (CGE) (n = 33) or 45 CGE (n = 2), with 13 patients having a
planned boost of 10 CGE (n = 9), 14 CGE (n = 1), 16 CGE (n = 1),
and 20 CGE (n = 1). Median total dose received was 50.51 CGE
(range: 45.11–70.36 CGE)
All patients experienced acute radiation dermatitis: grade 1 (n = 8),
grade 2 (n = 26), and grade 3 (n = 3). Five patients required a break
in treatment, and two patients did not complete their full course of
prescribed PT due to skin toxicity. Also, 16 patients experienced
grade 1 esophagitis, and 13 patients experienced grade 1 chest wall
pain. Two patients experienced skin infection following treatment,
requiring antibiotic treatment, which occurred the second week
following treatment completion.
CONCLUSIONs: These early results demonstrate the feasibility of
adjuvant breast cancer treatment with US PT on an IBL. Acute toxicity results appear acceptable. Longer follow-up is needed.
(P023) Dosimetric Evaluation of Accelerated Partial
Breast Irradiation Utilizing the ViewRay Magnetic
Resonance Image-Guided Radiation Therapy System Benjamin W. Fischer-Valuck, MD, Karl Sona, Sahaja Acharya, MD, Min
Yang, Rojano Kashani, PhD, Imran Zoberi, MD, Maria Thomas, MD,
PhD; Washington University
PURPOSE: External beam radiation therapy (EBRT) is a noninvasive alternative to deliver accelerated partial breast irradiation
(APBI). However, due to the larger target volume, cosmetic outcomes after EBRT APBI may be inferior to more invasive techniques, such as brachytherapy. Utilizing the ViewRay magnetic
resonance imaging (MRI)-guided radiation therapy system, MRI
can be used for planning and daily positioning, as well as for precise
targeting during treatment. This prefraction imaging allows for a
reduction in the planning target volume (PTV) margin, which may
improve acute skin toxicity and cosmetic outcomes compared with
36
traditional EBRT methods.
MATERIALS AND METHODS: Ten patients with ductal carcinoma
in situ (DCIS) or early-stage invasive breast cancer and negative
axillary lymph nodes were treated with APBI using the ViewRay
system. Prescription dose to the PTV was 38.5 Gy, delivered in 10
fractions, twice daily. The PTV for ViewRay treatment planning
included a 1-cm margin around the lumpectomy cavity.
Comparison three-dimensional conformal EBRT (3DCRT) plans
for each patient were generated using the Pinnacle planning system
and a 2-cm margin around the lumpectomy cavity. Dosimetric
parameters for the PTV, ipsilateral breast, and other critical structures for each treatment plan were compared.
RESULTS: Using the ViewRay system to obtain MR imaging for
setup prior to each fraction, we observed that the lumpectomy cavity could be precisely localized and aligned prior to each fraction.
A decrease in the PTV margin using the ViewRay system resulted
in a mean PTV volume of 85 cc compared with 177 cc for 3DCRT.
The median PTV receiving 95% of the prescribed dose for both the
ViewRay and 3DCRT plans was 100%. Mean volume of the ipsilateral breast receiving the prescription dose was 11.72% for ViewRay
treatment plans compared with 21.56% for 3DCRT treatment plans
(P < .04). Mean volume of the ipsilateral breast receiving 50% of the
prescribed dose using the ViewRay treatment plan was 31.34%
compared with 52.71% for the 3DCRT treatment plans (P < .02).
Reductions in the mean volumes of the ipsilateral lung, heart, and
contralateral breast with the ViewRay plans were also observed,
although they were not statistically significant.
CONCLUSION: MRI-guided EBRT using the ViewRay system is a
novel approach to deliver APBI. ViewRay APBI is noninvasive yet
maintains a high degree of precision by using prefraction MR
imaging, thus allowing a reduction in the PTV margin. The resultant decrease in the ipsilateral breast dose may reduce acute skin
toxicity and improve cosmetic outcomes. Thus, the ViewRay system is an attractive alternative to existing APBI techniques.
(P024) Predictors of Radiation-Induced Skin Toxicity:
Data From a Prospective Cohort Receiving Breast
Radiation Jean Wright, MD, Cristiane Takita, MD, Isildinha M. Reis, Wei Zhao,
MD, BS, Eunkyung Lee, MS, Jennifer Hu, PhD; Johns Hopkins University; University of Miami
PURPOSE/OBJECTIVES: Breast radiation (RT) is generally well tolerated, but acute skin toxicity is a common side effect that can
impact receipt of treatment and quality of life. We sought to identify predictors of radiation-induced skin toxicity in a racially and
ethnically diverse cohort of women receiving RT to the intact
breast.
MATERIALS AND METHODS: We evaluated the first 392 patients in
an ongoing prospective study assessing radiation-induced skin toxicity in patients receiving breast RT. We recorded patient demographics, body mass index (BMI), and disease and treatment characteristics. Skin toxicity grade using Common Terminology
Criteria for Adverse Events (CTCAE) and a modified scale captur-
ing moist desquamation were captured at Week 3 and at RT completion. Logistic regression analyses were conducted to evaluate the
effect of potential predictors on the risk of skin toxicity. RESULTS: A total of 20.2% self-identified as African American, 15%
self-identified as non-Hispanic white, 61.5% self-identified as
Hispanic white, and 3.3% self-identified as other. Mean age was
56.2 years, and 74.2% had a body mass index (BMI) ≥ 25. Disease
was stage 0 in 20.2% (in situ), I in 49.2%, and II or III in 30.6%.
Further, 17.2% of patients were treated with hypofractionated regimens to the breast +/− regional nodes with a whole-breast dose of
< 45 Gy, and 82.8% of patients were treated with conventionally
fractionated regimens with a dose of ≥ 45 Gy. On multivariate
analysis, both scales identified higher BMI, higher disease stage,
invasive ductal histology, progesterone receptor (PR)-negative status, and conventionally fractionated regimens with total radiation
dose ≥ 45 Gy as predictors for higher skin toxicity grade. The modified scale also identified larger breast volume as a predictor for
moist desquamation, and the CTCAE scale identified chemotherapy use as a predictor for grade 2/3 skin toxicity.
CONCLUSION: In this prospectively followed cohort of breast cancer
patients receiving RT to the intact breast, novel predictors for more
severe skin toxicity were identified, including PR-negative status,
invasive ductal histology, and receipt of chemotherapy, as well as
known risk factors, including BMI and fractionation scheme. (P025) T3 Tumors and Breast Conservation Richard J. Bleicher, MD, Karen Ruth, MS, Elin R. Sigurdson, MD, PhD,
Marcia Boraas, MD, Penny Anderson, MD, John M. Daly, MD, Brian L.
Egleston, PhD; Fox Chase Cancer Center
INTRODUCTION: Although breast conservation remains one stan-
dard for treatment of breast cancer, tumors > 5 cm have been consistently excluded from breast conservation clinical trials. While
many surgeons perform breast conservation in select patients
whose tumors are T3 primaries, very few small series have compared this with mastectomy for tumors > 5 cm. This study was
performed to determine if survival remains equivalent between the
two surgical options, using a large national dataset.
METHODS: Surveillance, Epidemiology, and End Results (SEER)Medicare–linked cases were identified for patients aged ≥ 66 years
undergoing breast conservation who had invasive noninflammatory, nonmetastatic breast cancer between 1992 and 2009.
Propensity score-based adjustment was used to account for age,
gender, race, year of diagnosis, Charlson comorbidity score,
Elixhauser comorbidity index, income, education, marital status,
SEER registry, urban/rural setting, United States (US) location,
tumor size, histology, tumor grade, number of lymph nodes examined, number of positive lymph nodes, American Joint Committee
on Cancer (AJCC) stage, administration of chemotherapy, and
administration of radiotherapy. RESULTS: There were 5,890 patients with tumors > 5.0 cm who
underwent breast surgery, with 16.1% having breast conservation
and 83.9% undergoing mastectomy. Mean age of the breast conservation and mastectomy patients was 77.6 and 77.3 years, and
the mean tumor size was 7.97 vs 7.51 cm, respectively. While
28.4% of stage II patients with T3 tumors had breast conservation,
only 8.1% of stage III patients did so. Over 64% of breast conservation patients and 68% of mastectomy patients had ≥ 5 years of
follow-up. Use of breast conservation was associated with younger
age at diagnosis, race, a history of other cancers, higher income, a
more rural setting, region of the country, lower Charlson comorbidity index, histology, fewer nodes examined, fewer positive
nodes, lower-grade tumors, lower AJCC stage, nonuse of chemotherapy, and the use of radiotherapy. Overall survival and breast
cancer–specific survival, adjusted for demographic, tumor, and
treatment factors, were not different between those having breast
conservation and those having mastectomy (breast cancer–specific survival: subdistribution hazard ratio [SHR] = 1.07; 95% confidence interval [CI], 0.75–1.51; P = .71; overall survival: SHR =
0.92; 95% CI, 0.75–1.13; P = .43).
CONCLUSIONS: For patients with tumors > 5 cm, survival in the
Medicare population remains similar between breast conservation
and mastectomy, as it does for smaller primaries. Despite the exclusion from prospective randomized trials, breast conservation
should remain a standard option for women with larger tumors
when deemed clinically and cosmetically amenable to resection.
(P026) Is Cause-Specific Survival Similar for Estrogen
Receptor- and Progesterone Receptor-Negative EarlyStage Invasive Lobular and Invasive Ductal Cancers?
A National Registry SEER Database Study Justin M. Mann, Weisi Yan, Guojiao Wu, Dattatreyudu Nori, Akkamma
Ravi; New York Presbyterian-Weill Cornell Medical Center
BACKGROUND: Invasive ductal carcinoma (IDC) and invasive
lobular carcinoma (ILC) are the two most common breast cancer
histologies. IDC is more common and confers a worse prognosis
than ILC. Biomarkers, including estrogen receptor (ER) and progesterone receptor (PR) status, improve prognostic accuracy and
will likely be added to a future edition of the American Joint
Committee on Cancer (AJCC) TNM classification. As a whole,
patients with an ER- and PR-negative phenotype have a worse
prognosis when compared with receptor-positive phenotypes.
Using Surveillance, Epidemiology, and End Results (SEER) data,
we performed statistical analysis to determine if receptor-matched
statuses in IDC compared with ILC differ in overall outcome.
METHODS: A total of 50,658 cases of early-stage (I–IIB) breast cancer (groups = IDC and ILC) diagnosed from 1998–2002 who
underwent breast conservation surgery were queried from the
SEER 18 database. Patients without known ER or PR receptor status were excluded. Kaplan-Meier survival analysis and log-rank test
were used to compare breast cancer cause-specific survival (BCSS).
RESULTS: There were 2,852 (5.63%) cases of ILC and 47,806
(94.37%) cases of IDC in this analysis. A total of 40,099 (79.2%)
cases were ER+, and 34,901 (68.9%) cases were PR+. For ER+ cases,
60-month BCSS was 98% for ILC and 97.7% for IDC (P = .79). For
ER− cases, 60-month BCSS was 95.5% for ILC and 89.7% for IDC
(hazard ratio [HR] = 0.45; P = .02). For PR+ cases, 60-month BCSS
was 98.3% for ILC and 97.8% for IDC (P = .35). For PR− cases,
37
60-month BCSS was 96.1% for ILC and 92.0% for IDC (HR = 0.77;
P = .03).
CONCLUSION: For early-stage breast cancer cases with ER+
and PR+ status, histology was not associated with a difference in
BCSS. Alternatively, ILC cases that were ER− or PR− had an
increased BCSS compared with receptor-matched IDC cases.
These findings add to the growing evidence supporting ILC as a
more favorable histology, which is important for guiding treatment and prognostication.
(P027) Increasing Use of Postlumpectomy Radiotherapy
for Ductal Carcinoma In Situ of the Breast in the United
States
Yi An, MD, Henry S. Park, MD, MPH, John M. Stahl, MD, Sue B. Evans,
MD, MPH, Charles E. Rutter, MD; Yale University School of Medicine
INTRODUCTION: Breast ductal carcinoma in situ (DCIS) is a preinvasive neoplasm historically treated with mastectomy prior to
the adoption of the breast conservation paradigm. Although postlumpectomy radiation therapy (RT) for DCIS reduces local recurrence risk, its role in patients with favorable-risk disease is controversial. As such, RT utilization rates for DCIS may vary. Here, we
are the first to study the change in usage of postlumpectomy RT
for DCIS and the factors associated with these changes on a
national level.
METHODS: We identified patients diagnosed with DCIS and treated with lumpectomy between 1998 and 2011 within the National
Cancer Database. Chi-square tests and multivariate logistical
regression analyses were used to identify demographic, tumor, and
treatment facility factors associated with increased likelihood of
receiving postlumpectomy RT.
RESULTS: We identified 144,861 DCIS patients who underwent
lumpectomy. Median age was 59 years, 84% of patients were white,
and 39% had high-grade disease. A total of 99,639 (69%) women
received postlumpectomy RT. The proportion receiving postlumpectomy RT increased from 61% in 1999 to 72% in 2008 (P <
.01). Statistically significant predictors of postlumpectomy RT
included younger age, higher grade, fewer comorbidities, rural
residence, and increased distance from treatment center (P < .01 for
all). Interestingly, medium-sized tumors and negative surgical margins were also significant predictors of postlumpectomy RT relative
to patients with larger tumors and positive margins, suggesting that
these higher-risk patients may undergo complete mastectomy rather than receive adjuvant radiotherapy.
CONCLUSION: The percentage of DCIS patients receiving postlumpectomy RT increased between 1999 and 2008. Younger
patients with higher grade, medium-sized tumors, and fewer
comorbidities were more likely to receive postlumpectomy RT. (P028) Adjuvant Radiation Therapy After Lumpectomy
According to Insurance Status Norman Yeh, Arya Amini, MD, Christine Fisher, MD; University of
Colorado Denver
38
PURPOSE: After a lumpectomy in early-stage breast cancer, adjuvant
radiation therapy as a component of breast conservation is standard
of care. The purpose of this study was to evaluate patterns of care for
postlumpectomy radiation according to insurance status.
PATIENT AND METHODS: The Surveillance, Epidemiology, and
End Results (SEER) database was examined for patients with breast
cancer aged under 65 years and with a stage of T1N0. The database
was queried from 2007 to 2011, with a total of 72,257 patients
included in the analysis. Multinomial logistic regression was used
to assess patient and tumor characteristics under multivariable
analysis.
RESULTS: All patients had the following insurance status: nonMedicaid insurance (90%), any Medicaid (9%), and uninsured
(2%). Medicaid (odds ratio [OR] = 0.77; 95% confidence interval
[CI], 0.66–0.89; P < .001) and uninsured status (OR = 0.53; 95% CI,
0.40–0.71; P < .001) were more likely to not receive postlumpectomy radiation on multivariate analysis after adjusting for age, race,
sex, residence (urban vs rural), marital status, percentage of county
below federal poverty limit, percentage of county below ninth
grade education, and estrogen receptor (ER)/progesterone receptor
(PR)/human epidermal growth factor receptor type 2 (HER2) status. Additional statistically significant predictors for patients not
receiving postlumpectomy radiation included African-American
race (OR = 0.86), being unmarried (OR = 0.88), living in a county
with a higher percentage of residents with less than a ninth grade
education (OR = 0.60), and higher percent of county below the
federal poverty level (OR = 0.57). Among uninsured patients, there
was also a significant association with African-American race and
residence in a county with a higher percentage of people below the
federal poverty level.
CONCLUSION: Patients with Medicaid coverage or without insurance are more likely to not receive radiation after lumpectomy. (P029) A Comparison of CT- and MRI-Defined
Lumpectomy Cavity for Radiotherapy Planning of
Breast Cancer Wei Huang, MD, PhD, Adam Currey, MD, Victor Chen, PhD, Frank Wilson, MD, Allen Li, PhD; Medical College of Wisconsin
PURPOSE: To compare lumpectomy (LC) and planning target volume (PTV) that is delineated using magnetic resonance imaging
(MRI) and computed tomography (CT) and examine the possibility of replacing CT with MRI for radiotherapy (RT) planning for
breast cancer.
MATERIALS AND METHODS: MRI and CT data were acquired for
14 patients with early-stage breast cancer who had undergone
lumpectomy at their radiation treatment positions (prone) using a
large-bore CT scanner (HighSpeed, GE) and a 3-T large-bore MRI
scanner (Vero, Siemens) during RT simulation. All patients had
dense breast tissues. The LCs were delineated manually on both
CT (LC-CT) and MRI acquired with three sequences (T1, T2, and
short TI inversion recovery [STIR]) (LC-T1, LC-T2, and LC-STIR,
respectively) by a radiation oncologist and verified by another
radiation oncologist. The PTV (PTV-MRI) was created by expand-
ing a uniform 15-mm margin from the union of the LC-T1,
LC-T2, and LC-STIR and was compared with those from CTs
(PTV-CT). Differences were measured in terms of cavity visualization score (CVS), volume, Dice coefficient (DC), and distance
between centers of mass (COMs).
RESULTS: The mean CVSs for T1-, T2-, STIR-, and CT-defined
LCs were 3.36, 3.36, 3.79, and 2.50, respectively, implying that LC
is mostly visible with the MR STIR sequence. For most cases
(12/14), the LC volumes or PTVs from T1, T2, and STIR were
smaller than those from CT. The mean reductions of LCs for T1,
T2, and STIR from those for CT were 20%, 44%, and 36%, respectively. However, the differences between the volumes of PTV-MRI
(the union of three sequences) and PTV-CT were smaller. The
DCs between CT- and MRI (union of T1, T2, and STIR)-defined
volumes were 0.60 ± 0.15 for LCs and 0.85 ± 0.08 for PTVs. The
COM shifts from PTV-MRI to PTV-CT were 0.31 ± 0.25, 0.35 ±
0.39, and 0.36 ± 0.33 cm in the x-, y- and z-axis, respectively. The
average PTV-MRI:PTV-CT volume ratio was 1.11±0.22, ranging
from 1.00 to 1.25 for most cases (10/14). In 12 of 14 cases, MRIdefined LC included extra regions that would not be visible
from CT.
CONCLUSIONS: MRI substantially improves the visibility and accu-
racy of lumpectomy cavity definition as compared with CT.
Although the LC and PTV volumes that are delineated from an
individual MRI sequence are generally smaller as compared with
those from CT, the volumes, shapes, and locations for the PTVMRI, defined by the union of T1, T2, and STIR, were comparable
with PTV-CT for most of the cases studied. It is feasible to use MRI
to replace CT in RT simulations for breast-conserving RT.
(P030) Metaplastic Breast Carcinoma at a Single
Institution: Clinical-Pathologic Characteristics and
Outcome Sharang Tenjarla, Sheema Chawla, MD, Jiqing Ye, MD, Brittany
Heatherington, Lori Medeiros, MD, Peter Bushunow, MD; Rochester
Regional Health System
OBJECTIVES: Metaplastic breast carcinomas (MBCs) are rare primary breast malignancies, constituting < 1% of all breast cancers.
They are characterized by differentiation of the neoplastic epithelium into squamous cells and/or mesenchymal-like elements.
There is a dearth of information on clinically relevant pathologic
features and clinical outcomes for these rare tumors.
METHODS: A search of MBCs in the tumor registry and pathology
archives of our center was performed. A review of the demographic and clinical-pathologic features and outcomes of all cases of
MBC was performed between 2005 and 2014. Cases were reviewed
retrospectively after institutional review board (IRB) approval.
RESULTS: A total of 32 cases were retrieved. Median age was 62
years (range: 42–79 yr). The median tumor size was 3.5 cm (range:
0.8–6.7 cm), and 72% (n = 23) of patients had grade 3 tumors.
Histology outcomes showed: squamous in 13 (41%), adenosquamous in 4 (12%), osseous and chondroid in 6 (19%), and spindle
cell/sarcomatoid in 9 patients (28%); 28 patients (88%) were triple
negative. Human epidermal growth factor receptor type 2 (HER2)/
neu overexpression was not seen in any of the patients. A total of
19 patients underwent mastectomy (59%), and the rest underwent
breast conservation surgery. The median follow-up was 17.5
months (range: 3–108 mo). Stage distribution was: stage IA in 11
(34%), IIA in 12 (38%), IIB in 7 (22%), and IIIA in 2 (6%) patients.
At a median follow-up of 22 months, five patients had recurrence:
one with local and four with distant (two brain, one bone, and one
with multiple sites), two of whom are alive with disease. Overall, 28
patients (87%) were alive at last follow-up.
CONCLUSION: Similar to other reported series, the majority of our
patients had triple-negative disease, and our patient population did
not express the HER2/neu oncoprotein. Our predominant histology was squamous differentiation, whereas heterogeneity in histology is described in the literature. Despite high-grade disease, the
outcomes in our study are favorable in comparison with previously
reported series, although the follow-up is short.
(P031) Effects of Oncoplastic Surgery on Delivery of
Standard Adjuvant Radiotherapy Elisabeth Arrojo, MD, Alvaro Martinez, MD, FACR, Michael Ghilezan,
MD, James Fontanesi, MD, Frank Vicini, MD, FACR; 21st Century Oncology; Botsford Hospital
BACKGROUND: Oncoplastic breast surgery (OBS) is a surgical
effort to remove additional breast tissue and improve cosmesis.
However, local control with routine lumpectomy and cosmesis
after adjuvant radiotherapy (A-RT) are both very good, questioning
the need for OBS. We wanted to explore if A-RT practices have
changed due to OBS.
METHODS: A search in the PubMed and Ovid MEDLINE databases was carried out from 2010 to 2014, using the keywords “therapeutic mammoplasty” and “OBS.” Use of boost and tumor bed
marking in OBS were analyzed and compared with the results of
the 2014 survey (Thomas et al, Pract Radiat Oncol.) reported as
“Radiation practice patterns among United States (US) radiation
oncologists (ROs) for postmastectomy breast reconstruction and
oncoplastic breast reduction (RT.OBS).”
RESULTS: We found six studies, totaling 1,180 patients. Four studies did not reported clip-marking. Three of these four studies did
not give a boost to any of the OBS patients, and the other one gave
a boost only to OBS patients with +/close margins. The two studies
that reported clips gave a boost to the patients. The overall analysis
showed that 71% of patients did not receive a boost treatment.
A total of 271 ROs from the US completed the RT.OBS survey,
showing that 65.4% of them did not give a boost to any of the
patients systematically, 8.3% indicated never having utilized a
boost, and 38.7% only gave a boost to patients with clips marking
the tumor bed. Only 33.1% of respondents indicated that they routinely collaborated with surgeons for clip placement at the time of
breast reduction or complex tissue rearrangement.
CONCLUSIONS: The standard patterns of care for breast conservation therapy include A-RT with a boost to the surgical bed. For the
39
PubMed and Medline articles, 71% of the 1,180 patients without
clips and clear margins did not receive a boost. These results correspond with the ROs’ survey, which showed that 65.4% of them
did not give a boost to the patients systematically. While OBS was
perceived by the surgeons as a technique to remove more tissue and
improve cosmesis, our review demonstrated that it negatively
impacts radiotherapy techniques that are proven to achieve adequate local control. OBS is clearly changing patterns of delivery of
adjuvant RT, without long-term outcomes supporting its safety.
(P032) Current Management of Low-Grade Central
Nervous System Glioma Ron R. Allison, MD, Dioval Reymond, Sharon Salenius, MPH, Andrej
Hnatov, MD, Cynthia Ballenger, MD, Constantine Mantz, MD, Eduardo
Fernandez, MD, PhD, Daniel Dosoretz, MD, Vershalee Shukla, MD,
Timothy Shafman, MD, Steven Finkelstein, MD; 21st Century Oncology; The Brody School of Medicine, East Carolina University
BACKGROUND: Low-grade central nervous system (CNS) glioma
is a rare diagnosis but is becoming more common as neuroimaging
is now often undertaken for headache and other nonspecific neurologic signs and symptoms. Current management may include
resection alone, radiation alone, or their combination, with chemotherapy as an adjunct. We reviewed the current management for
this diagnosis based on a large cohort of freestanding and hospitalbased cancer centers.
MATERIALS AND METHODS: An institutional review board (IRB)approved chart review for all patients with low-grade primary
CNS glioma who were treated at our facilities between 1989 and
2012 was undertaken. This search returned 25 patients (10 males,
15 females; mean age: 50.5 yr). Twenty patients were Caucasian.
Presenting signs and symptoms were nonspecific CNS complaints:
mainly generalized headache, vision changes, numbness, and
weakness. Workup included magnetic resonance imaging (MRI)
and/or computed tomography (CT). Biopsy reported low-grade glioma, though imaging alone was used for diagnosis in some
patients. Only two patients underwent gross total resection, and
one patient underwent surgical debulking. All patients underwent
external beam radiation therapy (RT), usually intensity-modulated
RT (IMRT) or three-dimensional (3D) treatment with a mean dose
of 48.6 Gy. Image guidance was employed in 24% of
patients. Temodar was delivered to six patients (24%).
RESULTS: All patients have been followed for a mean of 9.3 months
(range: 0.3–153.3 mo). Most patients were considered unresectable. RT was well tolerated, with most complications being grade I/
II. One patient developed seizures as a late complication. All failures were local, occurring in 28% of patients. With regard to survival, eight patients are currently alive (32%). Statistical analysis
showed no survival advantage for gender, age, performance status,
biopsy, IMRT, radiation dose, chemotherapy, or surgery.
CONCLUSION: Currently, low-grade glioma is commonly treated in
the community setting by RT alone. A relatively high rate of local
failure is noted (28%), and long-term survival appears to be shorter than might be expected. A number of patients are treated based
on imaging alone without a detriment to survival. Low-grade glio-
40
ma appears to be a more aggressive disease than usually considered,
and efforts to improve the outcome would be served through clinical trials. (P033) MRI Resection Cavity Dynamics Following
Brain Metastasis Resection and Permanent Iodine-125
Brachytherapy David R. Raleigh, MD, PhD, Zachary A. Seymour, MD, Bryan
Tomlin, PhD, Michael W. McDermott, MD, Manish K. Aghi, MD, Philip V.
Theodosopolous, MD, Mitchel S. Berger, MD, Penny K. Sneed, MD; University of California, San Francisco; California State University Channel
Islands
PURPOSE/OBJECTIVES: Surgical resection and permanent
iodine-125 (125I) brachytherapy provide good local control for
brain metastases. However, resection cavity remodeling has been
postulated to alter treatment efficacy and toxicity. The purpose of
this study was to investigate cavity volumetrics following surgery
and 125I brachytherapy for brain metastases.
MATERIALS AND METHODS: A total of 96 patients with 106 brain
metastases, treated from September 1997 to July 2013, were retrospectively identified. The efficacy and toxicity of 125I brachytherapy
in this cohort have previously been reported. In brief, the median
age at surgery was 59 years, with a median overall survival of 12
months and overall local control of 92%. The overall risk of necrosis was 15% and trended lower without prior stereotactic radiosurgery (SRS) to the surgical site or with activity ≤ 0.73 mCi per
source. All patients underwent magnetic resonance imaging (MRI)
prior to surgery and were followed with surveillance MRIs beginning a median of 1 day after implantation (MRI1). Volumetric data
were calculated from three-dimensional contours on T1-weighted
postcontrast images by a single radiation oncologist (DRR).
Cavities were censured from volumetric analyses at the time of
tumor progression or necrosis.
RESULTS: A total of 476 brain MRIs were analyzed (median 3 per
patient; range: 0–22) with a median imaging follow-up of 4 months
(range: 0 mo–13.6 yr). Median metastasis volume was 13.5
cm3 (range: 0.21–76.2 cm3), and median cavity volume on MRI1
was 5.2 cm3 (n = 101; range: 0.3–23.2 cm3). At a median of 1.7 (n =
32), 3.6 (n = 46), 5.9 (n = 38), 11.7 (n = 30), and 20.5 (n = 22)
months after surgery, cavity volumes decreased by 25%, 35%, 42%,
47%, and 60% relative to MRI1, respectively. Metastasis size was the
strongest predictor of cavity volume and shrinkage on both univariate and multivariate linear regression modeling (P < .0001).
Factors that were associated with an increase in cavity volume
included prior SRS to the surgical site, periventricular location, and
lobar tip location (P < .05). The cavity-to-metastasis volume ratio
decreased with increasing metastasis size, and the rate of cavity
shrinkage was greater for metastases > 13.5 cm3 (P < .0001). Despite
these findings, multinomial logistic regression modeling, with or
without adjustment for source activity and prior SRS, failed to predict the likelihood of local failure or necrosis using either metastasis or cavity volume.
CONCLUSIONS: Surgical resection with 125I brachytherapy is an
effective strategy for local control of brain metastases. Although
metastasis volume significantly influences resection cavity size and
remodeling, volumetric parameters do not appear to influence
local control or necrosis. larly in the setting of bevacizumab-refractory tumors.
(P034) Proton Therapy (PT) Large-Volume
Re-Irradiation for Recurrent Glioma: Overall
Survival (OS) and Toxicity Outcomes Yuan J. Rao, MD, Stephanie Perkins, MD, Jiayi Huang, MD; Washington University
(P035) Prognostic Factors of Early Deaths in Patients
With Craniopharyngioma From the SEER Registry Brijal M. Desai, MD, Russell C. Rockne, PhD, Irene B. Helenowski, MS,
PhD, Jeffrey J. Raizer, MD, Nina Paleologos, MD, Ryan Merrell, MD,
Sean Grimm, MD, Syed Azeem, MD, William F. Hartsell, MD, Patrick
Sweeney, MD, Kristin R. Swanson, PhD, Vinai Gondi, MD; Northwestern University Feinberg School of Medicine; Rush University Medical
Center; Northshore University Health Systems; Cadence Brain Tumor
Center; CDH Proton Center
PURPOSE: Craniopharyngioma is a locally invasive tumor that is
challenging to resect, and the roles of aggressive surgery or adjuvant radiation therapy (RT) are unclear. The current study analyzed
the Surveillance, Epidemiology, and End Results (SEER) registry to
identify prognostic factors of early deaths after the diagnosis of
craniopharyngioma, as well as to examine the impact of gross total
resection (GTR) or adjuvant RT on overall survival (OS).
BACKGROUND: The therapeutic benefit of targeting T2/fluid-attenuated inversion recovery (FLAIR) in addition to contrast-enhancing (CE) tumor during re-irradiation for recurrent glioma is attenuated by augmented toxicity. Given its steep dose falloff and narrow
penumbrae, proton therapy (PT) minimizes the volume of brain
parenchyma outside of the target volume, potentially permitting
safer delivery of large-volume re-irradiation.
METHODS: The SEER database was queried for craniopharyngioma patients from 2004 to 2011. Inclusion criteria included histologically confirmed craniopharyngioma with adequate information
on age, surgical extent, and adjuvant RT. Patients who were aged <
3 years or > 69 years were excluded. Follow-up time was determined from the time of diagnosis. Cox proportional hazards models were used for univariate analysis (UVA) and multivariate analysis (MVA). OS rates were calculated using the Kaplan-Meier method and compared between groups using log-rank statistics.
METHODS: From February 2011 to April 2014, a total of 21 consecutive adult patients with recurrent glioma who were treated with
PT re-irradiation at a single institution were retrospectively analyzed. Planning target volume (PTV) included T2/FLAIR and CE
abnormalities. The covariates that were assessed were age, gender,
Karnofsky performance status (KPS) at time of PT, number of prePT recurrences, grade at initial diagnosis, interval between PT and
prior radiotherapy (PRT), PT dose, PT PTV, bevacizumab failure,
concurrent use of temozolomide and/or bevacizumab, and post-PT
radiation necrosis. Overall survival (OS) time from PT start was
estimated with Kaplan-Meier analysis; comparisons used the logrank statistic. Multivariate analysis used the Cox proportional hazards model. RESULTS: Median age was 43 years, and median KPS was 90. The
median number of salvage treatments was 2 (range: 1–9). Median
interval between PRT and PT was 32.8 months (range: 6.9–162.9
mo). A total of 13 patients (62%) were bevacizumab-refractory.
Median PT dose was 50.51 Cobalt Gray Equivalent (CGE), and
median PTV was 224.2 cc. Five patients (24%) remain alive.
Median OS was 10.5 months overall, 6.3 months among bevacizumab-refractory patients, and 12.4 months among bevacizumabnaive patients. Prior bevacizumab failure (hazard ratio [HR] = 3.77;
P = .02), lower KPS score (HR = 1.03; P = .047), and decreased
interval between PRT and PT (≤ 40 mo; HR = 3.46; P = .04) were
prognostic of inferior OS. On multivariate analysis, decreased
interval between PRT and PT (P = .02) remained prognostic of
inferior OS, but lower KPS and prior bevacizumab failure trended
to significance (P = .07). One patient had grade 3 necrosis in the
setting of PT re-irradiation for progressive brainstem glioma. One
patient had grade 2 necrosis, and another had grade 2 stroke. No
other grade ≥ 3 toxicities were observed. RESULTS: A total of 788 patients met the inclusion criteria, and the
median follow-up was 38 months (range: 1–95 mo). Nine pediatric
patients died within 5 years of diagnosis, with 78% attributed to
craniopharyngioma. Further, 81 adult patients died within 5 years
of diagnosis, and the two most common causes of death were craniopharyngioma (36%) and cardiac/diabetic causes (31%). On
both UVA and MVA, older age (hazard ratio [HR] = 1.03; 95%
confidence interval [CI], 1.02–1.04), black race (HR = 3.52; 95%
CI, 2.29–5.40), adamantinomatous histology (HR = 1.84; 95% CI,
1.19–2.84), and papillary histology (HR = 2.07; 95% CI, 1.12–3.82)
were significant predictors of worse OS. In contrast, gender, GTR,
adjuvant RT, and tumor size were not significantly correlated with
OS. Adult patients (aged ≥ 18 yr) had significantly worse 5-year OS
than pediatric patients (80% vs 95%, respectively; P < .01). Patients
of black race had significantly worse 5-year OS than patients of
other races (67% vs 87%, respectively; P < .01). Adamantinomatous
histology and papillary histology were associated with worse 5-year
OS than classic craniopharyngioma histology (80% and 77% vs
88%, respectively; P = .05). Patients with GTR had a 5-year OS of
83%, while those with biopsy or subtotal resection had a 5-year OS
of 86% (P = .26). Patients with adjuvant RT had a 5-year OS of
89%, while those who did not receive RT had a 5-year OS of 83%
(P = 0.15).
CONCLUSIONS: Craniopharyngioma-related death represents the
most common cause of early deaths in both pediatric and adult
patients. GTR and adjuvant RT do not appear to have a significant
impact on OS within 5 years of diagnosis. Older age, black race, and
adamantinomatous/papillary histologies are significant prognostic
factors for early deaths after the diagnosis. CONCLUSION: Large-volume PT re-irradiation for recurrent glioma is safe and associated with promising OS outcomes, particu
41
(P036) Patterns of Care and Outcomes of Adjuvant
Radiotherapy for Meningiomas: A Surveillance,
Epidemiology, and End Results and Medicare-Linked
Analysis Mark J. Amsbaugh, MD, Beatrice Ugiliweneza, PhD, MSPH, Eric
Burton, MD, Maxwell Boakye, MD, MPH, MBA, Shiao Woo, MD;
University of Louisville
PURPOSE: To identify patterns of care and outcomes of adjuvant
radiotherapy for meningiomas in the linked Surveillance,
Epidemiology, and End Results (SEER) Medicare data.
MATERIALS AND METHODS: Patients over 66 years of age, diagnosed with meningioma, and treated with a craniotomy in the
SEER-Medicare data were included. Patients were grouped according to adjuvant treatment with fractionated radiotherapy (XRT),
stereotactic radiosurgery (SRS), or none. Demographic, tumor,
treatment, and outcome variables were collected. The MannWhitney U-test and chi-square test were used to analyze continuous and categorical variables. Time to event was analyzed with the
Kaplan-Meier methods and log-rank test. Multivariate comparisons were conducted with logistic regression and proportional hazard models. RESULTS: A total of 1,964 patients were included for analysis (1,701
with no adjuvant treatment, 175 with XRT, and 88 with SRS).
Patients were less likely to receive adjuvant therapy if they were
older than 75 years (odds ratio [OR] = 0.730; 95% confidence interval [CI], 0.548–0.973), female (OR = 0.731; 95% CI, 0.547–0.978),
or unmarried (OR = 0.692; 95% CI, 0.515–0.929). Patients were
more likely to receive adjuvant treatment for grade II/III tumors
(OR = 5.586; 95% CI, 2.135–13.589), tumors over 5 cm (OR =
1.850; 95% CI, 1.332–2.567) or partial resection (OR = 3.230; 95%
CI, 2.327–4.484). For those receiving adjuvant therapy, SRS was less
likely than XRT in patients diagnosed with grade II/III tumors (OR
= 0.061; 95% CI, 0.006–0.655) or a 1-unit increase in Gagne comorbidity score (OR = 0.761; 95% CI, 0.599–0.968). Yearly between
2000 and 2010, 10.65% to 19.77% of patients received adjuvant
therapy (7.143%–42.105% of those who received SRS). Although
no survival benefit was seen with the addition of adjuvant therapy
(P = .1236), the subgroup of patients receiving SRS had better survival compared with those receiving surgery alone (adjusted hazard
ratio [aHR] = 0.544; 95% CI, 0.318–0.929). Furthermore, when
stratifying patients by degree of resection, those who underwent
partial or local resection and did not receive SRS had an increased
risk of death compared with those who did (aHR = 1.934; 95% CI,
0.992–3.771).
CONCLUSIONS: Utilization of adjuvant XRT and SRS remained
stable between 2000 and 2010. Male sex, young age, marriage, partial resection, grade II/III tumors, and large tumors predicted for
use of adjuvant therapy. For all patients, SRS improved survival
compared with craniotomy alone. For patients with incomplete
resection, SRS improved survival compared with craniotomy alone
and adjuvant XRT. Randomized, prospective clinical trials are
needed to better define the role of adjuvant XRT or SRS.
42
(P037) Analysis of Survival Outcomes in Patients With
Multifocal Glioblastoma Omar H. Gayar, MD, Anant Gopal, PhD, Lisa Scarpace, MS, Steven
Kalkanis, MD, Tom Mikkelson, MD, Farzan Siddiqui, MD, PhD; Department of Radiation Oncology, Hermelin Brain Tumor Center, Henry
Ford Health System
INTRODUCTION: Glioblastoma multiforme (GBM) is associated
with extremely poor prognosis and survival. A small subset of these
patients present with more than one focus of disease (multifocal or
multicentric). We analyzed survival outcomes in patients with multifocal or multicentric GBM treated at our institution.
METHODS: An institutional review board (IRB)-approved retrospective analysis was performed to study patients with GBM who
were noted to have multifocal lesions at initial diagnosis and were
treated and followed up at our institution between 2005 and 2014.
We reviewed patient gender, age at diagnosis, tumor location(s),
extent of surgery, pathologic details, and treatment delivered: radiation therapy (RT) ± chemotherapy (CT). Median survival (MS)
was calculated for patients who had at least 6 months of follow-up
after completion of RT.
RESULTS: A total of 30 patients with multifocal GBM were treated
and had adequate follow-up for analysis; 21 patients (70%) were
male, and 9 (30%) were female. Median age at diagnosis was 58
years. Regarding surgery, only 6 patients (20%) had subtotal tumor
resection (STR), while 23 (77%) had biopsy. No patients had gross
total resection (GTR), and one patient did not have resection or
biopsy and was treated with RT. The O(6)-methylguanine-DNA
methyltransferase (MGMT) gene was found to be methylated in 9
(30%) and unmethylated in 11 (37%) patients. MGMT gene methylation status was unknown for the remaining 10 (33%) patients. A
total of patients (90%) had adjuvant RT; 14 patients (52%) were
treated to a dose of 60 Gray (Gy), and 5 (19%) received 40–45 Gy.
Three patients did not complete RT due to enrollment in hospice
or death. Two patients had stereotactic RT as part of their primary
RT. A total of 25 patients (83%) had CT: 23 had concurrent CT with
RT, and 13 had adjuvant CT. Also, 26 patients had at least 6 months
of follow-up after RT completion. Their overall MS was 10.1
months. MS was 16.6 months for patients who had STR and 5.5
months for patients who had biopsy.
CONCLUSIONS: Median survival of multifocal GBM is incredibly
short, even compared with the already short median survival of
single-lesion GBM. The majority of our patients had biopsy alone,
likely due to the nature of multifocal GBM. This most likely contributes to a worse MS.
(P038) Leukoencephalopathy Following Stereotactic
Radiosurgery for Brain Metastases
Daniel M. Trifiletti, MD, Cheng-Chia Lee, MD, David Schlesinger, PhD,
Jason P. Sheehan, MD, PhD, James M. Larner, MD; University of Virginia; National Yang-Ming University
PURPOSE/OBJECTIVE: The use of stereotactic radiosurgery (SRS)
in the treatment of brain metastases has increased dramatically
over the last decade in order to avoid the neurocognitive dysfunc-
tion that is induced by whole-brain radiotherapy (WBRT).
Technical improvements in SRS delivery have greatly enhanced the
SRS workflow and allowed for the treatment of numerous intracranial metastases in a single session. It is now common practice to
treat up to 5–10 lesions with SRS in a single session, followed by
subsequent SRS sessions based on surveillance imaging; however,
the cumulative neurocognitive effect of numerous SRS sessions
remains unknown. As leukoencephalopathy is a sensitive marker
for radiation-induced central nervous system (CNS) damage, we
investigated the dosimetric thresholds for SRS-induced leukoencephalopathy in patients treated with SRS alone, as well as SRS in
combination with WBRT.
MATERIALS AND METHODS: All patients treated at our institution
with at least two sessions of SRS for brain metastases between 2007
and 2013 were reviewed. Pre- and post-SRS fluid-attenuated inversion recovery and T1- and T2-weighted MRI sequences were
reviewed and graded for white matter changes associated with
radiation leukoencephalopathy using a previously validated scale.
Patient characteristics and SRS dosimetric parameters were
reviewed for factors that contributed to radiographic leukoencephalopathy using Cox proportional hazards modeling.
RESULTS: A total of 103 patients meeting the inclusion criteria were
identified. The overall incidence of leukoencephalopathy was 53%
at 3 years, and four factors predicted for radiation-induced leukoencephalopathy: the use of WBRT (P = .001), SRS integral cranial
dose of > 3 J (P = .026), total number of tumors (P = .001), and total
tumor volume (P = .009). The volumes receiving 8 Gy (V8), V10,
V12, and V15 were not predictive.
CONCLUSIONS: Our results establish that WBRT + SRS produces
leukoencephalopathy at a much higher rate than SRS alone.
Surprisingly, an SRS integral dose of over only 3 J predicts for leukoencephalopathy in patients treated with SRS alone. Our data
define a dosimetric threshold at which radiation-induced leukoencephalopathy is likely to occur following SRS. As the survival of
patients with CNS metastases increases and as the neurotoxicity of
chemotherapeutic and targeted agents becomes established, the
threshold of 3 J may influence the therapeutic management of
patients with multiple brain metastases.
(P039) Outcomes of Patients With Glioblastoma
Receiving Concurrent Radiation Treatment and
Antiepileptic Agents With Histone Deacetylase
Inhibitor Activity Nicholas S. Boehling, MD, Erik P. Sulman, MD, PhD; UT MD Anderson
Cancer Center
BACKGROUND: Preclinical studies have demonstrated increased
radiosensitivity of gliomas using histone deacetylase inhibitors
(HDACis), such as valproic acid (VA). We hypothesized that
patients with glioblastoma (GBM) who are treated with antiepileptics with HDACi properties during radiotherapy (RT) would exhibit improved outcomes.
METHODS: A retrospective analysis was performed of patients
treated with RT for GBM. Outcomes included overall survival
(OS), progression-free survival (PFS), and RT response. Patients
were noted for use of VA and other antiepileptic mediations, as well
as temozolomide (TMZ) during RT.
RESULTS: Data for 267 patients were available for analysis, with a
median age of 57 years. Median OS and PFS for the cohort were
13.9 months and 4.1 months, respectively. A total of 19 (11%)
patients received VA, and 42 (24%) patients received other antiepileptics with HDACi activity during the course of RT. Positive RT
response was significantly associated with improved median OS
(21.6 mo vs 10.1 mo; P < .01) and PFS (10.2 mo vs 2.7 mo; P < .01).
No significant benefit in OS (14.9 mo vs 13.8 mo; P = NS), PFS (5.0
mo vs 4.1 mo; P = NS), or RT response (odds ratio [OR] = 1.19; P
= NS) was seen for patients receiving VA. For patients receiving any
HDACi, there was a significant improvement in median OS (15.6
mo vs 13.5 mo; P < .05) but no significant change in median PFS
(5.2 mo vs 3.7 mo; P = NS). A total of 32 (55%) patients receiving
HDACis showed a positive response to RT compared with 98 (47%)
patients not receiving HDACi s(OR = 1.39; P = NS). When stratified by TMZ use, HDACi use did not result in any significant
change in median OS, PFS, or RT response. TMZ use was associated with a significant improvement in median OS (19.7 mo vs 11.4
mo; P < .01) and RT response (OR = 1.91; P = .01). On multivariate
analysis, a Cox proportional hazards model showed similar results
as compared with univariate analysis. HDACi use resulted in a
nonsignificant improvement in outcomes (HR = 0.92; P = .64).
CONCLUSIONS: The use of antiepileptic HDACi drugs during RT
for GBM did not significantly improve outcomes or RT response in
this retrospective analysis. Further study of the concomitant use of
HDACis and TMZ is necessary to elucidate clinically relevant
results.
(P040) Radiosurgery for Primary Central Nervous
System Lymphoma Zachary A. Seymour, MD, Sarah Westcott, James L. Rubenstein, Penny
K. Sneed, MD; Department of Radiation Oncology, Department of Medicine, University of California, San Francisco
BACKGROUND AND PURPOSE: The role of stereotactic radiosurgery (SRS) in primary central nervous system lymphoma (PCNSL)
is unknown. This represents a case series of five patients treated
with SRS for PCNSL.
METHODS: All patients who were treated with SRS for PCSNL were
retrospectively reviewed. All clinical and treatment parameters
were evaluated to assess treatment outcomes, symptomatic
response, complications, and disease control. Near-complete
response was defined as ≥ 75% volumetric reduction from the time
of treatment.
RESULTS: A total of five patients with PCNSL underwent SRS to seven
lesions following 5–10 cycles of chemotherapy, which consisted of a
regimen of high-dose methotrexate, rituximab, and temozolomide,
with the last administration at least 14 days before SRS. Three patients
were treated with SRS in lieu of whole-brain radiotherapy (WBRT),
one patient was treated for salvage SRS after focal failure after WBRT,
and one patient received no adjuvant radiation following chemotherARS PROCEEDINGS 2015
43
apy and was treated only at the time of focal recurrence. The median
age at the time of SRS was 60 years (range: 44–75 yr). The median
imaging follow-up post-SRS was 16.8 months (range: 1.2–46.9 mo).
The median dose was 15 Gy (range: 14–17 Gy), with a median prescription isodose line of 50% for a median target volume of 2.76 mL
(range: 0.69–14.6 mL). All lesions had at least a near-complete
response, with 82% response being the smallest volumetric reduction
and four lesions obtaining a complete response. No patients experienced a local failure. Prior to SRS treatment, four patients had focal
neurologic deficits, all of which improved with SRS. No neurotoxicity
or adverse effects were observed. Whole-brain control was not
achieved in any patient, with a median time to distant brain failure of
2.3 months (range: 0.7–21.6 mo) after first SRS treatment, and two
patients had salvage SRS for a focal distant recurrence 3 and 33
months after initial SRS, respectively.
CONCLUSIONS: SRS appears to be a reasonable treatment option
for focally persistent or recurrent PCNSL in select patients, especially in the setting of focal neurologic deficits. As a radiosensitive
entity, all PCNSL lesions had a substantial volumetric reduction
with at least 14 Gy, and all patients with a focal neurologic deficit at
treatment experienced symptomatic improvement with SRS.
Further investigation should be completed regarding the benefits
of SRS for focally appearing PCNSL as a potential way to avoid
neurotoxicity and improve symptoms in selected patients.
(P041) Clinical Outcomes of Gamma Knife Stereotactic
Radiosurgery (GK-SRS) for Painful Trigeminal
Neuropathy (TNP) David Zaenger, MD, M.N. Woodall, MD, Bryan M. Rabatic, PhD, MD,
John R. Vender, MD, Waleed F. Mourad, MD, PhD, Joseph Kaminski,
MD; Georgia Regents University
RESULTS: With a median follow-up of 20 months (range: 3–70 mo),
the overall response was 60%. Specifically, CR, near-CR, and PR
rates were 27%, 20%, and 13%, respectively. No response (NR) was
seen in 40% of patients, who had persistent, unchanged pain. For
the 60% of patients who responded to GK-SRS, the mean time
latency from SRS to response was 1 month (range: 0–2 mo). The
pattern of pretreatment pain in the responders group was described
as being dull rather than sharp compared with nonresponders.
Additionally, when compared with the NR group, the CR group
was significantly less likely to be exacerbated by daily activities pretreatment (0/4 [0%] vs 5/6 [83%]). No GK-SRS-induced grade ≥ 2
toxicities were reported.
CONCLUSIONS: SRS is both safe and efficacious for PTN.
Additionally, prior to treatment, PTN patients who characterize
their facial pain as dull and not exacerbated by daily activities are
more likely to receive therapeutic benefit, with a mean response
time of 1 month.
(P042) Toxicity and Treatment Outcomes in Single vs
Multifractionated Radiotherapy for Acoustic Neuromas Ajaykumar B. Patel, MD, Jennifer L. Peterson, MD, Colleen S. Thomas,
MS, Michael G. Heckman, MS, Stephen J. Ko, MD, Katherine S. Tzou,
MD, Robert C. Miller, MD, Laura A. Vallow, MD, Steven J. Buskirk,
MD; Department of Radiation Oncology, Division of Medical Statistics
and Informatics, Mayo Clinic Florida
PURPOSE: To review our institution’s experience in treating acoustic neuromas by comparing toxicity and treatment outcomes using
stereotactic radiosurgery (SRS) vs fractionated stereotactic radiation therapy (FSRT).
trigeminal neuralgia (TN) that necessitates prior trigeminal nerve
injury, in addition to facial pain. While the evidence supporting the
safety and efficacy of Gamma Knife stereotactic radiosurgery
(GK-SRS) for medically refractory TN is well established, there is a
limited body of literature concerning SRS for medically refractory
PTN. We report our long-term clinical outcomes using GK-SRS for
medically refractory PTN.
MATERIALS AND METHODS: A total of 57 consecutive patients
were treated with either single-fraction SRS (n = 26) or FSRT (n =
31) for acoustic neuroma at our institution between March 2000
and November 2013. Median dose was 1,200 cGy (range: 1,160–
1,600 cGy) for SRS and 2,000 cGy (range: 2,000–2,500 cGy) for
FSRT. Data were collected on treatment toxicities and progression
in 22 SRS and 29 FSRT patients with sufficient follow-up data.
Toxicities were graded by the Common Terminology Criteria for
Adverse Events version 4.0 (CTCAE v4.0).
METHODS: This is a single-institution retrospective study of 320
patients treated with GK-SRS for TN between 2000 and 2013.
From this cohort, 20 XRT-naive patients with PTN were identified. All patients failed initial treatment with medications, and
seven (35%) received other invasive treatment (eg, microvascular
decompression, rhizotomy) prior to SRS. All patients underwent
frame-based single-fraction GK-SRS. Mean age was 61 years
(range: 38–80 yr), and 75% of patients were female. Fifteen
patients (80%) were Caucasian, four (15%) were African American,
and one (5%) was Asian. Mean dose was 80 Gy (range: 80–90 Gy)
to the 100% isodose line in a single fraction to the root entry zone
of the involved trigeminal nerve (2–3 mm from the anterolateral
surface of the pons). Complete response (CR), near-CR, and partial response (PR) were defined as being pain-free without medication, being pain-free with medication, and having reduced pain
with medication, respectively.
RESULTS: Median follow-up length was 39 months in SRS patients
and 27 months in FSRT patients. Median maximum tumor dimension for SRS and FSRT was 1.4 cm and 1.6 cm, respectively (P =
.097). The most common complication was grade 3 ipsilateral hearing loss, which was experienced in 23% of SRS patients and 35% of
FSRT patients. Grade 2 vestibular disorder was experienced in 27%
of SRS patients and 21% of FSRT patients. No patient experienced
grade ≥ 3 vestibular disorder in either group. Grade 1 and 2 facial
nerve toxicity occurred in 14% of SRS patients and 10% of FSRT
patients. Grade 1 or 2 trigeminal nerve toxicity occurred in 23% of
SRS patients and 10% of FSRT patients. No patient experienced
grade ≥ 3 facial nerve or trigeminal nerve toxicity. Only three
patients (one in FSRT, two in SRS) had disease progression. At 1, 3,
and 5 years after the start of treatment, the cumulative incidence of
progression was 0%, 8%, and 8% for SRS patients and 0%, 0%, and
11% for FSRT patients, respectively (P = .47). There was no statisti-
PURPOSE: Painful trigeminal neuropathy (PTN) is a rare variant of
44
cally significant difference in likelihood of any individual type of
complication or disease progression between patients treated with
SRS or FSRT (all P >.12). There was no evidence of an association
with occurrence of different types of complications for maximum
tumor dimension, SRS dose, or FSRT dose (all P ≥ .19).
CONCLUSION: FSRT and SRS in treatment for acoustic neuromas had
similar outcomes and toxicity at our institution. Both modalities
appear to be successful at providing high tumor control with acceptable toxicities in the noninvasive treatment of acoustic neuromas.
(P043) Central Neurocytoma: Impact of Resection
Extent and Adjuvant Radiotherapy on Survival
Outcomes Yi An, MD, Yu B. James, MD, Jiang Wen, MD, PhD, Henry S. Park,
MD, MPH; Yale University School of Medicine; UT MD Anderson Cancer Center
INTRODUCTION: Central neurocytoma (CNC) is an uncommon
benign/borderline malignant tumor of the central nervous system
that often causes symptoms due to extension into the ventricular
system. Maximal surgical resection is the standard of care, but indications for adjuvant radiotherapy (RT) are unclear. Our goal was to
analyze the impact of resection extent and adjuvant radiotherapy
on survival outcomes using a population-based CNC dataset.
METHODS: We identified all patients in the Surveillance,
Epidemiology, and End Results (SEER) database diagnosed with
CNC (ICD-O-3 histology code 9506-1) in 2004–2011. Only those
who received gross total resection (GTR) and subtotal resection
(STR) were included. Chi-square analysis assessed the associations
between demographic/clinical characteristics and the utilization of
GTR and RT. Overall survival (OS) outcomes were analyzed using
Kaplan-Meier analysis and the log-rank test.
RESULTS: We included 203 patients, with a median age of 31 years;
46% of patients were male, and 80% of patients were white. GTR
was performed in 47% of patients, with the remainder receiving
STR. Adjuvant RT was delivered to 15% of patients, including 9%
after GTR and 20% after STR (P = .018). Age, sex, race, diagnosis
year, World Health Organization (WHO) grade, and tumor size
were not significantly associated with GTR or RT utilization. OS
was 87% at 5 years for all patients, with a median follow-up of 39
months. There was no significant OS benefit with GTR compared
with STR (89% vs 86%; P = .82). There was also no significant OS
benefit with RT after either GTR (86% with RT vs 90% without RT
at 5 years; P = .76) or STR (79% with RT vs 89% without RT at 5
years; P = .53).
CONCLUSION: Adjuvant RT was delivered to a minority of CNC
patients after either GTR or STR in this national database, though
patients were more likely to receive RT after STR. Long-term OS
was excellent for all subgroups, and there was no clear evidence of
resection extent or adjuvant RT influencing survival outcomes.
Since our database is subject to selection bias and limited by a lack
of information regarding local recurrence, salvage therapies, exact
extent of STR, and RT technique, further research is needed to
validate our findings.
(P044) Treatment Outcomes of WHO Grade III
Malignant Meningioma With and Without
Postoperative Radiation Therapy Hanako Yamauchi Farol, DO, Michael R. Girvigian, MD, Michael J.
Miller, MD, Joseph C. Chen, MD, Javad Rahimian, PhD, Christine
Chang-Halpenny, MD, Brandon N. Glousman, Najeeb Alshak, MD, Kenneth Lodin, MD; UCI; Kaiser Permanente; USC
OBJECTIVE: Malignant meningioma is a rare disease, the optimal
management of which is unclear. Our goal was to review our institution’s treatment and outcomes of World Health Organization
(WHO) grade III malignant meningioma.
METHODS: From January 2000 to December 2011, through a retrospective chart review, we identified 16 patients with a pathologic
diagnosis of WHO grade III meningioma; 11 of these patients had
presented with primary malignant meningioma, and 5 presented
after transformation into a malignant meningioma from earliergrade disease.
RESULTS: Median follow-up was 20.5 months (range: 0.4–140 mo).
All patients underwent surgical resection with or without radiation
therapy (RT). Doses given ranged from 5,040 to 6,000 cGy. Of the
11 patients with primary malignant meningioma, 6 had gross total
resection (GTR), 4 had subtotal resection (STR), and 1 had
unknown status. RT was given to 6 of the 11 patients. Median survival was 88.2 months with RT and 8.7 months without RT (P =
.022). Median time to progression was 48.1 months with RT and 5.1
months without RT (P = .045). Of the five patients with transformed meningioma, two received GTR and three had STR. RT
was given to four of the five patients. Median survival for these five
patients was 16.1 months, with median time to progression of 8.3
months. For all patients, overall survival (OS) and progression-free
survival (PFS) rates were 68.8% and 56.3% at 1 year and 39.4% and
21.4% at 5 years, respectively. CONCLUSIONS: Our study showed that patients with primary
malignant meningioma had better outcomes after maximal resection followed by postoperative radiation. In contrast, transformed
meningiomas demonstrated more aggressive behavior, with lower
median survival despite RT. Further multi-institutional or randomized studies are required to evaluate the effectiveness of postoperative RT to determine the best approach to managing these
tumors.
(P045) Multimodality Therapy With
Intensity-Modulated Radiotherapy for Locally
Advanced Esophageal Cancer
Nitesh N. Paryani, MD, Stephen J. Ko, MD, Corey Hobbs, MD, Kristin
Kowalchik, MD, Elizabeth Johnson, MD, Laura Vallow, MD, Jennifer
Peterson, MD, Katherine Tzou, MD, Steven J. Buskirk, MD; Mayo Clinic
PURPOSE: The current standard of care for locally advanced
esophageal cancer includes chemoradiotherapy with or without
surgery. Radiation is usually delivered via a three-dimensional (3D)
technique. Intensity-modulated radiation therapy (IMRT) has been
utilized in the treatment of multiple tumors and has demonstrated
similar efficacy while offering the possibility of decreased toxicity. ARS PROCEEDINGS 2015
45
MATERIALS AND METHODS: A total of 36 patients were treated
with IMRT and chemotherapy; 21 patients underwent surgical
resection—11 underwent open surgery, and the remainder underwent minimally invasive surgery. Chemotherapy consisted primarily of 5-fluorouracil (5-FU) with oxaliplatin or cisplatin. All but two
patients received 50.4 Gy; one patient received 41.4 Gy without
surgery, and one patient discontinued treatment after 25.2 Gy.
Eleven patients required a treatment break during radiotherapy.
The median age was 69 years (range: 46–87 yr). Approximately
two-thirds of tumors were adenocarcinomas located in the lower
thorax. Two-thirds of patients were stage T3 and had positive
lymph nodes. The median tumor size was 5 cm (range: 2–13 cm). RESULTS: With a median follow-up of 21.3 months for all patients
(range: 2.4–44.8 mo) and 33.9 months for survivors (range: 3.744.8 mo), overall survival (OS) at 24 months was 55%. The
24-month OS was 75% vs 24% for surgical and nonsurgical patients,
respectively. Seven patients had a complete pathologic response. A
total of 24 patients experienced grade ≥ 3 acute toxicity, and there
was one grade 5 toxicity. Acute toxicity was similar between surgery
and nonsurgery patients. Also, 14 patients experienced grade ≥ 3
late toxicity (9 surgery and 5 nonsurgery patients). The most frequent late toxicity was grade 3 stricture (21%). On multivariate
analysis, advanced age (relative risk [RR] for 10-year increase in age
= 2.01; P = .032) and heart maximum dose > 55 Gy (RR = 3.73; P =
.011) were associated with decreased survival.
CONCLUSION: Patients who undergo surgery after chemoradiotherapy demonstrate improved survival; however, this may be
related to underlying comorbidities that preclude surgery. IMRT
appears to be a reasonable treatment option that may reduce complications from radiotherapy. Careful attention should be given to
heart dose during treatment planning. (P046) Prediction of Pathologic Complete Response
After Neoadjuvant Chemoradiation Therapy for Rectal
Cancer Using Radiographic Texture Analysis Martin T. King, MD, PhD, William F. Sensakovic, PhD, Albert Koong, MD,
PhD, Daniel T. Chang, MD; Stanford Cancer Institute; Florida Hospital
PURPOSE: To determine if certain radiographic texture features
from pre–radiation therapy (pre-RT) computed tomography (CT)
scans can predict pathologic complete response (pCR) after neoadjuvant chemoradiation therapy for rectal cancer.
METHODS: We conducted an institutional review board (IRB)approved retrospective analysis of 30 patients with rectal cancer
who received neoadjuvant chemoradiation therapy, followed by
total mesorectal excision, between 2009 and 2012. We collected
relevant demographic, staging, and treatment-related information
from the electronic medical records. We also downloaded treatment planning CT scans and structure sets onto a specialized computerized workstation. Gross tumor volumes (GTVs) of the primary rectal lesion were adjusted, if necessary, based on careful
review of the pre-RT non–contrast-enhanced CT and positron
emission tomography (PET) data. GTV voxels corresponding to
air, defined as less than −50 Hounsfield units (HU), were excluded.
Multiresolution texture analysis was performed by passing CT
46
scans through a three-dimensional spatial bandpass (Laplacian of
Gaussian) filter using sigma values of 1.0 mm, 2.0 mm, and 3.0 mm
in order to enhance textural features at fine, medium, and coarse
scales, respectively. Mean texture feature values within the GTV for
entropy, uniformity, kurtosis, skewness, and standard deviation
were then calculated. The performance of each feature in predicting pCR was evaluated using receiver operating characteristic
(ROC) analysis. Then, 95% confidence intervals (CIs) for area
under the curve (AUC) values were estimated using a bootstrapping method with 2,000 iterations. Features with an AUC above a
0.75 threshold were identified as potential predictors of pCR.
RESULTS: Treatment planning PET scans were available for 29 of 30
patients. Six patients achieved a pCR at the time of surgery. Kurtosis
demonstrated AUC values above the 0.75 threshold for fine (0.78;
95% CI, 0.46–0.89), medium (0.77; 95% CI, 0.48–0.91), and coarse
(0.74; 95% CI, 0.38–0.87) scales. Skewness also exhibited AUC values above the 0.75 threshold for fine (0.77; 95% CI, 0.49–0.89),
medium (0.79; 95% CI, 0.51–0.90), and coarse (0.78; 95% CI, 0.51–
0.90) scales. Skewness on the medium scale allowed for a sensitivity of 66.3% at a specificity of 80.1% for predicting pCR.
CONCLUSION: Several radiographic texture features from the preRT CT scan were identified as potential predictors of pCR in rectal
cancer patients after neoadjuvant chemoradiation therapy. Future
work will focus on validating these features in a larger dataset.
(P047) The Role of Radiation Therapy Following
Adjuvant Chemotherapy in Pancreatic Adenocarcinoma Craig J. Baden, MD, MPH, Andrew McDonald, MD, Rojymon Jacob,
MD; University of Alabama, Birmingham
OBJECTIVES: Early studies of adjuvant treatment for resected pancreatic adenocarcinoma demonstrated significant improvements in
disease-related outcomes with the administration of radiation therapy. However, with the advent of gemcitabine and other newer chemotherapy regimens, the value and proper role of adjuvant radiation
have come into question. In this study, we examine disease-related
outcomes in patients treated with surgery and modern chemotherapy with or without subsequent radiation therapy in order to clarify
the role of adjuvant radiation in this particular setting and to identify subsets of patients most likely to benefit from radiation.
METHODS: We conducted an institutional retrospective review of
all patients with pancreatic adenocarcinoma treated with curativeintent surgery and adjuvant chemotherapy between December
2001 and January 2013. Actuarial estimates of local control (LC),
local failure–free survival (LFFS), overall survival (OS), and median survival (MS) were determined by the Kaplan-Meier method,
with examination of the benefit of adjuvant radiation completed
with the log-rank test. Patients were also stratified by node and
margin status in order to determine the effect of radiation within
these subsets.
RESULTS: A total of 71 patients (median age: 64.6 years) with pancreatic adenocarcinoma underwent treatment with curative-intent
surgery and adjuvant gemcitabine-based (n = 66) or (fluorouracil
[5-FU], leucovorin, irinotecan, oxaliplatin) (FOLFIRINOX) (n = 5)
chemotherapy. Surgical margins were negative in 44 patients, close
in 8 patients, and positive in 19 patients. Lymph nodes were pathologically involved in 46 cases. Following completion of adjuvant
chemotherapy, 21 patients went on to receive radiation therapy,
with nearly all receiving 5,040 cGy delivered in 28 fractions.
Sensitizing fluoropyrimidine-based chemotherapy was administered with radiation in 20 of the 21 patients. Median follow-up for
the cohort was 21.9 months. Patients receiving radiation (vs those
with no radiation) did not have statistically significant improvements in 18-month LC (64.1% vs 53.7%; P = .42), LFFS (51.6% vs
51.4%; P = .63), OS (69.6% vs 80.6%; P = .49), or MS (28.5 mo vs
32.6 mo; P = .49). In the subset of patients with positive nodes and
negative margins, radiation was associated with a trend toward
improved local control (18-mo LC: 62.2% vs 34.2%; P = .08). CONCLUSIONS: We discerned no significant improvements with the
addition of radiation therapy in these patients with resected pancreatic adenocarcinoma treated with modern adjuvant chemotherapy,
but statistical power was limited. The eventual results of the ongoing
Radiation Therapy Oncology Group (RTOG) study RTOG 0848
will provide definitive data regarding the appropriate role for radiation in the era of modern adjuvant chemotherapy.
(P048) Mutational Analysis by Next-Generation
Sequencing in Patients With Pancreatic
Adenocarcinoma Andrea L. Arnett, MD, PhD, Kenneth Chang, BS, Terence T. Sio, MD,
MS, Robert C. Miller, MD, MS; Department of Radiation Oncology,
Mayo Clinic, Rochester; Department of Radiation Oncology, Mayo Clinic, Jacksonville
BACKGROUND: Pancreatic adenocarcinoma carries a poor prognosis, and currently available systemic therapies have demonstrated only modest efficacy in advanced disease. In this retrospective
study, next-generation exomic sequencing (NGS) was utilized in
pancreatic adenocarcinoma samples to identify potential novel
therapeutic targets that are not routinely assayed in the clinical
setting.
MATERIALS AND METHODS: Eight patients with confirmed pan-
creatic adenocarcinoma were selected based on availability of tissues. These patients were treated at our institution from 2001 to
2013. A total of 236 somatic genes were surveyed in this review,
including 3,230 exons and 47 introns at > 900x mapping coverage.
NGS reports were generated from 2011 to 2013. Statistical analysis
was performed using Kaplan-Meier survival analyses.
RESULTS: The most frequent genomic alterations were found within KRAS (88%) and TP53 (75%). Three patients were found to have
mutations within the SMAD family of genes. All patients with
SMAD alterations were also found to have concurrent KRAS mutations, which is consistent with the reported literature. KRAS mutations most commonly involved codon 12, while the locations of
SMAD family mutations were heterogeneous. In addition, concurrent mutations were found within genes that have been shown to
potentially modulate or interact with KRAS-mediated signaling
pathways, including CCND3, CDKN2A/B, and RB1. Furthermore,
75% of patients had multiple, novel mutations that have not tradi
tionally been associated with pancreatic adenocarcinoma. The
average number of mutations was 8.1 (range: 0–17 mutations). The
majority of patients had greater than six mutations identified, but
there was substantial heterogeneity in the location and type of
genomic alterations. Median survival and 5-year overall survival
(OS) were 30.1 months and 41%, respectively. There was no significant correlation between the number of mutations and OS.
Median age at diagnosis was 54 years (range: 35–82 yr). Overall,
88% of patients were found to have mutations associated with targeted therapies. One-third of patients possessed multiple concurrent molecular targets for which US Food and Drug Administration
(FDA)-approved chemotherapeutic agents are currently available. CONCLUSION: Novel mutations were identified in the majority of
patients, including mutations within a number of genes that have
the potential to influence KRAS-mediated signaling, as well as
other prominent signaling pathways. These results could potentially serve to identify targets for novel chemotherapeutic agents
and guide personalized, combinatorial therapy in appropriately
selected patients.
(P049) Increased Portal Venous Enhancement of
Hepatocellular Carcinoma Following Transcatheter
Arterial Chemoembolization Alexander Lam, MD, Megha Nayyar, BS, Chandana Lall, MD; UCI
Medical Center Hepatocellular carcinoma (HCC) is a growing cause of mortality
throughout the United States, despite advancements in diagnosis
and treatment. As advanced HCC progresses, it becomes more
dependent on arterial blood. This translates to the typical imaging
characteristics of sharp contrast enhancement during arterial
phase, followed by brisk portal venous washout on multiphasic
computed tomography (CT). Liver-directed therapies, such as transarterial chemoembolization (TACE), have utilized this preferential
arterial flow to administer targeted chemotherapy agents and
embolize parasitized arterial branches.
By compromising arterial flow, these embolic therapies alter the
imaging characteristics that are typically dependent on hemodynamics, such as multiphasic CT. We hypothesize that the portal
venous supply to the tumor experiences a sustained, compensatory
increase following chemoembolization, resulting in increased
enhancement on portal venous phase when compared with the pretreatment tumor bed. To evaluate this hypothesis, the images of 102
patients with advanced HCC were retrospectively reviewed by two
fellowship-trained radiologists. Appropriate preprocedural and
posttreatment CT images were performed at noncontrast, arterial,
and portal venous phases. Digital subtraction angiographic images
were reviewed to confirm the target lesion for evaluation and
ensure adequate obliteration of the arterial vessels feeding the
tumor. Degree of enhancement was quantified by drawing a circular region of interest (ROI) within the lesion margin of at least 1
cm2. Differences in attenuation of the tumor bed were standardized
against normal liver parenchyma and underlying background on
the same slice. Enhancement was defined as a difference greater
than 15 Hounsfield units (HU) from baseline attenuation on the
noncontrast study. Enhancement patterns among the phases were
47
compared between the pre- and posttreatment scans.
A total of 50% (51 out of 102) of HCC cases following TACE demonstrated definite increased enhancement on venous phase compared with the preprocedural images, of which the majority consisted of increased peripheral enhancement. Arterial enhancement was decreased or unchanged for these patients. Also, 24% of
cases (25 patients) showed unchanged enhancement on arterial
phase images following TACE therapy, with no change in the
appropriate venous washout. A total of 11% of cases (11 patients)
showed unchanged enhancement on both arterial and portal
venous phase after therapy, and 15% of cases (15 patients) demonstrated increased enhancement on arterial phase and not on
venous phase.
The majority of cases exhibited increased enhancement on portal
venous phase following treatment with TACE, demonstrating the
importance of surveillance with proper multiphase imaging to
assess for recurrence, especially in light of a decrease in arterial phase enhancement following treatment.
(P050) Yttrium-90 Radioembolization for Unresectable,
Chemorefractory Colorectal Cancer Liver Metastases in
KRAS Wild-type and Mutant Patients Einsley Janowski, MD, PhD, Olga Timofeeva, PhD, Sergey Chasovskikh,
PhD, Max Goldberg, Alexander Kim, MD, Filip Banovac, MD, Dalong
Pang, PhD, Anatoly Dritschilo, MD, Keith Unger, MD; Georgetown University
INTRODUCTION: We report our institutional experience on the
efficacy of resin-based yttrium-90 (90Y) radioembolization for the
treatment of unresectable, chemorefractory colorectal cancer liver
metastases (CRCLMs).
METHODS: From 2011 to 2014, a total of 51 patients underwent 90Y
treatment for CRCLMs at our institution. A retrospective review
was conducted for clinical outcomes, demographic information,
and tumor mutation status. In 38 patients, interval imaging was
available for tumor response assessment using Response Evaluation
Criteria in Solid Tumors (RECIST) criteria. Serum (plasma) was
prospectively collected in patients both pretreatment (n = 9) and
posttreatment (n = 7), and circulating cell-free DNA (ccfDNA)
concentration and integrity index were measured using quantitative PCR. DNA integrity results were validated in two patients
using atomic force microscopy (AFM). RESULTS: Our patient population consisted of 51 patients diagnosed with colon cancer at a median age of 56 years (range: 31–85
yr). Tumor mutation information was available for 41 patients: 24
(58%) patients were KRAS mutant, 15 (37%) were KRAS wild-type,
and 2 (5%) had microsatellite instability (MSI). The average survival after 90Y was 5.7 months ± 4.1 (range: 0–21 mo) in the entire
cohort, with a 12-month survival of 10%. Average survival stratified by mutation status in KRAS wild-type, KRAS mutant, and MSI
patients was 6 months ± 3.5, 5.29 months ± 4.86, and 5 months ±
2.83, respectively. Imaging assessment showed a partial response in
8 patients (21%), stable disease in 16 (42%), and progressive disease in 14 (37%) at a median follow-up of 2 months after treatment.
48
Tumor local control after 90Y treatment averaged 2.17 months ±
2.97 for the entire cohort. Local control response, assessed according to tumor mutation, averaged 2.62 months ± 4.25 for KRAS
wild-type, 1.16 months ± 1.43 for KRAS mutant, and 4.5 months ±
3.54 for MSI patients. ccfDNA was detected in 100% of the analyzed samples. Median pretreatment plasma ccfDNA levels of 4.6
ng/mL decreased to 1.8 ng/mL after single-lobe treatment. DNA
integrity index was reduced from a median of 0.62 to 0.23 after
treatment. Analysis by AFM of paired pre- and posttreatment samples of a KRAS-mutant patient and an MSI patient revealed minimal change in the KRAS sample but a 35% average fragment size
drop in the MSI sample.
CONCLUSIONS: 90Y radioembolization is an effective treatment for
CRCLMs in extending local control for liver-dominant metastatic
disease. However, KRAS-mutant tumors may be more radioresistant to treatment.
(P051) Intraductal Papillary Neoplasm of the Bile Duct:
Prognostic Factors in SEER Outcomes of Benign and
Malignant Cases Sean Szeja, MD, Todd Swanson, MD, PhD; UT Medical Branch
INTRODUCTION: Intraductal papillary neoplasm of the bile duct
(IPNB) may be invasive or noninvasive. Given its rarity, there are
limited data on the management and clinical outcomes. The purpose of this study is to use the Surveillance, Epidemiology, and End
Results (SEER) database to evaluate prognostic factors: stage, anatomical location, extent of surgery, and the use of radiation therapy
(RT).
METHODS: Cases diagnosed from 1978–2011 were downloaded
from the SEER database. Inclusion criteria were first primary,
known status of surgery, and RT history. Analysis of malignant
diagnoses from 2004–2011 incorporated TNM staging. KaplanMeier curves calculated overall survival (OS) and disease-specific
survival (DSS) in months. Log-rank tests were performed to compare survival.
RESULTS: There were 31 benign cases, with an OS of 92 months;
surgery was used in 26 cases, definitive RT was used in 1 case, and
adjuvant RT was used in another. Ampulla of Vater (AoV) and
other extrahepatic ductal (EHD) locations had statistically similar
OS (120 vs 79 mo, respectively; P = .93). For EHD, trends suggested
that subtotal resection had the best OS (P = .157), and for AoV
locations, radical resection trended toward worse OS (P = .128),
with statistical power limited by having eight patients with defined
surgical extent at each location. There were 1,309 malignant cases;
542 of these patients did not have surgery, and of this group 77
received RT alone that extended median OS from 3 to 7 months (P
= .026) and DSS from 4 to 8 months (P = .074). There were 323
malignant cases diagnosed from 2004–2011: 54% with N0M0 and
20% being T1N0M0. Analysis of all stages combined by location
showed, in decreasing order, significantly different median survival times (P < .01): AoV: OS 48 mo, DSS 57 mo; EHD: OS 12 mo,
DSS 15 mo; and intrahepatic ductal (IHD): OS 5 mo, DSS 5 mo.
Analysis by treatment modality showed that, with regard to OS and
DSS, surgery alone was better than surgery and radiation (P < .01),
which was better than radiation alone (P < .01), which was similar
to results with no treatment. Analysis of T1N0M0 cases showed
that smaller extent of resection of primary location correlated with
better OS and DSS (P < .05, P < .02, respectively) at EHD but not
AoV locations.
CONCLUSIONS: Both benign and malignant cases had outcomes
dependent upon the location and extent of surgical resection. In
malignant cases that are not amenable to surgery, radiation offers a
survival benefit. Given the cohort in this analysis, selection bias
likely plays a significant role. Further study is required to define the
optimal management of IPNB.
(P052) Human Papillomavirus in Esophageal Cancer:
An Institutional Retrospective Analysis Sarah E. James, MD, PhD, Terence T. Sio, MD, Rondell P. Graham,
MBBS, Michael Keeney, MD, David I. Smith, PhD, Robert C. Miller,
MD; Department of Radiation Oncology, Department of Laboratory
Medicine and Pathology, Mayo Clinic, Rochester; Department of Radiation Oncology, Mayo Clinic, Jacksonville
OBJECTIVES: Human papillomavirus (HPV) is a well-established
oncogenic and prognostic factor in a number of cancers. This retrospective study aims to estimate the prevalence of HPV in esophageal cancer and investigate the potential effect of infection on
treatment response.
MATERIALS AND METHODS: Esophagectomy tissue samples were
obtained for 94 stage II/III esophageal cancer patients treated with
trimodality therapy at our institution between 1998 and 2003.
Patients with both adenocarcinoma and squamous cell histology
were included. Most patients were treated with 50.4 Gy in 28 fractions with concurrent chemotherapy. Chemotherapy consisted of a
platinum doublet of either cisplatin with 5-fluorouracil (5-FU) or
carboplatin with paclitaxel. Subsequent to the neoadjuvant therapy
course, patients underwent Ivor-Lewis esophagectomy. Freshfrozen paraffin-embedded specimens were evaluated using quantitative polymerase chain reaction (qPCR) to measure expression of
the HPV oncogenes E6 and E7 and human p16. Patient characteristics were obtained from a chart review of electronic medical
records. Hematoxylin and eosin (H&E)-stained slides of freshfrozen paraffin-embedded esophageal tumor specimens that were
taken at the time of surgery were carefully reviewed and graded for
treatment response. Chi-square testing was used for multivariate
analysis.
RESULTS: None of the 94 samples was positive for HPV oncogene
expression. Median age at time of diagnosis was 61 years. The
majority of patients was male (87%). Patients had advanced disease,
with most having T3N0 (13%) or T3N1 (57%) disease. A total of
89% of patients had adenocarcinoma, and 11% had squamous cell
carcinoma. At the time of esophagectomy, 28 (30%) patients were
found to have a complete pathologic response (pCR), 40 (43%) had
a partial response, and 26 (28%) had no significant treatment
response. There was no significant correlation found between pCR
and age, T stage, N stage, histology, tumor location, grade, or gender. However, patients aged > 70 years were more likely to have a
pCR when compared with younger counterparts (P = .07). CONCLUSIONS: There was no HPV oncogene expression in our
patient cohort, which corresponds with a low-to-no prevalence of
esophageal HPV infection in a population of patients in the United
States. However, further studies including a larger patient cohort
with pretreatment tissue analysis would still be helpful in determining the true prevalence of HPV in esophageal cancer. Patients who
are treated with trimodality therapy experienced a high rate of
pathologic response.
(P053) Esophageal Cancer Pathologic Complete
Response Rate After Neoadjuvant Chemoradiation:
Is There a Difference Between Academic Centers vs
Community Centers? Wendy Gao, MD, Gurleen Dhami, MD, Brant K. Oelschlager, MD,
Veena Shankaran, MD, Shilpen Patel, MD, Smith Apisarnthanarax,
MD, Jing Zeng, MD; University of Washington
INTRODUCTION: Trimodality treatment, consisting of preoperative chemoradiation followed by surgical resection, has been
established as the standard of care for locally advanced esophageal
cancer. Rates of pathologic complete response (pCR) range from
29% to 40% in phase III trials. We reviewed our institution’s pCR rate and assessed whether there is a difference for
patients treated at our academic institution vs in the community.
METHODS: Consecutive patients with esophageal cancer who
underwent esophagectomies at our institutionafter chemoradiati
on from January 2012 to October 2014 were included in this retrospective analysis. Patient characteristics, staging, histology, and
pathologic response data were collected. Chi-square and t-tests
were used to compare patient groups. RESULTS: A total of 51 patients were found to have undergone
resection after chemoradiation for esophageal cancer between
January 2012 to October 2014; 28 patients (55%) were treated at
our academic center, and 23 (45%) were treated in the community.
Patients treated in the community were older (median age: 65 vs
61 yr; P = .047). Staging distribution was similar for the two
patient groups: community stage: II = 34%, IIIA = 43%, and IIIB
= 23%; academic center stage: II = 39%, IIIA = 53%, and IIIB = 7%.
Most patients had adenocarcinoma (88.2%) vs 9.8% squamous cell
and 2% adenosquamous. Location of the tumors was distal esophagus in 47 patients (92.1%) and midesophagus in 4 (7.9%). Median
radiation dose was 50.4 Gy (range: 37.8–50.4 Gy) for all patients.
All patients treated at our center received carboplatin and paclitaxel (carbo/taxol) vs 10% of patients in the community receiving
regimens other than carbo/taxol (one docetaxel, cisplatin, and
5-fluorouracil [5-FU] [DCF]; one 5-FU/oxaliplatin; and one alternating carbo/taxol with 5-FU/oxaliplatin).
Pathologic complete tumor response occurred in 21.5% of patients.
By histology, the pCR rate was 50% for squamous cell (2/4 patients),
and 19% for adenocarcinoma (9/47 patients). For the primary
tumor, there was downstaging in 41.2% of tumors, no change in
35.3%, and upstaging in 2%. Pathologic complete nodal response
occurred in 41.2%, downstaging occurred in 3.9%, there was no
change in 35.3%, and upstaging occurred in 19.6% of patients.
There was no statistically significant difference in pCR rate between
49
patients who received neoadjuvant chemoradiation at University of
Washington Medical Center (21%) vs at an outside institution
(17%) (P = 1.0).
CONCLUSIONS: Pathologic outcomes after neoadjuvant chemoradiation for esophageal cancer were similar between patients treated
at an academic center and community setting, although patients
treated in the community tended to be older than patients treated
at our academic center. These results will need to be validated with
a larger dataset. The pCR rate after neoadjuvant chemoradiation at
our institution was 21%, consistent with published data.
(P054) Carbon Ion Therapy for Chinese Patients With
Prostate Cancer: Primary Reports Shen Fu, Qing Zhang, Xiaomeng Zhang, Xin Cai, Jin Meng, Jingfang
Zhao, Yinxiangzi Sheng, Kambiz Shahnazi, Michael F. Moyer; Shanghai
Proton and Heavy Ion Center/Fudan University Shanghai Cancer Center; Shanghai Proton and Heavy Ion Center; Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
PURPOSE: To evaluate the toxicities and efficacy of carbon ion
therapy for patients with prostate cancer.
MATERIALS AND METHODS: A total of 19 patients with pathologically confirmed prostate cancer were treated with carbon ion therapy from June 2014 to September 2014; 2 had low-risk, 10 had
intermediate-risk, and 7 had high-risk prostate cancer. The patients
with intermediate-/high-risk disease received neoadjuvant hormone therapy for 2–3 months, followed by concurrent hormone
and carbon ion irradiation (63–66 GyE/23–24 Fx with one fraction
per day, 5 days per week). The target area included the prostate and
partial seminal vesicle, depending on the prognostic risk. Conedown strategy was adapted in order to avoid the toxicities of the
bladder and rectum. Peripheral blood was withdrawn before, during, and after carbon ion therapy.
RESULTS: Immediate outcome: Prostate-specific antigen (PSA) was
used to evaluate the response to carbon ion therapy: 7 of 19 (37%)
patients had biochemical control (PSA < 0.1 ng/mL) just after the
conclusion of carbon ion therapy, and PSA values will be used to
determine efficacy of the treatment 3 months after treatment. Also,
7 of 19 patients were diagnosed with abnormal 11 choline–positron
emission tomography-computed tomography (PET-CT) before
carbon ion therapy. Therefore, 11 choline–PET-CT will be conducted for those patients 3 months after treatment, and the data
will be available at the time of the ARS meeting. A total of 7 of 19
patients had statistically higher apparent diffusion coefficient
(ADC) values detected by diffusion-weighted imaging (DWI)
before radiotherapy than after treatment (P = .0049). Circulating
tumor cells (CTCs) in peripheral blood samples could be detected
in 7 of 19 patients before carbon ion therapy, but there were no
CTCs in 6 of these 7 patients after treatment.
A total of 6 of 19 (32%) patients had variable acute toxicities per the
Common Terminology Criteria for Adverse Events version 4.03
(CTCAE v4.03): hematologic system (5), genitourinary (GU) (4),
and gastrointestinal (GI) (1). Most toxicities were grade 1; two
patients had grade 2 hematologic toxicities. There were no signifi50
cant differences in specific immunity (T cells: CD3, CD4, CD8 for
cellular immunity; B cells: CD19 for humoral immunity) or nonspecific immunity (NK cells: CD16, CD56) before and after carbon
ion therapy.
CONCLUSION: This is the first report about a Chinese population
with prostate cancer treated with carbon ion therapy. Our primary
data showed that carbon ion therapy was well tolerated, and the
immediate effect was encouraging. Long-term follow-up is needed
for the analysis of final treatment responses and toxicities.
(P055) Can High-Grade Prostate Cancer (Gleason 8–10)
Be Cured With Definitive Local Therapy Without
Testosterone Suppression? Five-Year Outcomes
Employing Up-Front Prostatectomy in Patients With
Clinically Localized, Nonmetastatic Disease
Darrion L. Mitchell, MD, PhD, Kyle Russo, MD, Mark C. Smith, MD,
Sarah L. Mott, MS, John M. Watkins, MD; Department of Radiation
Oncology, Holden Comprehensive Cancer Center, University of Iowa;
Bismarck Cancer Center
PURPOSE: High-grade prostate cancer (HGPC) is associated with
an aggressive clinical course and poor outcomes; thus, a common
approach involves the combination of long-term testosterone suppression with definitive local therapy. Small single-institution case
series report that long-term disease control can be obtained in
selected patients who undergo definitive local therapy alone; however, prognostic factors for this approach remain to be identified.
The current investigation seeks to describe disease control and survival outcomes for patients with clinically localized HGPC at biopsy who were managed with primary radical prostatectomy (RP)
without systemic therapy, with analyses performed to identify
prognostic factors associated with disease control. MATERIALS AND METHODS: Patients were retrospectively identified for inclusion by biopsy-proven Gleason 8–10 adenocarcinoma
managed with primary RP, without preoperative evidence of nodal
or distant metastasis. Patient who received any preoperative intervention or adjuvant hormone therapy were excluded, as were
patients with insufficient prostate-specific antigen (PSA) follow-up
(< 12 mo). Patient-, tumor-, and treatment-related factors were
analyzed for association with freedom from failure (FFF, defined as
PSA > 0.2 ng/mL and rising or upon initiation of salvage therapy),
employing Cox proportional hazards regression. The Kaplan-Meier
method was employed for estimation of FFF and survival. RESULTS: From 2003–2010, a total of 69 eligible patients were
identified. Median age was 63 years (range: 48–75 yr) and median
PSA was 11.7 ng/mL (range: 3.5–64.9 ng/mL). Gleason score (GS)
at RP was < 7, 8, and > 9 for 22, 17, and 29 patients, respectively.
Extraprostatic extension, involved surgical margin, seminal vesicle
invasion, and lymph node involvement were identified in 32, 33,
18, and 6 patients, respectively, with adjuvant radiotherapy delivered to 5 patients. At a median follow-up of 67.3 months (range:
13.3–141.2 mo), 40 patients had disease recurrence, and 8 patients
died (6 cancer-specific). The 5-year FFF and overall survival (OS)
rates were 39% (95% confidence interval [CI], 21%–58%) and 87%
(95% CI, 72%–94%), respectively. Primary and overall Gleason
score at RP, involved surgical margin, seminal vesicle involvement,
nodal involvement, and elevated initial postprostatectomy PSA
were significantly associated with FFF in the univariate analysis,
with primary GS at RP (hazard ratio [HR] = 1.80; P < .01) and
post-RP PSA (HR = 4.64; P < .01) significant in the multivariate
analysis.
CONCLUSIONS: Patients with HGPC at diagnosis have high rates
of early disease recurrence, though mortality at 5 years remains
low. Following RP without systemic therapy, high primary GS and
initial post-RP PSA were independently associated with worse FFF
outcomes.
(P056) Ten-Year Outcomes of Patients With Gleason
Score 9/10 Prostate Cancer Treated With Trimodality
Therapy Andrew T. Wong, MD, A. Sivathayalan, R. Salant, MD, L. Harrison,
MD, R. Stewart, MD, T. Carpenter, MD, D. Shasha, MD; Mount Sinai
Beth Israel; Carleton University
OBJECTIVE: Multiple publications have reported poor biochemical
control in patients with localized Gleason score (GS) 9/10 prostate
cancer treated with either surgery or external beam radiation therapy (EBRT). Few studies have specifically addressed brachytherapy outcomes in this cohort or reported outcomes beyond 5 years.
The purpose of this study is to report long-term clinical outcomes
in patients with GS 9/10 prostate cancer treated with combination
EBRT, low-dose-rate brachytherapy (LDRBT), and androgen
deprivation therapy (ADT).
MATERIALS AND METHODS: We retrospectively reviewed 73
patients with localized GS 9/10 prostate cancer treated with combination therapy from 1998 to 2012 at a single institution; 27
patients had one high-risk feature (stage T3a/b or PSA ≥ 20 ng/
mL), 33 had two features, and 13 had three features. Patients
received pelvic EBRT to 50.4 Gy followed by an LDRBT boost (108
Gy 125I, 90 Gy 103Pd). All implants and contours were performed
by a single physician (DS). Luteinizing hormone releasing hormone (LHRH) agonist was given for a median duration of 25
months. Biochemical failure was defined using the Phoenix criteria (PSA nadir + 2). Biochemical progression–free survival (BPFS),
prostate cancer–specific survival (PCSS), and overall survival (OS)
were calculated using Cox regression analysis. Univariate and multivariate Cox regression was performed to identify factors that
may impact BPFS: 1 high-risk feature vs > 1 feature (P = .0358),
stage < T3c vs T3c (P = .240), prostate-specific antigen (PSA) < 50
ng/mL vs ≥ 50 ng/mL (P = .753), and isotope 125I vs 103Pd (P =
.471). Toxicity was graded using the Common Toxicity Criteria for
Adverse Effects version 3.0 (CTCAE v3.0).
RESULTS: Minimum and median follow-ups were 20 and 55
months, respectively. Five-year actuarial BPFS, PCSS, and OS were
76.4%, 95.1%, and 88.2%, respectively. Ten-year BPFS, PCSS, and
OS were 63.4%, 80.5%, and 59.1%. Median time to biochemical
failure was 51 months. Multivariate Cox regression analysis
showed that a higher number of high-risk features was significant
(P = .057), but T3c (P = .378) and PSA ≥ 50 ng/mL (P = .600) were
not significant predictors of BPFS. No patients developed acute
urinary retention requiring urinary catheterization. One patient
developed grade 3 toxicity, and there was no other cases of grade
3/4 genitourinary or gastrointestinal toxicity.
CONCLUSIONS: In this large, retrospective series, we report very
good long-term oncologic outcomes and minimal toxicity in
patients with GS 9/10 prostate cancer treated with combination
EBRT, LDRBT, and ADT. Trimodality therapy is a well-tolerated
and effective treatment for these very-high-risk patients.
(P057) A Population-Based Study of Men With
Low-Volume, Low-Risk Prostate Cancer: Does
African-American Race Predict for More Aggressive
Disease? Arpit Chhabra, MD, Justin Rineer, MD, Jeremy Weedon, PhD, David
Schreiber, MD; State University of New York Downstate Medical Center; University of Florida Orlando Health; Department of Veterans Affairs, New York Harbor Healthcare System
INTRODUCTION: Recent studies have suggested that AfricanAmerican (AA) patients with clinical low-risk prostate cancer may
not be ideal candidates for active surveillance due to a higher likelihood of harboring aggressive disease. In this study, we utilized
the Surveillance, Epidemiology, and End Results (SEER) database
to analyze whether race plays a role in pathological upstaging after
radical prostatectomy (RP).
MATERIALS AND METHODS: This study consisted of patients in
the SEER database for whom race was identified either as white
or AA. Eligible men were diagnosed between 2010 and 2011 with
prostate-specific antigen (PSA) < 10 ng/mL as well as cT1cN0M0,
Gleason score 6 disease with adenocarcinoma in 2 or fewer cores
of a ≥ 12-core biopsy, treated by RP. Detailed pathologic information regarding pathologic T stage, margin status, and primary and
secondary pathologic Gleason scores were collected. Adverse
pathology was characterized individually, as well as in a composite metric, which was defined as pT2 and Gleason ≥ 4 + 3; pT3a
and Gleason 3 + 3 with positive margins; pT3a and Gleason ≥ 3 +
4; or pT3b–pT4 with any Gleason score. We also analyzed the
Cancer of the Prostate Risk Assessment score (CAPRA-S) for
each patient. Chi-square was used to characterize differences in
pathological extent of disease by race. Univariate and multivariate
logistic regression was used to look for potential predictors for
adverse pathology. Statistical significance was defined as a P value
of < .05.
RESULTS: There were a total of 1,794 patients who met the selection criteria, of whom 1,565 (87.2%) were identified as white and
229 (12.8%) were identified as AA. No statistical difference was
observed between white and AA men with regard to pathological
Gleason score (P = .99), pathological extent of disease (P = .34),
margin status (P = .43), CAPRA-S score (P = .56), or adverse features (P = .45). On multivariate analysis, only increasing PSA and
increasing age were significant predictors of adverse pathology.
AA race was not predictive for adverse pathology on univariate
(odds ratio [OR] = 1.19; 95% confidence interval [CI], 0.75–1.88;
P = .45) or multivariate (OR = 1.43; 95% CI, 0.87–2.33; P = .16)
analysis.
51
CONCLUSION: In this large population-based cohort of 1,794 men
with low-risk, low-volume prostate cancer, AA race was not associated with more aggressive pathology compared with Caucasians.
(P058) The Long-Term Economic Value of Hypofractionated Prostate Radiation: A Cost Minimization Analysis
of a Randomized Trial Khinh Ranh Voong, MD, MPH, Lincy S. Lal, PhD, Deborah A. Kuban,
MD, Thomas J. Pugh, MD, J. Michael Swint, PhD, Robert R. Trujillo,
Joy Godby, Seungtaek Choi, MD, Andrew K. Lee, MD, MPH, Pamela J.
Schlembach, MD, Usama Mahmood, MD, Steven J. Frank, MD, Sean E.
McGuire, MD, PhD, Karen E. Hoffman, MD, MPH; UT MD Anderson
Cancer Center; UT School of Public Health
PURPOSE: Hypofractionated prostate radiation (HIMRT) shortens
the treatment course while providing outcomes comparable with
conventionally fractionated radiation (CIMRT). To determine the
long-term economic value of HIMRT, including the costs of managing radiation toxicities that develop after treatment, a cost minimization analysis compared CIMRT with dose-escalated HIMRT
using data from a randomized trial.
PATIENTS AND METHODS: Men with localized prostate cancer
were randomized to CIMRT (75.6 Gy in 42 fractions over 8.4
weeks) or HIMRT (72 Gy in 30 fractions over 6 wk). A decision tree
modeled trial probabilities of maximum late bowel and urinary
toxicities using patient-level data with a median follow-up of 6
years. Costs were estimated from the healthcare perspective, using
2014 national reimbursement rates for services received. Patientlevel institutional costs, adjusted to 2014 dollars, verified reimbursements. Sensitivity analysis assessed model uncertainty.
RESULTS: The cost for HIMRT and toxicity management was
$22,957, saving $7,000 compared with CIMRT ($30,241). CIMRT
was the common factor among the five most influential scenarios
that contributed to total costs. Toxicity represented a small part (<
10%) of the average total cost for patients with either grade 2/3
bowel or urinary toxicity. However, toxicity management reached
up to 26% of total costs for patients with both high-grade bowel
and urinary toxicities. There was no threshold at which CIMRT
became the less costly regimen. Institutional costs confirmed the
economic value of HIMRT ($6,000 savings).
CONCLUSION: HIMRT is more cost-efficient than CIMRT for
treating prostate cancer, taking into account additional costs owing
to late radiation toxicities.
(P059) Trends in the Utilization of Radiotherapy in the
Management of Renal Cell Carcinoma Talha Shaikh, MD, Elizabeth A. Handorf, PhD, Colin Murphy, MD,
Alexander Kutikov, MD, Robert G. Uzzo, MD, Mark Hallman, MD, PhD,
Eric M. Horwitz, Marc C. Smaldone, MD, MSHP; Fox Chase Cancer
Center
PURPOSE: The role of radiotherapy in the management of renal cell
carcinoma (RCC) has been limited due to the belief that these
tumors are relatively radioresistant. More recently, retrospective
52
series have demonstrated good local control in patients undergoing
radiation. We examined the temporal trends and patterns of use of
radiotherapy in patients with localized RCC.
MATERIALS AND METHODS: Patients diagnosed with RCC were
identified using the National Cancer Data Base. Our primary
objective was to describe the temporal trends in the utilization of
radiotherapy. Our second objective was to identify patient and
treatment factors associated with receipt of radiation. Data were
analyzed using the chi-square and Cochran-Armitage tests for
trend.
RESULTS: A total of 330,426 were diagnosed with RCC between
1998 and 2010, with 18,522 (5.6%) patients receiving radiotherapy.
After excluding patients with metastatic disease, 280,208 patients
were diagnosed with localized RCC, with 3,552 (1.3%) patients
receiving radiation therapy to the primary site. Factors associated
with receipt of radiation included age > 71 years, no surgery (P <
.0001), chemotherapy use (P < .0001), higher stage (P < .0001),
higher grade (P < .0001), positive nodes (P < .0001), and sarcomatoid histology (P < .0001). A total of 257,304 patients underwent
surgical resection in this cohort. Of these patients, 2,265 (0.9%)
received adjuvant radiation. Patients receiving adjuvant radiotherapy were more likely to receive chemotherapy (P < .0001), have a
higher stage (P < .0001), have a higher grade (P < .0001), have
positive nodes (P < .0001), and have sarcomatoid histology (P <
.0001).
CONCLUSIONS: There has been a decrease in the use of radiotherapy for patients with localized RCC, although patients with more
aggressive disease were more likely to receive radiation. Modern
trials are needed to better identify the role of radiation in the management of these patients.
(P060) Impact of Major Psychiatric Disorders on
Tolerance and Outcomes for Men With Prostate Cancer
Undergoing Dose-Escalated Radiation Therapy
Joseph Safdieh, MD, J. Rineer, MD, A. Wong, MD, D. Schwartz, MD,
D. Schreiber; SUNY Downstate Medical Center; University of Florida
Health Cancer Center at Orlando; Department of Veteran Affairs, NY
Harbor Campus
PURPOSE/OBJECTIVES: Prior studies have revealed that patients
with psychiatric disorders and prostate cancer have worse survival
outcomes compared with the general population. However, many
of these studies have associated these outcomes with delayed diagnosis and/or reduced access to definitive treatment. The purpose of
this study was to investigate the toxicity and outcomes of patients
with or without psychiatric disorders who were a primarily prostate-specific antigen (PSA)-screened population and who accepted
definitive treatment with external beam radiation.
MATERIALS AND METHODS: The charts of 469 patients diagnosed
with prostate cancer from 2003–2010 who were treated with external beam radiation (minimum dose 7,560 cGy) were reviewed.
Patients were identified as having no psychiatric disorder (−Psy) or
having a psychiatric disorder (+Psy) consisting of a Diagnostic and
Statistical Manual of Mental Disorders (DSM)-IV diagnosis of
posttraumatic stress disorder, depression, schizophrenia, bipolar
disorder, or generalized anxiety disorder. Kaplan-Meier analysis
was used to analyze biochemical control, distant control, prostate
cancer–specific survival, and overall survival (OS). Multivariate
Cox regression was used to look for covariates associated with toxicity or biochemical control.
RESULTS: The charts of 469 patients were reviewed, and 100
patients (21.3%) were found to be +Psy. At a median follow-up of
73 months, there was no difference between the two groups regarding 6-year biochemical failure–free survival (79.8% −Psy vs 80.4%
+Psy; P = .50) or 6-year distant metastatic-free survival (96.4% −
Psy vs 98.0% +Psy; P = .36). There were also no differences regarding 6-year prostate cancer–specific survival (98.4% −Psy vs 99.0%
+Psy; P = .45) or 6-year OS (80.2% −Psy vs 82.2% +Psy; P = .35).
Likewise, short- and long-term genitourinary and gastrointestinal
toxicities were similar between the groups. On multivariate analyses, the presence of +Psy was not a significant predictor for toxicity
or biochemical recurrence.
CONCLUSIONS: This study did not find any significant differences
in treatment tolerance or any outcome endpoints between men
with and without psychiatric disorders undergoing definitive radiation treatment for prostate cancer. This finding suggests that early
diagnosis and reduced barriers to definitive treatment will alleviate
the decreased cancer-specific mortality in this patient population.
(P061) Anticoagulation Use and Improved Outcomes
in a Predominantly African-American Population With
High-Risk Prostate Cancer Elliot B. Navo, MD, Shan-Chin Chen, Justin Rineer, MD, David
Schreiber, MD; Department of Veterans Affairs, NY Harbor Healthcare
System, SUNY Downstate Medical Center; MD Anderson Cancer Center
Orlando
INTRODUCTION: Several studies have reported improved biochemical and prostate cancer–specific mortality (PSM) outcomes,
particularly for men with high-risk (HR) disease, associated with
the use of anticoagulation (AC), in addition to radiation therapy.
Numerous other studies have suggested that prostate cancer in
African-American (AA) men tends to be more aggressive than in
Caucasians and/or other races. Therefore, we analyzed our cohort
of predominantly AA men with HR disease to determine whether
anticoagulation use is associated with any improvements in biochemical or clinical outcomes.
MATERIALS AND METHODS: There were 469 consecutive men treated at the New York Harbor Veterans Hospital with dose-escalated
radiation therapy (minimum dose 7,560 cGy) for nonmetastatic
prostate cancer between 2003 and 2010. Of these patients, 143 had
HR disease and were included in this study. Men were categorized
by use of AC at the time of consultation and/or follow-up examinations. Chi-square or Fisher’s exact test was used to compare patient
characteristics. Kaplan-Meier curves were generated to compare
biochemical-free survival (bFS), distant metastasis–free survival
(DMFS), and PSM; outcomes were compared using the log-rank
test. Multivariate Cox regression was also performed to identify
covariates associated with increased risk for all clinical endpoints.
RESULTS: The median follow-up was 65 months. A total of 55.9%
of patients were identified as AA. There were no significant differences in patient characteristics between +AC and −AC. There was
significantly improved bFS for AC patients at 5 years (84.6% vs
65.1%; P = .048). The 5-year DMFS was 96.4% for +AC vs 92% for
−AC (P = .069). The 5-year PSM was 96.1% for +AC vs 95.9% for
−AC (P = .21). On multivariate analysis for biochemical control,
only use of AC was associated with improved bFS (hazard ratio
[HR] = 0.47; 95% confidence interval [CI], 0.23–0.95; P = .036). AA
race was not a significant predictor for biochemical failure (HR =
1.50; 95% CI, 0.50–4.50; P = .47). Similarly, in regard to multivariate analysis for distant metastases, AC was associated with
improved DMFS (HR = 0.24; 95% CI, 0.06–0.88; P = .03). However,
in regard to PSM, there was no benefit associated with the use of
AC (HR = 0.26; 95% CI, 0.05–1.32; P = .10).
CONCLUSIONS: In our population of predominantly minority men
with HR disease, the use of anticoagulation is associated with
improved bFS and DMFS on multivariate analysis. However, AA
race was not associated with any differences in outcome. (P062) Comparison of Stereotactic Body Radiotherapy
(SBRT) and Conventional External Beam Radiotherapy
(EBRT) in Renal Cell Carcinoma (RCC) Christopher L. Tinkle, MD, PhD, Stephen L. Shiao, MD, PhD,
Vivian K. Weinberg, PhD, Amy M. Lin, MD, Alexander R. Gottschalk,
MD, PhD; University of California, San Francisco; Cedars-Sinai Medical
Center
BACKGROUND: Renal cell carcinoma (RCC) is considered a radiation-resistant histology, often with poor response to conventionally fractionated external beam radiotherapy (EBRT). We compared outcomes for patients treated with EBRT vs stereotactic body
radiotherapy (SBRT) for RCC.
METHODS: From 2004 and 2012, a total of 89 patients were treated
with either EBRT or SBRT and retrospectively reviewed. Patients
with locally recurrent RCC, bone or soft tissue RCC metastases, or
primary RCC in a solitary kidney were included; 51 patients
received EBRT, while 38 patients received SBRT. The median biologically effective dose (BED), assuming an α/β ratio of 10, was 32.6
Gy10 for the EBRT group and 48.0 Gy10 for the SBRT group. Local
failure (LC) was defined pathologically or by imaging according to
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and
toxicity was reported according to Common Terminology Criteria
for Adverse Events version 4.0 (CTCAE v4.0) guidelines.
Univariable and multivariable analyses using Cox’s regression
model was performed to determine predictors of local control.
RESULTS: Median follow-up from radiotherapy was 9.8 months
(range: < 1–73 mo) with EBRT and 19.7 months (range: < 1–61
mo) with SBRT (P = .26). EBRT patients were younger (P = .02),
and more of them were M1 (P = .04); yet, other baseline features
did not differ significantly. Total RT dose, dose/fraction, and
BED10 were significantly higher in the SBRT group (P ≤ .002 for
each), while number of fractions was significantly lower (P < .001).
The 1-year LC estimate was 88% (95% confidence interval [CI],
72%–96%) with SBRT and 50% (95% CI, 32%–65%) with EBRT (P
53
= .001), with no significant difference in rate of distant recurrences
(P = .37). The 1-year progression-free survival (PFS) and overall
survival (OS) rates between the EBRT and SBRT groups were 17%
(95% CI, 8%–29%) vs 39% (95% CI, 24%–54%) (P = .06) and 39%
(95% CI, 25%–52%) vs 82% (95% CI, 65%–91%) (P = .002), respectively. The use of SBRT was the most important independent factor
that was significantly predictive of local control on multivariable
analysis (P = .001, log-likelihood ratio [LLR] test; hazard ratio [HR]
= 0.29; 95% CI, 0.13–0.61), while neither age nor metastasis at diagnosis was predictive. No grade 3/4 toxicity was observed in either
RT group. CONCLUSIONS: The data support that SBRT improves local control
over standard fractionation schemes. Higher dose per fraction,
with a BED in the range of 48 Gy10, is a safe and effective local
treatment modality for RCC.
(P063) Can Some High-Risk Prostate Cancer Patients Be
Treated With a Shorter Course of Androgen Deprivation
Therapy (ADT)? Seungtaek Choi, MD, Quynh-Nhu Nguyen, MD, Sean E. McGuire, MD,
PhD, Karen E. Hoffman, MD, MPH, Thomas J. Pugh, MD, Steven J.
Frank, MD, Usama Mahmood, MD, Deborah A. Kuban, MD, Andrew
K. Lee, MD, MPH; UT MD Anderson Cancer Center
PURPOSE: To determine the efficacy of a shorter course of androgen
deprivation therapy (ADT) in patients with high-risk prostate cancer.
MATERIALS AND METHODS: Charts of 472 high-risk prostate cancer (stage ≥ T3a, Gleason ≥ 8, or prostate-specific antigen [PSA] >
20.0 ng/mL) treated between 2000 and 2012 were reviewed. Eighty
patients who were treated with a shorter course of ADT (≤ 12 mo
of a gonadotropin-releasing hormone [GnRH] agonist) were analyzed for this study. All patients were treated with image-guided
radiation therapy with either intensity-modulated radiation therapy or proton therapy. The median total dose given was 76 Gy in
2-Gy fractions (range: 74–86.4 Gy in 1.8–2.0-Gy fractions). Patients
were followed with PSA measurements taken at 3–6-month intervals after the radiation therapy. Biochemical failure was defined as
nadir + 2 as per the Phoenix definition. Biochemical relapse–free
survival and prostate cancer–specific survival were calculated using
the Kaplan-Meier method.
RESULTS: Median age was 73 years (range: 52–89 yr). The ADT
duration was ≤ 6 months in 18 patients (22.5%) and 9–12 months
in 62 patients (77.5%). The distribution of T stage was as follows:
1 patient with TX (1.3%), 31 with T1c (38.8%), 23 with T2a
(27.5%), 10 with T2b (12.5%), 5 with T2c (6.2%), 6 with T3a
(7.5%), and 5 with T3b (6.2%). The distribution of Gleason scores
was as follows: 6 patients (7.5%) with Gleason 7 (3 + 4), 9 (11.2%)
with Gleason 7 (4 + 3), 53 (66.2%) with Gleason 8 (4 + 4), 11
(13.8%) with Gleason 9 (4 + 5), and 1 (1.3%) with Gleason 9 (5 +
4). Four patients had PSA < 4 ng/mL (5.0%), 48 patients had PSA
4.1–10 ng/mL (60.0%), 19 patients had PSA 10.1–20 ng/mL
(23.8%), and 9 patients had PSA > 20 ng/mL (11.2%). The majority of patients had disease at the lower end of the high-risk spectrum (stage ≤ T2 [85.0%], Gleason ≤ 8 [84.9%], and PSA ≤ 20 ng/
mL [88.8%]). Median follow-up was 38 months (range: 3–158
54
mo). Actuarial 4-year biochemical relapse–free survival was 91%.
There were four biochemical failures seen, with a median time to
failure of 33.5 months (range: 27–48 mo). There was no significant
correlation between T stage, Gleason score, PSA, or duration of
hormone ablation therapy and recurrence. Although there were 10
deaths in this patient population, none of the deaths was related to
prostate cancer.
CONCLUSIONS: This study suggests that certain patients with highrisk prostate cancer may be effectively treated with a shorter course
of hormone ablation therapy. Longer follow-up and more patients
will be needed to verify the efficacy of a shorter course of hormone
ablation therapy in this patient population.
(P064) Outcomes After Adjuvant Radiation Therapy for
Prostate Cancer at a Comprehensive Cancer Center Emma B. Holliday, Deborah A. Kuban, Lawrence Levy, Priya Master,
Seungtaek Choi, Steven J. Frank, Andrew K. Lee, Sean E. McGuire,
Usama Mahmood, Thomas J. Pugh, Karen E. Hoffman; UT MD Anderson Cancer Center
BACKGROUND: Randomized trials have shown that adjuvant radiation therapy (RT) improves prostate cancer control for men with
extracapsular extension (ECE), seminal vesicle (SV) involvement,
and/or positive surgical margins (SMs) at the time of prostatectomy. We report cancer control outcomes for men who received adjuvant RT at a comprehensive cancer center.
METHODS: Men who received adjuvant RT within 12 months of
prostatectomy from 1987 through 2010 were identified in an institutional database. All men had PSA < 0.2 ng/mL at the time of RT.
Failure was defined as a rising postradiation PSA of 0.2 ng/mL;
local, nodal, or distant recurrence; or the initiation of salvage treatment. Time to failure was calculated from the end of radiation
treatment. Cox proportional hazards models evaluated the association between patient characteristics, tumor characteristics, radiation treatment, and cancer control. Kaplan-Meier product-limit
estimator was used to estimate 5- and 10-year failure.
RESULTS: A total of 137 men received adjuvant RT. Median time
from prostatectomy was 5.1 months (interquartile range [IQR]:
1.4–6.4 mo). Most men had positive SM (n = 127, 92.7%) and ECE
(n = 98, 71.5%). A total of 38% had Gleason 8/9 disease (n = 52) at
prostatectomy. Median radiation dose was 60 Gy (IQR: 60–66 Gy).
Few men (n = 24, 17.5%) received concurrent hormone therapy
(HT) with RT. Patients were more likely to receive HT if their
prostatectomy was performed outside of the institution (P = .021)
or if they had involved SV (P < .001). With a median follow-up of
11.4 years (IQR: 5.6–17.5 yr), 22 men failed. The 5-year failure for
the entire cohort was 11.9%, and the 10-year failure was 16%.
Gleason score was the only factor significantly associated with failure. The 5- and 10-year failure rates for men with Gleason 8/9
disease were 18.4% and 20.8%, respectively, while the 5- and
10-year failure rates for men with Gleason < 8 disease were 6.7%
and 11.9%, respectively (P = .013). Radiation dose (< 66 Gy vs ≥
66 Gy), surgical margin status, and receiving HT were not associated with failure. American Radium Society Scientific Papers and Posters 2015
CONCLUSIONS: At a comprehensive cancer center, men who are
referred for adjuvant RT often have margin involvement and/or
ECE. Patients did well overall, with high 5- and 10-year freedom
from failure. Only Gleason 8/9 disease was associated with
increased failure after adjuvant RT. (P065) Lack of Variation in Pathologic Upgrading and
Upstaging by Race Among Patients With Low-Risk
Prostate Cancer Twisha Chakravarty, MD, Karen Hoffman, MD, Lawrence Levy, MS,
Tj Pugh, MD, Sean McGuire, MD, Seungtaek Choi, MD, Steven Frank,
MD, Andrew Lee, MD, Deborah Kuban, MD, Usama Mahmood,
MD; Department of Radiation Oncology, UT Medical Branch; Department of Radiation Oncology, UT MD Anderson Cancer Center
PURPOSE/OBJECTIVES: Previous studies have demonstrated that
the clinical presentation of prostate cancer varies according to race.
Nonetheless, it is unclear whether rates of pathologic upgrading
and/or upstaging vary according to race after accounting for factors
at clinical presentation. Such variation could potentially impact
management decisions.
MATERIALS AND METHODS: Using the Surveillance, Epidemiology,
and End Results (SEER) database, information was obtained for all
men diagnosed with low-risk or very-low-risk (per the National
Comprehensive Cancer Network [NCCN] definition) adenocarcinoma of the prostate who underwent prostatectomy in 2010 or
2011. Multivariable analyses were performed to determine predictors of pathologic upgrading (increase in total Gleason score) and
pathologic upstaging (presence of extraprostatic extension or
seminal vesicle invasion) at the time of prostatectomy. Both patient
demographic (age, race) and clinical factors (T stage, Gleason
score, prostate-specific antigen [PSA], number of positive cores,
and number of examined cores) were included in the analyses.
RESULTS: A total of 10,620 patients were identified, of whom 3,650
(34%) had very-low-risk disease. Median age for the entire cohort
was 60 years; 7,717 (73%) patients were white, 1,251 (12%) were
black, 1,023 (10%) were Hispanic, 441 (4%) were Asian, and 188
(2%) were Native American/unknown race. In total, 4,511 (42%)
patients had pathologic upgrading, and 992 (9%) had pathologic
upstaging at the time of prostatectomy. Among the entire cohort,
increasing age at diagnosis, increasing PSA, increasing number of
positive cores, and decreasing number of examined cores were all
significant predictors of the presence of both pathologic upgrading
and pathologic upstaging on multivariable analyses (all P < .001).
On the other hand, race was not found to be a significant predictor
of pathologic upgrading (P = .089) or pathologic upstaging (P =
.522). Similar findings were noted among patients with very-lowrisk disease, with race once again not found to be a significant predictor of pathologic upgrading (P = .068) or pathologic upstaging
(P = .410).
CONCLUSIONS: Our analysis of this large, population-based database demonstrates that after accounting for other demographics
and clinical factors at diagnosis, race does not predict for pathologic upgrading or pathologic upstaging at the time of prostatectomy among patients with low-risk prostate cancer. As such, race
by itself should not be used to select potential candidates for active
surveillance or treatment.
(P066) Dosimetric Analysis of Proton Therapy for
Prostate Cancer: A Single Institutional Experience Jing Zeng, Kent McCune, Matthias Cook, Grayden MacLennan,
Malin Mao, George E. Laramore, Kenneth Russell, Jay Liao; University
of Washington
BACKGROUND: With the increasing number of proton therapy centers in the United States, more patients with prostate cancer have
access to proton radiation as a treatment option. While dose constraints for organs at risk (OARs) are well defined for photon treatment, less is known for proton radiation, and photon constraints are
often used after correcting for relative biological effectiveness (RBE
= 1.1). However, it is often possible to achieve lower doses to OARs
with proton therapy. Therefore, we investigated dose to OARs in a
series of patients treated at our institution to consider lowering dose
constraints for the proton population.
METHODS: Consecutive patients with prostate cancer treated at our
center from April–September 2014 were analyzed. All patients were
treated with fiducial markers, daily kV image-guided radiation
therapy (IGRT), full bladder, and rectal balloon. Clinical characteristics and OAR doses were extracted. Low-risk patients were treated
to prostate plus 3–5-mm planning target volume (PTV) margin.
Intermediate- and high-risk patients were treated to prostate plus
proximal seminal vesicles, with optional pelvic nodal irradiation for
high-risk patients. Treatment groups were compared with t-tests.
RESULTS: A total of 40 patients with prostate cancer were treated,
with a median age of 68 years (range: 51–79 yr); 10 patients had
low-risk disease, 21 had intermediate-risk disease, and 9 had highrisk disease (5 received whole-pelvis radiation). A total of 31 patients
were treated with pencil beam scanning, and 9 patients were treated
with uniform scanning. Median prescription was 79.2 Cobalt Gray
Equivalent (CGE).
For the bladder: median V80 CGE = 4.9 cc (range: 0–13.8 cc) with
constraint < 8 cc; median V70 CGE = 6.6% (range: 3.6%–22.1%)
with constraint < 10%; and median V50 CGE = 11.5% (range: 6.1%–
32.8%) with constraint < 35%. For the bladder wall (3-mm internal
rind): median V80 CGE = 3.5% (range: 0%–14.5%) with constraint
< 15%; median V70 CGE = 13% (range: 8%–31%) with constraint <
35%, and median V55 CGE = 16.5% (range: 10.8%–36.5%) with
constraint < 50%.
For the rectum: median V81 CGE = 0 cc (range: 0–6.61cc) with
constraint < 1 cc; median V70 CGE = 10.8% (range: 3.0%–19.3%)
with constraint < 25%; and median V50 CGE = 19.6% (range:
10.9%–33.8%) with constraint < 35%. For the rectal wall (3–mm
internal rind): median V81 CGE = 0 cc (range: 0–5.36 cc) with constraint < 1 cc; median V70 CGE = 22.6% (range: 5.7%–34.3%) with
constraint < 25%; and median V50 CGE = 32.5% (range: 15.8%–
43%) with constraint < 50%.
Comparing the low-, intermediate-, and high-risk disease groups,
the only significant dose difference was in rectal wall V50 CGE (low
55
= 28.4%, intermediate = 32.1%, high = 35.0%).
CONCLUSIONS: Proton therapy for prostate cancer typically generates treatment plans that are below dose constraints defined in the
photon literature, with the exception of a small subset of patients. In
order to promote the best possible proton treatment plans, lower
dose constraints for OARs should be considered. (P067) The Role of Offline PET-CT Imaging in Evaluating
the Particle Beam Range and Beam Stop for Prostate
Cancer Treated With Heavy Ion Therapy Qing Zhang, Jingyi Cheng, Jiandong Zhao, Xiaomeng Zhang, Xin Cai,
Jin Meng, Shen Fu; Shanghai Proton and Heavy Ion Center; Fudan University Shanghai Cancer Center; Shanghai Jiao Tong University, Shanghai No. 6 People’s Hospital; Shanghai Proton and Heavy Ion Center/Fudan University Shanghai Cancer Center
PURPOSE: To evaluate the possibility of offline positron emission
tomography-computed tomography (PET-CT) in monitoring both
particle beam range and beam stop after carbon ion therapy.
MATERIALS AND METHODS: From June 2014 to September 2014, a
total of 19 patients with pathology-confirmed primary prostate
adenocarcinoma underwent carbon ion therapy in Shanghai
Proton and Heavy Ion Center. All patients received a PET-CT scan
shortly after carbon ion therapy. We divided these patients into two
groups; 3 of 19 patients were treated with a single lateral beam in
the first 4 days of carbon ion therapy, followed by a bilateral beam
from day (D) 5, and PET-CT images were collected on D1, D4,
D11, and the last day of the treatment. Another 16 patients were
treated with bilateral beam only, and PET-CT imaging was collected on D1, D4/5, and the last day of the treatment. After irradiation, patients were transferred immediately to the PET-CT room
nearby the irradiation center. A PET-CT scan was done on a
Siemens Biograph mCT 5–7 minutes after carbon ion therapy, with
no additional radioactive tracer injection. PET-CT images were
collected for approximately 30 minutes for each patient, while the
patient’s position during the PET-CT scan was the same as during
treatment using the same immobilization device. Finally, a total of
60 PET-CT images were investigated. PET-CT and planning CT
were further registered by matching the pelvic bones. An additional comparison with the expected β+ activity distribution was performed to identify either beam range or beam stop with accurate
anatomical coregistration.
RESULTS: Based on the different tissue densities, we found different
activation effects shown on PET imaging, such as skin, bone, fat,
and prostate. Compared with the diagnostic CT, the measured
activity with different anatomic structures was correlated, which
indicated an accurate beam range. For the three patients treated
with single-beam irradiation, the PET imaging also indicated the
beam stop well. Our data further showed that the PET-CT–defined
beam range covered the clinical target volume well, especially for
the isocenter, by matching the PET-CT imaging with treatment
planning.
CONCLUSION: Posttreatment offline PET-CT imaging has the
potential to evaluate the particle beam range and beam stop for
56
prostate cancer patients treated with heavy ion therapy, which
might overcome the pitfalls of simple bone structure fusions with
two-dimensional imaging, and provides another approach to monitor the treatment accuracy of prostate cancer treated with carbon
ion therapy. Further investigation needs to be performed.
(P068) VMAT vs Eight-Field IMRT: Dosimetric Comparison of Pelvic Radiotherapy for High-Risk Prostate
Cancer Patients in Terms of Bone Marrow Sparing Yasemin Bolukbasi, Vildan Alpan, Yucel Saglam, Ugur Selek; American
Hospital, MD Anderson Radiation Treatment Center, Istanbul
PURPOSE: Although there is no complete consensus on elective
pelvic nodal irradiation for high-risk prostate cancer patients, pelvic radiotherapy with androgen ablation have been more commonly used in many centers. An important part of bone marrow
(BM) reserve remains in the pelvic radiation treatment field. We
intend to evaluate and compare the intensity-modulated radiotherapy (step and shoot IMRT [ssIMRT]) and volumetric arc radiotherapy (VMAT) techniques for pelvic radiotherapy in terms of
pelvic bone marrow doses.
MATERIALS AND METHODS: This study was based on the simulation scan data of 10 prostate cancer patients as 3-mm slice thickness using a full bladder and rectal balloon. The first phase of the
treatment planning was prescribed to the pelvic lymphatics, prostate, and seminal vesicles (46 Gy, 2 Gy/fraction); then, the second
phase consisted of the seminal vesicles and prostate (32 Gy, 2 Gy/
fraction). Planning target volume (PTV) margin was 0.4 cm posteriorly due to the rectum and 0.6 cm in all other directions. Using
the same target volumes, ssIMRT with eight angles (225°, 260°,
295°, 330°, 30°, 65°, 100°, and 135°) and double-arc (182°–178° arc
angle) VMAT were planned for each patient dataset. The planning
objective was to cover the PTV by at least 95% of the prescribed
isodose and clinical target volume (CTV) by 98% of the prescribed
isodose line. No special dose constraint was given for bone marrow
sparing. Each technique was compared by using dose-volume histograms (DVHs) of V5, V10, V20, V30, and V40 of the sacrum BM,
iliac BM, ischium, pubis, proximal femora (lower pelvis), and femoral BM; V20, V30, V40, and V70 for the bladder; and V30, V40,
V76, and V80 for the rectum, homogeneity index ??and the monitor units (MU). Two-sided Wilcoxon’s test was used for statistical
analysis (P < .05).
RESULTS: For the same PTV coverage, VMAT and ssIMRT plans
had similar dose distributions for femur, iliac, sacrum, and total
BM, as well as the other critical structures. However, VMAT plans
in comparison with IMRT ensured significantly lower high-dose
volumes on the rectum, such as bringing V80 from 1.6% to 0.9% (P
= .01), and provided similar homogeneity index with lowered MUs
(1,048 vs 1,591; P = .018).
CONCLUSION: In this cohort, VMAT plans without a specific constraint for BM were not found to be superior to ssIMRT in terms of
BM reserve irradiation, while VMAT could be encouraged for
patients with higher rectum doses, such as V80.
(P069) Gleason 7 Prostate Adenocarcinoma Treated
With High- or Low-Dose-Rate Brachytherapy: Impact
of External Beam Radiotherapy and/or Androgen
Deprivation Therapy Julian Johnson, MD, Charles Hsu, I-Chow Hsu, MD, Vivian K.
Weinberg, PhD, Alexander Gottschalk, MD, PhD, Barby Pickett, MS,
Mack Roach; University of California, San Francisco; Texas Oncology
PURPOSE: To determine the impact of hormone therapy (HT) and/
or external beam radiotherapy (EBRT) on prostate-specific antigen
(PSA) nadir (nPSA) in patients with Gleason score (GS) 3 + 4 or 4
+ 3 prostate cancer treated with low-dose-rate (LDR) or high-doserate (HDR) brachytherapy (BT) at a single institution.
MATERIALS AND METHODS: A total of 148 men were retrospectively identified with GS 7 (21% GS4 + 3, 79% GS3 + 4) cT1–T2cN0
prostate cancer receiving LDR (76%) or HDR (24%) BT as a component of treatment. LDR or HDR monotherapy was administered
to 29% (EBRT was administered in 58%; HT was administered to
51%). Median follow-up from BT until last PSA or death was 72
months (range: 1–141 mo). nPSA was defined as current postimplant PSA nadir as of last visit. Disease failure was defined as PSA
failure, local recurrence, metastasis, or salvage therapy.
RESULTS: Median time to nPSA was 43.4 months vs 29.8 months
for patients treated with LDR vs HDR (P = .03). Patients treated
with HDR were more likely to have T2 disease (P = .01) and had
higher median baseline PSA (8.6 vs 6.2 ng/mL; P = .004). Patients
treated with HDR were more likely to receive HT (42% vs 69%; P =
.01) but not EBRT (54% vs 61%; P = .56). There was no statistically
significant difference between nPSA after LDR vs HDR (median:
0.1 vs 0.1 ng/mL; P = .27). Median nPSA after LDR for GS 3 + 4 vs
4 + 3 was 0.1 ng/mL and 0.05 ng/mL, respectively (P = .32). Median
nPSA after HDR for GS 3 + 4 vs GS 4 + 3 was 0.1 vs 0.06 ng/mL,
respectively (P = .62). Treatment with HT resulted in a median
nPSA of 0.045 vs 0.1 ng/mL (P < .0001). EBRT resulted in median
nPSA of 0.06 ng/mL vs 0.1 ng/mL (P = .05). Patients treated with
LDR brachytherapy had a lower nPSA if treated with HT (0.05 ng/
mL vs 0.1 ng/mL; P = .0002). HT did not result in a lower nPSA in
patients treated with HDR (P = .18). There was a statistically significant lower nPSA among LDR patients when combined with
EBRT vs no EBRT (0.05 ng/mL vs 0.1 ng/mL; P = .003) but not
among HDR patients (P = .52). Freedom from disease failure rate
at 5 years was 92% vs 94% for LDR vs HDR, respectively (P = .00).
There was no statistically significant difference with ADT (95% vs
89%; P = .33) or with EBRT (93% vs 91%; P = .37).
CONCLUSIONS: nPSA has been related to biochemical progression–free survival, freedom from metastasis, and death from prostate cancer. BT with either EBRT or HT achieves a lower PSA nadir.
There was no difference in disease failure. Longer follow-up may
be necessary to see differences in disease failure in this population.
(P070) High-Risk Prostate Adenocarcinoma Treated
With Whole-Pelvis Radiotherapy HDR Brachytherapy
Boost Results in Very High Disease-Specific Survival Julian Johnson, MD, Mack Roach, MD, Alexander Gottschalk, MD,
PhD, Adam Cunha, PhD, Zachary Seymour, David Raleigh, MD, PhD,
Katsuto Shinohara, MD, I-Chow Hsu, MD, Albert Chang, MD, PhD;
University of California, San Francisco
PURPOSE/OBJECTIVES: To report the long-term clinical outcomes
of patients with high-risk adenocarcinoma of the prostate treated
with pelvic radiotherapy followed by inverse planned, templatefree high-dose-rate (HDR) brachytherapy boost treated at a single
institution.
MATERIALS AND METHODS: A total of 115 patients with high-risk
prostate cancer (≥ cT3, Gleason score [GS] 8–10, or PSA ≥ 20 ng/
mL) treated between July 1997 and November 2005 were included
in this study. All patients underwent whole-pelvis external beam
radiotherapy to 45 Gy followed by HDR brachytherapy boost. HDR
brachytherapy boost consisted of 6 Gy × 3 (38 patients) or 9.5 Gy ×
2 (77 patients) to the prostate and seminal vesicles. A total of 47%,
48%, and 5% of patients received long-term (> 18 mo), short-term
(4–6 mo), or no androgen deprivation therapy, respectively.
RESULTS: The median age at diagnosis was 64.8 years; 50 (43%), 90
(78.2%), and 24 (20.8%) patients were diagnosed with GS 8–10,
cT3 disease, and PSA ≥ 20 ng/mL, respectively. Mean PSA was
14.94 ng/mL (range: 0.21–99.3 ng/mL). Further, 21 patients
(18.1%) had seminal vesicle invasion, and 42 patients (37%) had at
least two high-risk features. With a median follow-up time of 94
months, 5- and 10- year biochemical-free survival, as defined by
the Phoenix definition, was 90% and 73%, respectively. At 10 years,
four patients failed locally, as determined by biopsy, for a local control rate of 94%. The 5- and 10-year distant metastasis-free survival rates were 97% and 87%, respectively. The 5- and 10-year
disease-specific survival rates were 100% and 92.5%, respectively.
Six secondary malignancies (bladder carcinoma 1 year posttreatment, colon, lung, melanoma, and hepatocellular carcinoma)
developed. One patient developed grade 3 ureteral stricture that
caused hydronephrosis and required stent placement. There were
no other grade ≥ 3 genitourinary or gastrointestinal toxicities.
CONCLUSION: Pelvic radiotherapy followed by HDR brachytherapy boost is an effective treatment for high-risk prostate cancer. It
provides excellent long-term disease control and very low rates of
severe (grade ≥ 3) toxicity when delivered in two or three fractions.
(P071) Socioeconomic Disparities in Baseline Magnetic
Resonance Imaging (MRI) Utilization and Imaging
Characteristics for Prostate Cancer (PCa) Patients
Undergoing Radiotherapy Ayobami Ajayi, BA, Atu Agawu, BS, Neha Vapiwala, MD, Stefan Both,
PhD, Zelig Tochner, MD, Curtiland Deville, MD; Department of Radiation Oncology, Perelman School of Medicine
PURPOSE: To determine whether socioeconomic disparities exist
in magnetic resonance imaging (MRI) utilization and imaging
characteristics for prostate cancer (PCa) patients undergoing radiotherapy.
METHODS: An institutional database identified 598 nonmetastatic
PCa patients treated with proton and/or intensity-modulated
radiotherapy from 2005–2013 with pretreatment pelvic MRI
57
(T2-weighted, diffusion-weighted, and/or dynamic contrastenhanced sequences; 91% with endorectal coil). Dominant intraprostatic lesion (IPL) presence, size, extracapsular extension
(ECE), and seminal vesicle invasion (SVI) were reviewed. Patients
of higher socioeconomic status (SES) vs low SES (defined as geocoded census tract > 20% below the poverty level) overall and
stratified by risk group were compared using Fisher’s exact test for
categorical variables and Student’s t-test for continuous variables
(P < .05 significant).
RESULTS: In this cohort, 437 were classified as higher-SES (73%)
and 161 were classified as low-SES (27%). Mean age (67 ± 8 yr),
Gleason score, and clinical stage did not differ significantly for
higher-SES vs low-SES patients. Low-SES patients were more likely
to be black (71%) than higher-SES patients (16%) (P < .001). LowSES patients also had significantly higher prostate-specific antigen
(PSA) levels (higher-SES: 9.5 ± 21 ng/mL, low-SES: 15.6 ± 22 ng/
mL; P < .001) and were more likely to be high-risk (higher-SES:
22% vs low-SES: 34%; P = .006). Higher-SES patients had a greater
proportion of low-risk patients (38%) than did low-SES subjects
(25%; P = .005). Overall, 457 (76%) patients underwent baseline
MRI. Low-SES patients (69%) were less likely than higher-SES
patients (79%; P = .01) to undergo MRI. This disparity was greatest
for low-risk patients (higher-SES: 84%, low-SES: 56%; P < .001) and
not significant for intermediate-risk (77% vs 71%; P = .389) or
high-risk patients (77% vs 81%; P = .675). There were no significant
differences between SES groups in dominant IPL presence, diameter, area, ECE, or SVI—overall or within intermediate- and highrisk groups. Low-risk, low-SES patients demonstrated larger dominant IPL area (133.5 ± 141 mm2 vs 66.7 ± 58 mm2; P = .017), with
no differences in dominant IPL diameter or presence, additional
IPLs, ECE, or SVI.
CONCLUSIONS: In this urban, academic center cohort, PCa
patients of lower SES were significantly less likely to undergo
staging MRI, particularly in the low-risk group. No differences
were found in dominant IPL presence, area, ECE, or SVI, except in
the low-risk group. Further investigation is required to better
understand trends in pretreatment MRI utilization and dominant
IPL characteristics differing by SES.
(P072) Analysis of Composite EQD2 Dose
Distribution in Radiotherapy for Cervical Cancer
Using Central Shielding Technique Tomoaki Tamaki, MD, PhD, Shin-ei Noda, MD, PhD, Tatsuya Ohno,
MD, PhD, Shingo Kato, MD, PhD, Takashi Nakano, MD, PhD; Saitama
Medical University International Medical Center; Gunma University
Graduate School of Medicine
PURPOSE: To analyze the three-dimensional equivalent dose in
2-Gy fractions (EQD2) dose distribution of external beam radiotherapy (EBRT) plus intracavitary brachytherapy (ICBT) for cervical cancer using the central shielding technique.
MATERIALS AND METHODS: In a phantom study, a whole-pelvis
irradiation (WP) plan was created using the four-field box technique and pelvis irradiation with the central shielding technique
(CS) using AP-PA fields with a central block having a 3-cm or 4-cm
58
width. Three patterns of EBRT were created for WP and CS: 30
Gy/15 fractions plus 20 Gy/10 fractions (Plan 30+20); 40 Gy/20
fractions plus 10 Gy/5 fractions (Plan 40+10); and 45 Gy/25 fractions and 0 Gy (Plan 45+0). For ICBT, two plans were created using
Point-A prescription: 24 Gy/4 fractions (BTPlan 24/4) for Plan
30+20 and Plan 40+10, and 28 Gy/4 fractions (BTPlan 28/4) for
Plan 45+0. The physical doses were converted to EQD2, and the
composite EQD2 dose distributions were analyzed.
RESULTS: In Plan 30+20 plus BTPlan 24/4 and Plan 40+10 plus
BTPlan 24/4, the area covered with 60 Gy (EQD2) in the lateral
direction was larger than that in Plan 45+0 plus BTPlan 28/4. There
were no “cold” spots within the lateral axis, which indicates that
even with the use of CS, the treatment could provide adequate dose
coverage for the central tumor and the parametrial tissue. The
Point-A doses of Plan 30+20 plus BTPlan 24/4, Plan 40+10 plus
BTPlan 24/4, and Plan 45+0 plus BTPlan 28/4 were 78.0 Gy (CS: 3
cm) or 71.8 Gy (CS: 4 cm), 80.1 Gy (CS: 3 cm) or 77.0 Gy (CS: 4
cm), and 84.1 Gy, respectively. These values were higher than the
total Point-A doses reported in previous clinical studies, which
omitted the doses provided by CS. On the other hand, the coverage
in the anterior-posterior direction was smaller in Plan 30+20 plus
BTPlan 24/4 and Plan 40+10 plus BTPlan 24/4 as a result of CS,
indicating that the high dose to the bladder and the rectum can be
avoided, while the adequate tumor coverage in this direction needs
to be assessed carefully.
CONCLUSIONS: Three-dimensional composite dose distribution
analysis plays a significant role in the correct understanding of the
dose distribution of the combination of EBRT and ICBT for cervical cancer. The use of CS in radiotherapy for cervical cancer provided tumor doses higher than those referred by the Point-A dose
in previous reports, with no irregularly “cold” regions around the
central target.
(P073) Optimal Epidural Analgesia During Interstitial
Brachytherapy for Treatment of Gynecological Cancer Ashley K. Amsbaugh, MD, Mark J. Amsbaugh, MD, Moataz N. El
Ghamry, MD, Brian M. Derhake, MD, MS; Department of Anesthesiology, Department of Radiation Oncology, University of Louisville
PURPOSE: To determine optimal epidural analgesia for patients
receiving interstitial brachytherapy (ISBT) for gynecologic cancer.
MATERIALS AND METHODS: Records of all patients who underwent interstitial brachytherapy (ISBT) at our institution between
January 2009 and July 2014 were reviewed. ISBT was delivered over
the course of 2 to 3 days, and maximum pain scores (measured on
a scale from 1 to 10 points) were recorded every 8 hours. The primary analgesia method was epidural catheter. In addition to epidural anesthetic, patients received “as-needed” medications (intravenous narcotics, oral narcotics, and acetaminophen) from a standard order set. Antiemetics and diphenhydramine were available
for nausea and pruritus, respectively. Pain scores and administered
medications were collected, and all narcotic medications were converted to intravenous morphine equivalent (IVME). Statistical
analysis was performed with SAS (Statistical Analysis System) software (SAS Institute, Cary NC).
RESULTS: Epidural catheters were successfully placed in 71 of 73
patients. Twelve patients received ropivacaine alone, 14 patients
received ropivacaine with fentanyl, and 45 patients received ropivacaine with hydromorphone. Patients receiving ropivacaine alone
had higher pain scores than patients receiving ropivacaine with
fentanyl or ropivacaine with hydromorphone on the morning of
day 2 (4.2 vs 1.71 vs 0.6; P = .001), the afternoon of day 2 (4.9 vs
2.5 vs 1.7; P = .005), and the night of day 2 (2.4 vs 2.0 vs 0.6; P <
.001). Patients receiving narcotics in their epidural had lower pain
scores on the night of placement (P = .050), the morning of day 2
(P < .001), the afternoon of day 2 (P = .002), and the night of day
2 (P < .001). Patients receiving ropivacaine alone used more oral
narcotics than those receiving ropivacaine with fentanyl or ropivacaine with hydromorphone on day 3 (5.9 mg vs 3.8 mg vs 2.8 mg
IVME) and received more intravenous narcotics on day 1 (5.8 mg
vs 0.0 mg vs 0.7 mg IVME; P = .004) and day 2 (20.6 mg vs 4.8 mg
vs 1.0 mg IVME; P = .042). There were no differences in antiemetic use on days 1 (P = .146), 2 (P = .266), or 3 (P = .360). There
were no differences in diphenhydramine usage on days 1
(P = .829), 2 (P = .678), or 3 (P = .413). No epidural complications
occurred.
Obstetrics (FIGO) stage was I (n = 1), II (n = 2), and IV (n = 1); the
remaining three patients had vaginal cuff recurrence. All patients
were simulated and treated after insertion of a Foley urinary catheter with manual bladder filling to a predetermined volume.
Patients also underwent bowel preparation at the time of simulation and before each treatment fraction, and daily cone-beam
image-guided radiotherapy (IGRT) was utilized. The dose-volume
histograms for planning target volumes, as well as organs at risk,
were all analyzed.
CONCLUSIONS: Epidural analgesia provides safe and effective pain
control in patients undergoing ISBT. Epidural delivery of narcotics
with ropivacaine improves pain control and lowers oral and intravenous narcotic requirements without increased risk of adverse
effects.
CONCLUSION: SBRT boost appears to be an effective and welltolerated alternative treatment method for patients with gynecologic malignancies who cannot undergo brachytherapy. Target
coverage and dose to organs at risk with SBRT appear to be comparable with those of brachytherapy. Acute toxicity is minimal. These
initial clinical results substantiate the need for further evaluation of
this treatment approach and its long-term efficacy and safety.
(P074) The Use of Stereotactic Body Radiotherapy in
Lieu of Brachytherapy in Patients With Cervical or
Endometrial Cancer Nabila L. Waheed, DO, Michelle Ludwig, MD, PhD, Celestine Tung,
MD, Marian Williams-Brown, MD, Creighton L. Edwards, MD, Concepcion Diaz-Arrastia, MD, Matthew L. Anderson, MD, PhD, Lois Ramondetta, MD, Timothy Wagner, MD, Joshua Asper, PA, Danny Tran,
CMD, Umang Patel, MD, Mark Bonnen, MD; Department of Radiation Oncology, Department of Obstetrics and Gynecology, Baylor College
of Medicine; Department of Gynecologic Oncology, UT MD Anderson
Cancer Center
PURPOSE: To evaluate the use of stereotactic body radiation therapy (SBRT) as an alternative treatment method to brachytherapy in
patients with cervical or endometrial carcinoma with anatomically
difficult-to-implant tumor volumes or other contraindications to
brachytherapy.
MATERIALS AND METHODS: A total of seven patients undergoing
radiation therapy with curative intent for cervical or uterine cancer
were identified after they had been deemed ineligible for brachytherapy due to unfavorable anatomy, including large tumor size,
location, and/or prior hysterectomy. Patients diagnosed with either
cervical (n = 5) or endometrial (n = 2) cancer were treated using
45–48.6 Gy external beam radiation to the pelvis +/− para-aortic
lymph nodes. Either three-dimensional (3D) radiation or intensitymodulated radiotherapy (IMRT) was followed by Linac-based
SBRT to the cervix or vaginal cuff at a dose of 5–6 Gy in five daily
fractions to a total of 25–30 Gy. Median age was 52 years (range:
47–64 yr). The International Federation of Gynecology and
RESULTS: SBRT was well tolerated. No acute severe urinary or gastrointestinal toxicity > grade 2 was observed during treatment or
up to 5 months posttreatment. Target volume of 95% gross tumor
volume (GTV) coverage goal was > 95% (range: 95%–99%).
D0.2cc to the bladder was kept at or below 90 Gy (range: 87.3–90
Gy). Total bladder D0.2cc contribution from SBRT for all five
fractions was 20.5–40 Gy. D0.2cc to the rectum was kept at or below
75 Gy (range: 69–73.8 Gy). Total rectal D0.2cc contribution from
SBRT for all five fractions was 13.1–23.8 Gy. No patient has had any
sign of progression or local failure at follow-up thus far, with a
median follow-up of 3 months.
(P075) Management of Nodal Recurrences of
Endometrial Cancer With IMRT Jennifer Ho, Anuja Jhingran, MD, Shannon Westin, MD, Karen Lu, MD,
Patricia Eifel, Ann Klopp, MD, PhD; UT MD Anderson Cancer Center
PURPOSE: Pelvic and para-aortic lymph node regions are frequent
sites of relapse in women with endometrial cancer who have not
undergone adjuvant pelvic radiation. We investigated outcomes
following radiation therapy with intensity-modulated radiation
therapy (IMRT) for definitive treatment of nodal relapses of endometrial cancer at our institution.
MATERIALS AND METHODS: Between 2002 and 2012, a total of 42
patients with endometrial cancer who had no prior pelvic external
beam radiation were treated definitively using IMRT for pelvic
and/or para-aortic nodal recurrences. A total of 12 patients (29%)
had pelvic nodal recurrences only, 8 (19%) had para-aortic recurrences only, 10 (24%) had simultaneous pelvic and para-aortic
recurrences, and 12 (28%) had simultaneous pelvic and other
regionally confined recurrences. Also, 15 patients (35%) had chemotherapy before radiation, and 21 (50%) had concurrent chemotherapy with radiation. The median size of the largest nodal recurrence site was 2.9 cm (range: 1.3–9.1 cm). The nodal basins at risk
were typically treated to 45–50 Gy, with a boost to the gross tumor,
for a mean total dose of 64.8 Gy (range: 59–73 Gy). Survival rates
were calculated using the Kaplan-Meier method.
RESULTS: The median overall survival (OS) from date of recurARS PROCEEDINGS 2015
59
rence was 45.1 months (95% confidence interval [CI], 28.3–61.8
mo), and the 2-year survival was 71%. A total of 16 (38%) patients
developed local failures within the salvage radiation fields at a
median time of 7.2 months (range: 2.4–28.6 mo), of which 11 were
failures located within the high-dose regions. Further, 20 (48%)
patients developed distant recurrences at a median time of 6.8
months (range: 1.2–31.9 mo). Patients who received concurrent
chemotherapy had longer median survival than patients treated
without concurrent chemotherapy (61.9 mo vs 28.9 mo; P = .029).
Patients who received chemotherapy prior to radiation had shorter
median survival compared with those who did not (28.3 mo vs 61.9
mo; P = .001) and a lower rate of survival free of local recurrence
(28% vs 73% at 2 yr; P = .012). No significant survival difference
was detected in survival or local recurrence based on histology,
tumor size, or site of recurrence. A total of 11 patients (26%) experienced grade ≥ 3 gastrointestinal toxicity.
CONCLUSION: Long-term survival can be achieved following salvage radiation for nodal recurrence of endometrial cancer. However,
central and distant recurrences remain a challenge. Chemotherapy
prior to radiation was associated with an increased rate of central
recurrences and reduced survival, while the use of concurrent chemotherapy was associated with higher rates of survival.
(P076) Postoperative Treatment Recommendations for
Stage I Endometrial Cancer: A Survey of Society of
Gynecologic Oncology Members Brian S. De, BA, Elena Pereira, MD, Valentin Kolev, MD, Konstantin Zakashansky, MD, Peter R. Dottino, MD, Sheryl Green, MD,
Vishal Gupta, MD; Icahn School of Medicine at Mount Sinai
OBJECTIVES: To assess postoperative adjuvant therapy (AT) recommendations for International Federation of Gynecology and
Obstetrics (FIGO) stage I endometrioid endometrial cancer (EC)
among members of the Society of Gynecologic Oncology (SGO).
METHODS: A 19-question survey was developed, approved by our
institutional review board, and emailed to SGO members. Data
were collected anonymously using Internet-based survey software.
Demographic questions included specialty, years in practice, practice setting, and EC patient volume. Respondents were asked questions regarding preoperative workup, surgical approach, lymph
node dissection (LND), and AT based on various clinicopathologic scenarios. AT options included no further treatment or any
combination of brachytherapy (BT), external beam radiotherapy
(EBRT), and/or chemotherapy (CT). Here, we report the results of
AT recommendations. Statistical analysis was performed using
Statistical Package for the Social Sciences version 22.0 (SPSS v22.0).
RESULTS: Of the 1,399 SGO members, 320 (23%) completed the
survey: 97% of respondents were gynecologic oncologists or fellows, and 2% were radiation oncologists; 49% of respondents had
> 10 years of experience, 81% practiced at a university hospital or
a community hospital with an academic affiliation, and 87% treated > 30 EC patients yearly. As expected, AT was chosen more frequently with greater myometrial invasion, higher tumor grade
(G), and lymphovascular invasion (LVI). Respondents typically
did not select any AT for stage IA, G1–2 without LVI. For stage IA,
60
G3, +LVI disease, respondents chose BT only (55%), BT + CT
(16%), BT + EBRT (7%), EBRT only (5%), CT only (5%), or no
further therapy (8%); used alone or in combination, respondents
most frequently selected BT (82%), followed by CT (24%) and
EBRT (15%). For stage IB, G3, +LVI disease, respondents chose
BT only (29%), BT + CT (27%), EBRT only (13%), BT + EBRT
(10%), CT only (8%), BT + EBRT + CT (6%), EBRT + CT (5%), or
no further therapy (2%); used alone or in combination, respondents most frequently selected BT (73%), followed by CT (48%)
and EBRT (34%). A total of 70% of respondents considered age
when planning treatment. Older patients were recommended to
have AT, particularly BT, in earlier stages of disease, with similar
use of CT and EBRT.
CONCLUSIONS: BT is the most common AT modality recommended by SGO members in the postoperative management of
stage I EC. CT was recommended in a substantial number of scenarios and even exceeded the use of EBRT in G3 disease. Although
there was generally agreement about the management of low-risk
EC, there was much more variability in high-intermediate–risk
patients. Further studies are needed to compare these SGO members’ recommendations with those of radiation oncologists and to
determine optimal management.
(P077) Defining the Pendulum Swing From WholePelvic Radiation Therapy (WPRT) Alone to Vaginal
Brachytherapy (VB) in the Adjuvant Setting for
Endometrial Cancer: A SEER-Based Analysis From
Years 2000–2011 Sagar C. Patel, MD, Sudershan Bhatia, MD, PhD, William Rockey, MD,
PhD, Mindi Tennapel, BSMS, MBA, Wenqing Sun, MD, PhD; University
of Iowa Hospitals and Clinics
PURPOSE: To examine the change in the utilization trends of radiation therapy in the adjuvant setting for endometrial cancer in a
Surveillance, Epidemiology, and End Results (SEER) analysis from
2000–2011.
PATIENTS AND METHODS: We analyzed the change in utilization
of whole-pelvic radiation therapy (WPRT) alone, vaginal brachytherapy (VB) alone, and WPRT + VB in all patients with endometrial cancer in the adjuvant setting, stratified by age, race, marital
status, specific US registry, histology, and grade. In addition, a
subset analysis of endometrial cancer patients with localized-stage
uterine disease, endometrioid histology, and varying age and
grade was completed to model intermediate- and high-risk groups.
Percentage change (PC) and annual percentage change (APC) in
treatment utilization were calculated for each radiation therapy
modality. APC characterizes utilization trends over time and is
comparable across scales in SEER*Stat. Utilization rates were analyzed by using SEER*Stat with a log-linear regression model.
RESULTS: In the years 2000–2011, there was a 220.1% (PC) and
11.7% (APC) increase in the utilization of VB, while there was a
33.1% (PC) and 4.1% (APC) decrease in the utilization of WPRT
alone (P < .05). For each demographic and clinical variable, the
most pronounced increase in the utilization of VB over WPRT
alone was in individuals aged ≥ 70 years (248.4% [PC] and 12.2%
[APC]), in those of Asian race (584% [PC] and 13.4% [APC]), in
the SEER registry Louisiana (1,216.5% [PC] and 12.5% [APC]), in
grade 3 tumors (303.3% [PC] and 12.9% [APC]), and in those with
carcinosarcoma histology (1,251.5% [PC] and 32.3% [APC]). On
the contrary, the most pronounced decrease in the utilization of
WPRT alone was in individuals aged ≥ 70 years (41.4% [PC] and
5.2% [APC]), in those of white race (37.1% [PC] and 4.4% [APC]),
in the SEER registry Louisiana (60.1% [PC] and 7.0% [APC]), in
grade 2 tumors (52.2% [PC] and 6.8% [APC]), and in those with
carcinosarcoma histology (56.8% [PC] and 3.3% [APC]).
CONCLUSION: This SEER study demonstrates the pronounced
increase in the utilization of VB over WPRT alone in the adjuvant
setting for endometrial cancer. This observation may spark critical
evaluation of US practice patterns seen from 2000 to 2011 and
its potential impact on cost, new policies, and the patient’s quality
of life.
(P078) Radiation Therapy in the Management of
Carcinosarcoma of the Uterus Jillian R. Gunther, MD, PhD, Eva N. Christensen, MD, PhD, Pamela K.
Allen, PhD, Lois M. Ramondetta, MD, Anuja Jhingran, MD, Nicole D.
Fleming, MD, Elizabeth Euscher, MD, Karen H. Lu, Patricia J. Eifel, MD,
Ann H. Klopp, MD, PhD; UT MD Anderson Cancer Center; Radiation
Oncology Associates
PURPOSE: Uterine mixed Müllerian tumor (MMMT) is often
treated with multimodality therapy, including surgery, chemotherapy, vaginal cuff brachytherapy (VCB), and/or pelvic radiation.
However, the indications for pelvic and vaginal cuff radiation are
unclear. To investigate this, we reviewed our institutional experience with treatment of uterine MMMT.
METHODS: We performed a retrospective review of 155 women
with stage I–III uterine carcinosarcoma who underwent total
abdominal hysterectomy-bilateral salpingo-oophorectomy (TAHBSO) at our institution between 1990 and 2011. Overall survival
(OS), disease-specific survival (DSS), and pelvic relapse–free survival (PRFS) were calculated using the Kaplan-Meier method, with
differences assessed using a log-rank test. Multivariate Cox proportional hazards regression analyses were performed to evaluate the
influence of different factors on DSS and PRFS.
RESULTS: The study included patients with stage I (n = 98), II (n =
11), and III (n = 46) uterine MMMT. Median follow-up was 51
months (range: 2–278 mo). A total of 70 patients (45%) received
chemotherapy (21 concurrent, 58 adjuvant, 9 both). Also, 108
patients (70%) received radiation therapy (RT); 35% of these
patients received pelvic radiation, and 65% received pelvic radiation with or without additional brachytherapy. The 5-year OS for
all patients was 48.6% (stage I, 53.8%; II, 30.0%; and III, 42.5%).
The 5-year DSS was 57.17% (stage I, 60.88%; II, 44.44%; and III,
51.82%). The first site of recurrence was in the pelvis and/or paraaortic (PA) lymph nodes for 28 patients (44%), abdomen ± pelvis
for 13 patients (21%), and distant for 22 patients (35%). On univariate analysis, lower rates of DSS were seen in patients aged ≥ 65
years (P = .001) and with hypertension (P = .03), higher tumor
grade (P = .02), cervical involvement (P = .001), and lymphovascu
lar space invasion (LVSI) (P = .004). On multivariate analysis, age
≥ 65 years (P = .001), cervical involvement (P = .03), and LVSI (P =
.01) remained independently associated with lower DSS.
PRFS was higher in patients receiving pelvic radiation as compared
with VCB or no radiation (88.3% at 5 yr for pelvic radiation vs
67.4% for VCB and 71.2% for no RT; P = .04). Among patients who
did not receive pelvic radiation, cervical involvement (hazard ratio
[HR] = 3.2; P = .03) and heterologous elements (HR = 2.9; P = .04)
were associated with pelvic relapse. In stage III patients, pelvic
radiation was associated with higher rates of 5-year PRFS (90.0% vs
55.5%; P = .046), DSS (64.6% vs 46.4%; P = .13) and OS (64.6% vs
34.0%; P = .04). CONCLUSIONS: Pelvic radiation reduces the risk of pelvic relapse in
patients with MMMT and may be indicated with patients at high
risk for pelvic recurrence, including patients with cervical involvement, heterologous elements, and stage III disease.
(P079) Retrospective Review of Chemoradiation
in the Preoperative or Definitive Management of
Locally Advanced Vulvar Cancer
Melissa Joyner, MD, Gwyn Richardson, MD, Lyuba Levine, Sandra
Hatch; UT Medical Branch, Galveston
OBJECTIVES: To review historical use of preoperative chemoradiotherapy at a single institution in patients with locally advanced vulvar cancer who were not surgical candidates due to extent of disease. Patients were treated with intent to improve local control with
organ preservation.
METHODS: Historical chart review of 12 patients with an average
age of 52 years (range: 40–72 yr) treated between 1997 and 2014, all
with locally advanced clinical stage T3 or T4 squamous cell carcinomas of the vulva not amenable to surgical resection. A total of 2
of 12 patients presented with locally advanced recurrent disease
and nodal relapse. All patients were treated with external beam to
4,760 cGy (1.7 Gy per fraction × 28 fractions) using an accelerated
fractionation schema consistent with the Gynecologic Oncology
Group (GOG) 101 protocol with a planned treatment break in conjunction with concurrent cisplatin and 5-fluorouracil (5-FU). A
single patient treated with a modified fractionation schema after
the first cycle of radiation demonstrated superior treatment
response, which facilitated surgical resection; this patient was then
followed with additional radiation to treat residual microscopic
disease. Further, 7 out of 12 patients (58.3%) also received a boost
ranging from 7.2 Gy to 17.2 Gy, with a single patient receiving 12
Gy standard deviation [SD] via vaginal cylinder.
RESULTS: The study patients had an average of 75 months of follow-up. Sustained local control was achieved in 8 of 12 patients
(66.7%). A complete clinical response (cCR) was seen in 100% of
patients following treatment. Despite extensive disease at presentation, only 2 of 12 patients (16.7%) failed in the vulva. A significant
number of patients remained disease-free with no evidence of distant metastases (58%)—5 of 12 patients were alive without any disease, and an additional 2 of 12 expired without evidence of disease.
While 2 out of 12 patients exhibited evidence of active disease, they
61
are alive and undergoing additional therapy. Only 2 of 12 patients
to date have expired with evidence of disease, and 1 patient expired
with disease status unknown. Biopsies only were done of the primary and/or node in 4 of 12 patients (33%), which were negative
for disease. Organ preservation was achieved in 100% of patients.
CONCLUSIONS: This treatment schema provided excellent tolerance with sustained local control. All patients obtained cCR and
were able to avoid pelvic exenteration surgery and maintain preservation of bladder and rectal function.
(P080) Favorable Outcomes Using Radiation Therapy
After Chemotherapy in the Management of Primary,
Recurrent, and Metastatic Ovarian Cancer Carolina E. Fasola, MD, MPH, Daniel S. Kapp, MD, Elizabeth Kidd,
MD; Department of Radiation Oncology, Stanford University School of
Medicine
PURPOSE: This study aimed to evaluate treatment outcomes and
toxicity of radiation therapy (RT) in patients with primary, recurrent, or metastatic ovarian cancer following treatment with chemotherapy.
MATERIALS AND METHODS: We reviewed the medical records of
133 patients with stage I–IV ovarian cancer treated at our institution between 1997 and 2014. Patients underwent the following
treatment regimens after initial tumor debulking surgery and chemotherapy: whole-abdominopelvic RT (n = 15), RT at the time of
localized recurrence (n = 57), or palliative RT in the metastatic
setting (n = 61). Freedom from progression (FFP) and overall survival (OS) were estimated using Kaplan-Meier analysis.
RESULTS: The median follow-up time among all patients was 15.6
months (range: 1–200 mo) and 22.5 months among patients treated
with curative intent for primary or recurrent disease. For patients
treated with curative intent, the majority had International
Federation of Gynecology and Obstetrics (FIGO) stage III disease
at initial presentation (65%) with papillary serous histology (47%).
A total of 55 (76%) patients had platinum-sensitive disease, and 17
(24%) were considered platinum-resistant. The median prescription RT dose in this cohort of patients was 45.9 Gy (range: 30–57.6
Gy) delivered using three-dimensional (3D) conformal RT (n = 60)
or intensity-modulated radiotherapy (IMRT)/ stereotactic body
radiotherapy (SBRT) (n = 12). The 2-year FFP and OS rates among
this cohort were 84.4% and 63.6%, respectively. The 2-year OS rates
for platinum-sensitive disease vs platinum-resistant disease were
65.2% and 35.7%, respectively (P = .02). Predictors of decreased
FFP included a diagnosis of primary peritoneal carcinoma (P = .02)
and time to RT < 12 months (P = .03). RT was well tolerated, with
the majority of patients reporting no acute effects (56%) or developing mild symptoms, such as grade 1 gastrointestinal or urinary
toxicity (19%). Late toxicity consisting of small bowel obstruction
occurred in seven patients with other risk factors, including previous surgical resections; five (71%) of these patients had received
whole-abdominopelvic radiation. For patients with metastatic
ovarian cancer treated with palliative intent, the median dose of RT
was 30 Gy (range: 10–50.4 Gy), delivered using 3D conformal RT
(n = 44) and IMRT/stereotactic radiosurgery (SRS) (n = 17).
62
Symptom palliation was achieved in 96% of cases. Reports of toxicity were low for this cohort of patients, with no grade ≥ 3 toxicity.
The 2-year OS for patients treated with palliative intent was 53.8%.
CONCLUSIONS: The use of RT for primary or recurrent ovarian
cancer is well tolerated, with durable rates of FFP. RT with palliative
intent achieved high rates of symptom palliation without much
additional toxicity. RT should be considered for patients with
advanced ovarian cancer.
(P081) SBRT Boost as a Substitute for Brachytherapy in
the Definitive Treatment of Gynecologic Malignancies
With Radiotherapy Neilayan Sen, MD, Jessica Zhou, MD, Ryan Jozwiak, Yixiang Liao, PhD,
Krystyna Kiel, MD; Rush University Medical Center
PURPOSE: Delivery of high doses of radiation within a prescribed
period of time is associated with local control when treating primary or recurrent gynecologic cancers. Occasionally, patients can
not undergo a brachytherapy boost. We report our experience with
alternative stereotactic body radiation treatment (SBRT) boost.
MATERIALS AND METHODS: From 2012 to 2014, a total of 8
patients with locally advanced squamous cell carcinoma of the cervix (2 patients) and recurrent endometrial cancer in the vaginal
cuff (6 patients) received an SBRT boost after pelvic external beam
(EB) radiotherapy (range: 45–50 Gy). One patient received SBRT
after EB and 2 high-dose-rate (HDR) brachytherapy fractions.
Patients either refused brachytherapy or were high-risk (by medical
comorbidities) for brachytherapy. Patients were immobilized using
a CIVCO body frame (CIVCO Medical Solutions, Coralville, IA)
with abdominal compression. Vaginal and fiducial markers were
used to localize tumor at simulation and treatment. Doses typically
used for brachytherapy were prescribed to D90 of the planning
target volume (PTV) (0–5-mm expansion on clinical target volume
[CTV] excluding the rectum when not involved by the tumor).
Dose was limited by organ-at-risk tolerances. The Eclipse planning
system (Varian, Palo Alto, CA) was used to generate RapidArc
plans with 6-MV photons. Treatment was delivered using a True
Beam STx linear accelerator (Varian, Palo Alto, CA). Daily conebeam computed tomographies (CTs) were performed using the
rectum, bladder, visible tumor, and markers for image guidance,
and ExacTrac (BrainLab, Germany) was used to ensure precision of
delivery. Tumor status and toxicities were recorded at regular follow-up intervals; toxicity was graded according to Common
Terminology Criteria for Adverse Events version 4.0 (CTCAE
v4.0).
RESULTS: Dose/fractionation schemes were 7 Gy × 2 for one patient
(after two HDR brachytherapy fractions), 6 Gy × 5 for six patients,
and 5.8 Gy × 5 for one patient. Cumulative equalized total dose in
2 Gy/fraction (EQD2Gy) to D90 of the target volume ranged from
74.6 Gy to 84.3 Gy (mean 81.3 Gy). Mean D2cc rectum and bladder
doses were 66.3 Gy (range: 59.4–75.8 Gy) and 77.3 Gy (range: 69.6–
83.6 Gy), respectively. Mean overlap between the rectum as contoured on daily cone-beam CTs and the PTV was 0.29 cc (range:
0.00–1.42 cc). There were no local recurrences at a mean follow-up
of 14.5 months. One patient developed distant metastases at 7
months. One patient developed grade 3 vaginal fibrosis. No grade
4 toxicities were observed.
CONCLUSIONS: With respect to local control and toxicity, SBRT
may be a reasonable method of boosting patients who cannot safely undergo brachytherapy boosts for locally advanced gynecologic
malignancies.
(P082) Outcomes of Definitive Radiotherapy for T2N0
Squamous Cell Carcinoma of the Glottis: A SingleInstitution Retrospective Study
Bassem Y. Youssef, MD, Abdallah S. Mohamed, MD, MSc, Blaine
D. Smith, G. Brandon Gunn, MD, Jack Phan, MD, PhD, William H.
Morrison, MD, Adam S. Garden, MD, David I. Rosenthal, MD, Clifton
D. Fuller, MD, PhD; UT MD Anderson Cancer Center
BACKGROUND: The aim of this study is to report the oncologic and
functional outcomes of patients with T2N0M0 squamous cell carcinoma (SCC) of the glottis treated with radiation therapy (RT).
METHODS: Sequential patients treated with definitive RT for T2
glottic SCC at our facility between 2000 and 2013 were retrospectively reviewed under an approved institutional review board (IRB)
protocol. Demographics, disease stage, and treatment characteristics were extracted. Local control and survival outcomes at 2 and 5
years of follow-up were calculated. Both univariate analysis and
multivariate Cox proportional hazards assessment were performed
to investigate the correlation of patient- and treatment-related factors with disease control and survival endpoints.
RESULTS: A total of 68 patients were included in the analysis. The
median follow-up was 55 months (range: 5–173 mo); 58 (85%) of
the patients were male, and the median age was 63 years (range:
18–88 yr). Of the 68 patients, 20 (29%) were treated using intensitymodulated radiotherapy (IMRT), and the remainder was treated
using conventional three-dimensional conformal radiotherapy
(3DCRT). Further, 18 patients (26%) were treated using altered
fractions schemes, while the rest were treated conventionally. The
local control (LC) and locoregional control (LRC) rates at 2 and 5
years were 89% and 84%, and 87% and 82%, respectively. The rate
of ultimate LRC was 100%, with no single second recurrence after
successful surgical salvage. The disease-specific survival (DSS) was
95% at both 2 and 5 years, with a corresponding OS of 92% and
88%, respectively. In both univariate and multivariate analyses,
none of the examined variables (age, pathologic grade, radiation
technique, fractionation scheme, total dose, and chemotherapy)
was associated with local recurrence or mortality, except for older
age, which was associated with worse OS only in the univariate
analysis (P < .0001).Regarding functional outcome, only one
patient was feeding tube–dependent at the 1 year follow-up due to
persistence of grade 3 dysphagia; 60% of patients had no hoarseness
of voice at the last follow-up assessment.
CONCLUSIONS: Excellent 5-year oncologic and functional outcomes were achieved for patients presented in the study. The use of
altered fractionation, concurrent chemotherapy, and different
radiation techniques did not show any significant differences in
outcomes. However, the reduced radiation dose delivered to the
carotid arteries using IMRT suggests that it is potentially advantageous for reduction of long-term vascular toxicity and is therefore
recommended as the treatment of choice. (P083) Concurrent Chemotherapy + IMRT in Locally
Advanced Squamous Cell Carcinoma of Head and Neck:
What Is the Appropriate Chemotherapy? Jeanann L. Suggs, MD, PhD, Shankar P. Giri, MD, Madhava
Kanakamedala, MD; University of Mississippi Medical Center
PURPOSE: To evaluate patterns of failure and survival among
patients with locally advanced squamous cell carcinoma of the
head and neck treated definitively with cetuximab, low-dose cisplatin, or high-dose cisplatin together with intensity-modulated
radiation therapy (IMRT).
MATERIALS AND METHODS: A total of 158 patients treated between
2005 and 2010 were reviewed retrospectively. All had biopsy-proven squamous cell carcinoma of the head and neck and were treated
with IMRT with concurrent chemotherapy. Low-dose weekly cisplatin, high-dose cisplatin every 3 weeks, or weekly cetuximab was
utilized for each patient. Local treatment failure, distant failure, and
median survival were analyzed using Fisher’s exact test.
RESULTS: Among 158 evaluated patients, 66 (41.8%) were treated
with cetuximab, 57 (36.1%) were treated with low-dose cisplatin,
and 32 (20.3%) were treated with high-dose cisplatin.
Median age at diagnosis was 53.5 years. Primary tumor locations
included the oropharynx (32%), larynx (32%), oral cavity (8%),
paranasal spine (5%), hypopharynx (4%), nasopharynx (4%), and
other (32%). Median radiation dose was 70 Gy (range: 60–70 Gy).
Locoregional failure was not statistically different between the
cetuximab, low-dose cisplatin, and high-dose cisplatin groups
(15.15%, 7.01%, and 12.5%, respectively; P = .377).
Distant failure was not statistically different between the cetuximab, low-dose cisplatin, and high-dose cisplatin groups (10.6%,
17.54%, and 15.63%, respectively; P = .525).
Median survival for cetuximab, low-dose cisplatin, and high-dose
cisplatin was 18 months, 19 months, and 22 months, respectively
(P = .384).
CONCLUSIONS: Cetuximab may be considered as an alternative to
cisplatin with concurrent RT, particularly for patients with locally
advanced head and neck squamous cell carcinoma who are not
candidates for platinum therapy. These results indicate no difference in patterns of local or distant failure between cetuximab, lowdose weekly cisplatin, or q3 weekly high-dose cisplatin in this
patient population.
(P084) Long-Term Functional and Oncologic Outcomes
of Esthesioneuroblastoma David Zaenger, MD, Bryan M. Rabatic, PhD, MD, Joseph M. Kaminski,
MD, Waleed F. Mourad, MD, PhD; Georgia Regents University
63
PURPOSE: We report our multimodality functional and oncologic
outcomes in the management of esthesioneuroblastoma (ENB).
MATERIALS: This is a single-institution retrospective study of 22
patients treated between 1998 and 2014 for ENB. The median age
was 47 years (range: 29–68 yr); 13 patients (59%) were male. The
percentages of patients in Kadish stages A, B, and C were 45%, 32%,
and 23%, respectively. Two patients (9%) received definitive induction chemotherapy, followed by chemoradiation therapy (CRT) (70
Gy), and 20 patients (91%) received postoperative RT (PORT) to a
median dose of 59.4 Gy (range: 54–63 Gy). Intensity-modulated
radiation therapy (IMRT) was utilized in 64% of the whole cohort.
PORT fields included the preoperative tumor bed and elective
bilateral upper neck lymph node (LN) levels IB and II.
RESULTS: The median follow-up for the whole cohort was 40
months (range: 12–150 mo). The actuarial 4-year disease-free survival (DFS) was 68%. The 4-year actuarial overall survival (OS) was
86%. The 4-year actuarial locoregional control (LRC) was 68%, and
distant control (DC) was 95%. Of the seven failures, two developed
infield local failure and underwent successful salvage surgery and
SRS boost, three patients failed locoregionally (primary site and
neck), one failed regionally (neck alone), and one developed simultaneous local and distant failure. Recurrences manifested as late as
112 months. No adverse events related to vision were reported. A
total of 10% developed short-term grade 3 dysphagia, without
long-term percutaneous endoscopic gastrostomy (PEG) tube
dependency.
CONCLUSIONS: ENB is a rare malignancy, with optimal management remaining uncertain. Our experience suggests that aggressive
management seems successful in providing sustained LRC with
acceptable long-term toxicity. The role of elective nodal irradiation
to the upper neck remains unclear.
(P085) Oncologic and Functional Outcomes of
Salivary Gland Tumors (SGTs) With Pathologically
Proven Perineural Invasion (PNI) 13% of cases were parotid, minor salivary, and submandibular
gland primaries, respectively. Pathologically adenoid cystic carcinoma and adenocarcinoma were the most common histologies
(39% and 24%, respectively).
RESULTS: The median age was 53 years (range: 20–78 yr). Males
and Caucasians made up 50% and 50% of the population, respectively. With a median follow-up of 5 years (range: 1–10 yr), the
5-year actuarial disease-free survival (DFS), locoregional control
(LRC), and distant control (DC) rates were 85%, 94%, and 91%,
respectively. The median time to LR failure (LRF) and distant
metastases (DMs) was 8 months (range: 6–16 mo) and 30 months
(range: 18–60 mo), respectively. Late RT toxicity was grade ≤ 2
xerostomia (20%), altered taste (15%), trismus (6%), dysphagia
(4%), and neck stiffness (2%).
CONCLUSIONS: A multimodality approach to SGTs with PNI
provides excellent LRC. Further studies are warranted to identify the patients at higher risk of LRF and DMs to optimize their
management.
(P086) Proton vs Photon/Electron-Based Therapy in
the Treatment of Pediatric Salivary Gland Tumors:
A Comparison of Dosimetric Data and Acute Toxicities Stephen R. Grant, BS, David R. Grosshans, MD, PhD, Anita Mahajan,
MD; Baylor College of Medicine; Department of Radiation Oncology,
UT MD Anderson Cancer
PURPOSE: Adjuvant radiotherapy (RT) is frequently indicated for
high-risk salivary gland tumors. For pediatric patients, minimizing
radiation to surrounding normal tissues is of particular importance. We retrospectively compared clinical outcomes and toxicity
profiles for pediatric patients with parotid and submandibular
tumors treated with either adjuvant proton- or photon/electronbased RT.
PURPOSE: To report the clinical outcomes and patterns of failure
of salivary gland tumors (SGTs) with perineural invasion (PNI)
status postmultimodality approach (ie, surgery, postoperative radiation therapy [RT], and chemotherapy).
MATERIALS AND METHODS: We retrospectively identified all
patients aged ≤ 18 years treated with radiation for salivary gland
tumors between 1996 and 2014 at our institution. Demographic,
disease-control, and survival data were recorded, and dosimetric
data were compiled. Toxicities were scored according to National
Cancer Institute (NCI) Common Terminology Criteria for Adverse
Events version 4.0 (CTCAE 4.0) criteria. Statistical analyses were
performed using GraphPad Prism, with two-sided t-tests determined to be significant when P < .05.
MATERIALS: This is a single-institution retrospective study that
was fully approved by our institutional review board (IRB). From
March 1997–2010, a total of 62 patients with SGTs underwent the
multimodality approach due to the presence of PNI ± other highrisk features (recurrent tumor, R1 or R2 resection, positive margins, multiple positive lymph nodes, and extracapsular extension).
Intensity-modulated RT (IMRT) was utilized in 50% of the
patients. RT fields included the tumor bed, ipsilateral neck, and
occasionally the contralateral neck. The most common pathologically involved nerves (facial, V2, and V3) were included in the RT
fields to the skull base. The median RT dose delivered was 63 Gy
(range: 50–70 Gy at 1.8–2 Gy/fraction). A total of 53%, 34%, and
RESULTS: A total of 24 pediatric patients treated with adjuvant RT
were identified (20 parotid, 4 submandibular). Histologies included mucoepidermoid carcinoma (12), adenoid cystic carcinoma
(5), adenocarcinoma (2), acinic cell carcinoma (2), myoepithelioma (1), undifferentiated carcinoma (1), and pleomorphic adenoma (1). A total of 13 patients received proton therapy, and 11
received photon/electron-based therapy. The mean prescribed
dose was 60 Gy in each cohort (range: 54–66 Gy). No acute grade
3 dermatitis or mucositis was seen in the proton cohort vs 27% and
18% in the photon/electron cohort, respectively. Significantly
greater weight loss was reported in those receiving photon/electron radiotherapy (median 5.2% vs 0%), with one patient requiring
Bryan M. Rabatic, PhD, MD, David Zaenger, MD, Joseph M. Kaminski,
MD, Waleed F. Mourad, MD, PhD; Georgia Regents University
64
placement of a feeding tube (compared with none in the proton
cohort). With a mean follow-up of 49 months (range: 2 mo–18 yr),
no disease recurrence or deaths were observed in either cohort.
Compared with photon/electron-based therapy, proton therapy
was associated with significantly lower mean doses to the spinal
cord (0.2 Gy vs 19 Gy), pituitary gland (0.0 Gy vs 5.7 Gy), optic
nerves (0.0 Gy vs 3 Gy), oral cavity (4.6 Gy vs 19 Gy), thyroid
gland (1.5 Gy vs 24 Gy), larynx (11 Gy vs 39 Gy), and contralateral structures, including the eye (0.0 Gy vs 1.4 Gy), mandible (0.0
Gy vs 7.7 Gy), and parotid (0.0 Gy vs 5.2 Gy) and submandibular
glands (0.0 Gy vs 8.1 Gy) (all P < .05).
to G1. There were no other G3 events. G0, 1, 2, and 3 dysphagia
rates were 87%, 4%, 9%, and 0% at baseline and 48%, 26%, 26%,
and 0% at the end of RT, respectively. Among patients without G2
dysphagia at baseline, there was no difference between the rates of
G0/1 and G2+ dysphagia at the end of RT compared with baseline
(P = .104). Similar results were noted for xerostomia, dysgeusia,
and weight loss. G2 mucositis occurred in 35% of patients—a significant change from baseline (P = .046)—but 43% of patients had
no mucositis upon completing RT. The median weight at the end
of RT was 97.4% of baseline. Only six patients (23%) lost > 5% of
their baseline weight, and one patient (4%) lost > 10%.
CONCLUSION: This report of adjuvant RT for pediatric salivary
gland tumors is one of the largest to date and the only one to document outcomes following proton therapy. Compared with conventional photon/electron-based therapy, proton therapy significantly
reduced doses to multiple normal tissues. Moreover, clinically, no
grade 3 toxicities were observed in the proton group vs 45% in the
photon/electron cohort. Continued follow-up is required to determine long-term outcomes. CONCLUSIONS: Proton therapy for parotid cancers results in very
low rates of GI toxicity. Nutritional status and weight were preserved throughout therapy. These results should be validated with
patient-reported outcomes. (P087) Proton Therapy Results in Low Rates of
Acute GI Toxicity for Parotid Cancers Roi Dagan, MD, MS, Curtis Bryant, MD, MPH, Christopher G. Morris,
MS, Daniel J. Indelicato, Julie A. Bradley, MD, William M. Mendenhall,
MD; University of Florida
BACKGROUND: Acute gastrointestinal (GI) toxicity from headand-neck radiotherapy (RT) results in decreased quality of life.
Increasingly, conformal RT has improved toxicity outcomes. The
target for parotid tumors is ideal for proton therapy, because distal
to the Bragg peak, there is no exit of radiation to the oral cavity,
swallowing musculature, or contralateral major salivary glands.
PURPOSE: To evaluate acute GI toxicity from proton therapy for
parotid cancers.
METHODS: A total of 23 patients were treated with primary (n =7)
or adjuvant (n = 16) proton therapy for cancers of the parotid
region, including salivary gland carcinoma (n = 16), skin carcinoma with perineural invasion (n = 5), and Ewing sarcoma (n =
1). The most common indication for proton therapy was skull base
invasion. Double-scattered conformal proton therapy, typically
involving three fields, was delivered to a median dose of 70 Gy
(relative biological effectiveness [RBE]) (range: 55,8–74.4
Gy[RBE]) using various fractionations (range: 1.8–2 Gy[RBE])
once daily, 5 fractions/week (n = 15); 1.2 Gy(RBE) twice daily, 10
fractions/week (n = 7); and 2 Gy(RBE) once daily, 6 fractions/week
(n = 1). Seven patients received concurrent chemotherapy. Acute
toxicities were prospectively evaluated weekly during radiotherapy
using Common Terminology Criteria for Adverse Events version
3 (CTCAE v3).
RESULTS: Grade (G) 3 dysphagia occurred during 1 week of therapy in one patient with baseline G2 dysphagia before RT after
undergoing parotidectomy, mandible resection, and full-mouth
extractions. A percutaneous gastrostomy tube was placed before
RT and removed upon completing RT when dysphagia improved
(P088) Nonadherence to NCCN Guidelines Negatively
Impacts Survival in Early-Stage Squamous Cell
Carcinoma of the Larynx Chi-Hsiung Wang, PhD, Erik Liederbach, BS, Arif Shaikh, MD, Mihir K.
Bhayani, MD; Center for Biomedical Research Informatics, Department
of Surgery, Department of Radiation Oncology, Department of Head and
Neck Surgery, NorthShore University HealthSystem
INTRODUCTION: Primary treatment for early-stage squamous cell
carcinoma of the larynx (LSCC) is radiation therapy (RT) alone or
larynx-preserving surgery per National Comprehensive Cancer
Network (NCCN) guidelines. The guidelines do not recommend
the addition of chemotherapy in this setting. We investigated the
National Cancer Data Base (NCDB) to determine adherence to
these guidelines and its effects on overall survival (OS).
METHODS: Utilizing the NCDB, we selected 34,461 stage I–IV
LSCC patients treated with RT from 1998 to 2011. Patients who
received primary surgery were excluded. Chi-square tests, logistic
regression models, and Cox proportional hazards models were utilized for analyses.
RESULTS: In the cohort, there were 19,610 (56.9%) early-stage
(stage I/II) LSCCs and 14,851 (43.1%) late-stage (stage III/IV)
LSCCs; 1,634 (8.5%) early-stage LSCCs received chemotherapy
(CRT), as did 11,468 (77.9%) of the late-stage patients, over the
entire time period studied. For early-stage cancers, the proportion
of patients receiving CRT increased from 3.3% in 1998 to 9.4% in
2011 (P < .001). For late-stage cancers, the proportion of patients
receiving CRT increased from 55.2% in 1998 to 87.8% in 2011 (P
< .001). In a multivariate model, patients with early-stage LSCC
were significantly more likely to receive chemotherapy if patients
were younger (aged < 50 yr), female, African American or
Hispanic, treated at a community-based hospital, and living in the
Middle Atlantic (NJ, NY, and PA) or East North Central (IL, IN
MI, OH, and WI) regions of the United States. Survival analyses
were restricted to 1998–2006, and patients had a median follow-up
of 4.4 years (range: 1–13 yr). Early-stage LSCC patients receiving
RT alone had superior 5-year unadjusted OS rates compared with
CRT patients (64.3% vs 52.7%; P < .001). These results persisted
after adjusting for patient, facility, and tumor characteristics; and
65
patients with CRT had worse OS (hazard ratio [HR] = 1.18; 95%
confidence interval [CI], 1.07–1.31; P < .001). Late-stage LSCC
patients receiving CRT had superior 5-year unadjusted OS rates
compared with patients treated with RT alone (42.6% vs 25.9%; P
< .001), and after similar risk adjustment, patients with CRT had
superior OS (HR = 0.69; 95% CI, 0.65–0.73; P < .001) compared
with those who received RT alone.
CONCLUSION: NCCN guidelines were not followed in 9.4% of
patients with early-stage LSCC in 2011, because chemotherapy was
added to their RT-based regimen. In these patients, the addition of
chemotherapy reduced patient survival by 18%. These results indicate the importance of adherence to NCCN guidelines when prescribing RT-based regimens in the early-stage LSCC setting.
(P089) p16 as a Complementary Prognostic Marker for
EBV-Positive Nasopharyngeal Carcinoma Wen Jiang, MD, PhD, Paul Chamberlain, Erich Sturgis, MD, Adam S.
Garden, MD, Jack Phan, MD, PhD; UT MD Anderson Cancer Center
BACKGROUND: p16, also known as cyclin-dependent kinase inhibitor 2A, is a tumor suppressor protein that hinders cell cycle progression by inhibiting the formation of cyclin-dependent kinase
complexes. Overexpression of p16 is associated with improved
outcomes in oropharyngeal carcinoma patients. However, its role
in nasopharyngeal cancer pathogenesis remains incompletely
understood. Here, we set out to determine whether p16 overexpression status acts as a prognostic marker among nasopharynx cancer
patients. METHODS: We retrospectively identified 86 patients with nasopharyngeal carcinoma who were treated at MD Anderson from 2000
to 2014. Epstein-Barr virus (EBV) status was determined by in situ
hybridization, while p16 expression was analyzed by immunohistochemistry. All statistical analyses were performed using the IBM
Statistical Package for the Social Sciences (SPSS) v22.0 software
package.
RESULTS: A total of 44 patient samples were EBV-positive, and 40
were p16-positive. EBV positivity was associated with improved
survival (44.9 vs 95.0 mo; P < .004), progression-free survival
(PFS) (28.1 vs 80.4 mo; P < .013) and time to locoregional failure
(expressed as duration of locoregional control [LRC]) (65.5 vs
104.4 mo; P < .043). Although p16 overexpression showed trends
toward improved PFS and LRC, they failed to reach statistical
significance. Overexpression of p16, however, was found to be a
significant predictor for improved PFS (27.1 vs 106.3 mo; P <
.02) and LRC (64.5 vs 93.6 mo; P < .02) in EBV-positive nasopharyngeal cancer patients using both univariate and multivariate
analysis.
CONCLUSION: Our results suggest that p16 overexpression can act
as a marker for PFS and LRC in EBV-positive nasopharyngeal carcinoma patients. This interesting finding raises the possibility of
further stratifying more aggressive phenotypes within EBVpositive tumors. Therefore, molecular testing of p16 expression
may complement EBV status to provide more detailed and comprehensive guidance in determining the prognosis and predicting
66
treatment outcomes for patients diagnosed with nasopharyngeal
carcinoma.
(P090) Pediatric Metastatic Odontogenic Ghost Cell
Carcinoma: A Multimodal Treatment Approach Safia K. Ahmed, Masayo Watanabe, MD, Daphne E. deMello, MD,
Thomas B. Daniels; Department of Radiation Oncology, Mayo Clinic;
Phoenix Children’s Hospital for Cancer and Blood Disorders; Department of Pathology and Laboratory Medicine, Phoenix Children’s Hospital
INTRODUCTION: Odontogenic ghost cell carcinoma (OGCC) is an
extremely rare tumor, wherein the optimal management remains
uncertain. We report the first pediatric metastatic OGCC case
treated with multimodal therapy: surgery, adjuvant chemoradiation, and adjuvant immunotherapy.
CASE DESCRIPTION: A 10-year-old Hispanic male presented with
facial swelling. A right maxillary mass was appreciated on exam.
Imaging demonstrated a 3.3-cm soft tissue mass in the right maxilla with destruction of adjacent bone and displacement of molars.
Pathology confirmed OGCC. Presurgical imaging obtained 5
weeks later noted growth of the mass to 6.7 cm, with right submandibular and posterior cervical adenopathy. Surgery entailed
right-sided modified radical maxillectomy, palatectomy, and neck
dissection. Multiple re-excisions were performed to obtain negative margins. Seven level 1 and 2 lymph nodes were positive for
tumor. Immunohistochemistry was positive for epidermal growth
factor receptor (EGFR), indicating cellular expression of EGFR
protein. Adjuvant chemoradiation was recommended, the given
rapid presurgery growth, adenopathy, and concern for microscopic residual disease. A dose of 44 Gy in 22 fractions was administered to the postoperative bed and bilateral neck via intensitymodulated radiation therapy (IMRT) prior to treatment break for
toxicity. Reimaging then demonstrated new 1.7-cm left gingivolabial disease. Radiation plans were redesigned, with the postoperative bed treated to total doses of 60 Gy/30 fractions and the left
gingivolabial disease treated to 39 Gy/13 fractions. Treatmentrelated toxicity included dehydration, dermatitis, and malnutrition. Monthly cetuximab was initiated, and the patient remains
disease-free at 14 months.
DISCUSSION: Adjuvant treatment was recommended, given the
metastatic disease, rapid growth, and concern for microscopic
residual disease. As adjuvant chemoradiation and immunotherapy
are associated with improved outcomes in primary head and neck
cancer, a similar approach was adopted. Multimodal therapy is
thought to be unsuitable in OGCC due to the poor outcomes documented in seven patients treated with radiation and/or chemotherapy in the current literature. These conclusions are difficult to
draw, given the small number of cases. Moreover, these modalities
were utilized over 15 years ago. As significant advances have been
made with multimodal therapy since then, further investigation is
warranted, especially since this approach was tolerated in our
patient and since he remains disease-free.
CONCLUSION: OGCC can exhibit aggressive progression, warranting investigation into multimodal therapy. Given that adjuvant
chemoradiation and immunotherapy are associated with improved
outcomes in primary head and neck cancer, a similar application
in OGCC may help guide optimal treatment. This approach was
well tolerated in our pediatric patient, and he remains disease-free
at 14 months.
(P091) Sarcopenia/Cachexia Is Associated With Reduced
Survival and Locoregional Control in Head and Neck
Cancer Patients Receiving Radiotherapy: Results From
Quantitative Imaging Analysis of Lean Body Mass
Sasikarn Chamchod, MD, Clifton D. Fuller, MD, PhD, Aaron J. Grossberg, MD, PhD, Abdallah S. Mohamed, MD, MSc, Jolien Heukelom,
MD, Hillary Eichelberger, BA, BS, Michael E. Kantor, BS, Gary B. Gunn,
MD, Adam S. Garden, MD, Steven J. Frank, MD, Jack Phan, MD, PhD,
Beth M. Beadle, MD, PhD, Heath D. Skinner, MD, PhD, William H.
Morrison, MD, Debra A. Ruzensky, RD, David I. Rosenthal, MD; Radiation Oncology Unit, Chulabhorn Hospital; Department of Radiation
Oncology, UT MD Anderson Cancer Center; Department of Radiation
Oncology, Netherlands Cancer Institute; UT Medical School, Houston
BACKGROUND: Major weight loss before or during head and neck
squamous cell cancer (HNSCC) treatment is common. We investigated the impact of weight loss, cachexia, and sarcopenia—the
isolated loss of lean body mass—as determined by a novel method
using routine staging positron emission tomography-computed
tomography (PET-CT) scans on cancer treatment outcomes.
METHODS: Biometric data were collected on consecutive patients
with American Joint Committee on Cancer (AJCC) stage IVA–IVB
HNSCC treated with radiation therapy (RT) with or without concurrent chemotherapy between 2003 and 2013 and who had paired
pre- and posttreatment PET-CTs. Cachexia was defined as > 5%
weight loss for < 6 months or body mass index (BMI) < 20 kg/m2
with 2% weight loss. Sarcopenia was defined by CT-measured L3
skeletal muscle index of < 52.4 cm2/m2 for men and < 38.5 cm2/
m2 for women, as described by Prado et al (2013). We evaluated the
effect of pre- and post-RT sarcopenia on outcomes. Survival curves
were constructed using the Kaplan-Meier technique. Log-rank test
was used to compare outcomes. Univariate and multivariate overall
survival (OS) modeling was performed using parametric survival
fitting to allow intramodel comparison using corrected Bayesian
information criteria (BIC).
RESULTS: A total of 175 patients were identified, and the median
follow-up was 67.9 months. We detected sarcopenia in 65 patients
(37.1%) prior to RT. Sarcopenia was identified in an additional 47
of 110 patients (42.7%) on the post-RT scan. All patients who
developed sarcopenia on the post-RT study had decreased locoregional control (LRC), OS, and disease-specific survival (DSS) (P <
.05 for all). Sarcopenia that was identified on the pre-RT PET-CT
showed the same patterns but only for nonoperated patients, where
the 5-year OS was decreased from 66.7 ± 1.0% to 17.8 ± 10.2% (P
< .001). Posttreatment sarcopenia was more substantive in competing multivariate models of mortality risk than simple weight and
BMI-based cachexia metrics (ΔBIC ≥ 12.9).
DISCUSSION: We confirm that analysis of routine CT scans for
sarcopenia can predict outcomes for HNSCC patients. Pre-RT
sarcopenia is associated with more poor outcomes for nonoper
ated patients and post-RT sarcopenia for all HNSCC patients.
Post-RT sarcopenia, as measured by routine CT, outperformed
simple weight loss and BMI-derived cachexia metrics, because
loss of lean muscle mass can occur independently of BMI status.
These findings suggest the potential benefit for investigating
intervention with aggressive nutritional and physiatric methods
to prevent sarcopenia during RT and to study how these inter
ventions might affect outcomes in nonoperated, pre-RT sarcopenia patients.
(P092) Definitive Chemoradiotherapy or Radiotherapy
for Unresectable, Very Locally Advanced, or Medically
Inoperable Paranasal Sinus and Nasal Cavity Cancer Lindsay M. Burt, Ying Hitchcock; Huntsman Cancer Institute, University
of Utah
PURPOSE: To review radiotherapy (RT) technique and outcomes
for definitive RT or chemoradiotherapy (CRT) for unresectable, very locally advanced, or medically inoperable paranasal sinus
(PNS) or nasal cavity (NC) cancer at a single institution.
METHODS: Between 1998 and 2010, there were 11 patients with
unresectable, very locally advanced, or medically inoperable PNS/
NC cancers treated with definitive CRT (7) or RT alone (4) at the
University of Utah. There were 10 males and 1 female, with a mean
age of 57.3 years (range: 28–75 yr). CRT was given to stage IVA (5)
and stage IVB (2) patients, and RT alone was given to stage II (1),
stage III (1), and stage IVA (2) patients. One patient was treated
with a three-dimensional (3D) conformal technique, and 10 were
treated with intensity-modulated RT (IMRT). The median dose
was 70.2 Gy (range: 70–72.4 Gy). In order to adapt to tumor
shrinkage and prevent critical structures from receiving a high dose
due to tumor regression and weight loss, most patients underwent
two treatment planning phases, with a resimulation at a dose of
45–50 Gy. One patient received a boost of 11 Gy using stereotactic
radiosurgery (SRS) following 70.2 Gy external beam RT (EBRT).
The most common chemotherapy agent was cisplatin at 40 mg/m2,
given on a weekly basis for 6–7 cycles. A flexible nasal endoscopy
with a biopsy was performed 3 months posttreatment to evaluate
tumor response.
RESULTS: There was a median follow-up of 39 months (range: 1–70
mo). Six patients underwent a debulking surgery. Overall, six
(55%) patients remained disease-free, two (18%) developed local
recurrences, one (9%) developed regional recurrence, and 2 (18%)
developed distant metastasis. Local control was seen in 9 of 11
(81.8%) patients. The treatment was well tolerated, with only one
patient experiencing a grade 3 late toxicity (trismus), two patients
experiencing grade 2 late toxicities (cataract, retinal detachment,
and trismus), and five patients experiencing grade 1 late toxicities
(dysgeusia, dry mouth, fibrosis, skin telangiectasia, and nasal congestion). Three patients had no late toxicities.
CONCLUSION: Definitive CRT or RT is feasible for unresectable,
very locally advanced, or medically inoperable PNS/NC cancer
with minimal late toxicity. Local disease control is encouraging,
with acceptable treatment-related complications, when treating
with the described two-phase IMRT treatment technique.
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(P093) Cesium-131 Brachytherapy in High-Risk and
Recurrent Head and Neck (HN) Cancers: Long-Term
Results of a Pilot Study patients with sinonasal neuroendocrine tumors who were treated
with a combination of surgery, radiation therapy, and/or chemotherapy at the Mayo Clinic in Arizona.
Bhupesh Parashar, Anthony Pham, Dattatreyudu Nori, A. Gabriella
Wernicke; Weill Cornell Medical Center
MATERIALS AND METHODS: An institutional review board (IRB)approved retrospective study of 27 patients treated at the Mayo
Clinic from January 25, 1996 through November 6, 2013. Of these
patients, 9 (33%) had olfactory neuroblastoma (ONB), 11 (41%)
had sinonasal undifferentiated carcinoma (SNUC), 5 (19%) had
small-cell carcinoma, and 2 (7%) had neuroendocrine carcinoma.
BACKGROUND: The feasibility and efficacy of re-irradiation using
contemporary radiation techniques to treat recurrent head and
neck cancer have been demonstrated, but the role of brachytherapy
is unclear. Here, we describe the use of cesium (Cs)-131 brachytherapy with concurrent salvage surgery in 18 patients.
MATERIALS AND METHODS: Eligible patients underwent maximal
gross resection of the tumor with implantation of Cs-131 brachytherapy seeds, delivering a minimum dose of 80 Gy to the tumor
bed. Rates of overall survival (OS), locoregional progression-free
survival (LRPFS), disease-free survival (DFS), and radiationinduced toxicity were analyzed.
RESULTS: Between 2010 and 2013, a total of 18 patients with 20
implants were enrolled and treated with surgical resection and
brachytherapy for the management of locoregional recurrences of
head and neck cancer. The majority of histology was squamous cell
carcinoma (10 of 18). All but one patient had a history of prior
radiation in the area of tumor recurrence. One patient had gross
residual disease following surgical resection. Two patients underwent an additional surgical resection and brachytherapy implantation 2 months and 5 months later for local recurrence that developed outside of the treatment volume. A total of 13 patients had
previous locoregional recurrence treated with surgical salvage
therapy. The total dose following initial definite external beam
radiation therapy (RT) ranged from 5,000 cGy to 7,000 cGy.
Two patients developed grade 3 toxicity; no grade 4 or 5 complications were observed. With a median follow-up of 38 months (range:
1–44 mo), 11 patients developed another recurrence or progression
of head and neck cancer. In 6 of these 10 cases, the failure was
locoregional, and in 4 patients, it was isolated distant failure. One
patient was found to have simultaneous locoregional and distant
progression of disease. The median OS was 15 months, and median
DFS was 11 months. The 6-, 12-, and 18-month OS rates in this
study were 77%, 71%, and 45%, respectively. The 6-, 12-, and
18-month LRPFS rates in this study in patients were 69%, 62%, and
52%, respectively. The 6-, 12-, and 18-month DFS rates in this
study were 57%, 45%, and 37%, respectively.
CONCLUSION: Compared with prior literature, our study shows
comparable rates of survival with a decreased rate of radiationinduced toxicity. (P094) Treatment Outcomes of Sinonasal
Neuroendocrine Cancer: A Retrospective Review Priya Parikh, BA, Samir H. Patel, MD, Mauricio Gamez, MD,
William Wong, MD, Michele Halyard, MD, Kelly Curtis, MD, Devyani
Lal, MD; Department of Radiation Oncology, Department of Medical
Oncology, Department of Otorhinolaryngology, Mayo Clinic Arizona
PURPOSE/OBJECTIVES: To report the treatment outcomes of
68
Of the 27 patients, 22 patients received a combination of surgery,
radiation therapy, and/or chemotherapy: 9 (41%) underwent surgery plus adjuvant radiation, 8 (36%) underwent surgery plus adjuvant chemoradiation, 4 (18%) were treated with chemoradiation,
and 1 (5%) had neoadjuvant chemotherapy followed by surgery
and adjuvant radiation. Two patients were treated with surgery
alone, one was treated with radiation therapy alone, and two were
treated with chemotherapy alone. The median dose of radiation
was 60 Gy (range: 42–66 Gy).
RESULTS: Median follow-up was 16.3 months (range: 3–315 mo).
The 5-year actuarial overall survival (OS), distant metastasis–free
survival (DMFS), and local control (LC) rates were 44%, 62%, and
51%, respectively. When comparing outcomes of ONB vs nonONB histologies, 5-year OS was 56% vs 38% (P = .4), and 5-year LC
was 67% vs 37%, respectively (P = .6). Specifically, SNUC patients
had the worst 5-year OS of 25% and 5-year LC of 39%. Moreover,
50% of SNUC patients developed distant failure within 1 year.
There were five regional recurrences in the neck—all in ONB
patients. One of these five patients had a regional-only recurrence
and did not receive elective radiation to the neck.
CONCLUSIONS: Sinonasal neuroendocrine tumors are a challenging group of diseases to manage, due to their rarity and heterogeneous natural histories. New multimodality strategies need to be
explored to potentially enhance outcomes, especially in non-ONB
histologies.
(P096) Late Radiation-Associated Dysphagia
(Late-RAD) With Lower Cranial Neuropathy After
Oropharyngeal IMRT Katherine A. Hutcheson, PhD, Denise A. Barringer, MS, CCCSLP, G.
Brandon Gunn, MD, Stephen Y. Lai, MD, Merrill S. Kies, MD, David
L. Schwartz, MD, Jan S. Lewin, PhD; UT MD Anderson Cancer Center; UT Southwestern Medical Center
PURPOSE: Late radiation-associated dysphagia (late-RAD) is a
debilitating, delayed toxicity of nonsurgical organ preservation for
head and neck cancers. Herein, we examine late-RAD in long-term
oropharyngeal cancer survivors after intensity-modulated radiation therapy (IMRT).
METHODS: A pooled dataset was analyzed from two institutional
single-arm clinical trials of nonsurgical organ preservation with
radiation. Prospective functional analysis included radiographic
swallow studies (videofluoroscopy) and questionnaires pretreatment and 6, 12, and 24 months after treatment. Functional recovery
at 1 year was assessed by index measure: solid food diet, feeding
tube–free, functional airway protection, and no lower cranial neuropathy or stricture. A diagnostic algorithm was developed to classify late-RAD events based on significant dysphagia on late (≥ 2 yr)
videofluoroscopic swallow referrals among patients with early
functional recovery from acute toxicities of IMRT by 1 year.
RESULTS: A total of 57 oropharyngeal cancer survivors with a minimum 2-year disease-free clinical follow-up after IMRT (range:
66–72 Gy) with systemic therapy were included. T-stage distribution was: TX (4), T1 (13), T2 (21), T3 (15), and T4 (4). Also, 52
patients (91%) achieved functional recovery by 1 year. At a median
follow-up of 5 years, the cumulative incidence of late-RAD was 9%
(5 of 57), 3 of whom had delayed lower cranial neuropathy (XII or
X). An additional five patients were considered at risk for late-RAD
per self-report of progressive dysphagia symptoms ≥ 2 years after
treatment without videofluoroscopic confirmation.
CONCLUSION: Although the majority of oropharyngeal cancer survivors enjoy functional recovery in early survivorship, almost 10%
suffer severe, late deterioration of swallowing abilities. Delayed
lower cranial neuropathies often precipitate late-RAD.
(P097) Tumor Density, Size, and Histology in the
Outcome of Stereotactic Body Radiation Therapy
for Early-Stage Non–Small-Cell Lung Cancer:
A Single-Institution Experience Jason C. Ye, MD, Jenghwa Chang, PhD, ZhiQiu Li, PhD, A.
Gabriella Wernicke, MD, MSc, Dattatreyudu Nori, MD, Bhupesh Parashar, MD; Stich Radiation Oncology, Weill Cornell Medical College;
Vantage Oncology
PURPOSE: Stereotactic body radiation therapy (SBRT) for early-
stage non–small-cell lung cancer (NSCLC) has been shown to have
excellent local control (LC). NSCLC has diverse sizes and histologies, which can affect treatment response. It also has variable densities, which may affect radiation dose accumulation within the target to therapeutic dose. This study represents a single-institution
outcome of lung SBRT with respect to various factors.
METHODS: A retrospective chart review was conducted of all localized NSCLCs, with no lymph node metastasis or distant metastasis
(DM), treated in 2001–2014. Patient and disease characteristics and
treatment outcomes (eg, primary tumor control [PTC], intralobar
recurrence–free survival [LRFS], disease-free survival [DFS], overall survival [OS], and toxicity) were examined. Further treatment
planning details, including dose, fractionation, and gross tumor
volume/internal target volume (GTV/ITV) densities, were obtained
in the treatment planning system.
RESULTS: A total of 96 patients with 109 lesions who were treated
had follow-up information available and were included. There were
42 (44%) men and 54 (56%) women, with a median age at time of
diagnosis of 77 years (range: 52–95 yr). A total of 46% of patients
had documented chronic obstructive pulmonary disease (COPD),
and 66% had at least one prior malignancy (51% had prior NSCLC;
range: 0–5). Further, 58% of patients could not undergo surgery
due to pulmonary reserve, 17% could not undergo surgery due to
other comorbidities, and 22% chose SBRT, even though they were
deemed surgical candidates. A total of 80% of patients were stage
IA, and median tumor size was 1.7 cm (range: 0.6–6.9 cm); 75%
had adenocarcinoma (AC), and 17% had squamous cell carcinomas (SCC). The most commonly used dose and fractionation was
48 Gy in four fractions over 2 weeks (77%). There were seven (6%)
grade 1 (four skin, two pain, one cough) and two (2%) grade 2 skin
toxicities. With a median follow-up of 25 months, the 2-year OS
was 84%, and DFS was 74%, while PTC was 91% (LRFS: 85%).
Patients with AC and SCC had similar PTC (P = .939) and DFS
rates (P = .909). Compared with stage IA, patients with stage IB
disease had similar PTC (P = .462) but were more likely to develop
DM (P = .003). The mean GTV/ITV density varied from 0.236–
1.010 g/cm3 (mean: 0.697 g/cm3; standard deviation [SD] = 0.182).
Density did not have a statistically significant effect on PTC, but
those with denser GTV/ITV values (> 0.7 g/cm3) had inferior DFS
(P = .027).
CONCLUSIONS: Our institutional experience confirmed that SBRT
to primary NSCLC is well tolerated and provides excellent LC,
regardless of tumor size or histology. Tumor density did not appear
to have a significant effect on PTC, but denser tumors were more
likely to have poorer outcomes, likely owing to associated larger
tumor burden.
(P098) Dosimetric Predictors of Pulmonary Toxicity
in Patients With Malignant Pleural Mesothelioma
Receiving Radiation Therapy to the Intact Lungs Yaseen Zia, MD, Vishruta Dumane, PhD, Kenneth Rosenzweig; Icahn
School of Medicine at Mount Sinai
INTRODUCTION: Pleurectomy and decortication is gaining wider
acceptance as a standard surgery for malignant pleural mesothelioma. Adjuvant radiation is particularly challenging, due to the
need to treat the pleura while sparing the underlying intact lung.
Typical dosimetric constraints are of limited value in this patient
population. This study aimed to establish whether there was a
functional subunit of lung that needed to be spared that was predictive of development of radiation pneumonitis in patients with
malignant pleural mesothelioma receiving radiation therapy to the
intact lungs.
MATERIALS AND METHODS: A total of 18 patients with malignant
pleural mesothelioma (MPM) were treated with definitive or adjuvant hemithoracic pleural intensity-modulated radiation therapy
(IMRT) after radical pleurectomy and decortification between
2010 and 2014. The dose was prescribed to the planning target
volume (PTV), which included the entire parietal and visceral
pleura, with a median dose of 4,500 cGy (range: 3,000–5,940 cGy).
Specific dosimetric parameters pertaining to both lungs were
recorded. Toxicity was assessed during weekly on-treatment visits
and in follow-up examinations using Common Terminology
Criteria for Adverse Events version 4.0 (CTCAE v4.0) criteria.
RESULTS: The median follow-up was 4 months (range: 1–18 mo).
Six patients (33%) developed grade 3 pneumonitis or higher, and
12 patients (67%) did not. Mean lung dose and V30 of the total
lungs were found to be statistically significant for the development
69
of pneumonitis. Contralateral lung V5 and mean lung dose were
found not to correlate with the development of pneumonitis, in
contrast to previously published reports. We found that for each
1,000 cc of ipsilateral lung, if 150 cc was treated to less than 20 Gy,
there was significantly less pneumonitis. No patients with 150 cc
spared per 1,000 cc of normal lung developed pneumonitis vs 43%
(6 of 14) of patients who failed to reach that threshold (P < .05).
CONCLUSIONS: Sparing the ipsilateral lung of at least a finite functional unit per 1 L of the ipsilateral lung is a predictor of the development of radiation pneumonitis. This represents a new dosimetric measure in plan evaluation and correlates significantly with the
development of toxicity in patients with malignant pleural mesothelioma receiving radiation to the ipsilateral lung. This factor
might be a more effective and useful parameter in these challenging cases.
(P099) Influence of Surveillance PET/CT on Detection
of Early Recurrence Following Definitive Radiation in
Stage III Non–Small-Cell Lung Cancer Jay Reddy, MD, PhD, Chad Tang, MD, Zhongxing Liao, MD, Daniel
Gomez, MD; UT MD Anderson Cancer Center
PURPOSE/OBJECTIVES: There are little data to support the use of
varying imaging modalities in evaluating recurrence in non–smallcell lung cancer (NSCLC). We compared the efficacy of surveillance positron emission tomography–computed tomography
(PET-CT) vs CT scan of the chest in detecting recurrences following definitive radiation for NSCLC.
MATERIALS AND METHODS: We retrospectively analyzed 189
patients treated between 2000 and 2011 who met the inclusion
criteria of biopsy-proven stage III NSCLC and completion of
definitive radiation treatment (dose ≥ 60 Gy). These patients were
then grouped based on the ratio of PET-CT scans: CT scans of the
chest during the postradiation surveillance window, defined as
2–18 months posttreatment. A ratio of 0 described the CT-only
group, and a ratio of > 1 described the PET-high group. We compared survival times from the end of treatment to the date of death
or last follow-up utilizing log-rank tests. Multivariate analysis was
conducted to identify factors associated with decreased survival.
RESULTS: In the entire cohort, median event-free survival (EFS)
was 8.7 months, and median overall survival (OS) was 29.9 months.
The CT-only group had a median EFS of 9 months vs 8.7 months
for the PET-high group (P = .85). There was no difference in OS
between the CT-only and PET-high groups (median OS: 35.3 mo
and 29.3 mo, respectively; P = .66). There was also no difference in
local recurrence-free survival or distant metastases-free survival
between the CT-only and PET-high groups (P = .06 and P = .32,
respectively). Similarly, on multivariate analysis, stratification into
the PET-high group was not associated with improved EFS (hazard
ratio [HR] = 0.978; 95% confidence interval [CI], 0.688–1.391; P =
.902) or OS (HR = 1.032; 95% CI, 0.723–1.472; P = .864).
CONCLUSIONS: In stage III NSCLC patients treated with definitive
radiation, increased frequency of PET-CT scan surveillance did not
result in decreased time to detection of locoregional or distant
70
recurrence or improved survival. If validated, further investigation
is warranted to elucidate the benefit, if any, of NSCLC posttreatment surveillance with PET-CT scan.
(P100) Intensity-Modulated Radiation Therapy After
Extrapleural Pneumonectomy With and Without
Chemotherapy for Malignant Pleural Mesothelioma:
No Fatal Pulmonary Toxicity and Long-Term Survival Sameer Jhavar, J. Pruszynski, Y. Liu, A. Gowan, P. Rascoe, N. Thawani,
N. Deb, Mehul Patel; Baylor Scott and White Hospital, Texas A&M
Medical Sciences Center
PURPOSE: Intensity-modulated radiation therapy (IMRT) after
extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM) has been associated with fatal pulmonary toxicity.
A single-institution experience with IMRT following EPP for MPM
is reported.
METHODS: Between 2005 and 2014, a total of 18 patients with MPM
were treated with EPP followed by hemithoracic IMRT. IMRT target
volume was the entire hemithorax and the thoracotomy and chest
tube incision sites. Patients were treated with a median dose of 4,500
cGy in 25 fractions. Kaplan-Meier curves were used to graphically
asses the overall survival (OS) and relapse-free survival (RFS).
Median survival times are reported for both OS and RFS.
RESULTS: Of the 18 patients analyzed, 17 were males, and 11 had
right-sided tumors. Median age was 54 years (range: 40–76 yr). The
most common histology was epithelioid type. Chemotherapy was
neoadjuvant in four and adjuvant in seven patients. A total of 3, 12,
and 3 patients had pathological American Joint Committee on
Cancer (AJCC) stages II, III, and IV, respectively. Involvement of
surgical margin, lymphovascular space, pericardium, and chest
wall was seen in 9, 7, 12, and 3 patients, respectively. The highest
and lowest mean lung dose (MLD) was 9.3 Gy and 5 Gy, respectively, with a mean of 7.14 Gy. The highest V20 (normal lung volume receiving ≤ 20 Gy) was 7%, and the mean V20 was 2.23%
(range: 0%–7%). At a median follow-up of 3 years, 8 patients were
alive and 10 patients were dead. Ten (55%) patients experienced
disease recurrence. The median RFS and OS were 29.67 months
(95% confidence interval [CI], 11.79–78.1 mo) and 38.2 months
(95% CI, 17.4–78.1 mo), respectively. No grade 3 acute toxicities
were seen. No grade 3 or fatal pulmonary toxicities have been
reported. CONCLUSION: In our patient population, strict adherence to lung
dose constraints during IMRT resulted in improved outcomes
without fatal toxicity.
(P101) Does Maximum SUV From F-18 PET Scan Predict
Outcomes for Early-Stage Non–Small-Cell Lung Cancer
Treated With Stereotactic Body Radiotherapy (SBRT)? Corey J. Hobbs, MD, Stephen J. Ko, MD, Nitesh N. Paryani, MD, Michael
G. Heckman, MS, Nancy N. Diehl, BS, Jennifer L. Peterson, MD, Katherine S. Tzou, MD, Robert C. Miller, MD, Laura A. Vallow, MD, Steven J.
Buskirk, MD; Mayo Clinic Florida
PURPOSE: Prior studies have shown mixed results regarding the
predictive value of positron emission tomography (PET) scan following definitive treatment of early-stage lung cancers. The primary outcome of this study was to evaluate the association of
maximum standard uptake value (SUVmax) on PET scan with
recurrence and survival in patients with lung cancer who were
treated with stereotactic body radiotherapy (SBRT). Secondary
outcomes were to evaluate associations of baseline patient characteristics with SUVmax, recurrence, and survival.
MATERIALS AND METHODS: A total of 61 lung cancer patients
with a documented pretreatment SUVmax and treated with SBRT
between 2008 and 2014 were included in this study. Baseline information was collected regarding age, gender, lesion size, SUVmax,
glucose at time of PET, T stage, histology, nodal evaluation, and
total radiation dose. Examined recurrences included local, nodal,
ipsilateral lung, contralateral lung, and distant metastases. Time to
death and cause of death were also recorded. Median clinical follow-up was 12.7 months (range: 2.8–52.9 mo). The median SUVmax
of the cohort was 6.4. A total of 54 patients (89%) had biopsy-proven malignancy.
RESULTS: Baseline characteristics between patients with a low (<
6.4) and high (≥ 6.4) SUVmax were similar, except for lesion size in
the high-SUVmax group (median: 2.2 cm vs 1.7 cm; P < .001) and
higher T stage (1b or 2a: 71.0% vs 36.7%; P = .018). Adenocarcinomas
were more common in the low-SUVmax group (76.0% vs 41.1%),
while squamous cell carcinomas were less common (8.0% vs
44.8%).
A total of 16 patients (26.2%) experienced any recurrence; 9
patients (14.8%) experienced nodal recurrence, 3 patients (4.9%)
experienced same lung recurrence, and 5 patients (8.2%) experienced distant recurrence. Also, 18 patients (29.5%) died during
follow-up.
There was no evidence of a difference in recurrence outcomes
between the two groups. An evaluation of associations of baseline
patient characteristics with the three most common outcomes of
nodal or same lung recurrence, any recurrence, and death was performed. The only baseline variable that was significantly associated
with any of these outcomes was serum glucose at time of PET;
patients with a glucose value higher than the median of 103 mg/dL
had an increased risk of nodal or same lung recurrence (relative
risk [RR] = 6.77; P = .017) and any recurrence (RR = 3.76; P = .027).
CONCLUSION: We did not find an association of SUVmax with
recurrences or death; however, the sample size was relatively small,
and the power to detect differences was low. These findings will be
further evaluated in a larger multicenter study in the future.
(P102) Surgery Improves Survival in 14,228 Patients
With Malignant Pleural Mesothelioma Andrea S. Wolf, MD, MPH, Emanuela Taioli, MD, Marlene
Camacho-Rivera, ScD, MPH, Kenneth E. Rosenzweig, MD, Raja M.
Flores, MD; Mount Sinai Medical Center; North Shore/Long Island Jewish Health System, Hofstra School of Medicine
OBJECTIVES: Left untreated, malignant pleural mesothelioma
(MPM) has uniformly poor prognosis. Prolonged survival has been
reported with surgery-based multimodality therapy, but to date, no
trial has demonstrated independent survival benefit of surgery over
other therapies for MPM. We evaluated whether cancer-directed
surgery independently influenced survival in a large populationbased dataset.
METHODS: The Surveillance, Epidemiology, and End Results
(SEER) database was explored from 1973 to 2009 to identify all
cases of pathologically proven MPM. Age, sex, race, diagnosis year,
stage, cancer-directed surgery, radiation, and vital status were analyzed (chemotherapy data not available). The association between
prognostic factors and survival was estimated using a Cox proportional hazards model.
RESULTS: There were 14,228 patients with pathologically proven
MPM. On multivariable analysis, female gender, younger age,
early stage, and cancer-directed surgery were independent predictors of longer survival. In comparison with no treatment, surgery
alone was independently associated with significantly longer survival, with an adjusted hazard ratio (aHR) for mortality of 0.65
(0.62–0.68), while radiation alone was not (aHR = 1.17 [1.10–
1.25]). The combination of surgery and radiation was associated
with a survival outcome similar that with to surgery alone (aHR =
0.69 [0.63–0.75]). In patients diagnosed from 2000–2009, the aHR
for mortality with radiation was 1.26, 0.68 for surgery, and 0.63 for
surgery plus radiation, with similar results obtained in patients
diagnosed from 1973–1999. This suggests that improvements in
technique over time have not altered the impact of therapy on
patients with MPM.
CONCLUSIONS: Despite developments in surgery, perioperative
management, and radiotherapy, the prognosis for MPM patients
has not improved over the past four decades. In this SEER study of
14,228 patients over 36 years, cancer-directed surgery was associated with better survival in MPM, independent of other prognostic
factors. These data support the role of surgery-based therapy as the
cornerstone of treatment for this challenging disease.
(P103) A New Score Predicts Survival in Patients With
Non–Small-Cell Lung Cancer Steven E. Schild, MD, Angelina D. Tan, BS, BA, Jason A. Wampfler, BS,
Julian R. Molina, MD, PhD, Helen J. Ross, MD, Ping Yang, MD, PhD, Jeff
A. Sloan, PhD; Mayo Clinic
PURPOSE: This analysis was performed to create a scoring system
to estimate the survival of patients with non–small-cell lung cancer
(NSCLC).
METHODS: Data from 1,274 NSCLC patients were analyzed to create and validate a scoring system. Univariate (UV) and multivariate
(MV) Cox models were used to evaluate the prognostic importance
of each baseline factor. Prognostic factors that were significant on
both univariate and multivariate analyses were used to develop the
score. They included quality of life, age, performance status, primary tumor diameter, nodal status, distant metastases, and smoking
cessation. The score for each factor was determined by dividing the
71
5-year survival rate (%) by 10 and summing these scores to form a
total score. Multivariate models and the score were validated using
bootstrapping with 1,000 iterations from the original samples.
RESULTS: The score for each factor ranged from 1–7 points, with
higher scores reflective of better survival. Total scores of 32–37 correlated with a 5-year survival of 8.3% (95% confidence interval
[CI], 0%–17.1%), 38–43 correlated with a 5-year survival of 20%
(95% CI, 13%–27%), 44–47 correlated with a 5-year survival of
48.3% (95% CI, 41.5%–55.2%), 48–49 correlated to a 5-year survival of 72.1% (95% CI, 65.6%–78.6%), and 50–52 correlated to a
5-year survival of 84.7% (95% CI, 79.6%–89.8%). The bootstrap
method confirmed the reliability of the score.
CONCLUSIONS: Prognostic factors that were significantly associated
with survival on both UV and MV analyses were used to construct
a valid scoring system that can be used to predict survival of NSCLC
patients. The score can be used for trial stratification or for choosing
patients specifically for high-risk trials. Optimally, this score will
be helpful when counseling patients and designing future trials.
(P104) Esophagus- and Contralateral Lung–Sparing
IMRT for Locally Advanced Lung Cancer in the
Community Hospital Setting Johnny Kao, MD, Jeffrey Pettit, MS, Shanata S. Ramsaran, Terry Palatt,
MD; Good Samaritan Hospital Medical Center
INTRODUCTION: The optimal technique for performing lung
intensity-modulated radiation therapy (IMRT) remains poorly
defined. Due to concerns regarding acute and late toxicity, the
potential benefit of dose escalation beyond 60 Gy has not been
established. We hypothesize that improved dose distributions
associated with normal tissue-sparing IMRT can allow for safe
dose escalation that will translate into decreased acute and late
toxicity. MATERIALS AND METHODS: We performed a retrospective analysis of 82 consecutive patients with stage II/III or stage IV lung cancer with a single distant metastasis (median age: 69 yr, 53% male,
21% small-cell lung cancer, 83% white, 70% Eastern Cooperative
Oncology Group [ECOG] performance status score 0 or 1, 13%
stage IV, and 87% receiving concurrent chemotherapy) treated
from January 2010 to September 2014. From January 2010 to April
2012 (cohort A), patients were treated with the community standard of predominantly three-dimensional conformal radiotherapy
(76%) without specific esophagus or lung constraints. From May
2012 to September 2014 (cohort B), patients were treated with predominantly IMRT (95%) while selectively sparing uninvolved lung
and esophagus. The study endpoints were dosimetry, toxicity, and
overall survival (OS).
RESULTS: Despite higher mean prescribed radiation doses in
cohort B (64.5 Gy ± standard deviation [SD] 5.0 vs 60.8 Gy ± SD
6.2; P = .04), patients in cohort B had significantly lower lung V20,
V10, V5, mean lung, maximum esophagus, and mean esophagus
doses (P ≤ .001). Mean lung V20 was 23.3 Gy ± SD 7.2 in cohort B
vs 32.2 Gy ± SD 11.6 for cohort A. Mean esophagus dose was 20.2
Gy ± SD 10.2 in cohort B vs 34.3 Gy ± SD 12.7 for cohort A (P =
72
.001). Patients in cohort B had reduced acute grade ≥ 3 esophagitis
(0% vs 11%; P < .001) and late grade ≥ 2 pneumonitis (5% vs 21%;
P = .01). The incidence of hospitalization for dehydration and/or
pulmonary complaints was 11% for cohort B vs 37% for cohort A
(P = .008). Three patients in cohort A who developed grade 5 pneumonitis had lung V20 values of 41%, 48%, and 58% and lung V5
values of 90%, 99%, and 88%, respectively. Median survival in
cohort B has not been reached at 24 months vs 13 months for
cohort A (P = .13).
CONCLUSION: These data provide proof of principle that suboptimal radiation dose distributions are associated with significant
acute and late lung and esophageal toxicity that may result in
hospitalization or even premature mortality. We propose a relatively simple four-field IMRT technique with strict attention to
commonly accepted lung and esophageal dose-volume constraints as a preferred approach for the majority of locally
advanced lung cancers. (P105) Community-Based Early-Stage Treatment (BEST)
Outcomes for NSCLC Austin N. Arnone, BS, Christopher Biggs, MD, PhD, Daniel Reed, DO,
Terry Lee, MD, Cheri Pantoja, CCRP, Kevin Rogers, MS; Arizona Center
for Cancer Care
PURPOSE/OBJECTIVES: Stereotactic body radiation therapy
(SBRT) has been established as an effective treatment for earlystage non–small-cell lung cancer (NSCLC) in patients who are
medically inoperable or refuse surgery. This retrospective study
analyzes outcomes of lung SBRT in the setting of a communitybased cancer treatment center in Arizona.
MATERIALS AND METHODS: Between 2008 and 2013, a total of 146
tumor sites in 126 patients with stage I NSCLC were definitively
treated using SBRT administered via the Varian RapidArc, a continuous dynamic IMRT system with cone-beam computed tomography (CT) localization. Simulation was gated, and treatment targeted a static volume. Patients were determined to be medically
inoperable (n = 96) or refused surgery (n = 30). Treatment was
delivered using a risk (tumor site, size)-adapted dose of 60 Gy (73
sites), 55 Gy (4 sites), or 50 Gy (52 sites) or a lower dose (17) in five
fractions. Treatment outcomes were interpreted using KaplanMeier analysis of overall survival (OS), local control (LC), and
disease-free survival (DFS). Correlation of patient, tumor, and
treatment factors with survivability was analyzed using Cox proportional hazards.
RESULTS: Median age was 78 years; 44 patients were male, and 82
were female. The 3-year OS for all patients was 76%, with a median follow-up of 20 months (range: 2–67 mo). Median OS was 57
months. The 3-year LC for the entire cohort was 90.5%, and 3-year
DFS was 68%. The 10 sites that developed local recurrence all
received less than 60 Gy, yielding a 3-year LC of 81.7% for this
subgroup (n = 65). Currently, LC is 100% for sites receiving 60 Gy
(n = 73). Multivariate analysis demonstrated that no patient,
tumor, or treatment factor was significantly predictive of survival.
There was a 7.1% rate of grade 3 toxicity by Radiation Therapy
Oncology Group (RTOG) criteria, with no grade 4 or 5 toxicities
within 90 days of treatment.
CONCLUSIONS: LC, survival, and toxicity of stage I NSCLC treated
with SBRT in this community setting are comparable to those
reported in university and multi-institutional trials. The efficacy,
safety, and convenience of SBRT have been translated to a large
cohort of patients in an outpatient community cancer center.
These results also indicate that doses < 60 Gy delivered in five
fractions may be less effective at achieving LC. As lower doses are
examined in central lesions, it will be important to closely evaluate
any possible reduction in LC.
(P106) Dosimetric Comparisons of Treatment by
Different Radiotherapy Techniques for Stage III
Non–Small-Cell Lung Cancer Veronica Finnegan, MD, Kiernan May, CMD, Jeffrey Bogart, MD, Paul
Aridgides, MD, Varun Chowdhry, MD, Seung Hahn, MD; SUNY Upstate; Massachusetts General Hospital
PURPOSE: Standard dose for stage III non–small-cell lung cancer
was established 30 years ago with Radiation Therapy Oncology
Group (RTOG) 7301, where patients treated to 60 Gy had improved
outcomes. Phase I and II studies have shown that higher doses are
safe but have not been investigated in a phase III trial until recently. Optimal radiation dose was investigated in RTOG 0617, demonstrating that 60 Gy (standard) was superior to 74 Gy (high dose)
with chemoradiotherapy ± cetuximab. We hypothesize that this is
due to increased normal tissue toxicity. We performed a comparative dosimetric study between different radiation techniques.
MATERIALS AND METHODS: Review of 10 patients treated accord-
ing to RTOG 0617. Dosimetric differences to normal organs were
compared using three-dimensional (3D), intensity-modulated
radiation therapy (IMRT), and volumetric-modulated arc therapy
(VMAT).
RESULTS: A paired-difference test (two-sample t-test) for various
dose parameters was performed. For plans to 74 Gy, there were
statistically significant differences for lung V20 (P = .016), mean
lung (P = .015), and mean esophagus (P = .046) between 3D and
IMRT. There were statistically significant differences for the spinal
cord (P = .38), mean lung (P = .021), mean esophagus (P = .001),
esophagus V60 (P = .001), heart V60 (P = .031), heart V45 (P =
.022), and heart V40 (P = .011) between 3D and VMAT. Comparing
IMRT and VMAT, there was a statistically significant difference for
mean esophagus dose (P = .013). These results were similar for
plans to 60 Gy. There were statistically significant differences for
lung V20 between 3D and IMRT. There were statistically significant differences for the spinal cord, mean esophagus, and heart V45
between 3D and VMAT.
CONCLUSION: For both the 60-Gy and 74-Gy dose levels, signifi-
cant dosimetric advantages (normal tissue sparing) were observed
with IMRT, and a larger benefit was observed for 74-Gy dose
plans. The dose to the esophagus, heart, and lung are likely to be
clinically meaningful in terms of toxicity. VMAT provided benefit
over conventional IMRT at the 60-Gy dose level. Additional studies are warranted to further investigate the impact of advanced
radiotherapy techniques for the delivery of high-dose thoracic
radiotherapy.
(P107) Vero SBRT Treatment of Moving Lung Tumors Charles A. Kunos, MD, PhD, John P. Shanahan, MS; Summa Cancer
Institute
PURPOSE: Intrafraction motion management of moving lung
tumors during stereotactic ablative body radiotherapy (SBRT)
remains challenging. We investigated whether 40%-thresholded
2-[18F] fluoro-2-deoxy-D-glucose (18F-FDG) positron emission
tomography (PET) images enhanced intrafraction tracking capabilities of the Vero SBRT platform.
MATERIALS AND METHODS: Three patients with six total moving
lung tumors had gross tumor volume (GTV) contours created on
free-breathing, end-inspiration, and end-expiration breath-hold
computed tomography (CT) images. A thresholded 40% maximum
standard uptake value 18F-FDG PET contour was generated. The
four individual contours contributed to a single image-guided
internal target volume (ITV). Vero SBRT treatment planning was
conducted on the free-breathing CT dataset, with the ITV expanded all around by 5 mm for a final planning target volume (PTV).
The prescription for each lesion was 40 Gy in four fractions of 10
Gy given every other day. Non-coplanar radiation doses were
determined using a Monte Carlo algorithm. T-test statistics were
calculated to compare parameter means.
RESULTS: The PTV was 23 cm3 on average (standard deviation
[SD] = 18 cm3) without the 18F-FDG PET contour and 36 cm3 on
average (SD = 32 cm3) with the 18F-FDG PET contour (P = .41).
The lung V20 Gy was 2.6% on average (SD = 0.9%) without the 18FFDG PET contour and 2.8% on average (SD = 0.5%) with the 18FFDG PET contour (P = .68). Vero SBRT gimbal pan-and-tilt range
of 4 cm was not exceeded by the addition of the 18F-FDG PET contour to the ITV.
CONCLUSIONS: Overall, 40%-thresholded 18F-FDG PET contours
nonsignificantly enlarge PTVs when multiphase free-breathing,
inspiration, and expiration breath-hold scans are used for Vero
SBRT. Whether 18F-FDG PET contours improve local control of
moving lung tumors treated by Vero SBRT needs further study.
(P108) Stereotactic Body Radiation Therapy for the
Treatment of Large (> 5 cm) Primary Non–Small-Cell
Carcinoma Michael C. Roach, MD, Sana Rehman, MD, Dan Mullen, DDS, Jeff D.
Bradley, MD, Cliff G. Robinson, MD; Washington University
PURPOSE: Patients with inoperable large primary non–small-cell
lung carcinoma (NSCLC) present a therapeutic challenge, given the
concern for radiation delivered to a large volume of the lung. As
such, these patients have so far been excluded from most prospective trials of stereotactic body radiation therapy (SBRT). We evaluated the outcomes of SBRT in the treatment of large primary
NSCLC at our institution.
73
MATERIALS AND METHODS: A total of 25 patients with biopsyproven large NSCLC treated with SBRT alone with definitive
intent were identified from an institutional review board (IRB)approved prospective thoracic SBRT registry. Tumors were
defined as large if they were greater than 5 cm in diameter on
computed tomography (CT) (American Joint Committee on
Cancer [AJCC] T2b or T3). All had positron emission tomography (PET) scans without evidence of nodal metastasis. Patients
were treated to 45–60 Gy in three or five fractions. Patients were
reviewed for overall survival (OS), local control (LC), progression-free survival (PFS), and toxicity, with survival and control
calculated from completion of therapy using the Kaplan-Meier
method. Toxicity was graded according to Common Terminology
Criteria for Adverse Events version 4.03 (CTCAE v4.03).
RESULTS: Mean follow-up was 21 months (range: 2–83 mo).
Median tumor size was 5.5 cm; 23 patients had T2b, and 2 had T3
tumors. Actuarial 2-year OS was 39%, and median survival was
20.1 months. The 2-year PFS was 68%. One patient failed in the
mediastinum, two failed locally and in the mediastinum, one
failed distantly, and one failed both locally and distantly. Both
distant failures occurred in the two patients with T3 tumors. Two
patients developed second primaries in different lobes. At 2 years,
the actuarial rates of local failure and of distant failure were both
9%. Treatment was well tolerated, with 24% developing any chest
wall toxicity (12% grade 1, 8% grade 2, and 4% grade 3). A single
patient (4%) developed a rib fracture, and another developed a
chest wall ulcer. A single patient (4%) required steroids for pneumonitis. CONCLUSIONS: The use of SBRT for T2bN0 primary NSCLC is a
safe, effective, and well-tolerated treatment.
(P109) Standard Immunochemotherapy Plus
Radiation vs Dose-Intense Chemotherapy With
Rituximab in Stage I/II Primary Mediastinal Large
B-Cell Lymphoma: A Single-Institution Experience Michael S. Binkley, BA, Susan M. Hiniker, MD, Sharon Wu, MD, Yaso
Natkunam, MD, PhD, Erik S. Mittra, MD, PhD, Ranjana H. Advani,
MD, Richard T. Hoppe, MD; Stanford University
BACKGROUND: Primary mediastinal large B-cell lymphoma
(PMBCL) is an uncommon variant of diffuse large B cell lymphoma, representing 2% to 3% of cases of non-Hodgkin lymphoma.
Given the limited prospective data and predominantly single-center retrospective reports, the optimal chemotherapy regimen
remains undefined, as does the role of radiation therapy (RT) to the
mediastinum. We sought to investigate factors associated with outcomes among patients who received rituximab with standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and
prednisone [R-CHOP] or etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [R-VACOP-B]) with
RT, compared with those who received dose-adjusted etoposide,
vincristine, doxorubicin, cyclophosphamide, and rituximab
(DA-EPOCH-R).
METHODS: We retrospectively analyzed patients with stage I/II
PMBCL treated in the rituximab era at our institution. Exclusion
74
criteria included stage III/IV disease and follow-up of less than 3
months. Response to chemotherapy was assessed with interim or
postchemotherapy positron emission tomography-computed
tomography (PET-CT) using the Deauville score. We used the
Kaplan-Meier method to determine freedom from progression
(FFP) and overall survival (OS). Patient characteristics were compared using Fisher’s exact test for dichotomous variables and
Wilcoxon rank-sum test for continuous variables.
RESULTS: A total of 28 patients with stage I/II PMBCL were identified and treated at our institution from 2003–2012. Pretreatment
characteristics included age (median 37.5, range: 20–68 yr), female
gender (n = 14), performance score (median 1, range: 0–2), international prognostic indicator (IPI) score (median 1, range: 0–2), B
symptoms (n = 8), elevated lactate dehydrogenase (LDH) (n = 19),
bulk of disease (median 10 cm, range: 4–19.4 cm), and extranodal
disease (n = 10). A total of 14 patients received six cycles of
R-CHOP or 12 weeks of R-VACOP-B and RT (median 36 Gy,
range: 36–45 Gy) and had a median follow-up of 94 months.
Following R-CHOP/R-VACOP-B with irradiation, 5-year FFP and
OS were both 100%. Also, 14 patients received four to eight cycles
DA-EPOCH-R and had a median follow-up of 38 months, with one
patient receiving RT (36 Gy) with postchemotherapy PET-CT
Deauville score 4. Following DA-EPOCH-R, 3-year FFP and OS
were both 100%. Univariate analysis found no significant association between FFP or OS with pretreatment patient characteristics,
chemotherapy type, or PET-CT Deauville score ≥ 4. Acute toxicities included neutropenia (absolute neutrophil count [ANC] < 500
cells/mm3, n = 10), hospitalization for neutropenic fever (n = 6),
and grade 2 radiation pneumonitis (n = 2). Late effects following
RT included hypothyroidism (n = 2).
CONCLUSION: Both R-CHOP/R-VACOP-B with RT and
DA-EPOCH-R demonstrate excellent outcomes. Long-term follow-up will be required to assess potential complications of contemporary RT. Our data support use of standard immunochemotherapy with RT or DA-EPOCH-R as monotherapy.
(P110) Hodgkin Lymphoma and Pregnancy: Treatment
Patterns and Survival Outcomes of Women Treated
With Modern Chemotherapy and Radiotherapy
Eleanor Osborne, MD, Michelle Fanale, MD, Leslie Ballas, MD,
Yasuhiro Oki, MD, Andrea Milbourne, MD, Grace Smith, MD, PhD,
Sarah Milgrom, MD, Valerie Reed, MD, Isidora Arzu, MD, Bouthaina
Dabaja, MD, Chelsea Pinnix, MD, PhD; UT MD Anderson Cancer Center; University of Southern California
PURPOSE: Hodgkin lymphoma (HL) is the fourth most common
malignancy diagnosed during pregnancy. However, the appropriate
management of HL during pregnancy is disputed, and the effect of
suboptimal staging imaging and modified treatment regimens is
unclear. Here, we report treatment approaches and survival outcomes of pregnancy-associated Hodgkin disease at our institution.
METHODS: We performed a single-institution, retrospective analysis of 36 women diagnosed with HL during pregnancy between
1991 and 2014. Kaplan-Meier and chi-square analyses were used to
determine survival outcomes.
RESULTS: Of the initial 36 charts reviewed, 6 patients were excluded due to inadequate long-term follow-up. Among the 30 remaining patients, 24 patients (80%) had stage I/II disease. Six patients
had B symptoms (20%). The median gestational age at diagnosis
was 20 weeks (range: 2–37 wk), with most patients (60%) being
diagnosed in the second trimester. A total of 19 patients (63%) initiated treatment while pregnant (4 with radiation, 15 with chemotherapy). Two women terminated their pregnancies to initiate
treatment, and there were two spontaneous abortions in women
who initiated chemotherapy at 4 weeks and 15 weeks of gestation.
Further, 18 women (60%) had full-term pregnancies (> 37 wk gestation); the median gestational age at delivery was 37 weeks (range:
26–42 wk). A total of 15 women (50%) received both chemotherapy and radiation, 10 (33%) received chemotherapy alone, and 5
(17%) received radiation alone. The majority of patients had a complete response after finishing therapy, but six women (20%) had
progressive or primary refractory disease, and six women (20%)
relapsed.
After a median follow-up of 57.5 months, the mean progressionfree survival (PFS) was 43.4 months (range: 1–261 mo), and the
mean overall survival (OS) was 80.8 months (range: 8–273 mo).
Patients with progressive or primary refractory disease had poorer
outcomes (mean PFS: 10.3 mo vs 49.3 mo, P < .0001; mean OS: 31.2
mo vs 93 mo, P = .0031). Initiating treatment during pregnancy was
not associated with improved outcomes (mean PFS: 13.4 mo vs
46.7 mo, P = .89; mean OS 41.5 mo vs 85.3 mo, P = .81).
CONCLUSION: Overall, outcomes in patients diagnosed with HL in
pregnancy in the modern era of chemotherapy and radiation are
good. As in HL not diagnosed during pregnancy, outcomes are
better in patients with a complete response following initial therapy. Delaying all therapy until the postpartum period is appropriate
in properly selected patients and is not associated with poorer outcomes.
(P111) Single-Isocenter Frameless VolumetricModulated Arc Radiosurgery for Multiple Intracranial
Metastases Steven Lau, MD, PhD, Kaveh Zakeri, MD, Xiao Zhao, MD, Ruben
Carmona, MAS, Erik Knipprath, Daniel R. Simpson, MD, Sameer K.
Nath, MD, Gwe-Ya Kim, PhD, Parag Sanghvi, MD, Jona A. Hattangadi,
MD, Clark C. Chen, MD, PhD, Kevin T. Murphy, MD; University of
California, San Diego; University of California, Davis; Yale University
PURPOSE: Stereotactic radiosurgery is a well-accepted treatment
for patients with intracranial metastases, but outcomes with volumetric-modulated arc radiosurgery (VMAR) are poorly described.
We report our initial clinical experience applying a novel singleisocenter technique to frameless VMAR for simultaneous treatment of multiple intracranial metastases.
METHODS: Between 2009 and 2011, a total of 15 patients underwent
frameless VMAR for multiple intracranial metastases using a single,
centrally located isocenter. Among them, three patients were treated
for progressive or recurrent intracranial disease. A total of 62 metastases (median 3 per patient, range 2–13) were treated to a median
dose of 20 Gy (range: 15–30 Gy). Three patients were treated with
fractionated SRS. Follow-up, including clinical examination and
magnetic resonance imaging (MRI), occurred every 3 months.
RESULTS: Median follow-up for all patients was 7.1 months (range:
1.1–24.3 mo), with 11 patients (73.3%) followed until death. For the
remaining four patients alive at the time of analysis, median followup was 19.6 months (range: 9.2–24.3 mo). Overall survival (OS) at
6 months was 60.0% (95% confidence interval [CI], 40.3%–88.2%).
Local control rates at 6 and 12 months were 91.7% (95% CI, 84.6%–
100.0%) and 81.5% (95% CI, 67.9%–100.0%), respectively. Regional
failure was observed in nine patients (60.0%), and seven patients
(46.7%) received salvage therapy. Grade ≥ 3 treatment-related toxicity was not observed. Median total treatment time was 7.2 minutes (range: 2.8–13.2 min).
CONCLUSIONS: Single-isocenter, frameless VMAR for multiple
intracranial metastases can produce clinical outcomes comparable
with those of conventional radiosurgery techniques.
(P112) Spine Stereotactic Radiosurgery in the Treatment of Metastatic Pheochromocytoma: A Case Series Brian J. Deegan, MD, PhD, Amol J. Ghia, MD, Mary Frances McAleer,
MD, PhD, Xin A. Wang, PhD, Paul D. Brown, MD, Jing Li, MD, PhD;
UT MD Anderson Cancer Center
PURPOSE: Metastasis occurs in approximately 10% of all cases of
pheochromocytoma and can cause significant morbidity and mortality. The axial skeleton is the most frequent site of these metastases. Since good systemic therapy options are lacking, local therapy
remains the cornerstone of palliation for many of these patients.
Due to the poor response of pheochromocytoma to standard fractionated radiotherapy, stereotactic radiosurgery (SRS) is an attractive option to overcome potential radioresistance and provide more
durable local control (LC) of these tumors. Here, we report our
institutional experience in the treatment of spine metastases from
pheochromocytoma with spine SRS (SSRS). METHODS: The available records of patients with metastatic pheochromocytoma treated with SSRS between 2000 and 2014 were
retrospectively reviewed. Four patients with nine treated metastatic spinal lesions were identified. Follow-up spine magnetic resonance imaging (MRI) was used to evaluate LC. Pain and symptom
data were assessed to evaluate toxicity. Kaplan-Meier method was
used to assess LC and overall survival (OS).
RESULTS: Median age at time of SSRS was 55 years (range: 46–63
yr). Median follow-up for each treated site was 11 months (range:
4.5–54.6 mo). Treated areas included C-spine (22%), T-spine
(33%), L-spine (33%), and sacrum (11%). The most common fractionation scheme was 27 Gy in three fractions (55.6%), followed by
24 Gy in one fraction (22.2%), 16 Gy in one fraction (11.1%), and
18 Gy in three fractions (11.1%). Crude LC rate was 100%, with no
local treatment failures observed in the follow-up period. There
were two patient deaths in the group (50%). The Kaplan-Meier OS
from SSRS at 1 year was 75% and 50% at 2 years. Median time to
SSRS from metastatic presentation was 17.6 months (range: 9.2–
72.7 mo). Toxicities included pain (two cases), fatigue (two cases),
and vertebral fracture (one case).
75
CONCLUSION: To our knowledge, this work is the first study
describing the utility of SSRS in the treatment of metastatic pheochromocytoma. Our data suggest that SSRS is an effective, safe, and
durable treatment option. Given the robust tumor control of SSRS
and the possibility for metastatic foci to serve as sources for further
systemic spread, proactive treatment of spinal metastasis earlier in
the disease course may offer therapeutic benefit to these patients.
Larger patient numbers and longer follow-up are required to
address this issue more fully.
(P113) Posttreatment Sequelae for Long-Term
Survivors of Brain Metastases Jared R. Robbins, MD, Raphael L. Yechieli, MD, Parag Sevak, MD, M.
Salim Siddiqui, MD, PhD; Medical College of Wisconsin; University of
Miami; Henry Ford Hospital
PURPOSE/OBJECTIVES: Brain metastases typically portend a poor
outcome, but long-term survival is possible. The purpose of this
study is to evaluate intracranial progression after initial therapy, the
need for salvage treatments, and rates of late toxicity in long-term
brain metastases survivors. MATERIALS AND METHODS: In this institutional review board
(IRB)-approved study, we identified 44 patients with brain metastases surviving > 3 years treated at a single institution from 1987 to
2009. All outcomes were calculated starting at the time of initial
brain metastases. Univariate and multivariate logistic regression
modeling, as well as Kaplan-Meier and log-rank test methods, was
used to characterize outcomes. RESULTS: Median age was 56 years (range: 28–83 yr). Primary sites
were lung 52%, breast 23%, melanoma 11.4%, and other 13.6%.
Initial treatments were 71% surgery followed by radiosurgery to
the cavity (Sx+SRS), 16% whole-brain radiation therapy (WBRT),
9% radiosurgery alone (SRS), and 5% surgery followed by WBRT
(Sx+WBRT). The 5-year, 10-year, and 15-year overall survival
(OS) was 60%, 34%, and 19%, respectively (range: 3–26.5 yr).
Seven failures at the site of initial brain metastasis were observed,
with 1-year, 3-year, and 5-year local control of 98%, 93%, and 84%,
respectively. Salvage for local failures included Sx (43%), Sx+SRS
(29%), SRS (14%), and hospice (14%). New brain metastases
developed in 52%, with 1-year, 3-year, and 5-year freedom from
new brain metastases rates of 79%, 63%, and 44%, respectively.
Initial salvage treatments for new metastases were SRS (45%),
WBRT (14%), surgery (14%), Sx+SRS (18%), Sx+WBRT (5%), and
hospice (5%). After initial treatment, additional salvage therapies
included 20% of patients receiving surgery, 40% receiving SRS, and
25% receiving WBRT. Radiation necrosis (RN) occurred in 27% of
patients, with 1-year, 3-year, and 5-year rates of 5%, 19%, and 32%,
respectively. The median time to RN was 24 months (range: 7–54
mo), and the median survival after RN was 39 months (range:
2–280 mo). Overall, 41% of patients experienced no intracranial
progression, but 22% of them did develop RN. On multivariate
analysis, higher initial Karnofsky performance status (KPS) (P =
.008; hazard ratio [HR] = 0.943) and freedom from new brain
metastases after initial treatment (P ≤ .001; HR = 0.183) were associated with improved survival.
76
CONCLUSIONS: For patients with brain metastases, long-term survival is possible, but the majority of long-term survivors will still
experience intracranial progression and require salvage therapies
after initial treatment. While salvage therapies may control disease,
the development of new metastasis seems to adversely affect survival. RN risk increases over time and may affect a significant portion of long-term survivors. (P114) Radiotherapeutic Care Within the Veterans
Health Administration of US Veterans With Metastatic
Cancer to the Brain: Supportive Measures (Part 1 of 2
Reports) George A. Dawson, MD, Shruti Jolly, MD, Helen Fosmire, MD,
Maria Kelly, MD, Stephen Lutz, MD, Micheal Hagan, MD, PhD, Ruchika Gutt, MD, Drew Moghanaki, MD, MPH, Lori Hoffman-Hogg,
MS, RN, CNS, AOCN, Mitchell Ancher, MD, Alice Cheuk, MD; US
Veterans Healthcare Administration National Palliative Radiotherapy
Task Force
Metastatic cancer to the brain is estimated to occur in 170,000
Americans annually. Of them, over 600 cases occur in US veterans.
Management of brain metastases is complex. Prognostic scoring
criteria and evidence-based guidelines have been developed by
societies, including the American Society of Radiation Oncology
(ASTRO), to provide guidance in the care of patients with metastatic brain cancer. Patterns of care among Veterans Health
Administration radiation oncologists (VHA ROs) in the treatment
of brain metastases are not known.
METHOD: An electronic survey was sent to all (82) VHA ROs at 38
active VHA radiation oncology centers. Follow-up phone calls were
made to nonresponders. The survey inquired about supportive
measures, including the number of brain metastases consults seen
per year, steroid usage and dosing, use of the Radiotherapy
Oncology Group (RTOG)-recursive partitioning analysis (RPA) or
diagnosis-specific graded prognostic assessment (GPA) prognostic
score, onsite availability of stereotactic radiosurgery (SRS), and
demographics. Additional information about VHA ROs regarding
their employment status, years in practice, and academic appointments was also obtained.
RESULTS: A total of 62 of 82 VHA ROs responded to the questionnaire (76%). Most respondents had academic appointments (70%).
Most respondents (79%) received more than 10 consults annually.
A total of 89% only used steroids in the setting of neurological
changes or edema, while ~10% always used steroids for brain
metastases. Prognostic scores for brain metastases were used routinely by only 42% of VHA ROs. The RTOG-RPA classification was
used the most (73%). Physicians in practice for less than 5 years (P
= .024) and full-time employees (P < .001) were more likely to use
prognostic scoring. Also, 69% of surveyed sites referred to another
VA or VA-contracted facility for SRS services when required (31%
+ SRS onsite). The most common dexamethasone dose was 16 mg/day, used by
54% of the respondents.
CONCLUSIONS: Veterans with brain metastases treated at VHA
radiation oncology centers receive appropriate care. Still, the use of
prognostic indices in treatment decision-making is statistically significantly more likely in cases treated by recent training program
graduates. Given the relatively recent development of these scoring
systems, educational efforts need to be devoted to increasing their
use in the clinic.
(P115) The Experience of a Radiation Oncology Center
in Gauging the Use of Single-Fraction Radiotherapy for
Painful Bone Metastases
George A. Dawson, MD, Ignat Glushko, MBA, Alice V. Cheuk, MD; Veterans Health Administration
BACKGROUND: There is mounting category 1 evidence of the effectiveness of single-fraction radiotherapy (SFRT) in the treatment of
uncomplicated, painful bone metastases [Jones, CA Cancer J Clin
2014]. Surveys indicate that physicians in the United States still
prefer multiple fractions of RT for uncomplicated bone metastases
compared with their Canadian or European colleagues [Popovic et
al, Radiother Oncol 2014].
In this report, we used current procedure terminology (CPT) code
tracking to determine the scope of use of SFRT for painful malignant bone lesions compared with multiple-fraction RT (MFRT).
METHOD: We searched for encounters with an International
Classification of Diseases (ICD) code 198.5—Secondary malignancy of bone and/or bone marrow either in primary or secondary
positions—and current procedural terminology (CPT) code
77431—Physician weekly visit for 1–2 treatments. Data points
below represent 77431 usage only.
From 2002 to 2008, usage was as follows: 2002 (0), 2003 (0), 2004
(5), 2005 (1), 2006 (7), 2007 (4), and 2008 (0). From 2009 to
October 13, 2014, usage was as follows: 2009 (0), 2010 (0), 2011 (4),
2012 (12), 2013 (10), and 2014 (8). These periods were chosen to
reflect a surge in interest in SFRT usage at the end of life, such as
the Choosing Wisely Campaign of the American Society of
Radiation Oncology in 2013.
Data limitations/assumptions: Not all providers code appropriately
for both procedures and diagnosis.
RESULTS: We noted a 133% increase in the use of SFRT for painful
bone lesions at our center from 2002–2008 to 2009–October 13,
2014. On average, CPT code 77431 was used 2.43 times a year for
patients with ICD code 198.5 of bone metastases from 2002–2008,
and 5.67 times (8.50 times, excluding 2009 and 2010) from 2009–
October 13, 2014. Of note, in 2002, 2003, 2008, 2009, and 2010,
CPT code 77431 was not used at all.
CONCLUSION: We observed an increase in the use of SFRT for
bone metastases over the time period covered. Tracking the
encounters by ICD codes and CPT codes, when properly coded,
served as a useful tool in providing a snapshot view of SFRT usage.
Additionally, physician education is a prerequisite for the proper
use of a CPT 77431 to capture the true rate of usage of SFRT in
clinical practice.
(P116) Pain and Radiographic Control After Stereotactic
Radiosurgery for Spinal Metastases From Hepatocellular Carcinoma: A Comparison With Other Radioresistant
Histologies
Todd J. Carpenter, MD, Michael H. Buckstein, MD, PhD, Eddie Zhang,
BS, Seth Blacksburg, MD, MBA, Isabelle M. Germano, MD, Sheryl
Green, MBBCH; Department of Radiation Oncology, Department of
Neurosurgery, Icahn School of Medicine at Mount Sinai; Department of
Radiation Oncology, Winthrop University Hospital
PURPOSE: We sought to determine the relative radioresistance of
hepatocellular carcinoma (HCC) by evaluating the clinical efficacy
of stereotactic radiosurgery (SRS) for spinal metastases from HCC
compared with outcomes in patients with classically radioresistant
histologies in terms of local control (LC) and pain control.
MATERIALS AND METHODS: We performed a retrospective review
of all patients treated at our institution with spine SRS for metastatic HCC, renal cell carcinoma, melanoma, and sarcoma from
January 2007 through May 2014. Radiographic control and
patient-reported pain control were analyzed as a function of various patient- and treatment-related parameters.
RESULTS: Of 134 lesions in 96 patients treated with spine SRS
during the study period, 41 were radioresistant histologies,
including 18 HCC, 1 mixed HCC/cholangiocarcinoma, 15 renal
cell carcinoma, 6 melanoma, and 1 leiomyosarcoma. Median age
was 61 years. Extraosseous disease was present in 63% overall
(74% and 55% in HCC and non-HCC patients, respectively; P =
NS). Spinal cord compression was present in 29% (32% and 27%
in HCC and non-HCC patients, respectively; P = NS), and 24%
had decompressive surgery prior to SRS (26% and 23% in HCC
and non-HCC patients, respectively; P = NS). Median dose was
18 Gy (range: 14–18 Gy), with no difference between groups.
Follow-up imaging was available for 35 patients. With a median
follow-up of 6.4 months, actuarial 3-, 6-, and 12-month LC rates
for HCC and non-HCC patients were 74%, 65%, and 35% and
94%, 94%, and 85%, respectively (P = .0383). Median time to local
failure was 3.5 months for HCC patients and 10.7 months for
non-HCC patients. On multivariate analysis (MVA), there was
significantly worse LC with HCC histology (P = .0257). Of the 29
patients reporting pretreatment pain, initial pain relief was
achieved in 27 (93%); both patients who did not experience initial
pain relief had HCC. Actuarial 3-, 6-, and 12-month pain control
rates for HCC and non-HCC patients were 73%, 61%, and 23%
and 100%, 90%, and 90%, respectively (P = .0405). This interaction remained significant on MVA (P = .0414).
CONCLUSIONS: When treated with SRS to the spine, metastatic
HCC has worse pain and radiographic control than other highly
radioresistant histologies, suggesting that HCC should be included in the category of highly radioresistant tumors. Whether these
lesions may benefit from further dose escalation and/or alternate
treatment strategies will be the subject of future studies.
77
(P117) Outcomes, Patterns of Failures, and Toxicity
for Patients Diagnosed With Pulmonary Metastases
Treated With Stereotactic Body Ablative Radiotherapy
(SABR) Quynh-Nhu Nguyen, MD, William C. Chance, MD, Peter Balter, PhD,
Jim Welsh, MD, Daniel Gomez, MD, Ritsuko Komaki, MD, Zhongxing
Liao, MD, Joe Chang, MD, PhD, Reza J. Mehran, MD; UT MD Anderson
Cancer Center
PURPOSE: To report patterns of failure, outcomes, and toxicity for
patients with pulmonary metastases treated with stereotactic body
ablative radiotherapy (SABR).
METHODS: From 2007 to 2014, a total of 49 patients with 61 pulmonary metastases were irradiated with SABR doses. Primary histology included: lung (n = 14), gastrointestinal (GI) (n = 15), sarcoma (n = 5), head/neck (n = 6), genitourinary (GU) (n = 3),
melanoma (n = 3), endometrial (n = 2), and adrenal (n = 1). SABR
doses were prescribed by tumor location and proximity to critical
structures (central vs peripheral). The majority of metastases
received 50 Gy in four fractions (n = 48), 70 Gy in 10 fractions (n
= 3), 40 Gy in four fractions (n = 4), 50 Gy in five fractions (n = 1),
or 45 Gy–60 Gy in 10 fractions (n = 5). Local failures were defined
as recurrence within the high-dose region; locoregional failures
included recurrences outside of the high-dose region, within the
same lobe, or lymph nodes; and distant failures occurred in a separate lobe or outside of the thorax.
RESULTS: The 1-year and 2-year overall survival (OS) rates were
88% and 66%, respectively, with a median OS time of 29.1 months.
The 1-year and 2-year progression-free survival (PFS) rates were
64% and 45%, respectively, with a median PFS time of 19.9 months.
The 1-year and 2-year freedom from local failure rates were 94%
and 84%, respectively. The 1-year and 2-year freedom from locoregional failure rates were 80% and 63%, respectively. The 1-year and
2-year distant metastases–free survival rates were 72% and 51%,
respectively, with a median time to new distant metastases of 26.9
months. The toxicities included brachial plexopathy (grade 2, n =
2), radiation pneumonitis (grade 3, n = 1), and chest wall toxicity
(grade 2, n = 7).
CONCLUSION: SABR is an effective treatment modality for patients
with pulmonary metastases, with excellent local control. Further
studies are warranted to elucidate which patients with pulmonary
metastases would benefit from the local control with SABR and
determine when to treat with systemic therapy due to quick progression of distant metastases.
(P118) Radiotherapeutic Care Within the Veterans
Health Administration of US Veterans With Metastatic
Cancer to the Brain: Part 2 Clinical Treatment Patterns Alice V. Cheuk, MD, Ruchika Gutt, MD, Drew Moghanaki, MD, MPH,
Michael Hagan, MD, PhD, Stephen Lutz, MD, Shruti Jolly, MD, Helen
Fosmire, MD, Maria D. Kelly, MD, Lori Hoffman-Hogg, MS, RN, CNS,
AOCN, Mitchell Anscher, MD, George A. Dawson, MD; US Veterans
Healthcare Administration National Palliative Radiotherapy Taskforce
PURPOSE: Optimal radiation treatment (RT) for brain metastases
78
must be individually tailored. Treatment guidelines by the
American Society for Radiation Oncology (ASTRO) were used as
the basis for a study of practice patterns among Veterans Health
Administration (VHA) radiation oncologists (ROs).
Radiotherapeutic interventions for three clinical scenarios were
correlated with ASTRO guidelines.
METHODS: A survey was sent to all VHA ROs (n = 82). ROs were
asked for treatment recommendations, which were analyzed by
employment status, academic appointment, and years in practice.
SCENARIOS: (1) Uncontrolled non–small-cell lung cancer
(NSCLC) with hemiplegia, > 10 brain metastases, Karnofsky performance status (KPS) 30, and life expectancy (LE) < 3 months. (2)
Controlled NSCLC with hemiplegia, 4–6 brain metastases, KPS 70,
and LE > 4 months. (3) New NSCLC without symptoms, 2 small
brain lesions, KPS 90, and LE > 6 months.
Treatment options for scenarios 1 and 2 were: supportive care
alone, steroids only, whole-brain RT (WBRT), and stereotactic
radiosurgery (SRS). Options for scenario 3 were: resection with
postoperative WBRT, SRS plus WBRT, SRS alone, and WBRT
alone. ROs were asked to provide a WBRT dose fraction scheme for
each selected case.
RESULTS: The survey response rate was 76%. Scenario 1: The
majority (66%) of respondents chose WBRT, with 58% prescribing
3,000 cGy in 10 fractions and 42% delivering 2,000 cGy in 5 fractions. The others (34%) chose no intervention or steroids only.
Full-time (FT) employees were more likely to choose WBRT (P <
.001) compared with part-time (PT) employees and contractors.
Those with an academic appointment and greater number of years
in practice (P < .001) also chose WBRT more frequently. Scenario
2: Nearly all (98%) ROs recommended WBRT; 3,000 cGy in 10
fractions was the most common fractionation. There was an association with having an academic appointment, being an FT
employee, being in practice less than 5 years, and choosing WBRT
(P < .001). Scenario 3: FT employees (64%) and those with academic appointments were more likely to choose SRS alone (P <
.001) compared with others. ROs in practice for 6–20 years preferred to do SRS with WBRT (P < .001).
CONCLUSIONS: ROs in practice less than 5 years, with academic
appointments, or with an FT status had statistically significant
associations with WBRT/SRS choice. In poor-prognosis patients,
consideration of best supportive care measures is done, and shortcourse RT is often recommended. For patients with good KPS and
limited small brain metastases, SRS with or without WBRT is recommended by most practitioners in accordance with ASTRO
guidelines.
(P119) Electronic Brachytherapy Management of
Atypical Fibroxanthoma: Report of Seven Cases Stephen W. Doggett, MD; Aegis Oncology
PURPOSE: To evaluate the suitability of treating an uncommon
skin malignancy, atypical fibroxanthoma (AFX), with electronic
brachytherapy.
MATERIALS AND METHODS: From February 2013 to September
2014, we were referred a total of seven cases of AFX, all involving
the scalp. All were treated with electronic brachytherapy 50 kV
radiation (Xoft Inc., Fremont, California). All lesions received 40
Gy in two fractions per week; 5-mm margins were utilized.
RESULTS: As of October 2014, there has been one local recurrence,
which was the only lesion that was not debulked surgically prior to
electronic brachytherapy.
CONCLUSIONS: AFX is a rare skin cancer that is believed to be of
mesenchymal origin, likely histiocytic. A less likely possibility is
that it is derived from dedifferentiated squamous cell cancer. This
is the largest reported series of AFX treated with radiation therapy
in the literature. No contraindication to the use of radiation is
found in the literature. Prior series all utilized surgery, likely due to
the clinically rapid progression of this tumor. Risk of recurrence is
mitigated with surgical debulking prior to brachytherapy.
Electronic brachytherapy appears to be a safe and effective treatment for AFX.
(P120) Pregnancy and Parenthood in Radiation
Oncology, Views and Experiences Survey (PROVES):
Results of a Blinded Prospective Trainee Parenting
and Career Development Assessment Emma B. Holliday, Awad A. Ahmed, Reshma Jagsi, Natalie Clark,
Wendy A. Woodward, Clifton D. Fuller, Charles R. Thomas, Jr; UT MD
Anderson Cancer Center; UT Southwestern Medical Center; University
of Michigan; Oregon Health and Science University Knight Cancer Institute
BACKGROUND: Medical school and residency span nearly a
decade, during which many students and residents traditionally
begin families. As the number of women entering medicine
increases, the effects of pregnancy and childbearing on residency
experience, research productivity, and career aspirations should be
explored. Although men increasingly share childrearing responsibilities in the modern era, recognizing gender differences in time
spent in childcare duties and the potential effect on residency
experience is paramount to understanding the generational evolution of modern family dynamics for physician-led families.
METHODS: An anonymous, voluntary, 102-item online survey was
distributed via email to 540 current radiation oncology residents
and 2014 graduates. Respondents were asked about demographics,
marital and parental status, pregnancy during residency, publication productivity, career aspirations, and experiences working
with pregnant co-residents. Respondents with children were additionally asked about childcare arrangements. Women who had
been pregnant during residency were further asked questions
regarding radiation safety, maternity leave, and breastfeeding
experiences.
RESULTS: A total of 190 respondents completed the survey—107
(56.3%) men and 84 (43.7%) women—for a 35.2% response rate;
97 respondents (51.1%) were parents, and 84 (44.2%) reported
that they or their spouse/partner had become pregnant during
residency. Also, 52 women (54.2%) and 31 men (33%) (P = .003)
reported delaying starting a family due to residency-related reasons. Respondents with children were more often male (65% vs
47.3%; P = .014), were in a higher level of training (79.3% vs 54.8%
of respondents were PGY4 or higher; P = .001), were older (median age 32 yr, interquartile range [IQR]: 31–35 yr vs 30, IQR: 29–33
y; P < .001), had a PhD (33% vs 19.3%; P = .033), were married
(99% vs 43%; P < .001), and had a spouse/partner who did not
work (24.7% vs 1.9%; P < .001). There was no difference in the
number of manuscripts published or expressed likelihood of pursing an academic career by parental status. Among parents, men
more often had spouses/partners who did not work (38.1% vs 0%;
P < .001), reported that their spouse/partner performed a greater
percentage of childcare duties (70%, IQR: 60%–80% vs 35%, IQR:
20%–50%; P < .001), and reported that their spouse/partner was
more likely to take care of unexpected childcare duties (74.6% vs
31%; P < .001). Common concerns expressed by women with children included radiation safety, maternity leave, breastfeeding, and
effects of pregnancy on clinical training, research experience, and
their co-residents’ workload.
CONCLUSIONS: Pregnancy and parenthood are common during
residency. Women are responsible for more childcare duties than
men but have similar research productivity and career aspirations.
Further follow-up is necessary to determine the relationship
between pregnancy and parenthood over time.
(P121) Image-Guided Radiation Therapy Utilization
and Practice Patterns: Results From a National Survey
of ASTRO Membership Nima Nabavizadeh, MD, David A. Elliott, MD, Aaron Kusano, MD,
Yiyi Chen, PhD, Timur Mitin, MD, PhD, John M. Holland; Oregon
Health and Science University; University of Washington
INTRODUCTION: Image-guided radiation therapy (IGRT) practices differ widely across institutions, with no consensus regarding
ideal pretreatment imaging modality, frequency, or verification
process. The purpose of this study is to survey clinical IGRT practice patterns and their impact on clinical workflow.
METHODS: A total of 5,979 surveys were emailed to the membership of the American Society of Radiation Oncology (ASTRO). The
disease site–specific survey consisted of questions pertaining to
planning target volume (PTV) margins, pretreatment image guidance modality/frequency, and method of image verification, as well
as questions regarding the utility and value of IGRT. Online image
verification was defined as images checked and corrected prior to
the day’s treatment. Offline image verification was defined as images obtained prior to treatment and then verified prior to the following day’s treatment. Associations between IGRT practice patterns
and PTV margin size were examined using a linear regression
model.
RESULTS: Of 671 responses (11%), 70 were nonphysician, resulting
in 601 evaluable responses. The majority of respondents used IGRT
(99%) for at least one fraction, with cone-beam computed tomography (CBCT) being the most commonly used modality (85%).
Daily CBCT was obtained most frequently for intact prostate
(63%), followed by prostatic fossa (60%), head and neck (H/N)
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(52%), pelvic intensity-modulated RT (51%), lung (50%), esophagus (40%), central nervous system (39%), and breast (7%).
Regardless of imaging modality, daily online or offline image verification was the most common schedule (range: 72%–96% daily,
4%–24% weekly, and 1%–3% first few fractions only). Online
image verification was most common for H/N (92%) and least
common for breast (77%), with first-few-fractions–only online
schedules most common for all disease sites except breast. The
majority of respondents felt comfortable with therapists verifying
IGRT independent of a physician (54%) and did not believe IGRT
techniques negatively impacted clinical productivity (53%) or the
physician-patient relationship due to excessive interruptions (57%).
Additionally, the majority of respondents agreed that for pediatric
cases, the benefits of IGRT outweighed the risks of additional radiation exposure (85%). No association was seen between IGRT frequency or method of verification and PTV margin size (P > .05 for
all comparisons).
CONCLUSION: IGRT use is widespread, without standardization of
pretreatment imaging modality, frequency, or verification process.
Additionally, PTV margin size selection does not appear to be
based on IGRT frequency or method of verification. Further
research aimed at optimizing IGRT techniques is needed to ensure
accurate, safe, timely, and cost-effective treatment delivery. (P122) Older African Americans’ Use of Religious Music
to Cope With Cancer Jill B. Hamilton, PhD, Angelo D. Moore, PhD, FNP, Kayoll Galbraith,
BSN, Peter A. Johnstone, MD; Johns Hopkins University School of Nursing; Center for Nursing Science and Clinical Inquiry, Womack Army
Medical Center, US Army; University of North Carolina, Chapel Hill;
Moffitt Cancer Center
OBJECTIVE: Among Americans, African Americans are more like-
ly to pray at least daily, report affiliations with a religious group,
indicate that religion is very important in their lives, and indicate
that they are certain God exists. An extensive body of literature on
African-American spirituals informs regarding the use of religious
songs to manage life stressors, such as a cancer diagnosis.
METHODS: A total of 65 African-American men and women
residing in the southeastern United States were interviewed.
Inclusion criteria included: African-American ethnicity by selfreport, age at least 50 years, and having experienced the loss of a
loved one or a life-threatening illness. Semistructured interviews
lasting 15–60 min were conducted between 2008 and 2010. These
interviews were held in participants’ homes or private rooms
located in their churches. Participants were given a $25 gift card
for participating. All interviews were audiotaped and transcribed
verbatim. Initial steps of content analysis were to construct a table
that organized the data collected, including participants’ responses on whether a song, scripture, or prayer was used; the words of
the songs, scriptures, and prayers; the personal meanings of the
songs, scriptures, or prayers; and the outcomes derived from using
any of these religious expressions. Five categories of religious
songs derived from the data were: Thanksgiving and Praise,
Instructive, Memory of Forefathers, Communication With God,
and Belief in Life After Death. 80
RESULTS: Of the participants interviewed, 23 indicated that cancer
was their most stressful life event. The most frequent type song used
was Thanksgiving and Praise (n = 9, 39%), followed by Instructive
(n = 8, 35%), Communication with God (n = 7, 30%), Belief in Life
after Death (n = 5, 22%), and Memory of Forefathers (n = 3, 13%).
The most frequently reported outcomes were comfort (n = 9, 39%),
hope (n = 9, 39%), and strength (n = 9, 39%). The least frequently
reported outcomes were peace of mind (n = 8, 35%), support (n = 6,
26%), protection (n = 1, 4%), and guidance (n = 1, 4%).
CONCLUSIONS: Religion and particularly the use of religious songs
are important aspects of coping with the cancer experience among
older African Americans. During diagnosis and treatment, a religious song is likely to be a viable complement to therapies for
symptom reduction and mood elevation among this population.
(P123) Reducing Time From Patient CT Simulation
(CT SIM) Appointment Time to Start of Actual CT Scan:
Lean Thinking in the VA System Alice V. Cheuk, MD, George A. Dawson, MD, Jorge H. Restrepo, AS;
James J. Peters VA Medical Center
PURPOSE: Computed tomography simulation (CT SIM) is vital to
planning a patient’s radiation treatment (RT) and often takes a considerable amount of time to perform. This is particularly true of
prostate patients, who have to drink until their bladders are full for
the scan. CT SIM appointments are scheduled for 60 minutes, but
preliminary observations have found that images are often acquired
after the hour mark. The goal of the study was to reduce the time
from CT SIM appointment/registration time to actual CT image
acquisition for prostate CT SIMs, using Lean methodology.
METHODS: Observation of the process was performed (Gemba
walking) to map out the current process and to document time
from appointment/registration to actual CT image acquisition.
Each step in the process was diagrammed, timed, and recorded.
The current map underwent workflow analysis, and areas of delay/
redundancy were modified or eliminated. A new process map was
generated and put into practice. Five CT SIMs were timed and
recorded as before. A sustain plan was implemented, involving
measures to maintain use of the new map, and CT SIMs were timed
to ensure continuation of the new process.
RESULTS: A total of 10 CT SIMs were timed with the old process,
and the average time was 46.6 minutes. On analysis, the old process
map had 16 steps with major barriers, which included time needed
to consume water before CT SIM, time for consent, and delays
caused by patients needing to urinate before the scan, requiring the
process to be restarted from the beginning. Several steps were eliminated/consolidated, including waiting for the consent to be completed before starting the drinking process (consolidated), having
the front desk call therapists to notify them that the patient is ready
(eliminated), and having therapists tell the patient to start drinking
(eliminated). After these changes were made, there were 10 steps in
the new process map, and the average time for CT acquisition was
shortened to 36.2 minutes, a 22% improvement. These changes
were maintained with the sustain plan, as revealed by an acquisition time of 32 minutes during the sustain phase.
CONCLUSIONS: By applying Lean thinking, we were able to reduce
the time for CT image acquisition for prostate cancer patients
requiring radiotherapy planning by 22%. By reducing the time for
CT SIM, veterans’ experiences and satisfaction were improved, flow
through the radiation oncology department was optimized, and
capacity for CT SIMs was increased.
(P124) Dosimetric Comparison of Three-Dimensional
Conformal Proton Radiotherapy and IntensityModulated Proton Therapy for Treatment of Pediatric
Hodgkin Lymphoma Jamie M. Pinckard, BS, William W. Chance, MD, Cody N.
Crawford, CMD, Shengpeng Jiang, Xiaodong Zhang, PhD, Anita
Mahajan, MD; UT Health Science Center, San Antonio; UT MD Anderson Cancer Center
OBJECTIVES: Thoracic irradiation in pediatric patients is associated with serious long-term adverse effects. We compared the target coverage and dose distribution in normal tissues in pediatric
patients with Hodgkin lymphoma using three-dimensional conformal proton radiotherapy (3DPRT) and intensity-modulated proton
therapy (IMPT).
METHODS: From 2009–2014, seven pediatric patients with
Hodgkin lymphoma with intrathoracic involvement received proton therapy to 21–25.2 Cobalt Gray Equivalents (CGE) in 15 fractions. Five patients received 3DPRT, and two patients received
IMPT. To compare dosimetric endpoints between the modalities,
an additional 3DPRT or IMPT plan was generated for each patient
(n = 14 plans). Mean doses to target and nontarget tissues were
then compared between 3DPRT and IMPT using the Wilcoxon
matched-pair signed-rank test.
RESULTS: The planning target volume was adequately treated using
both techniques. When compared to 3DPRT, IMPT resulted in a
lower mean total lung dose (632 cGy vs 737 cGy; P < .05) and mean
heart dose (797 cGy vs 972 cGy; P < .05). The mean dose to the
breasts, thyroid gland, esophagus, pancreas, stomach, and liver
were similar between the modalities.
CONCLUSIONS: In pediatric patients with intrathoracic involvement, IMPT produced significantly lower doses to the lung and
heart compared with 3DPRT. Additional studies will be needed to
determine the clinical benefit of these findings. (P125) Glioblastoma Multiforme Outcome Comparison
Between Pediatrics and Adults: Is There a Difference? Dayssy A. Diaz, MD, Duran Mitchell, Isildinha Reis, PhD, Joseph Panoff,
MD; Department of Radiation Oncology, Division of Biostatistics, Department of Public Health Sciences, University of Miami
PURPOSE: There is a paucity of data regarding the clinical outcome of glioblastoma multiforme (GBM) in the pediatric population. Previous data suggest that there is a difference in overall survival (OS) between pediatric patients and adult patients with
GBMs; however, there have been no direct comparisons in the
literature. We compared pediatric and adult GBM outcome mea
sures using the Surveillance, Epidemiology, and End Results
(SEER) database, a program of the National Cancer Institute that
collects cancer incidence and survival data from approximately
28% of the US population.
MATERIALS AND METHODS: Patients with pathologically confirmed grade 4 gliomas diagnosed between 1980 and 2011 were
included in this analysis. Patients aged older than 60 years were
excluded from the analysis. Pediatric cases were classified as those
aged ≤ 21 years. Cause-specific survival (CSS) and overall survival
(OS) were estimated by Kaplan-Meier (product-limit) method. Cox
proportional hazards analyses were performed, evaluating potential predictors of CSS and OS.
RESULTS: There were 6,351 patients available for comparison;
6,099 patients were adults, and 252 patients were pediatric. The
median age for the pediatric patients was 13 years, and the median
age for the adults was 52 years. The OS time was the same as the
CSS for pediatric patients (16 mo). The same observation was seen
for adults (12 mo). Pediatric patients had a significantly better OS
(P < .001) and CSS (P < .0001) when compared with adults. The
3-year OS was 23.4% for pediatrics vs 11.8% for adults, and the
3-year CSS was 24.3% for pediatrics vs 12.9% for adults. These
results persisted when stratified by decade of diagnosis (1980s: P =
.0008; 1990s: P = .0229; and 2000s: P < .0001). Univariate analysis
indicated female sex (P = .03), use of radiation (P < .0001), surgical
resection (P < .0001), age (P < .0001), recent year of diagnosis (P <
.0001), and pediatric patients (P < .0001) to be significant predictors of improved OS. Multivariate analysis demonstrated that pediatric status, use of surgery, use of radiation, and recent decade of
diagnosis were significant predictors of OS and CSS (P < .0001 for
all variables). Race was found to be a significant predictor of CSS
(P = .0132) but not of OS (P = .667).
CONCLUSION: This is the first report to directly compare pediatric
and adult patients with GBM. Pediatric patients had significantly
superior OS and CSS when compared with adults, and these differences remained significant over time and on multivariate analysis.
The underlying cause of these survival differences between pediatrics and adults requires exploration, with attention to molecular
biological tumor differences.
(P126) Long-Term Volumetric Follow-Up of Juvenile
Pilocytic Astrocytomas Treated With Proton Beam
Radiotherapy Edward M. Mannina, MD, MPH, MS, Greg Bartlett, CMD, Peter A.
Johnstone, MD, Kevin P. Mcmullen, MD; Indiana University School of
Medicine; University Of South Florida
INTRODUCTION: Juvenile pilocytic astrocytomas (JPAs) are World
Health Organization (WHO) grade 1 glial neoplasms treated by
resection with radiotherapy reserved for inoperable cases or following subtotal resection. Proton radiotherapy minimizes integral
dose and is thus preferred in children. We analyzed the magnetic
resonance imaging (MRI) follow-up of patients with JPA treated
with proton radiotherapy to define the volume changes, response
rate, need for postradiotherapy intervention, and survival.
81
METHODS: A total of 15 pediatric patients histologically diagnosed
with JPA made up this retrospective report. From August 2005
through March 2012, patients were treated to a median dose of
5,400 cGy (relative biological effectiveness [RBE]) using proton
radiotherapy and then followed with serial MRIs for 3 years. MRIs
were imported into Eclipse 11 treatment planning software, where
contours of the T1 contrast-enhancing volumes, including cystic
components, were generated by one clinical radiation oncologist
(EMM). Volume in cm3 was plotted against time since completion
of therapy to track volumetric changes. Demographics, prior therapies, and postradiotherapy interventions were cataloged.
RESULTS: This is a retrospective review of 15 patients with a mean
age of 10.9 years (range: 4–20 yr) and mean number of 8.9 MRIs
(range: 4–12). A total of 10 of 15 (67%) patients had prior R2
resections, with 3 patients having two R2 resections. Further, 12 of
15 (80%) patients had cerebrospinal fluid (CSF) shunts prior to
radiotherapy, and 9 of 15 (60%) patients received prior chemotherapy, all with at least a platinum agent and vincristine. With a
median follow-up of 55.3 months, 14 of 15 (93%) patients were
alive, for an estimated 5-year overall survival (OS) of 93.3%.
Median event-free survival (EFS) was 86.6 months, with an estimated 5-year EFS of 72.2%. A total of 11 of 15 (73.3%) patients
were declared to be responders by 6 months, with 3 of 11 (27%)
demonstrating pseudoprogression (increase in volume followed
by spontaneous regression), with a mean time to maximum volume of 177 days. Also, 4 of 15 (26.7%) patients were nonresponders, including one who died of progression 9 months after
radiotherapy and another who restarted chemotherapy. Three
patients underwent shunt revisions, while two received hyperbaric oxygen, one for presumed radionecrosis and another for
biopsy-proven radionecrosis (the only patient with prior radiation). Stereotactic cyst aspiration was required in one case. One
heavily pretreated patient developed a hematologic malignancy
requiring further chemotherapy. A total of 8 of 15 (53.3%) patients
required no further therapy or intervention after radiotherapy.
Gross tumor volume changes ranged from a 91% reduction to a
207% increase during the evaluation period. CONCLUSIONS: Pediatric patients with PAs can have extended survival following proton beam radiotherapy. This volumetric study
illustrates that responders are declared within 6 months, but vigilant surveillance is necessary due to the potential need for postradiotherapy interventions.
(P127) Stereotactic Accelerated Partial Breast Irradiation (SAPBI) for Early-Stage Breast Cancer: Rationale,
Feasibility, and Early Experience Using the CyberKnife
Radiosurgery Delivery Platform
Olusola Obayomi-Davies, MD, Bridget Oppong, MD, Sonali Rudra,
MD, Erini Makariou, MD, Lloyd D. Campbell, CMD, Kaiguo Yan, PhD,
Leonard Chen, MD, PhD, Simeng Suy, PhD, Sean P. Collins, MD, PhD,
Keith Unger, MD, Eleni Tousimis, MD, Brian T. Collins, MD; Georgetown University Hospital
BACKGROUND: The efficacy of accelerated partial breast irradiation (PBI) utilizing brachytherapy or conventional external beam
radiation has been studied in early-stage breast cancer treated with
82
breast-conserving surgery. Data regarding stereotactic treatment
approaches are emerging. The CyberKnife linear accelerator
enables excellent dose conformality to target structures while
adjusting for target and patient motion. We report our institutional experience on the technical feasibility and rationale for stereotactic accelerated PBI (SAPBI) delivery using the CyberKnife radiosurgery system.
METHODS: From February 2013 to December 2013, a total of 10
patients received CyberKnife SAPBI. Four gold fiducials were
implanted around the lumpectomy cavity prior to treatment
under ultrasound guidance. Fiducials were tracked in real time
using the Synchrony tracking system. The clinical target volume
(CTV) was defined on contrast-enhanced computed tomography
(CT) scans using surgical clips and postoperative changes. Inverse
CyberKnife plans were generated to deliver 30 Gy in five fractions
to a 5-mm uniform expansion around the CTV (PTV30Gy). PTV
and organs at risk (OARs) dosimetry were assessed as per the
National Surgical Adjuvant Breast and Bowel Project (NSABP)
B-39 study, and cosmesis was assessed using the Harvard breast
cosmesis scale.
RESULTS: At least three fiducials were tracked in 100% of cases.
The mean PTV30Gy was 70 cm3, and the mean prescription isodose line was 80%. A total of 100% of the PTV30Gy received the
prescription dose, with a mean maximum dose of 36 Gy. The mean
ipsilateral breast V30Gy and V>15Gy were 14% and 31%, respectively. The ipsilateral lung V9Gy was 3%, and the contralateral lung
V1.5Gy was 8%. For left-sided breast cancers, the heart V1.5Gy was
31%, with a mean heart dose of 1 Gy. The mean contralateral breast
maximum dose was 3 Gy. The maximum skin and chest wall doses
were 32 Gy and 33 Gy, respectively. One patient experienced grade
1 skin induration 3 weeks after treatment, which resolved with
observation. At a median follow-up of 46 weeks, all patients have
experienced good/excellent cosmetic outcomes, and no significant
adverse outcomes have been reported.
CONCLUSIONS: SAPBI via CyberKnife is a suitable platform for
partial breast irradiation, offering improvements over existing
APBI techniques, with excellent normal tissue-sparing. Our early
findings indicate that CyberKnife SAPBI delivered in five fractions
is a feasible, well-tolerated, and reliable platform for delivering PBI. (P128) Statistically Significant Calibration Curve
for Ir-192 HDR Source Using Multichannel Gafchromic
Film Analysis J. Barbiere, J. Napoli, A. Ndlovu; HUMC
PURPOSE: This work presents a unique methodology to create statistically valid calibration curves required to validate high-doserate (HDR)–planned dose distributions during brachytherapy
treatment planning commissioning. A robust calibration curve is
essential to accurately convert measured planar Gafchromic film
density to dose for comparison with calculated dose distributions
using standard metrics. The process presented herein is appropriate
for widespread application since it can be used with any planning/
analysis system that is capable of DICOM (Digital Imaging and
COmmunication in Medicine) dose import/export, does not
require specialized phantoms, and can be performed rapidly on the
actual film sheet used for plan validation in a single exposure.
MATERIALS AND METHODS: A section of Gafchromic EBT3 film
was positioned in contact with an HDR bronchial catheter surrounded by water-equivalent material. The film was irradiated for
1,350 Cisec with a Nucletron Ir-192 HDR line source and then
digitized with an Epson 10000 XL color scanner. The remaining
section of the film can be used for plan evaluation.
Film analysis was performed in MatLab with the imaging toolbox.
Transmission values for the red, green, and blue channels were converted into optical density (OD) as a function of perpendicular
distance from the center of the line source. A corresponding theoretical dose curve for each exposure was calculated using the TG43
formalism. The calculated dose was fitted to the measured OD in
the clinically significant range to a fourth-order polynomial.
A single dwell position plan, normalized for the appropriate irradiation time, was created using the Oncentra treatment planning
system. The three-dimensional (3D) DICOM dose matrix was
imported into a Varian Eclipse external beam treatment planning
system, and the two-dimensional (2D) dose in a coronal plane was
extracted for comparison in MatLab with the corresponding measured film dose plane.
RESULTS: (1) The green channel had greater range, contrast scale,
and accuracy than either the blue or red channel and was therefore
used for analysis. (2) The calibration curve, consisting of nearly
200 points, was statistically valid and robust. (3) Agreement
between the measured film and plan dose was within +/− 1.5%
throughout the clinical range in 0.1-mm increments. (4) Our
results provide a significant improvement in both dose and distance to agreement over current practice, which typically uses
fewer than 10 calibration points.
CONCLUSION: An accurate and robust calibration curve using the
green channel of Gafchromic film can be easily created for use in
validating HDR planning systems.
(P129) Bone Marrow Aspiration Under CT Guidance:
Technique and Value Cory Pfeifer, MD, Tyler Ternes, Shannon St. Clair, William Palko, MD,
Christopher Dakhil; University of Kansas, Wichita; Lenox Hill Hospital;
Wesley Medical Center; Cancer Center of Kansas
PURPOSE: (1) Describe the quality basis for our institution’s transition toward computed tomography (CT)-guided bone marrow
aspiration. (2) Identify the equipment and approach used in bone
marrow aspiration, as well as its pitfalls. (3) Outline the steps
employed at our institution. (4) Emphasize the role of the partnership between radiologists, pathologists, and oncologists in the successful execution of the procedure.
BACKGROUND: The shift toward quality-based health care delivery
models has underlined the need to provide accurate diagnoses with
as few complications as possible. These changes in our health care
structure parallel procedure-complicating factors, such as changes
in typical patient body habitus and clinician availability to perform
standard bone marrow aspiration. At our institution, radiologists
have partnered with oncologists to address these challenges by providing high-quality service with minimal complication rates utilizing CT guidance.
PROCEDURE DETAILS: Standard CT guidance is utilized to localize
the bilateral posterior iliac crests, and a posterior technique is
employed with the patient in the prone position. We approach the
patient from the contralateral side of the iliac target. Our experience has shown that pathologists prefer to supply T-handle twisttype biopsy needles for sampling, as opposed to the hammer-based
needle setup. Feedback from the pathology service has suggested
that the hammer method results in greater contamination by
peripheral blood. Once the marrow cavity is accessed, we aspirate
separate marrow aliquots for slide fixation with a histotechnologist
at the bedside who prepares the fresh specimens. A sample core is
then obtained and preserved separately. Communication with the
ordering oncologist is essential for specimen acquisition, as flow
cytometric analysis and specific marker assays require disparate
bedside preservation techniques. Our stepwise technique will be
described pictorially.
CONCLUSION: Bone marrow aspiration under CT guidance is a
safe procedure that has become commonplace at our institution.
Pain is minimal, even in the absence of sedation. All biopsies performed at our institution with participation from the pathology
department have resulted in diagnostic specimens, and relationships with healthcare stakeholders have improved.
(P130) An Exploratory Pilot Study of Perfusion Patterns
in Locoregionally Advanced Head and Neck Cancer
Using a Novel Analysis Technique of Dynamic ContrastEnhanced (DCE)-MRI Jonathan Verma, MD, Radka Stoyanova, PhD, N. Andres Parra, PhD,
Kyle Padgett, PhD, Michael Samuels, MD, Nagy Elsayyad, MD; University of Miami Sylvester Comprehensive Cancer Center
PURPOSE: Recently, an unsupervised pattern recognition (UPR)
technique was developed by one of the investigators to analyze
dynamic contrast-enhanced magnetic resonance imaging (DCEMRI). The technique utilizes non-negative matrix factorization
(NMF) and has hitherto not been studied in head and neck cancers
(HNCs). This study aims at implementing this technique in HNCs
in order to explore its potential value in characterizing perfusion
patterns within these tumors. The presence of subvolumes in the
HNC that are differentially perfused may have future therapeutic
implications with respect to dose painting, intensification, or deintensification of treatment.
METHODS: Eight patients who received definitive chemoradiotherapy for locoregionally advanced HNC were randomly selected. All
received 70 Gy/33–35 fractions/6–7 weeks with concurrent cisplatin. As part of the radiotherapy planning, MRI had been obtained for
each patient, and DCE sequences were acquired, in addition to the
usual T1 and T2 sequences. DCE-MRI datasets with contoured
gross target volumes (GTVs) were imported for image analysis into
MIM software (MIM Corporation, Cleveland, Ohio). The NMF
83
(non-negative matrix factorization) algorithm was implemented in
MIM. There are three characteristic patterns of signal-vs-time
curves that UPR identifies within each GTV—namely, Pattern A,
which identifies subvolumes with fast contrast uptake and fast washout; Pattern B for subvolumes with delayed uptake and washout; and
Pattern C, with slow or no contrast uptake. RESULTS: The aforementioned three patterns identified corresponding subvolumes in each GTV. The mean GTV volume was
56.8 cc (range: 22–146.6 cc). Subvolumes for each of Patterns A, B,
and C averaged 31% ± 3.6%, 30% ± 5.3%, and 39% ± 8.4% of the
total GTV, respectively. The standard deviations showed relatively
tight dispersion of these values around their respective means, suggesting relative constancy throughout the patients studied.
Although no clear geographically consistent relationship between
the subvolumes emerged, necrotic regions identified by computed
tomography (CT) or MRI were consistently located within Pattern
C subvolumes. All three patterns were qualitatively identical to
those reported in a previously published preclinical study by our
group, wherein Pattern B subvolumes corresponded to regions of
tumor hypoxia on 18F-fluoro-misonidazole (MISO) images and
radiolabeled pimonidazole histological slices.
CONCLUSION: UPR is a novel technique that has been developed
in a preclinical tumor model and that is potentially applicable in
HNCs. This exploratory study appears consistently to identify subvolumes within the GTV that may have therapeutic implications
and that may be promising areas for further research (eg, correlation with hypoxia and clinical outcome).
(P131) Improved Prostate Delineation in Prostate HDR
Brachytherapy With TRUS-CT Deformable Registration
Technology Xiaofeng Yang, Peter Rossi, MD, Ashesh Jani, MD, Hui Mao, PhD, Tomi
Ogunleye, Walter J. Curran, Tian Liu; Emory University
PURPOSE: The main challenge for computed tomography (CT)-
based prostate high-dose-rate (HDR) treatment planning is to
accurately define prostate volume in CT images due to the poor
soft-tissue contrast. To address this issue, we have developed a
novel approach that integrates intraoperative transrectal ultrasound (TRUS)-based prostate volume into HDR treatment planning through TRUS-CT deformable registration (TCDR) based on
the catheters. This study’s purpose is to assess the clinical feasibility of the TCDR-based approach and compare its performance with
the standard physician’s CT contours in the setting of HDR prostate
brachytherapy.
METHODS: To improve prostate contour accuracy, the proposed
TCDR-based approach utilizes two unique features in the HDR
procedures: (1) Accurate prostate volume obtained from threedimensional (3D) TRUS images—during HDR procedure, 3D
TRUS images of the prostate are acquired with 1- or 2-mm step size
right after the catheters are inserted. (2) Accurate TRUS-CT image
registration using HDR catheters—both TRUS and CT images are
obtained after the catheter insertions.
The catheters are reconstructed on the TRUS and CT images and
84
subsequently used as landmarks for the TRUS-CT image registration using a fuzzy-to-deterministic algorithm. The intraoperative
TRUS-based prostate volume is then deformed to the CT image to
obtain the CT prostate volume, which is used for HDR treatment
planning. In a pilot study, 16 prostate HDR brachytherapy procedures were evaluated retrospectively. CT-based prostate volumes
were contoured by two experienced physicians. Both TCDR-based
prostate volume and the standard CT-based prostate volumes are
compared with the MRI-defined prostate contours (gold standard).
A t-test was used to examine the significance of the difference
between the two physicians’ CT-based contours, the TCDR-defined
contours, and the MRI-defined prostate volumes.
RESULTS: A 20% to 40% improvement in prostate volume accuracy
can be achieved with the TCDR-based approach as compared with
the standard CT-based prostate volumes. TCDR-defined prostate
volumes match closely to the MRI-defined prostate volumes (mean
difference: 0.9 ± 7.3%; P = .54). CT-based contours assessed by the
two physicians overestimated the size of the prostate gland by 7.3%
(7.3 ± 18.7%) and 59.7% (59.7 ± 37.8%) and were associated with
significant variability, even between these two experienced physicians (P < .01).
CONCLUSIONS: We have developed a novel TCDR-based approach
to improve prostate delineation utilizing intraoperative TRUSbased prostate volume in prostate HDR brachytherapy and demonstrated its improvement in prostate volume accuracy over the standard CT-defined prostate volumes. Integration of TRUS into the
HDR brachytherapy treatment planning workflow has the potential
to enable accurate dose planning and delivery and enhance prostate
HDR treatment outcome.
(P132) Evaluation of the Chest Wall Skin Dose
Associated With Bolus Application in Postmastectomy
Radiation Therapy (PMRT) Using Nanodot OSLD Yuenan Wang, PhD, Janelle Park, MD; Florida Cancer Specialists
PURPOSE: A wide variation in the use of bolus has been observed
in postmastectomy radiotherapy (PMRT), which affects dose delivery to skin and may have an impact on locoregional recurrence.
However, even treatment planning systems (TPSs) with advanced
algorithms do not provide accurate dosimetry in the buildup
region. This study aims to perform in vivo measurements of the
chest wall (CW) skin dose using optically stimulated luminescence
dosimeters (OSLDs) and to ensure that adequate skin dose is
obtained for all patients undergoing PMRT.
MATERIALS AND METHODS: In total, 37 patients undergoing
PMRT were treated with either conformal technique or volumetricmodulated RT (RapidArc, Varian Medical Systems). Each patient
had two plans for CW radiation: one with 0.5-cm bolus and the
other without bolus, originally prescribed as every other day
(QOD). During the first treatment of bolus and no-bolus plans, the
physicist placed four to six nanoDots (Landauer, Glenwood, IL), a
type of OSLD suitable for accurate in vivo dosimetry, at the scar
and the superior, inferior, medial, and lateral locations of the CW
field. For each patient, there were 8–12 nanoDots sent to Landauer
for absolute dose reading. The skin dose difference between the
no-bolus and bolus plans was analyzed at our clinic for each patient.
Furthermore, if the composite CW skin dose was less than the
clinically desired dose (ie, 45 Gy), then we would increase the number of fractions for the bolus plan and reduce the number of fractions for the no-bolus plan to ensure that CW skin obtains the
clinically desired dose coverage.
RESULTS: A total of 8 out of 37 patients had skin dose below 45 Gy
with the 0.5-cm QOD bolus application, and we had to revise the
plan fractionation. Among them, two were conformal plans and
seven were RapidArc plans. For the conformal planned patients,
the average skin dose increase for bolus use compared with no
bolus was 34% ± 12%. In contrast, for RapidArc plans, the average
skin dose increase for the bolus plan was 57% ± 27%. This was
probably due to the oblique incidence of tangential photon beams
in the three-dimensional (3D) conformal technique already providing relatively high skin dose.
CONCLUSION: Skin dose is dependent on patient anatomy, the incident beam geometry, and planning techniques. For example,
RapidArc plans with tissue expanders should be monitored for skin
dose coverage. In conclusion, the skin dose should be measured to
ensure that the clinically desired dose is obtained for the various
bolus applications in patients undergoing PMRT.
(P133) Spinal Cord Dose Comparison With and Without
Contrast Density Correction on CT Myelogram
Simulations for Patients Treated With Stereotactic
Body or Conventional Radiotherapy Sukhjeet S. Batth, MD, MS, Raymond Chiu, CMD, Nicholas Trakul,
MD, PhD; USC Norris Cancer Center
PURPOSE/OBJECTIVES: Patients treated with stereotactic body
radiotherapy (SBRT, also known as stereotactic ablative radiotherapy) or conventional RT to spinal targets often undergo a computed tomography (CT) simulation with a myelogram to accurately identify the spinal cord. Treatment planning algorithms use
Hounsfield units and a CT density table to calculate radiation dose.
Accuracy of these calculations may be improved by correcting for
the contrast’s actual density, which is not present at the time of
treatment delivery. We hypothesize that the spinal cord receives a
higher radiation dose than calculated after correction of the contrast’s physical density. MATERIALS AND METHODS: CT simulations with a myelogram for
treatment of 10 spinal targets from nine patients were retrospectively reviewed. Seven of these targets were treated with SBRT, one
was treated with intensity-modulated RT, and two were treated
with three-dimensional conformal RT. The contrast from the
myelogram was contoured in the treatment planning software, and
the physical density was adjusted to 1 g/cm3. The uncorrected spinal cord maximum and mean doses were then compared with the
doses after correction of the density. A two-tailed, paired t-test was
used to compare the calculated doses. RESULTS: The corrected spinal cord doses were all significantly
higher than the uncorrected doses based on paired t-test for the
maximum dose (P = .0073) and the mean dose (P = .00087). The
mean maximum cord dose was 2,065 cGy and 2,077 cGy after correction. The mean of the average cord dose was 1,302 cGy and
1,315 cGy after correction. CONCLUSIONS: These data suggest that the use of a CT myelogram
with simulation significantly underestimates the spinal cord maximum and mean doses. The clinical significance of this finding is
uncertain, and this study is limited by its small sample size. Density
correction should be further investigated in a larger study, given the
high doses used in SBRT and potential morbidity of spinal cord
injury.
(P134) An Overview of the First One Hundred Patients
Treated With a New Cutting-Edge, Frameless, ImageGuided, Stereotactic Radiosurgery System Ning Wen, PhD, Karen Chin-Snyder, MS, Haisen Li, PhD, Kwang Song,
PhD, James Gordon, PhD, Indrin Chetty, PhD, Munther Ajlouni, MD,
Farzan Siddiqui, MD, Benjamin Movsas, MD, Salim Siddiqui, MD;
Henry Ford Health System
PURPOSE: To summarize our experience with treating our first
100 patients treated using an innovative linear accelerator (Linac)based stereotactic radiosurgery (SRS) system.
MATERIALS AND METHODS: A novel platform for Linac-based
SRS treatment, the Edge (Varian Medical Systems, Palo Alto, CA),
offers multiple imaging modalities for treatment localization,
including an optical surface monitoring system (OSMS) for surface
tracking, 2.5 MV portal imaging, triggered monoscopic kV imaging to track intrafractional motion, four-dimensional (4D) conebeam computed tomography (CBCT) to evaluate tumor motion
offline, extended CBCT images by stitching multiple CBCT scans
together, and a Calypso/Varian electromagnetic beacon-based
tracking system. The new robotics couch supports six-degrees-offreedom corrections from multiple imaging modalities for precise
patient setup. We have comprehensively commissioned this system
and have worked out a clinical workflow for treating patients with
different cancer types. RESULTS: The breakdown of tumor sites treated with SRS/
stereotactic body radiation treatment (SBRT) techniques was central nervous system (CNS) (31%), lung (29%), spine (23%), GI
(9%), adrenal glands (7%), and head and neck (1%). The treatment
techniques used were as follows: volumetric-modulated arc therapy
(39%), intensity-modulated RT (35%), dynamic conformal arc
(21%), and three-dimensional (3D) conformal RT (5%). For CNS
sites except glioblastoma multiforme (GBM), the dose was delivered in a single fraction (range: 10–18 Gy), and the target volume
(TV) ranged from 0.10 cc (acoustic neuroma) to 21.05 cc (metastasis). GBM patients were treated with four fractions using the
simultaneous integrated boost technique (32 Gy to the enhanced
lesion and 24 Gy to the edema). Volume sizes of the enhanced
lesions ranged from 7.86 cc to 128.05 cc. All lung patients were
treated with 48 Gy in four fractions, except three recurrent treatments with 36 Gy in three fractions. Median TV volume was 36.53
cc (range: 4.09–85.12 cc). V20 for the total lungs was 3.59% on
average (range: 0.50%–7.37%). All T-spine metastases were treated
in a single fraction, with the dose ranging from 14 Gy (primary:
85
multiple myeloma) to 18 Gy (all other primary diagnoses). The
median TV volume was 43.82 cc (range: 11.80–121.77 cc). The
maximum dose to 0.03 cc of the spinal cord was 10.86 cc (range:
7.90–15.15 cc). The clinical flow designed for each treatment site
using multiple imaging modalities and treatment techniques will be
presented. The setup time, imaging fusion time, and beam on time
will be categorized according to the treatment site.
exceptionally high, although significantly lower agreement was
noted postoperatively. Technique and dose prescription between
experts were substantively consistent, and these preliminary results
will be utilized to create an expert-consensus contouring atlas to
aid the nonexpert radiation oncologist in the planning of these
challenging, rare tumors. CONCLUSION: The Edge RS system possesses the high-accuracy
localization and delivery requirements for safely treating patients
with tumors in the CNS and other sites using SRS/SBRT-based
techniques.
(P136) Quantitative Measurement of Contrast
Enhancement in Myxoid Liposarcomas: Response to
Neoadjuvant Therapy With Volumetric and Pathologic
Correlates (P135) Quantitative Assessment of Target Delineation
Variability for Thymic Cancers: Agreement Evaluation
of a Prospective Segmentation Challenge
Emma B. Holliday, MD, Clifton D. Fuller, MD, PhD, Jayashree KalpathyCramer, PhD, Daniel Gomez, MD, Andreas Rimner, MD, PhD, Ying Li,
MD, PhD, Suresh Senan, MD, PhD, Lynn D. Wilson, MD, MPH, Jehee
Choi, MD, Ritsuko Komaki, MD, Charles R. Thomas, MD; UT MD Anderson Cancer Center; Martinos Center for Biomedical Imaging Center,
Massachusetts General Hospital, Harvard Medical School; Memorial
Sloan-Kettering Cancer Center; UT Health Science Center, San Antonio;
VU Medical Center; Yale University; Loyola University; Oregon Health
and Science University Knight Cancer Institute
PURPOSE: We sought to quantitatively determine the relative
interobserver variability of expert target volume delineation as part
of a larger standardization effort to develop an expert-consensus
contouring atlas to complement radiotherapy recommendations
for thymic cancers.
METHODS: A pilot dataset was created, consisting of a standardized
case presentation with anonymized pre- and postoperative DICOM
computed tomography (CT) image sets from a single patient with
Masaoka-Koga stage III thymoma. Participating expert thoracic
radiation oncologists delineated tumor targets on the pre- and postoperative scans as they would for a definitive and adjuvant case,
respectively. Respondents then completed a survey detailing the
dose prescription and planning target volume (PTV) margins that
they would recommend in definitive and postoperative (ie, R1 vs
R2) scenarios. Interobserver variability was analyzed quantitatively
with Warfield’s simultaneous truth and performance-level estimation (STAPLE) algorithm and the Dice similarity coefficient (DSC). RESULTS: Seven users completed the contouring tasks for definitive
and adjuvant cases; of these users, five completed online surveys.
Segmentation performance was assessed, with high mean ± SD
STAPLE-estimated segmentation sensitivity for definitive-case
gross tumor volume (GTV) and clinical target volume (CTV) at
0.77 and 0.80, respectively, and postoperative CTV sensitivity of
0.55; all volumes had a specificity of ≥ 0.99. Interobserver agreement was markedly higher for the definitive-case target volumes,
with mean ± SD DSC of 0.88 ± 0.03 and 0.89 ± 0.04 for GTV and
CTV, respectively, compared with postoperative CTV DSC of 0.69
±0 .06 (Kruskal-Wallis: P < .01). CONCLUSION: Expert agreement for definitive-case volumes was
86
Tobias R. Chapman, MD, MPharmacol, George Jour, MD, Darrin J.
Davidson, MD, MHSc, FRCSC, Robin L. Jones, MD, MRCP, Ben Hoch,
MD, Gabrielle Kane, MD, Edward Y. Kim, MD; University of Washington
PURPOSE: Clinical assessment of response to neoadjuvant therapy
(NeAT) in soft tissue sarcoma (STS) is often based on Response
Evaluation Criteria in Solid Tumors (RECIST) criteria, which may
not reflect changes in tumor biology. Myxoid liposarcomas (MLs)
have favorable responses to NeAT by RECIST and exhibit contrast
enhancement on T1-weighted, postcontrast magnetic resonance
imaging (MRI) (T1+). Tumor response may also manifest as
changes in contrast enhancement. We present a quantitative assessment of contrast enhancement and correlate these findings with
volumetric and pathologic data.
MATERIALS AND METHODS: After institutional review board
(IRB) approval, 67 patients from 1999–2013 were identified with
ML. Five patients received neoadjuvant radiation therapy (RT) with
MRI prior to each NeAT and surgery. Tumor volumes (TVs) were
contoured on the relevant T1+ MRI. Mean contrast enhancement
(MCE) was calculated by subtracting the T1 precontrast MRI signal
from the T1+ MRI after normalization to normal muscle. Percent
change was calculated using MIM software. Specimen analysis was
performed by an STS pathologist.
RESULTS: The majority of patients was male, and most tumors were
of the limb, low-grade, large (> 5 cm), and deep (T2b). Three
patients received neoadjuvant chemotherapy. Pre- and postchemotherapy mean MCE values were 71% (range: 54%–82%) and 24%
(range: 2%–47%), respectively. The mean postchemotherapy
change in TV was −0.2%. All patients received neoadjuvant RT,
with pre- and post-RT mean MCE of 50% and 47%, respectively.
Mean post-RT change in TV was −64%. Two patients received neoadjuvant RT alone, with pre- and post-RT mean MCE of 95% and
23%, respectively. The mean post-RT-alone change in TV was
−72%. All patients had significant pathological responses to NeAT,
with > 80% treatment effect. With median follow-up of 23.5
months, there were no local or distant recurrences.
CONCLUSION: Patients with ML treated with neoadjuvant chemotherapy exhibit decreased MCE, with no associated change in TV.
Subsequent RT postchemotherapy causes no additional change in
MCE but does cause tumor shrinkage. Treatment with RT alone
causes changes in both. These data from ML patients with excellent
pathologic responses to NeAT suggest that differential tumor
responses may not be captured using size criteria alone and that
responses to chemotherapy may be better evaluated using MCE.
CLINICAL RELEVANCE/APPLICATION: MLs exhibit favorable clinical responses to NeAT by size criteria; however, this may not
account for biological tumor changes. We present a technique for
quantifying changes in contrast enhancement that may better predict biological tumor response.
treat patients. Based on the results of ongoing machine and patientspecific tests and with independent confirmation, the treatments
are being delivered accurately and safely.
(P137) Seeing Is Believing: Concerns and Solutions
in Implementing Magnetic Resonance Image–Guided
Radiation Therapy Andrew W. Orton, MD, John D. Gordon, MS, DABR, Tyler P. Vigh,
Allison E. Tonkin, MD, George M. Cannon, MD; Huntsman Cancer Institute; Intermountain Medical Center
Olga L. Green, PhD, H.O. Wooten, PhD, Yanle Hu, PhD, Rojano
Kashani, PhD, Lakshmi Santanam, PhD, Harold Li, PhD, Sasa Mutic,
PhD; Washington University School of Medicine
PURPOSE: We describe the potential problems and solutions developed in initiating first treatments with a commercially available
magnetic resonance image–guided radiation therapy (MR-IGRT)
system. Specifically, we address the following: (1) effect of magnetic fields on dose distributions, (2) patient and staff safety in the
presence of magnetic and radiation fields, and (3) quality assurance
for MR-IGRT.
MATERIALS AND METHODS: The foremost problem of integrating
an MRI system with a radiation delivery system has been solved by
combining a 0.35-T split-doughnut MRI with a gantry carrying
three 60 Co sources. This system was installed in our institution in
2012, and since then, we have conducted ongoing work toward its
clinical implementation. The problem of the effect of magnetic
fields on dosimetric distributions was investigated by comparing
measurements with an in-house phantom to Monte Carlo calculations. The problem of patient and staff safety was addressed by
measuring the specific absorption ratio (SAR) to ensure that it was
safe for patients to be imaged continuously while being treated and
by implementing safety checks in our daily workflow. The problem
of quality assurance for MR-IGRT was solved by establishing the
accuracy of measurement devices (ionization chambers, detector
arrays) in the presence of the magnetic field and developing tests
that checked both the geometric and dosimetric accuracy of the
system on a daily, weekly, monthly, and annual basis. Independent
confirmation of dosimetric accuracy was provided by the Imaging
and Radiation Oncology Core (IROC) service—reference dosimetry via optically stimulated dosimeters and overall delivery quality
via the head-and-neck phantom (film and thermoluminescent
dosimeters).
RESULTS: The 0.35-T magnetic field was found to have a negligible
effect on dose distributions for the type of patient plans used clinically. The measured SAR value was 1.14 W/kg, which ensured that
patients do not experience excessive heating during the ongoing
real-time imaging at four frames per second. MR training was conducted for all staff, and procedures were implemented to ensure that
patients were cleared to be MR-safe before every treatment. Quality
assurance included spatial integrity and homogeneity of the MR
field, MR and RT isocenter coincidence, and pre- and posttreatment
patient-specific QA. Satisfactory results were reported by the IROC
for four independent OSL (Optically Stimulated Luminescence) reference dosimetry checks and the head-and-neck phantom.
CONCLUSION: The system has been used since January 2014 to
(P138) Dosimetric Evaluation of Parotid Dose in
Whole-Brain Radiation Plans Covering C1 vs C2 BACKGROUND AND PURPOSE: Dosimetric analysis has demonstrated a higher-than-anticipated dose to the parotid glands during
whole-brain radiation therapy (WBRT). Even in the computed
tomography (CT) planning era, WBRT fields continue to be
designed based on anatomic landmarks identified on digitally
reconstructed radiographs (DRRs) of the skull. The dose of radiation delivered incidentally to the parotid glands is influenced by the
location of the inferior border of the treatment field. The purpose
of this study is to compare the dose delivered to the parotid glands
and associated normal tissue complication probabilities (NTCPs)
in plans covering the C1 vs C2 vertebral level.
MATERIALS AND METHODS: A total of 15 patients underwent CT
simulation of the brain, followed by dosimetric evaluation of parotid dose. Two treatment plans were produced for each patient using
the CT simulation images: the first extended the inferior field border to the inferior edge of the C1 vertebra, and the second extended the field to the inferior edge of C2. Two dose prescriptions were
compared: 30 Gy and 37.5 Gy. NTCPs were estimated using the
Lyman-Burman-Kutcher model with parameters obtained from
studies published by Eisbruch, Emami, and Roesink. Mean dose to
the parotids and NTCPs were compared between the two groups,
and statistical significance was determined using a patient-matched
two-sided t-test.
RESULTS: The mean parotid dose was significantly higher when C2
was covered. For the 30-Gy prescription, coverage to C2 increased
the parotid dose from 14.3 Gy to 18.3 Gy (P < .01). For the 37.5-Gy
plan, coverage to C2 increased the parotid dose from 18.5 Gy to
23.4 Gy (P < .01). NTCPs for the parotid gland were also higher
when covering C2 vs C1. At 30 Gy, NTCP estimates for C1 coverage
ranged from 0.0 to 0.08 compared with a range of 0.0 to 0.12 in
plans covering C2. At 37.5 Gy, C1 coverage resulted in predicted
rates of 0.0 to 0.12 vs 0.01 to 0.21 in plans covering C2.
CONCLUSIONS: Clinicians who choose to cover C2 with WBRT
should be aware of the increased radiation dose delivered to the
parotid glands. NTCP modeling predicts an increased rate of treatment-associated xerostomia as a result.
(P139) Clinical Outcomes and Patient-Reported
Outcomes After Local Treatment for High-Risk,
Localized Prostate Cancer Lora S. Wang, MD, Colin T. Murphy, MD, Tianyu Li, MS, Marc C.
Smaldone, MD, Matthew E. Johnson, MD, Mark Hallman, MD, Yu
Ning Wong, MD, Daniel Geynisman, MD, Mark L. Sobczak, MD, David
Chen, MD, Eric Horwitz, MD; Fox Chase Cancer Center
87
INTRODUCTION: Men with high-risk prostate cancer (CaP) have
low rates of disease control and long-term survival compared with
their low-risk counterparts. We sought to investigate CaP-specific
and patient-reported outcomes for high-risk CaP men treated
with prostate-directed therapy.
METHODS: From 1989–2011, a total of 1,091 patients with localized, high-risk CaP treated at our institution were analyzed. All
patients were staged clinically (prostate-specific antigen [PSA] > 20
ng/mL, biopsy Gleason score > 8, or > clinical T3) and were included if they received radical prostatectomy (RP) plus radiation (RT),
RT plus androgen deprivation therapy (ADT), and RT alone. Cox
proportional hazards regression models and Kaplan-Meier estimates were used to assess the risk of biochemical failure (BF), distant metastasis (DM), cause-specific mortality (CSM), and overall
mortality (OM). Patient-reported outcomes included International
Prostate Symptom Score (IPSS) results, Sexual Health Inventory for
Men (SHIM) scores, and ADT side effects.
RESULTS: There were 315 patients who received RT alone, 681 who
received RT + ADT, and 95 who received RP + RT identified.
Median follow-up was 68 months. Men who underwent surgery
were significantly younger than those who received RT alone or RT
+ ADT (P < .001). Patients in the RT + ADT cohort had significantly more advanced T-stages and fewer patients with only one
high-risk feature compared with men who received RP + RT (P <
.001). Men in the RT + ADT group had significantly lower 5-year
BF rates (19% vs 36% for RT alone vs 40% for RP + RT), but patients
in the RP + RT arm had significantly lower 5-year OM rates (0% vs
14% for RT alone vs 15% for RT + ADT).
After adjusting for covariates, patients in the RT + ADT cohort
were less likely to have BF compared with the RP + RT group (P <
.001), with no significant difference in the development of DM or
CSM. Receipt of RT, either alone (P = .006) or with ADT (P = .010),
was associated with a significantly increased risk of OM compared
with men who received surgery.
There were significantly fewer men in the RT-alone group who experienced any ADT side effects (P < .001) compared with men who
received RT + ADT or RP + RT. There were 446 patients with evaluable IPSS scores, with median baseline scores of 7, 7, and 4 for RT
alone, RT + ADT, and RP + RT, respectively (P = .002). The median
baseline SHIM scores were 5, 19, and 15 for RP + RT, RT alone, and
RT + ADT, respectively (P < .001), with 96 evaluable patients.
CONCLUSIONS: Long-term CaP-specific survival is equally high
after RT + ADT and RP + RT in clinically high-risk CaP patients.
Further investigation should be aimed at integrating quality of life
measures when considering the optimal treatment for men with
high-risk CaP.
(P140) Clinical Predictors of Survival for Patients With
Stage IV Cancer Referred to Radiation Oncology Emily Copel, DO, Johnny Kao, MD, Kenneth Gold, MD, Gina Zarilli,
MD, Samuel Ryu, MD, David Yens, PhD; Good Samaritan Medical
Center; State University of New York, Stony Brook; New York College
of Osteopathic Medicine
88
PURPOSE: To develop a clinically useful predictive model for survival in a heterogeneous group of patients with metastatic cancer
referred to radiation oncology.
PATIENTS AND METHODS: From May 2012 to August 2013, a total
of 143 consecutive patients with stage IV cancer were prospectively evaluated by a single radiation oncologist. We retrospectively
analyzed the effects of 29 patient-, laboratory-, and tumor-related
prognostic factors on overall survival (OS), using univariate analysis. Variables that were statistically significant on univariate analysis were entered into a multivariable Cox regression model to identify independent predictors of long-term survival.
RESULTS: The median OS was 5.6 months. Five prognostic factors
significantly predicted survival on multivariable analysis: Eastern
Cooperative Oncology Group (ECOG) performance status (0/1 vs
2 vs 3/4), number of active tumors (1–5 vs ≥ 6), albumin levels (≥
3.4 mg/dL vs 2.4–3.3 mg/dL vs < 2.4 mg/dL), altered mental status
(no vs yes), and primary tumor site (breast, kidney, or prostate vs
other). Risk group stratification was performed by assigning points
for adverse prognostic factors, resulting in favorable-, standard-,
and poor-risk groups. The median survival was 21.8 months for
favorable risk vs 5.5 months for standard risk and 1.5 months for
poor risk (P < .001). CONCLUSIONS: These data suggest that a model that considers
performance status, extent of disease, serum albumin, mental status, and primary tumor site represents a clinically relevant tool
in radiation oncology to predict survival for patients with stage
IV cancer.
(P141) Rectal Spacer Injection in Postprostatectomy
Patients Undergoing High-Dose Salvage External
Beam Radiation Jekwon Yeh, MD, Kenneth Tokita, MD, Jeffrey Chien, John Ravera, MD;
Cancer Center of Irvine
OBJECTIVE/PURPOSE: There is now increasing literature to support the use of a rectal spacer to decrease rectal side effects during
radiation therapy (RT) for patients with intact prostate cancer.
There have been no reports on its usage in patients who are undergoing salvage RT after a prostatectomy. This study aims to report
on the gastrointestinal toxicity of patients who have had a prostatectomy and received high-dose (>72 Gy) salvage RT with the rectal spacer.
MATERIALS AND METHODS: From January 2010 to October 2013,
a total of 32 patients had the rectal spacer placed via transperineal
injection posterior to the residual Denonvillier’s fascia under
ultrasound guidance. All patients were treated to a minimum of 72
Gy to the prostatic fossa with intensity-modulated RT (IMRT)
with daily cone-beam computed tomography (CT) to ensure treatment accuracy. All patients had at least 6 months of follow-up.
Radiation Therapy Oncology Group (RTOG) scoring for gastrointestinal morbidity was assessed at the end of treatment and 6
months afterward.
RESULTS: At the end of treatment, 23 patients (72%) had no change
in rectal symptoms. Nine patients (28%) developed grade 1 gastrointestinal (GI) toxicity. No patients developed grade ≥ 2 GI toxicity.
At 6 months after treatment, 29 patients (91%) were back to their
baseline GI function, with only 3 patients (9%) with residual grade
1 GI toxicity. No patients developed grade ≥ 2 GI toxicity.
CONCLUSIONS: Our study shows that rectal spacer placement in
patients who have had a prostatectomy is feasible. Despite the high
dose of salvage RT, GI toxicity rate was low, and no patient developed grade ≥ 2 GI toxicity with the rectal spacer.
(P142) Older Patients Derive Greater Benefit From
Adjuvant and Neoadjuvant Radiotherapy in Diverse
Solid Malignancies Noah K. Yuen, MD, Arta Monjazeb, MD, PhD, Chin-Shang Li, PhD,
Dariusz Borys, MD, Richard Bold, MD, Robert Canter, MD; University
of California, Davis Medical Center
BACKGROUND: Radiation therapy (RT) is a standard component
in the contemporary multimodality management of numerous
solid malignancies. Increasing studies have shown that age-related
immunologic changes may impact the bioactivity of RT. We
hypothesized that outcomes of RT would be influenced by age
across various solid cancers.
METHODS: Using Surveillance, Epidemiology, and End Results
(SEER) data (1990–2011), we identified 959,731 adult patients (aged
> 18 yr) with common nonmetastatic solid malignancies, including
breast, lung, and rectal cancer, undergoing surgery ± RT. We compared patient demographics, tumor characteristics, and treatments
by age. Multivariable analyses were used to examine the effect of
these variables on overall survival (OS) and disease-specific survival (DSS). Hazard ratios were calculated based on multivariable
Cox proportional hazards models and logistic regression analysis.
RESULTS: The study cohort consisted of 70.0% breast, 13.5% lung,
11.9% rectal, 3.4% sarcoma, and 1.2% esophageal cancer. Mean age
at diagnosis was 61.1 ± 13.8 years, and 42% of patients were aged ≥
65 years. A total of 43.2% received either adjuvant (39.0%) or neoadjuvant (4.2%) RT. With the exception of lung cancer (OS hazard
ratio [HR] = 1.21; 1.19–1.23), RT was associated with improved
survival in patients of all ages: breast (OS HR = 0.72; 0.71–0.73),
rectal (OS HR = 0.81; 0.79–0.83), esophageal (OS HR = 0.83; 0.75–
0.91), and sarcoma (OS HR = 0.63; 0.56–0.70). These positive
effects were amplified in elderly patients (aged ≥ 65 yr), with breast
(OS HR = 0.66; 0.65–0.66) and rectal cancers (OS HR = 0.74; 0.72–
0.76) having the most benefit. On logistic regression, the HR for
risk of death per year of age was lower in patients receiving RT vs
those not receiving RT: breast (1.057–1.060 vs 1.072–1.074), rectal
(1.043–1.048 vs 1.081–1.085), esophageal (1.006–1.023 vs 1.026–
1.046), and lung cancer (1.039–1.047 vs 1.050–1.054).
CONCLUSIONS: This is the largest analysis to date examining the
effects of RT in a broad population of solid tumor patients.
Although we were unable to control for chemotherapy use in this
cohort, RT was associated with superior oncologic outcome compared with surgery alone among patients with multiple solid malignancies. This positive effect was most pronounced in older patients
with breast and rectal cancer, suggesting age-dependent effects of
RT. Further investigation into the mechanism of these age-related
effects is indicated.
(P143) Multisite Review of Twenty-Six Head and
Neck Cancer Patients Who Have Developed
Osteoradionecrosis: Location, Etiology, and Treatment
Rex Hoffman, MD, Daniel Copps, DDS, Earl Freymiller, MD, DDS,
Sopirios Tetradis, DDS, PhD; Roy and Patricia Disney Family Cancer
Center, Providence Saint Joseph Medical Center; private practice; UCLA
School of Dentistry
INTRODUCTION: Osteoradionecrosis (ORN) is felt to be secondary
to decreased blood flow through the inferior alveolar artery to the
mandible. It has been well documented that if the dose of radiation
exceeds a certain threshold, patients are at increased risk for this
devastating treatment-related side effect. The effect that systemic
therapy has on this altered blood flow is less clear. The medical and
dental literature has conflicting reports that the rate of ORN
increases or decreases when systemic therapy (chemotherapy or
Erbitux) has been given with radiation. Here, the authors review 26
head and neck cancer patients who have developed ORN to see if
systemic therapy increased their risk during radiation.
MATERIALS: A total of 26 head and neck cancer patients, treated at
six different radiation oncology departments, were diagnosed with
ORN by a single maxillofacial prosthodontist (DC), a dental radiologist, and a maxillofacial oral surgeon. ORN was defined as a
condition of nonviable bone in the site of radiation injury.
Diagnosis of ORN was made by both physical exam and radiographic imaging, which consisted of both a Panorex and a conebeam computed tomography (CT) scan. For the purpose of this
study, the patients’ records were reviewed, looking specifically at
how radiation and systemic therapy had been delivered (induction
vs concurrent), as well as what systemic agent(s) they received during radiation.
RESULTS: Median time to diagnosis of ORN after treatment by
both physical exam and radiographic imaging was 77 months
(range: 12–147 mo). Of the 26 patients, 5 had received radiation
therapy alone, 7 had received induction chemotherapy followed by
concurrent chemotherapy and radiation, and 14 had been treated
with concurrent therapy (either Erbitux or platinum-based chemotherapy) and radiation. In each case, necrosis of the bone occurred
in the posterior aspect of the mandible. None of the cases was iatrogenic. After the diagnosis was made, treatment consisted of
either pharmacologic treatment or hyperbaric oxygen, followed by
conservative oral surgery or hemimandibulectomy.
CONCLUSION: The medium time from the completion of treatment to diagnosis of ORN was over 6 years. All patients in this
review developed ORN in the posterior aspect of the mandible.
Neither the specific systemic agent (Erbitux or chemotherapy) nor
the manner in which the agent was delivered (induction vs concurrent) appeared to increase the risk of ORN. It is hoped that having
a better understanding as to the location, etiology, and treatment of
ORN will help to minimize this potentially devastating complication for future generations of head and neck cancer patients.
89
(P144) Radiation-Associated Toxicities in Obese Women
With Endometrial Cancer: More Than Just BMI? Savita Dandapani, MD, PhD, Ying Zhang, MD, Richard Jennelle, MD,
Yvonne Lin, MD; City of Hope; USC
PURPOSE: The current study characterizes the impact of obesity on
postoperative radiation-associated toxicities in women with endometrial cancer (EC).
MATERIALS AND METHODS: A retrospective cohort study identified 96 women with EC referred to a large urban institution’s radiation oncology practice for postoperative whole-pelvic radiotherapy
(WPRT) and/or intracavitary vaginal brachytherapy (ICBT).
Demographic, clinicopathologic, and patient-reported toxicity data
were obtained from medical records. Anthropometric information,
including body mass index (BMI), was collected from nursing
intake records at each clinic visit. Radiation-related toxicities were
graded according to Radiation Therapy Oncology Group (RTOG)
Acute Radiation Morbidity Scoring Criteria. The follow-up period
ranged from 1 month to 11 years (median 2 yr). The data were
analyzed by chi-square, logistic regression, and recursive partitioning analyses.
RESULTS: A total of 68 evaluable EC patients who received WPRT
and/or ICBT were included in the primary analysis. The median
age was 52 years (range: 29–73 yr). The majority of patients were
Hispanic (48, 71%), with 6 (9%) Caucasian, 1 (1%) AfricanAmerican, and 13 (19%) Asian. The median BMI at diagnosis was
34.5 kg/m2 (range: 20.5–56.6 kg/m2). A total of 58 patients (85%)
had abdominal hysterectomies, and 10 (15%) had laparoscopic hysterectomies; 43(63%) had a pelvic lymphadenectomy, and 15 (22%)
had para-aortic lymphadenectomies. BMI was independently associated with reported radiation-related cutaneous toxicities (P =
.022) and gynecologic toxicities (P = .027). Younger women also
reported more gynecologic toxicities (P = .039). Adjuvant radiation
technique was associated with increased gastrointestinal- and genitourinary-related toxicities but not gynecologic toxicity. There was
no association of International Federation of Gynecology and
Obstetrics (FIGO) stage, use of adjuvant chemotherapy, or hysterectomy type with reported radiation toxicities.
CONCLUSIONS: The impact of obesity on adjuvant treatment is
poorly understood. Increasing BMI was associated with increased
frequency of gynecologic and cutaneous radiation-associated toxicities. Additional studies to critically evaluate the radiation treatment dosing and treatment fields in obese EC patients are warranted to identify strategies to mitigate the radiation-associated
toxicities in these women.
90

2015 ARS Supplement

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