post forum report

Transcription

post forum report

POST FORUM REPORT
CONTENTS
Dear Colleagues,
I think we’ve finally cracked it!
INTRODUCTION
p3
2_ Delineation of organs-at-risk in the pelvic area:
developing guidelines for RTTs
p 28
CLINICAL
p4
3_ Can O-MAR increase precision of delineation in
Head and Neck Cancer?
p 30
INTRODUCTION
Overview of the Clinical & Translational Meeting
Component
p5
1_ A randomised controlled trial of Intensity Modulated
Radiotherapy (IMRT) for early breast cancer: results at
5 years
p6
2_ Recurrence pattern within the CROSS trials I and II,
comparing surgery alone with chemoradiotherapy
followed by surgery for esophageal cancer
p7
3_ Development and validation of a prognostic model
incorporating clinical and functional MRI variables in
head and neck cancer
p8
4_ A prospective study to compare doctor versus model
predictions for outcome in lung cancer patients: pick the
winner!
p9
5_ Hypoxia biomarkers for prognostic evaluation and
the prediction of outcome following prostate
radiotherapy
p 10
6_ Phase I/II Study of Palliative Radiation and Sorafenib
for Metastatic Renal Cell Carcinoma and Bone
Metastases
p 12
PHYSICS p 14
INTRODUCTION
Overview of the Biennial Physics Meeting Component
p 15
1_ A National Dosimetric Audit of Volumetric Modulated Arc Therapy and Tomotherapy in the UK
p 16
2_ Time dependent pre-treatment verification for VMAT
plans using flattened or FFF beams
p 18
3_ Validation of three deformable image registration
algorithms using the TEST method
p 20
4_ Kilovoltage intrafraction motion monitoring and
target dose reconstruction for liver SBRT delivered by
VMAT
p 22
5_ An algorithm to assess the need for clinical Monte
Carlo dose calculations for proton therapy fields
p 23
RTT
INTRODUCTION
Overview of the RTT Meeting Component
p 24
p 25
1_ A Planning Strategy for Generating a Library of Plans
for Cervical Cancer
p 26
2
CONTENTS | 2ND ESTRO FORUM - REPORT
BRACHYTHERAPY
INTRODUCTION
Overview of the GEC-ESTRO-ISIORT Meeting
Component
p 32
p 33
1_ High Dose Rate (HDR) Brachytherapy Treatment
Verification using an Electronic Portal Imaging Device
(EPID) p 34
2_ HDR brachytherapy dosimetric predictors of
biochemical control of prostate cancer
p 36
3_ Dose-response for local control in image guided cervix brachytherapy in the retroEMBRACE study
p 37
4_ Brachytherapy in the treatment of anal canal cancers:
a large monocentric retrospective series.
p 38
5_ HDR brachytherapy of the base of tongue. Ten-year
results of a prospective study
p 40
RADIOBIOLOGY
INTRODUCTION
Overview of the PREVENT Meeting Component
p 42
p 43
1_ Second Cancer Risks after Radiotherapy for Breast
Cancer: What is the Impact of Advanced Treatment
Techniques?
p 44
2_ LET dependent response of the rat cervical spinal cord
after carbon ion irradiation
p 45
3_ ACE-inhibition reduces acute cardiac damage to
ameliorate radiation-induced lung dysfunction
p 46
AWARDS
p 48
INTRODUCTION
p 49
1_ ESTRO - Varian Award p 50
2_ ESTRO - Accuray Award
p 52
3_ ESTRO - Nucletron Brachytherapy Award
p 54
4_ ESTRO - Jack Fowler University of Wisconsin
Award 2013
p 56
5_ GEC-ESTRO Best Junior Presentation
Sponsored by Nucletron
p 58
This 2nd ESTRO Forum, hosted in Geneva, Switzerland in April, was a tremendous success and a feat
that I think we can all be proud of from several different perspectives. The very positive feedback we
received from delegates, speakers, partnering societies, exhibitors and industry partners proves that
we are on the right track with our meeting, and this gives us exciting prospects for further consolidating the ESTRO Forum format in the future. The event can in effect be considered as a homage to
radiation oncology itself, whereby all aspects of the field are covered and whereby interdisciplinarity
and collegiality between all involved professionals are omnipresent.
This Forum represented our second trial run – the first being the London Anniversary Meeting in 2011 – of a combined
meeting format. We once again brought together the clinical & translational meeting, the GEC-ESTRO-ISIORT meeting,
the Physics biennial meeting, the RTT meeting, and the PreVent (Prediction, recognition, eValuation and eradication of
normal tissue effects of radiotherapy) meeting.
The joining of forces has resulted in a ‘tour de force’ when considering the scientic programme that was put before you.
The scientific experts of the five meetings did an outstanding job that culminated in a programme of interest for clinicians,
medical physicists, biologists, radiation technologists, nurses, and anyone with an interest in the field of radiation oncology. Moreover, the younger professionals were also specifically catered for with dedicated sessions.
This programme could not have been presented to you without all those fine abstracts that were sent to us. Here in this
report each Scientific Committee Chair has made a selection of those that they wish to further bring into the limelight; we
have compiled these noteworthy abstracts, as well as certain Award abstracts, for you in this report.
I would also like to present you with some numbers that stand testament to the solid basis of the ESTRO Forum format.
For the forum in Geneva we had:
3647 delegates in total
Attendees from 67 countries, with 78% coming from Europe.
Physicists and radiation oncologists each made up 37% of the attendees, followed by RTTs (14%) and clinicians (5%)
A total of 161 sessions, of which 26 were interdisciplinary
1175 abstracts were received
335 abstracts selected for oral and poster presentations
260 invited speakers
88 exhibiting companies demonstrated their wares and know-how
121 persons attending the contouring workshops
438 persons attending the 6 pre-conference courses
10 commercial satellite symposia hosted
Now that we know we’ve cracked it, we can continue along this organisational course and host future congresses that we
know for sure will appeal to you…and together persevere with our efforts of developing optimal patient care and equitable
access to cutting-edge radiation therapy.
Vincenzo Valentini
President of ESTRO
2ND ESTRO FORUM - REPORT | INTRODUCTION
3
CLINICAL
Introduction
OVERVIEW OF THE CLINICAL & TRANSLATIONAL MEETING COMPONENT
p5
1_
A RANDOMISED CONTROLLED TRIAL OF INTENSITY MODULATED RADIOTHERAPY
(IMRT) FOR EARLY BREAST CANCER: RESULTS AT 5 YEARS
p6
2_
RECURRENCE PATTERN WITHIN THE CROSS TRIALS I AND II, COMPARING SURGERY ALONE
WITH CHEMORADIOTHERAPY FOLLOWED BY SURGERY FOR ESOPHAGEAL CANCER
p7
3_
DEVELOPMENT AND VALIDATION OF A PROGNOSTIC MODEL INCORPORATING CLINICAL
AND FUNCTIONAL MRI VARIABLES IN HEAD AND NECK CANCER
p8
4_
A PROSPECTIVE STUDY TO COMPARE DOCTOR VERSUS MODEL PREDICTIONS FOR
OUTCOME IN LUNG CANCER PATIENTS: PICK THE WINNER!
5_
HYPOXIA BIOMARKERS FOR PROGNOSTIC EVALUATION AND THE PREDICTION
OF OUTCOME FOLLOWING PROSTATE RADIOTHERAPY
6_
PHASE I/II STUDY OF PALLIATIVE RADIATION AND SORAFENIB FOR METASTATIC
RENAL CELL CARCINOMA AND BONE METASTASES
p9
p 10
p 12
OVERVIEW OF THE CLINICAL & TRANSLATIONAL MEETING COMPONENT
based approach seems relevant as well as promising to
predict both treatment response and toxicity.
In the past decennium, and pointing
onwards to the immediate future,
clinical radiotherapy has undergone
considerable developments, essentially including technological advances
in radiation delivery, the demonstration of the benefit of adding concomitant cytotoxic agents to
radiotherapy for a range of tumour types and the increasing integration of targeted therapeutics for biological
optimisation of radiation effects. Within this frame of
reference, the Clinical & Translation Meeting of the 2nd
ESTRO Forum highlighted a number of important study
breakthroughs, which were reported in meeting abstracts
that I have had the privilege to summarise in this overview.
The abstract with the appealing title ‘A prospective study to
compare doctor versus model predictions for outcome in
lung cancer patients: pick the winner!’ by Oberije et al. presented data that many of us, in our role as clinicians, may
regard as somewhat provocative. For lung cancer patients
receiving definitive radiotherapy, applying a prospective
study design to compare the physicians’ ability to predict
patient survival and treatment toxicity with the accuracy of a prediction model based on patient, tumour and
treatment characteristics, showed that the doctors’ clinical
foresight was inferior to that of the model!
Two of the abstracts, in particular, epitomised classic
randomised clinical trials of treatment response and
toxicity outcome, but at the same time reported on new or
controversial topics.
The abstract entitled ‘A randomised controlled trial of
Intensity Modulated Radiotherapy (IMRT) for early breast
cancer: results at 5 years’ by Coles et al. reported on the
randomisation of more than 800 breast cancer patients
between intensity modulated radiotherapy (IMRT) and
two-dimensional breast radiotherapy (2DRT). As the largest prospective trial in the world so far to test breast IMRT
against 2DRT, this study demonstrated that the former
translated into superior overall long-term side effects, and
also embodied this aspect as an important outcome parameter in modern radiotherapy trials.
The other abstract specifically attracting my attention was
the one entitled ‘Effect of preoperative chemoradiotherapy
on recurrence pattern in esophageal tumors’ by the Dutch
multi-centre CROSS I and II trials group. Study patients
with oesophageal carcinoma were randomised between
chemoradiotherapy (CRT) followed by surgery and surgery
alone. The CRT plus surgery approach improved local recurrence outcome, and also decreased the rate of systemic
disease recurrence, suggesting a change in the standard
of care of this disease to take into account the general
biological effects of what has been thought of as treatment
to control local disease.
Biological modelling is increasingly important in clinical
radiotherapy, and I looked with great interest at a number
of studies applying the promising opportunities of such
approaches. Of these I will highlight two in particular.
The abstract ‘Development of a predictive model incorporating clinical and functional MRI variables in head and
neck cancer’ by Lambrecht et al. described the correlation
of functional magnetic resonance imaging (MRI) tumour
data with disease free survival in head-and-neck cancer
patients after CRT. Additionally, this functional MRI data
was used to develop a prognostic model, which at this stage
needs more statistical evaluation; however, this biologically
4
CLINICAL | 2ND ESTRO FORUM - REPORT
From a clinical perspective, as knowledge accumulates
from molecular radiobiology, there is a complex and exciting opportunity for rational patient treatment stratification
in radiotherapy. Within this context, a number of novel
studies were reported, from which with difficulty I had to
select two to highlight here.
In the study ‘Hypoxia biomarkers for prognostic evaluation
and the prediction of outcome following prostate radiotherapy’, Alonzi et al. had analysed three hypoxia biomarkers in tumour biopsy samples from almost 200 patients
that had been enrolled in a trial comparing conventional
versus high-dose radiotherapy for prostate cancer. The investigators showed that tumour expression of the biomarkers was associated with shorter recurrence-free survival
following radiotherapy and, for tumours expressing one of
the biomarkers, that there was a significant patient benefit
of radiation dose escalation.
Finally, in the ‘Phase I/II Study of Palliative Radiation and
Sorafenib for Metastatic Renal Cell Carcinoma and Bone
Metastases’, Han et al. had used sorafenib, an anti-angiogenic, multi-targeted tyrosine kinase inhibitor, in combination
with palliative radiation of painful bone metastases in renal
cell carcinoma patients. In line with preclinical evidence
of a radiosensitising activity of sorafenib, the investigators
demonstrated both symptomatic and radiographic treatment
response (pain relief and reduced target lesion metabolic activity, respectively), while there were no severe adverse effects
reported from the combined-modality therapy.
The 2nd ESTRO Forum Clinical & Translational
Meeting provided a combination of translational
science, proof-of-principle early clinical studies
and randomised controlled clinical trials, enabling
radiation oncology to continue to position itself with
the highest level of evidence within existing clinical
practice. The selected studies referenced above
strongly manifest the principal vision of the ESTRO
2012 Strategy Document on the development of the
discipline within future cancer care.
Anne Hansen Ree
Member of the Clinical & Interdisciplinary Meeting Committee
In collaboration with Donal Hollywood (†), Chair of the meeting
2ND ESTRO FORUM - REPORT | CLINICAL
5
1
2
A RANDOMISED CONTROLLED TRIAL OF INTENSITY MODULATED RADIOTHERAPY (IMRT) FOR EARLY BREAST CANCER: RESULTS AT 5 YEARS
By Dr Charlotte Coles
Cambridge University Hospitals NHS Foundation Trust, UK
RECURRENCE PATTERN WITHIN THE CROSS TRIALS I AND II, COMPARING SURGERY ALONE WITH CHEMORADIOTHERAPY FOLLOWED BY SURGERY FOR ESOPHAGEAL CANCER
By MCCM Hulshof
Academic Medical Center, Amsterdam, The Netherlands
CONTEXT OF THE STUDY / PRELIMINARY
INFORMATION:
Uneven radiotherapy dose can cause changes to the normal
breast tissue, which can result in a poorer cosmetic appearance months and years after completion of treatment. A
poor cosmetic outcome from treatment of primary breast
cancer has been shown to adversely affect patient’s psychosocial well-being.
Intensity Modulated Radiotherapy (IMRT) is a radiation
technique, which enables an even dose to be given across
the breast, but is more time consuming and requires more
resources than standard two-dimensional breast radiotherapy (2DRT). The aim of this randomised trial was to
investigate whether IMRT reduces toxicity to breast tissue
and produces a better appearance at 5 years from completion of treatment.
ABSTRACT OVERVIEW:
Intensity Modulated Radiotherapy (IMRT) is a radiation
technique, which enables an even dose to be given across
the breast. The aim of this large randomised trial was to
investigate whether IMRT reduces toxicity to breast tissue
and produces a better appearance at 5 years after treatment compared with two-dimensional breast radiotherapy
(2DRT). Treatment plans of 1145 patients with early breast
cancer were analysed to see if they would produce an uneven radiation dose with 2DRT. 71% of the plans fell into
this category, and those patients were randomised between
standard 2DRT and IMRT.
WHAT WERE THE THREE MAIN FINDINGS OF
YOUR RESEARCH?
This study is unique as it is the largest prospective trial
in the world to test breast IMRT against 2DRT. The three
main findings at 5 years after completion of breast treatment are:
1. IMRT produces a better cosmetic breast appearance
2. IMRT reduces the risk of skin telangiectasia (dilated
blood vessels near the surface of the skin)
3. The surgical cosmesis should be optimised as this
also has a significant effect on late breast toxicities
6
WHAT IMPACT COULD YOUR RESEARCH
HAVE?
The researchers intend to follow up their work by analysing
the patients’ questionnaires to see whether IMRT has an
influence on quality of life. The trial has also contributed
1000 blood samples to the UK translational research study
RAPPER (Radiogenomics: Assessment of Polymorphisms
for Predicting the Effects of Radiotherapy), which ultimately aims to develop individualised radiotherapy plans
based on analysis of patient’s unique genetic make up.
IS THIS RESEARCH INDICATIVE OF A BIGGER
TREND IN ONCOLOGY?
Although IMRT is employed increasingly in breast cancer,
its use is far from universal throughout the world. We
hope that the evidence of benefit shown in our trial will
encourage its greater use, resulting in improved patient access and, ultimately, improved outcomes for breast cancer
patients.
INFORMATION:
Preoperative chemo radiotherapy (CRT) followed by
surgery for patients with esophageal carcinoma has
demonstrated to improve overall and disease free survival
compared to surgery alone. The context of the study is to
analyse the exact effect of preoperative CRT on site and
rate of tumour recurrences, based on a randomised study.
ABSTRACT OVERVIEW :
To analyze the difference in recurrence pattern for patients
with esophageal or gastro-esophageal carcinoma between
treatment with surgery alone versus preoperative chemo
radiotherapy followed by surgery, using a dose of 41,4 Gy
plus concurrent weekly paclitaxel and carboplatin,
What were the three main findings of your research?
After a minimum follow-up of 24 months 58% patients
had a recurrence after surgery alone and 35% after CRT +
surgery. CRT reduced the locoregional recurrences from
36% to 13%. Peritoneal carcinomatosis occurred in 14%
after surgery alone versus 4% after CRT + Surgery. Loco
regional recurrences occurred within the radiation field in
5% of the patients, borderline in 2%, out-field in 6% and
unclear in 1%. The majority of loco regional recurrences
had concurrent distal failures.
Figure: Locoregional recurrence free survival; recurrences at anastomotic site
and/or in mediastinal, celiac trunk or supraclavicular lymph nodes. P<0.0001.
Arm 0 = preoperative CRT + surgery, arm 1 = surgery alone
HAVE?
Preoperative CRT has impact on survival by reducing the
loco regional recurrences rate and by reducing peritoneal
seeding. Some further improvement in loco regional recurrence rate can be achieved by extending the radiation fields
and improving treatment accuracy, although a large effect
on survival is not expected
TREND IN ONCOLOGY?
The study confirms that a moderate preoperative radiation
dose combined with mild concurrent chemotherapy improves survival by improving the locoregional tumor control rate. It further suggests that pre operative CRT reduces
peritoneal seeding by reducing peroperative tumorspill in
the abdomen
7
3
4
DEVELOPMENT AND VALIDATION OF A PROGNOSTIC MODEL INCORPORATING CLINICAL AND FUNCTIONAL MRI VARIABLES IN HEAD AND NECK
CANCER
A PROSPECTIVE STUDY TO COMPARE DOCTOR VERSUS MODEL PREDICTIONS FOR OUTCOME IN LUNG CANCER PATIENTS: PICK THE WINNER!
By Lambrecht Maarten, MD
MAASTRO Clinic, Maastricht, The Netherlands
By Cary Oberije
Department of Radiation Oncology, University Hospitals Gasthuisberg, UZ Leuven, Leuven, Belgium
INFORMATION:
Diffusion weighted imaging (DWI) is a functional MRI
technique which allows us to characterize tissues based
on the mobility of water protons. This information can be
quantified and visualized and thus provides us with valuable insight in the tumor’s microstructure.
ABSTRACT OVERVIEW:
The main purpose was to investigate whether DWI has a
prognostic value for disease free survival (DFS) in head
and neck cancer patients treated with (chemo-) radiotherapy. Secondly we wanted to develop a prognostic model
incorporating clinical, anatomical and DWI parameters,
which could be helpful in patient selection, based on their
expected response, prior to treatment.
YOUR RESEARCH?
After multivariate analysis we found that the pretreatment
ADC value, derived from high b-values was a significant
prognostic factor in head and neck cancer patients treated
with (chemo-) radiotherapy (for DFS, HR 1.14; 95%CI
1.04-1.25; p:0.005) . The resulting prognostic model was
able to differentiate poor responders from good responders
(3 year DFS: 44% in poor responders vs 67% and 69% for
the intermediate and good responders respectively). This
information was put into a nomogram (Figure 1) correlating all relevant parameters to DFS probability. Although
promising, the performance of the model is still suboptimal and requires further improvement (c-index:0.62). The
addition of biological, molecular and genetic information
might further increase its performance.
in biological, molecular and genetic factors. The ability to
identify these factors, would enable us to select patients for
treatment adaptation beforehand, potentially increasing
tumor control while reducing therapy related morbidity
for the entire population. Non-invasive functional imaging
technique can be a very useful asset in this respect.
TREND IN ONCOLOGY?
Up to now treatment in many cancer sites is based on histological and anatomical findings. However, it is becoming
increasingly clear that while these tumors might be identical in basic anatomy and histology, their response to standard treatment differs greatly. This heterogeneity suggests
that a more patient tailored treatment approach is essential
if we want to further improve our results both for tumor
control and treatment related toxicity. However, there are
many factors which potentially play a role in the response
of a tumor to treatment, making evidence-based clinical
interpretation a nearly impossible task. Therefore solid
statistical analysis is essential to assess the true value of all
different factors and integrate them into an evidence-based
and robust clinical decision model.
INFORMATION:
The number of treatment options available for lung cancer
patients are increasing, as well as the amount of information available for an individual patient (genomics, proteomics, radiomics). Doctors have to choose the optimal
treatment option for an individual patient by combining
all this information, but this is a difficult task for humans.
However, prediction models can incorporate and combine this information and thus offer assistance in clinical
decision making.
ABSTRACT OVERVIEW:
Models for lung cancer patients to predict treatment-induced dysphagia (difficulty with swallowing), dyspnea
(shortness of breath) and survival were already developed
and tested. We hypothesized that these models would
outperform the doctors’ predictions. Experienced radiation
oncologists were asked to predict 2 year survival, dyspnea
and dysphagia at two time points: 1) after they had seen a
patient for the first visit, and 2) after the treatment plan was
made. Patient, tumor and treatment characteristics were
used by the models to calculate the probability for each outcome. We compared the performance of models to doctors’
in terms of AUC. An AUC of 1 indicates a perfect prediction
while an AUC of 0.5 is as good as chance (tossing a coin).
YOUR RESEARCH?
Prediction models for lung cancer patients substantially
outperformed the physicians’ prediction for all outcomes. The difference between doctors and models did
not decrease after the doctors had seen the patient or the
treatment planning. The models were especially superior
in identifying high risk patients and should therefore be
implemented in clinical practice to guide decisions.
HAVE?
By showing that models outperform radiation oncologists,
we hope that more people are willing to use prediction
models and to collect and exchange data to improve the
existing models. This will eventually lead to optimal treatment decisions for individual patients.
TREND IN ONCOLOGY?
It becomes more and more evident that some patients benefit from a specific treatment while others don’t and some
patients suffer from severe side-effects while others don’t.
The amount of information to explain these findings is increasing (genomics, proteomics, radiomics). This will lead
to an individualized treatment. In our opinion, individualized treatment can only succeed if prediction models are
used in clinical practice. These models can combine many
factors, while this is a difficult task for humans. If models,
based on patient, tumor and treatment characteristics,
already outperform the doctors, these results can be used
as a strong argument in favour of using prediction models
and changing current clinical practice. Eventually, in the
future, it will be regarded as unethical to make treatment
decisions based solely on doctors’ opinion.
HAVE?
Over the last decades the treatment of head and neck cancer has intensified and significantly improved both tumor
control and overall survival rates. However, this has come
at the cost of both acute and late toxicity, rendering further
uniform treatment intensification impossible. Furthermore
it is becoming increasingly clear that while these tumors
can be identical in location and basic histology, their response to chemoradiotherapy (CRT) differs greatly. These
differences in sensitivity can be explained by variations
8
Figure 1: Nomogram correlating clinical and imaging variables to probability
of disease free survival (DFS).
Comparison of models’ versus radiation oncologists’ predictions. The surface or area below the plotted the line is used for measuring the accuracy of predictions, 1
represents a perfect prediction, while 0.5 represents predictions that were right in 50% of cases, i.e. the same as chance.
9
5
HYPOXIA BIOMARKERS FOR PROGNOSTIC EVALUATION AND THE PREDICTION OF OUTCOME FOLLOWING PROSTATE RADIOTHERAPY
By Roberto Alonzi
Mount Vernon Cancer Centre, UK
INFORMATION:
Radiotherapy is commonly used as a curative treatment
for prostate cancer. We now understand that the higher the
radiation dose administered to a prostate cancer, the greater the chance of long-term tumour control. This increased
dose inevitably results in greater normal tissue toxicity. However, even before the use of modern high-dose
radiotherapy for prostate cancer, a proportion of patients
was cured using the ‘conventional’ doses prescribed at that
time. If we were able to detect in advance which patients
actually need the higher radiation dose and which men
could be safely treated with lower doses, then a significant
number of men would be spared the toxicity of dose-escalated radiation therapy. Prostate cancers frequently contain
regions of low oxygenation. We have known for a long
time that hypoxic tumours require a higher radiation dose
than non-hypoxic tumours to provide an equivalent level
of control. It is therefore possible that hypoxia biomarkers may predict which men specifically require high dose
radiotherapy.
ABSTRACT OVERVIEW:
In this research we analysed the prostate biopsy samples
of 191 men who were enrolled in a trial that compared
conventional versus high dose radiotherapy for prostate
cancer. Three immunohistochemical biomarkers of tumour
hypoxia were evaluated for each patient (Glut1, HIF1α
and Osteopontin) using monoclonal antibodies. Tumours
were assessed for biomarker expression by two independent investigators, blinded to patient outcome and scored
as negative or positive depending on the proportion of
cells staining for the marker in question. The relapse free
interval for all patients was then determined using the
Kaplan-Meier method.
YOUR RESEARCH?
1. Expression of any of the three hypoxia biomarkers
confers a poorer prognosis for patients receiving
prostate radiotherapy compared to those that do
not express these biomarkers. For Glut1, HIF1α and
Osteopontin respectively there was a 20.2 (p=0.005),
23.0 (p=0.019) and 22.5 (p=0.012) month reduction
in mean relapse free interval associated with biomarker expression.
10
2. Osteopontin expression predicted a need for radiotherapy dose escalation. In patients without osteopontin expression there was no benefit from the
administration of a high radiation dose (p=0.349),
whereas for those men whose biopsy samples
expressed osteopontin, there was a significant benefit
from dose escalation (p=0.017). However, the
converse was true for Glut1 with negative expression predicting a benefit for dose escalation
(p=0.006), (figure 1).
3. These results generate the following hypothesis:
osteopontin becomes positive in the presence of
mild/moderate hypoxia, whereas Glut1 only becomes
positive under conditions of severe hypoxia. Therefore, If both osteopontin and Glut1 are negative (i.e.
minimal hypoxia), there is no benefit from dose escalation. If osteopontin is positive and Glut1 is
negative (moderate hypoxia), there is a benefit for
dose escalation. However, If Glut1 is positive (severe
hypoxia), there is no benefit from dose escalation
because patients will do badly despite very high doses
of radiotherapy. This hypothesis is supported by the
fact that the Glut1 positive men (regardless of the expression of the other markers) had the poorest
median relapse free interval of all, (figure 2).
of those who receive them. Better predictive markers are
urgently required to direct treatments to those who will
actually benefit from them. This will spare many patients
from unnecessary side effects and free resources for more
effective use.
Figure 1. Kaplan-Meier survival curves for each of the hypoxia biomarkers, each showing that expression of any of the three hypoxia biomarkers confers a poorer
prognosis for patients receiving prostate radiotherapy compared to those that do not express these biomarkers.
HAVE?
The above hypothesis is currently being tested using an independent dataset. If confirmed, these results could cause
a significant change in clinical practice. Firstly, men with
non-hypoxic tumours (i.e. Glut1 negative and osteopontin
negative) could be spared the toxicity of high dose radiotherapy. Secondly, men with moderate tumour hypoxia
would be identified and given the opportunity to receive
high-dose radiation. Thirdly, those with severely hypoxic
tumours (Glut1 positive) may need to consider an alternative treatment option such as surgery or alternatively be
enrolled into a clinical trial of radiotherapy in conjunction
with hypoxia modification (as in the PROCON study, UK)
TREND IN ONCOLOGY?
Biomarker-guided therapy is currently a focus of intense
research in many tumour types. Most cancer therapies
are toxic and only result in an advantage for a proportion
Figure 2. Kaplan-Meier survival curves for each hypoxia category. Blue = minimal hypoxia (Glut1 negative and osteopontin negative), green = moderate hypoxia
(Glut1 negative and osteopontin positive) and yellow = sever hypoxia (Glut1 positive and osteopontin positive). The test equality of survival distributions for the
different hypoxia categories demonstrates significance (p=0.004).
11
6
PHASE I/II STUDY OF PALLIATIVE RADIATION AND SORAFENIB FOR METASTATIC RENAL CELL CARCINOMA AND BONE METASTASES
By Kathy Han
Princess Margaret Cancer Centre, Canada
INFORMATION:
Bone metastases from renal cell carcinoma (RCC) are
common and often less responsive to palliative radiotherapy (RT) than metastases from other tumors. Sorafenib
is a multi-targeted tyrosine-kinase inhibitor that inhibits
angiogenesis, and has been shown to improve progression-free survival as a mono-agent in metastatic RCC in
clinical trials. There is pre-clinical evidence to indicate that
inhibition of angiogenesis with sorafenib can improve the
effectiveness of RT. The purpose of this study was to examine the efficacy and toxicity of sorafenib in patients with
RCC receiving palliative RT for painful bone metastases.
ABSTRACT OVERVIEW:
Objectives:
1. Determine the pain response to a combination of
palliative RT and sorafenib in patients with RCC and
symptomatic bony metastases.
2. Determine the toxicity of palliative RT and sorafenib.
3. Determine preliminary biological activity of RT and
sorafenib from PET-CT scan results before and after
treatment.
4. Obtain preliminary information about the effect of
RT and sorafenib on disease control, as measured by
clinical or radiographic evidence of disease progression at the treated site, the need for subsequent RT or
the need for other interventions because of progression at the treated site.
HAVE?
Given that the combination of RT and sorafenib did not result in severe side effects directly, and provided good pain
relief and radiographic response in this study, sorafenib
and palliative RT show promise as a combined modality
treatment for metastatic RCC. This study provides a treatment schema for RT and sorafenib to be tested in a larger
clinical trial for safety and efficacy.
Fused PET-CT images at (a) baseline and (b) 7 weeks (4 weeks after completing radiotherapy) showing lower FDG uptake in the target lesion at 7 weeks (Figure 1)
but higher uptake in a non-target lesion at 7 weeks (Figure 2).
Figure 1 (a)
Figure 2 (a)
Figure 1 (b)
Figure 2 (b)
TREND IN ONCOLOGY?
There is increasing interest in combining RT with molecularly targeted agents to improve radiation response.
Sorafenib, an oral multi-targeted tyrosine kinase inhibitor
that has been shown to prolong progression-free survival
in patients with metastatic RCC, is a standard treatment
option for metastatic RCC. There is emerging evidence that
sorafenib has synergistic effects with radiation in preclinical studies. To our knowledge, this is the first clinical
study to investigate the efficacy and toxicity of combining
sorafenib and palliative RT for the treatment of symptomatic bony metastasis in patients with RCC. The number
of studies investigating the efficacy of sorafenib in combination with RT for other cancers is rising.
YOUR RESEARCH?
Mean ‘present’ pain scores at baseline, 7 weeks and 12
weeks were 3.9, 1.6, and 1.6, respectively (p=0.04). Only
two patients required re-irradiation of a previously treated
index lesion. Seven other patients required subsequent
RT for symptomatic progression of previously untreated
lesions.
1. There were no severe side effects directly attributable
to the combination of RT and sorafenib.
2. There was a significant difference in the metabolic
response of target lesions versus non-target lesions
(p=0.002). For target lesions, SUV decreased (5.4
to 3.9) after RT and sorafenib (p=0.003). However,
for non-target lesions, there was a trend towards an
increase in SUV (3.9 to 5.0) (p=0.08).
12
13
PHYSICS
OVERVIEW OF THE BIENNIAL PHYSICS MEETING COMPONENT
The physics abstracts highlighted here represent a selection of the very best proffered papers presented at the 12th edition of ESTRO’s Biennial Physics Conference. These abstracts have been selected as
they provide important guidance for both the current and future practice of radiotherapy, underlining the key role of medical physics for both scientific and clinical progress in this field.
Introduction
OVERVIEW OF THE BIENNIAL
PHYSICS MEETING COMPONENT
p 15
1_
A NATIONAL DOSIMETRIC AUDIT OF VOLUMETRIC MODULATED ARC
THERAPY AND TOMOTHERAPY IN THE UK
p 16
2_
TIME DEPENDENT PRE-TREATMENT VERIFICATION FOR VMAT PLANS USING
FLATTENED OR FFF BEAMS
p 18
3_
VALIDATION OF THREE DEFORMABLE IMAGE REGISTRATION ALGORITHMS
USING THE TEST METHOD
One of the abstracts (Clark et al.) describes the findings of the first detector array based dosimetry
audit for rotational IMRT, which was performed on a nationwide basis in the UK. The importance
of this study is that it demonstrates that a treatment modality of such high complexity can be safely
implemented on a widespread basis. A second abstract (Podesta et al.) also deals with dosimetric verification of rotational
IMRT. This study more specifically addressed the temporal aspect of the delivery and dosimetry process, presenting a new
method that allows for verification of each portion of the complex delivery course of a rotational IMRT fraction, rather
than the total integrated beam delivery verification used in current approaches.
Another highlighted abstract (Wittendorp et al.) presents a new method to validate deformable image registration algorithms, a key tool for a number of image-guided and adaptive radiotherapy applications. The method combines several
features of the registration, giving a more complete characterization of the registration quality. The method is likely to
become a very useful instrument in the implementation process of adaptive radiotherapy.
Finally, the two last selected abstracts present studies related to upcoming RT delivery techniques: real-time monitoring/
tracking of tumours (Poulsen et al.) and proton therapy (Bueno et al.). The Poulsen study specifically presents a new
method to calculate the dose actually received in moving targets using CBCT-based target trajectory estimation, providing a widely accessible tool to evaluate the consequences of intra-fractional motion in terms of target dose distributions.
The Bueno study focuses on the challenges of treatment planning calculations for protons, and in particular developed a
measure – based on the degree of density heterogeneity lateral to the beam – that indicates when the more time-consuming Monte Carlo calculations are required instead of the conventional pencil beam algorithm.
Make sure to read the very interesting physics abstract featured in the Awards section of this report.
p 20
Ludvig Paul Muren
14
Chair of the Biennial Physics Meeting
4_
KILOVOLTAGE INTRAFRACTION MOTION MONITORING AND TARGET DOSE
RECONSTRUCTION FOR LIVER SBRT DELIVERED BY VMAT
p 22
5_
AN ALGORITHM TO ASSESS THE NEED FOR CLINICAL MONTE CARLO DOSE
CALCULATIONS FOR PROTON THERAPY FIELDS
p 23
PHYSICS | 2ND ESTRO FORUM - REPORT
2ND ESTRO FORUM - REPORT | PHYSICS
15
1
A NATIONAL DOSIMETRIC AUDIT OF VOLUMETRIC MODULATED ARC
THERAPY AND TOMOTHERAPY IN THE UK
By Catharine Clark
Royal Surrey County Hospital and National Physical Laboratory, UK
CONTEXT OF THE STUDY /
PRELIMINARY INFORMATION:
Volumetric Modulated Arc Therapy
(VMAT) and Tomotherapy (collectively named rotational radiotherapy
(RRT)) have the capability to sculpt
the radiotherapy dose to the shape of
the tumour target and spare normal
tissue. A survey of UK cancer centres in 2011 indicated
that there was a rapid uptake of RRT (Varian RapidArc,
Elekta VMAT or Helical Tomotherapy), and that by 2012,
50% of the centres would be offering this treatment. This
highlighted the need for a national audit of dose measurement of RRT in order to ensure safe and accurate implementation.
ABSTRACT OVERVIEW:
We had previously investigated the use of a detector array
system, which allows simultaneous measurement of dose
at hundreds of points in a patient plan, for dosimetry audit
and developed a methodology for comparison of calculated plans with measurement at plan delivery. The present
work represented the performance and comparison of
measurements across 30 centres in the UK. The results
have shown that the majority of centres offering RRT are
able to model the dose distribution and deliver the plans
accurately both in terms of the dose to a point and the
distribution of the dose.
HAVE?
This work has confirmed that centres are safely able to
deliver the calculated plans generated for this advanced
radiotherapy technique. It has also set standards for future
centres in their implementation process. The collaborative
nature of the audit with the national radiotherapy trials
quality assurance team also meant that centres were certified to join a clinical trial using their rotational technique
on successful completion of the audit. The methods developed for use of an array detector system could be used for
other advanced radiotherapy techniques.
TREND IN ONCOLOGY?
This work is the first audit of VMAT and Tomotherapy to
use a detector array system. As radiotherapy techniques
become more complex, so the audit procedures which
validate them need to develop to provide appropriate
measurement approaches. The process of employment of
advanced techniques benefits from external review and
audit to ensure safe and accurate implementation.
PTW 2D array used for measurements in each hospital
YOUR RESEARCH?
Centres were asked to create both a generic plan and a
patient-specific clinical trial plan. Following measurement
of the delivered plan with the array, differences between
the calculated and delivered plans were investigated in two
ways: (a) looking at specific points associated with individual target volumes and areas of avoidance and (b) using an
index (gamma index) which gives a measure of how closely
the delivered and calculated plans match in terms of dose
distribution. The results showed that the dose at specific
points for all plans gave a mean difference of less than 0.5%
across the 30 centres. For the dose distributions, in 93% of
all the measurements 95%of the measured plane matched
within accepted criteria of 3% and 3mm.
The 3DTPS plan which all hospitals planned and delivered, measured in two coronal planes and one sagittal plane
16
17
2
TIME DEPENDENT PRE-TREATMENT VERIFICATION FOR VMAT PLANS
USING FLATTENED OR FFF BEAMS
By Mark Podesta
Maastro Clinic, The Netherlands
INFORMATION:
External beam treatments for radiotherapy require testing
before they are performed on a patient to ensure the equipment and software performs as intended and to minimise
the possible problems that can occur during patient therapy. While several solutions exist to perform these checks,
arguably the method requiring the least amount of time
and additional equipment, is to use the Electronic Portal
Image Device (EPID), typically provided as standard on
the equipment used to deliver external beam treatments.
The EPID is akin to a digital camera for radiation and
with proper calibration the EPID can be used to measure
radiation dose.
To date, pre-treatment verification uses EPID dosimetry
in a long-exposure fashion, turning on the camera and
accumulating the signal over the whole treatment. This
allows each accumulated radiation field to be verified but
does not verify the steps during the field which can be
numerous and widely variant. We propose a method where
the EPID can be used in more of a movie mode where each
step of the planned treatment can be verified in small time
intervals.
ABSTRACT OVERVIEW:
Portal dosimetry is a robust way to verify external beam
therapies before the treatment is administered. Until now
portal dosimetry has only been performed using integrated field images and typically using flattened beams. For
fast, dynamic therapies such as VMAT, which can contain
hundreds of field shapes, this may not be sufficient. For
example, a VMAT fraction can be delivered in ~1-3 minutes using ~180 control points with varying field shapes
and dose rates. These deliveries are much more dependent
on equipment precision and accuracy when compared
to static treatments. We think it necessary to verify these
deliveries with added scrutiny and so we present a portal
dosimetry method to verify VMAT plans in a time-dependent manner using flattened or unflattened beams.
Doses delivered at a particular point in time may deviate
from predicted doses, as shown by time-dependent verification. These errors are typically hidden in integrated field
images.
New action levels are required to indicate how much deviation during a treatment is permissible as current action
levels are not immediately applicable.
HAVE?
The method described here will allow for a higher level of
verification for currently implemented dynamic external
beam therapies such as IMRT and VMAT. It will also provide added confidence for centres considering flattening
filter free beams in their therapy options.
Future work will include development of time-dependent
2D transit dosimetry and full 4D in-vivo dose reconstruction.
Fig. 1. Continuous verification of a VMAT plan, deviation versus beam angle.
Red and blue areas indicate over/under dose respectively.
Fig. 2. Gamma distributions (3%, 3mm, 3sec) between measurement and
prediction of 2D doses for a single VMAT 6MV FFF arc. Red and blue areas
indicate over/under dose respectively.
TREND IN ONCOLOGY?
Standardisation, reliability, consistency, and quality
assurance are key aspects of modern complex radiation
oncology which can appear to be in opposition to the other
key aspect of patient specific treatment. EPID dosimetry
and time-dependent EPID dosimetry in particular can
standardize the verification of different external beam
therapies. This can result in less variation in treatment
consistency through inter-fractional adaptation, while
still catching more day-of-delivery errors using correctly
chosen action levels.
YOUR RESEARCH?
We show time-dependent pre-treatment portal dose
verification is possible, without the need of any additional
equipment (detector or specialised phantom) and no additional set-up is required to include unflattened beams.
18
19
3
VALIDATION OF THREE DEFORMABLE IMAGE REGISTRATION ALGORITHMS USING THE TEST METHOD
By Paul. W.H. Wittendorp
University of Groningen, University Medical Center Groningen, Department of Radiation Oncology, Groningen,
The Netherlands
INFORMATION:
The anatomy of patients can change during radiotherapy
treatment, which can last up to 7 weeks, For example, patients can lose weight or the tumour can change shape. The
ability to map these and other changes in the patient allows
the possibility of adapting the radiotherapy treatment. The
changes can be mapped with deformable image registration (DIR). As DIR algorithms are still under development, it is essential to verify the accuracy of the calculated
deformations.
Methods currently used to quantify DIR accuracy often
only provide information about image regions with high
contrast (e.g. anatomical landmarks). However, in adaptive
radiotherapty (ART) it is important to know the deformation accuracy in the entire irradiated volume. Therefore,
we developed a method that quantifies the DIR accuracy
both in high and low contrast regions in the image.
ABSTRACT OVERVIEW:
The objective of the current study was to determine which
of three frequently used DIR algorithms (Demons, SFBR,
and B-Spline) give the best performance, when used for
the deformation from planning CT (pCT) to repeat CT
(rCT) in patients treated for head and neck cancer. For this
purpose we developed the TEST method which combines
four different verification methods: 1) Target registration
error, 2) expansion, 3) shear strain, and 4) transitivity.
Using these multiple methods we were able to quantify
the deformations in the high and low contrast regions and
to determine whether the deformation was anatomically
plausible, see figure 1.
WHAT IMPACT COULD YOU RESEARCH HAVE?
We showed that the TEST method can be used to compare
the accuracy of different DIR algorithms. This quantitative
method to verify the deformations can help compare the
DIR accuracy in different radiotherapy departments or
help a single department to choose the best DIR algorithm
for their application. Furthermore, the TEST method gives
quantitative information both in high and low contrast
regions and gives information about the anatomical
plausibility of deformation. This information is essential to
determine whether a DIR result is accurate enough to use
in an adaptive radiotherapy procedure.
IS THE RESEARCH INDICATIVE OF A BIGGER
TREND IN ONCOLOGY?
All radiotherapy departments want to provide the best
treatment to their patients. An increasing number of
departments believe that the way to achieve this is to use
adaptive strategies. Automated methods that quantify the
accuracy of DIR results and the accuracy of the actual patient dose have to be developed before adaptive strategies
can be implemented in the clinic on a large scale. With the
TEST method the accuracy of DIR results can be quantified and the determination of the expansion, shear strain,
and transitivity can be automated. Therefore, the TEST
method can be an important tool in the clinical introduction of adaptive radiotherapy.
Figure 1: a) shows the deformation vector field projected on the deformed image, where the length of the deformation vectors was magnified three times. In b) the
same deformed image is shown in combination with the expansion calculated from the deformation vector field. It can be seen in the orange circle in b) that the
vertebrae have an expansion of about 0.15, while the limit is set to 0.01 for bone, therefore this is not an acceptable deformation.
YOUR RESEARCH:
For the deformations from pCT to rCT, the target registration error showed minor variation between the different
algorithms, as shown in table 1. However, the expansion
and shear strain of the DVF (deformation vector field)
showed a larger difference. The Demons algorithm exceeded the limits on almost all aspects; for example 5.8% of the
soft tissue voxels are out of limit for the expansion. The
B-Spline and the SFBR both stayed within the limits for
soft tissue and air cavities. The expansion and shear strain
in the bony anatomy exceeded the limits for all algorithms.
The average transitivity exceeded the limits for SFBR, while
it remained within limits for B-Spline and Demons.
20
Table 1: Overview of the accuracy of deformations with the B-spline, Salient Feature Based Registration (SFBR) and Demons algorithm from the planning CT to a
repeat CT for ten different patients. The proposed limits for clinical use are indicated.
21
4
5
KILOVOLTAGE INTRAFRACTION MOTION MONITORING AND TARGET
DOSE RECONSTRUCTION FOR LIVER SBRT DELIVERED BY VMAT
AN ALGORITHM TO ASSESS THE NEED FOR CLINICAL MONTE CARLO
DOSE CALCULATIONS FOR PROTON THERAPY FIELDS
By Per Rugaard Poulsen
By Marta Bueno
Aarhus University Hospital, Denmark
INFORMATION:
Tumors in the thorax or abdomen may undergo substantial
breathing motion during radiotherapy beam delivery. The
respiratory motion is a challenge for the accuracy in stereotactic body radiotherapy (SBRT), where high radiation
doses are delivered in a few treatment fractions to small
lesions. The motion may result in target doses that differ
markedly from the planned dose.
ABSTRACT OVERVIEW:
Five patients with implanted gold markers were treated
with VMAT liver SBRT in three fractions. Intra-treatment
x-ray fluoroscopy with an On-Board Imager was used to
estimate the 3D target motion throughout all treatments
(Figs 1a-c). The accuracy of the 3D estimations was
determined using portal images whenever the tracked
gold marker was inside the VMAT field aperture (Fig. 1,
bottom). For each treatment fraction, the measured 3D
trajectory was used to reconstruct the delivered target dose
distribution by a previously validated method that models
the target motion as a sequence of isocenter shifts in the
treatment planning system (Fig. 1d).
YOUR RESEARCH?
The main findings were that:
1. The standard imaging system of a conventional linear
accelerator can be used to measure the time-resolved
3D target trajectory during VMAT beam delivery
with sub-millimeter accuracy.
2. Even with daily image-guided patient setup, the
dosimetric impact of intrafraction target motion
can be substantial. The largest observed impact was
a reduction of D95 (the minimum dose to 95% of
the CTV) from 98% in the plan to 82% in the
delivered fraction dose.
3. The presented methods provide useful tools for dose
prescription evaluation, e.g. to evaluate whether it
is optimal to have the current dose prescription with
a peaked, non-uniform PTV dose that gradually
decreases from >95% to >67% between CTV and
PTV.
22
Institut de Tècniques Energètiques (Universitat Politècnica de Catalunya), Barcelona, Spain and Institute for
Bioengineering of Catalonia, Barcelona, Spain.
HAVE?
The demonstrated methods provide a widely accessible
approach for intra-treatment motion monitoring and dose
reconstruction since only standard equipment of a conventional linear accelerator was used. The reconstructed
dose distribution that accounts for the actual intrafraction
motion provides a strong tool for (1) quality assurance of
individual treatments, (2) optimization of margins and
dose prescription approaches in SBRT, and (3) improved
understanding of dose-response relationships in radiotherapy outcome studies. With robust automatic real-time segmentation of the gold markers in the kV images the target
motion monitoring can be used for real-time adaptation of
the beam to the target motion.
TREND IN ONCOLOGY?
Radiation oncology has seen an increasing interest in IGRT
for improved patient setup accuracy prior to treatment.
The current work brings this development a step further
by using IGRT for intra-treatment motion monitoring and
individualized reconstruction of the delivered target dose.
Another exciting topic is tumor tracking where continuous
monitoring is used for real-time beam adaptation during
treatment delivery. So far, robotic tracking and gimbal
tracking have been implemented clinically using highly
specialized treatment machines (Cyberknife and Vero,
respectively). The current work demonstrates that the
standard IGRT equipment of conventional linear accelerators provides the necessary tools for image-based motion
monitoring during beam delivery, which may be used for
couch tracking or MLC tracking on conventional treatment machines.
INFORMATION:
In proton therapy, dose distributions inside the patient
must be accurately determined to ensure a successful
treatment outcome. Patient tissue heterogeneities pose a
challenge to current analytical dose calculation algorithms
such as the pencil beam (PB) method. Multiple Coulomb
scattering causes the degradation of the Bragg peak when
a proton beam traverses complex inhomogeneous media.
Commonly, PB algorithms model this effect within the
dose kernel itself but the radial distribution at each depth
only accounts for heterogeneities upstream of the pencil
central axis. The assumption of such slab geometry might
induce large dose errors in the presence of lateral heterogeneities. The detrimental consequences of such dose
calculation deficiencies become more important as the
target volume is reduced and the shadow effects due to
the presence of heterogeneities have a greater impact on
the overall dose coverage in the tumour. An alternative is
to use Monte Carlo (MC) calculations, which can provide
highly accurate doses and are considered to be the benchmark. However, they are likely to entail long computation
times, which is not practical for routine clinical work.
ABSTRACT OVERVIEW:
We aimed at obtaining an index capable of estimating the
level of tissue heterogeneities within the beam path that
could be used as an indicator for the accuracy of dose
delivery based on analytical dose calculations for small
proton fields. We defined a heterogeneity index (HI) that
computes, for each field, the lateral tissue heterogeneities
following the dose calculation approach taken by the PB
algorithm. The PB predictions were verified against MC
simulations in terms of dose to the target (GTV) for a
number of patients. Finally, we evaluated the correlation
between HI and the dose error in the GTV.
a good indicator for the accuracy of proton field delivery in
terms of GTV prescription dose coverage. Third, with the
established correlation a threshold value – HIthres – can be
used to identify those patients for which MC recalculation
is recommended.
HAVE?
The HI can be obtained in less than three minutes, allowing routine clinical implementation of this methodology
to readily predict whether a specific field arrangement is
associated with significant absolute dose uncertainties. If
this were the case, either a change in the beam incidence
(if feasible) or a MC dose calculation of the plan should be
considered.
TREND IN ONCOLOGY?
Although PB algorithms can provide accurate dose distributions in the absence of complex density heterogeneities,
dose predictions might be questioned when the proton
beam traverses very inhomogeneous regions in the patient,
which is the situation for most head and neck tumours.
The HI as defined in this study estimates the reliability
of the PB dose predictions in a straightforward manner
so that the plan can rapidly be either accepted, if HI<HIthres, or rejected, if HI>HIthres. The efficiency of the HI
algorithm leaves the workflow in the clinics unaltered.
When HI>HIthres, MC dose calculations can significantly
improve the reliability of dose distributions. This may lead
to a beneficial increase in tumour control probability for
the patient, which is worth the relatively long computation
time.
YOUR RESEARCH:
The three main findings of our research were the following.
First, errors in dose delivered to the GTV predicted by
the PB algorithm were up to 5.4%, which exceeds current
tolerance levels. For these cases, using MC calculations is
warranted. Second, the errors were strongly correlated to
our HI (Spearman’s ρ=0.8), which demonstrates that HI is
23
RTT
OVERVIEW OF THE RTT MEETING COMPONENT
At the 2nd ESTRO forum in Geneva, the RTT track included presentations on current research and
innovation within all aspects of the RTT profession. Of these, we have selected three abstracts that
best illustrate the current status of the RTT profession in relation to target and OAR delineation as
well as treatment planning.
Peter de Ruiter from The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital discussed
the efficacy of a VMAT ‘library plan’ solution to deal with bladder volume variations in chemo-radiation therapy of cervical cancer. This research indicated how departments can utilise cone-beam CT
and the expertise of their RTTs to optimise their workflow strategies to best meet the need for adaptive processes, in this
era of personalised radiation therapy.
Introduction
OVERVIEW OF THE RTT MEETING COMPONENT
p 25
1_
A PLANNING STRATEGY FOR GENERATING A LIBRARY OF PLANS FOR
CERVICAL CANCER
p 26
2_
DELINEATION OF ORGANS-AT-RISK IN THE PELVIC AREA: DEVELOPING
GUIDELINES FOR RTTS
p 28
3_
CAN O-MAR INCREASE PRECISION OF DELINEATION IN HEAD AND NECK CANCER?
p 30
Bruno Speleers and Maddalena Rossi from University of Ghent, Belgium and the NKI, Amsterdam, respectively, presented
their research on the development of guidelines for the delineation of OARs in the pelvic region for RTTs, whose centres
are involved in EORTC clinical trials. The first aim of this research was to assess logistical and evaluation methods. The
second aim was to investigate interobserver variability when general guidelines for delineation were provided to observers.
Based on these results, the final aim of this ongoing research is to determine the interobserver variability when more rigorous guidelines are provided to RTT participants. This presentation at the Forum highlighted the importance of unambiguous guidelines in increasing precision in the delineation process by RTTs.
Our final abstract also focuses on the important topic of precision in delineation, this time in the head and neck region.
Rasmus Christiansen and his colleagues from Odense University Hospital and the University of Southern Denmark, Institute of Clinical Research presented their research on the ability of the commercially-available ‘Metal Artefact Reduction
for Orthopaedic Implants’ (O-MAR) algorithm to increase delineation precision in the head and neck, where metallic
dental implants can cause significant streaking artefacts.
Dice indices comparing delineations with and without the O-MAR algorithm were reported for the GTV-T, GTV-N and
parotid glands, with interesting results.
We hope you enjoy this selection of abstracts from the RTT track of the second ESTRO Forum in Geneva, which
best represents current RTT research in the fields of delineation and treatment planning.
Danilo Pasini
Chair of the RTT Meeting
24
RTT | 2ND ESTRO FORUM - REPORT
2ND ESTRO FORUM - REPORT | RTT
25
1
A PLANNING STRATEGY FOR GENERATING A LIBRARY OF PLANS FOR
CERVICAL CANCER
By Peter de Ruiter
The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
INFORMATION:
HAVE?
ABSTRACT OVERVIEW:
TREND IN ONCOLOGY?
Inoperable cervical cancer can be treated with chemo-radiation therapy. The radiation dose is delivered not only to
the cervix, but also to the uterus, as (microscopic) tumor
invasion may be present there. The uterus lies on top of
the bladder, and thus moves on a day-to-day basis due to
variations in bladder filling. These movements can be large,
up to 5 cm.
To deal with these variations, we use a Library of Plans
(LoP), consisting of 4 treatment plans for the same patient
with various bladder fillings (ranging from full to empty).
At each treatment fraction, the most appropriate plan
is selected at the Linac, based on a conebeam CT image
acquired prior to treatment.
The concept of a LoP is an effective solution to cope with
the day-to-day variation of the target volume for cervical
cancer. It is a challenge though to fit the creation of a LoP
into the clinical workflow, as it is time-consuming to make
4 Volumetric Modulated Arc Therapy (VMAT) plans for
one patient. The purpose of this study was to develop a
planning strategy for generating a clinically acceptable
library of 4 “Library Plans” (LP1-4), within an acceptable
time period.
YOUR RESEARCH?
The method we developed makes it possible to generate
4 clinically acceptable plans for different bladder filling
situations for cervical cancer, without the need of creating
4 CT scans, delineating targets and OARs on 4 scans and
manually constructing 4 separate treatment plans. As the
script automatically generates the plan LP1, 3 and 4, the
planning time remains acceptable.
Using a LoP may improve target coverage without increasing dose to OARs and, as motion is compensated for,
margin and thus toxicity on OARs could be reduced.
The concept of LoP might also be used for other target areas with a predictable variation in either position or shape,
such as bladder tumours.
The trend of personalisation and adaptation of treatment
plans is expected to improve the quality of each individual treatment, however it also generates a severe pressure
on RT departments. Treatment plans are getting more
complex and more plans might need to be made for a
single patient. RT departments must therefore search for
methods that make it possible to handle the increasing
amount of work.
This research is a good example on how RT departments
can work on optimising their workflow for adaptive strategies.
Fig 1: Library of plans for cervical cancer. LP1 represents the full bladder situation (100%), LP4 the empty bladder situation (0%). CTVs for LP2 and LP3 are
reconstructed based on LP1 and LP2. Initial treatment planning takes place on LP2, as this is expected to be the most common situation during treatment. All
other plans are generated automatically.
The aqua-blue line represents the 95% isodose line of the prescribed dose.
In our method, one initial VMAT plan needs to be manually created for the target volume, corresponding to the
66% bladder filling. Based on this plan, three additional
plans are generated automatically for modified target
volumes corresponding with bladder filling of 100%, 33%,
and 0%, respectively (Fig 1). All plans are made on the
same CT scan.
The study showed that the automatic plan generation leads
to homogeneous plans, with adequate PTV coverage (Table
1). The conformity index (CI V95%) indicated a good
sparing of tissue outside the PTV. To validate the safety of
planning the non-full bladder situations (LP2-4) on a full
bladder scan, the LP4 plans were transferred to the empty
bladder scans and dose was recalculated and evaluated.
This showed a comparable PTV coverage.
Table 1: Results for the total PTV of 5 patients. The plans indicated with a * indicate a plan automatically generated from LP2. The data indicated by LP4** is the
plan calculated as LP4*, recalculated on the empty bladder scan. CI V95% is defined as the volume of the 95% dose region divided by the volume of the PTV.
26
27
2
DELINEATION OF ORGANS-AT-RISK IN THE PELVIC AREA: DEVELOPING
GUIDELINES FOR RTTS
By Bruno Speleers and Maddalena Rossi
University of Ghent, Belgium and NKI Amsterdam, The Netherlands
INFORMATION:
The EORTC performs numerous multi-centre trials, many
involving radiotherapy. Target areas for radiotherapy are
delineated on CT scans with or without the help of other
image modalities by the Radiation Oncologist. However,
organs-at-risks (OARs) are delineated in most institutes
by a Radiation TechnologisT (RTT). The delineation is
frequently based on CT-scans and performed during the
treatment planning procedure. Defining strict guidelines
on CT based information would reduce the inter-observer
variability between institutes.
ABSTRACT OVERVIEW:
The purpose of the research was to define delineation
guidelines for organs at risk (OARs) for RTTs involved in
EORTC multi-centre clinical trials. Prior to commencing
the study, logistics and evaluation methods were assessed
using an OAR (bladder) within a small group of RTTs.
In the second phase the same institutes were involved
with general guidelines provided for the observers for the
OARs in the pelvic region (bladder,anus, rectum, sigmoid,
femoral heads and penile bulb). Guidelines were adjusted
for those OARs demonstrating large variances between
observers. The third phase involves a larger number of observers with stricter guidelines for the same set of OARs. A
software package developed in the NKI-AVL, Amsterdam
was used for delineation and assessment of delineation
accuracy.
TREND IN ONCOLOGY?
Delineation errors still need to be taken into account when
calculating the margin expansions between CTV (clinical
target volume) and PTV (Planning target volume).
Delineation errors and variability should be taken into account. One option, still the object of scientific discussion,
could be to calculate these delineation uncertainties in the
margin expansions between CTV (Clinical Target Volume)
and PTV (Planning Target Volume).
Many studies have shown large variations between observers in target volume delineation. These discrepancies
also occur in delineations of organs at risk. Research into
automatic segmentation algorithms is ongoing for target
areas and OARs. However, these automatic segmentation
algorithms are not currently in general use. Therefore, in
current practice, providing accurate delineation guidelines
for OARs could assist in a more optimal objective toxicity
scoring and provide a more accurate evaluation of a clinical trial.
Fig 1
Fig 2
Example of the discrepancy between observers for the delineation of the rectum (fig 1) and sigmoid (fig 2) especially at the cranially and caudally border of the
structure.
Scale from blue to red. Blue means a good correlation between observers (small standard deviation) and red, a standard deviation of ≥ 1 cm between observers
YOUR RESEARCH?
Large variations were seen between observers especially
in the cranial and caudal delineations of the OARs where
guidelines were not well defined. Strict guidelines describing anatomical borders are required for OAR delineation
in order to avoid discrepancies and reduce variation in
OAR delineation.
HAVE?
Providing guidelines for delineating OARs in EORTC radiotherapy studies will allow for a more accurate comparison
and evaluation of treatment results in multi-centre trials.
28
29
3
CAN O-MAR INCREASE PRECISION OF DELINEATION IN HEAD AND NECK
CANCER?
By Rasmus Lübeck Christiansen
Odense University Hospital, Denmark
INFORMATION:
Delineation of the GTV is a main source of inaccuracy in
radiotherapy (RT) planning for Head and Neck Cancer
partly because precise delineation is often impaired by artefacts from metallic dental implants affecting visualisation
of the tumour and organs at risk (OAR).
Imaging modalities less susceptible to metal artefacts, such
as PET and MRI, are widely used to compensate for this,
but can at the same time introduce new causes of inaccuracies. Therefore, elimination of artefacts on CT scan is still
desirable.
An image processing algorithm (O-MAR) has been
developed to reduce artefacts from orthopaedic metal
implants. It has previously been shown that this algorithm
has very little effect on the dose calculation (Hansen CR, et
al.IJROBP, vol. 84 issue 3, 2012, p. S520-S521). However, its
effect on delineation has not been tested so far.
ABSTRACT OVERVIEW:
This study investigates whether the O-MAR algorithm has
an effect on the delineation of GTVs and OARs in Head
and Neck Cancer patients. For this purpose, 11 patients
planned for curative RT (66-68 Gy/33 Fx) for oropharyngeal carcinoma were included in this study based on
streaking artefacts in the tumour area. These 11 patients
constituted 20 % of all curative Head and Neck Cancer
patients scanned during this period.
Three experienced clinical oncologists and one radiologist
first contoured the GTVs on standard CT reconstructions
without the O-MAR algorithm. Approximately one month
later, the GTVs were delineated on the same 11 CT data
sets, this time reconstructed with O-MAR. Likewise, 4
experienced RTTs contoured the parotid glands on both
reconstructions. The parotid glands were included in this
study as they are often affected by metal artefacts.
To evaluate inter-observer variation, mean of SørensenDice indices for all combinations of contour pairs, in each
reconstruction dataset, was calculated.
The results are summarised in Table 1. Reduction of major
metal artefacts with O-MAR reconstruction resulted in
larger volumes of all delineated structures compared to
standard reconstruction. Delineation of the parotid glands
also showed a decrease in inter-observer variation after
reduction of metal artefacts.
YOUR RESEARCH?
Reduction of metal artefacts has the potential to improve
the delineation of GTVs and OARs, both regarding
inter-observer variation as well as volume-wise. Although
the decrease in inter-observer variation was not statistically significant for all structures delineated in this study,
we were able to demonstrate large and clinically relevant
delineation differences in the individual patient before and
after artefact reduction, as shown in Figure 1.
Volumes of delineated structures are generally larger after
reduction of metal artefacts. This may be interpreted as a
result of the delineators’ reluctance to delineate in areas
void of signal.
HAVE?
This study shows that delineation of tumour and OARs in
Head and Neck Cancer may be affected by metal artefacts
which can ultimately lead to altered RT plans. At Odense
University Hospital, O-MAR has become standard for all
curative Head and Neck Cancer patients. It is important to
keep in mind that metal artefacts may affect the delineation as well as dose calculation. It is plausible, that these
results for Head and Neck Cancer patients may be extrapolated to other patient groups.
Table 1. Mean Sørensen-Dice indexes and mean volumes of delineated structures +/- Standard Deviation on standard and O-MAR reconstructions.
TREND IN ONCOLOGY?
Quality of OAR delineation in radiotherapy planning is a
priority, mainly focused on delineation training of RTTs.
Also, supplementary imaging modalities such as MR and
PET are introduced for dose planning. However, CT based
dose planning is the foundation of dose calculation as well
as OAR delineation. Therefore, the image quality of CT
scans must still have high priority in our daily routines.
Figure 1. Example of GTV-Tumour delineated on the same CT scan, by the same oncologist before and after reduction of metal artefacts with O-MAR.
30
31
BRACHYTHERAPY
Introduction
OVERVIEW OF THE GEC-ESTRO-ISIORT MEETING COMPONENT
1_
HIGH DOSE RATE (HDR) BRACHYTHERAPY TREATMENT VERIFICATION USING
AN ELECTRONIC PORTAL IMAGING DEVICE (EPID)
OVERVIEW OF THE GEC-ESTRO-ISIORT MEETING COMPONENT
We had an excellent selection of high-quality proffered papers for the GEC-ESTRO meeting within
the ESTRO Forum 2013. These reflect many aspects of modern image guided brachytherapy. Alongside this there are important mature clinical results which underpin our practice. To highlight some
of the more important abstracts received, we incorporated, a ‘best of brachytherapy’ proffered paper
session into the programme where these were given added prominence.
p 33
p 34
2_
HDR BRACHYTHERAPY DOSIMETRIC PREDICTORS OF BIOCHEMICAL
CONTROL OF PROSTATE CANCER
p 36
3_
DOSE-RESPONSE FOR LOCAL CONTROL IN IMAGE GUIDED CERVIX BRACHYTHERAPY
IN THE RETROEMBRACE STUDY
p 37
4_
BRACHYTHERAPY IN THE TREATMENT OF ANAL CANAL CANCERS:
A LARGE MONOCENTRIC RETROSPECTIVE SERIES.
p 38
5_
HDR BRACHYTHERAPY OF THE BASE OF TONGUE. TEN-YEAR RESULTS OF A
PROSPECTIVE STUDY
p 40
The first of these highlights a new treatment verification system –developed in Melbourne – based
on electronic portal imaging for high dose rate brachytherapy. This illustrates the way in which
brachytherapy parallels modern external beam radiotherapy, incorporating real time imaging and high levels of quality
assurance in treatment delivery. The theme of quality assurance is taken further by the paper from Mount Vernon showing
for the first time that implant quality is important in high dose rate brachytherapy for prostate cancer. This has been
shown previously in several series of low dose rate brachytherapy and the additional data for HDR, highlights the need for
post implant dosimetry and meticulous attention to technique to ensure optimal results. This data is also able to propose
a dose response for biochemical control of prostate cancer across the high dose range with a cut-off around the median
value of 104Gy (EQD 2).
One of the major advances in brachytherapy in the last decade has been the advent of image guided techniques for cervix
cancer. This has culminated in the Embrace initiative, which coordinates multi-centre experience in this technique. A
retrospective analysis from the Embrace centres – all delivering high quality image guided brachytherapy for cervical cancer – is one of several papers presented at this meeting from that group. Again this shows a dose response for local control
in cervical cancer with a threshold D90 for the high risk CTV of between 85 and 93Gy in advanced disease. This data is
critical in defining optimal treatment regimes in this setting.
Brachytherapy for anal canal cancers is well recognised as an effective treatment, although with the widespread use of
chemo radiation and more complex external beam techniques it has not been as widely practiced as in the past. We have
therefore given prominence to an important series from Lyon representing one of the largest long term datasets in this
disease. They report a 10 year local control rate of 73.9% in 209 patients. Such mature and impressive datasets support the
further development of this approach in the radical treatment of anal canal cancer.
Head and neck cancer is another site where brachytherapy has proven highly effective in the past, but current practice
often favours surgery or complex external beam chemoradiation. Again, therefore, it is reassuring to find the mature data
from Budapest on high dose rate brachytherapy to the base of tongue of 60 patients having advanced disease. They report
10 year follow up data, showing a 5 year local control rate of 57%. Once again the outstanding results obtained in this
series are strong support for on-going efforts to increase the use of brachytherapy in head and neck cancer.
In addition don’t miss out on reading the abstract from Leuven in the Awards section of this report, which has been selected for the Best Junior Presentation Award. This addresses the important area of boost radiotherapy to the breast where
brachytherapy has an important and increasing role. This is another mature series, with almost 9 year follow up of 1381
patients evaluating three different boost techniques and demonstrating the efficacy of brachytherapy in comparison to
electrons or photon techniques.
The above represent just a few of the exciting programme highlights that we had at the ESTRO forum where
the entire spectrum of brachytherapy practice was represented. We hope you derived considerable benefit from
these and the other presentations included in the programme and that they will inspire and stimulate future
brachytherapy research and practice.
Peter Hoskin
Chair of the GEC-ESTRO-ISIORT Europe Meeting
32
BRACHYTHERAPY | 2ND ESTRO FORUM - REPORT
2ND ESTRO FORUM - REPORT | BRACHYTHERAPY
33
1
HIGH DOSE RATE (HDR) BRACHYTHERAPY TREATMENT VERIFICATION
USING AN ELECTRONIC PORTAL IMAGING DEVICE (EPID)
By Ryan L Smith
School of Applied Sciences and Health Innovations Research Institute, RMIT University, Melbourne, Australia &
William Buckland Radiotherapy Centre, The Alfred Hospital, Melbourne, Australia.
INFORMATION:
High dose rate (HDR) brachytherapy treatment delivery currently lacks a comprehensive verification system.
Accurate treatment delivery requires correct source dwell
positions and dwell times to be administered relative to
each other and to the surrounding anatomy. As high doses
are delivered in seconds, and mistakes in an individual
fraction cannot be easily rectified, a high standard of quality assurance is required. This work details a system that
can potentially satisfy the requirements of verifying both
geometric and dosimetric information.
ABSTRACT OVERVIEW:
We describe a new real-time in vivo verification system for
HDR brachytherapy employing an electronic portal imaging device (EPID). Extensive characterisation of the EPID
was undertaken to yield appropriate correction factors necessary for this novel application. To demonstrate the utility
of the approach for treatment verification, a treatment
plan was delivered to a phantom and the planned dose was
compared to the dose distribution determined from the
EPID measurements. The source position in 3D was also
determined accurately from the EPID images. The system
thus has the potential to identify incorrect dose delivery to
patients in real-time.
YOUR RESEARCH?
1. This work describes the first real-time in vivo
position- and dose-verification system for HDR
brachytherapy. Following comprehensive characterisation, we have demonstrated that an EPID device,
originally designed as a patient positioning tool for
external beam radiotherapy, can provide source
position and two-dimensional dosimetric information when used with an 192Ir HDR brachytherapy
source.
2. The position of the source can be determined to be
better than ± 0.5 mm in the x,y plane (i.e. the plane
of the EPID) up to a source to detector distance
(SDD) of 150mm. The resolution of the z coordinate
(perpendicular distance from the detector plane) is
SDD-dependent with 95 % confidence intervals of
± 0.1 mm, ± 0.5 mm and ± 2.0 mm at SDDs of 50,
100 and 150 mm respectively.
34
3. The dose can be monitored real-time (dwell-bydwell) during treatment. The total dose distribution
can be calculated via integration of individual dwells
and likewise the total distribution can be deconvolved
into its constituent contributions. Dose differences
between planned (TG-43) and measured doses are
less than 2 % for 98 % of voxels.
HAVE?
The clinical implementation of this system will provide
HDR brachytherapy treatment with a mechanism to
validate the dose delivery and ‘trap’ errors that are not
currently identifiable. It also has the potential to identify
implant movement within the patient, thus allowing plan
modification before treatment delivery. As well as online
verification, the system can capture the dose delivered to
the patient as a record of treatment delivery. As a pre-treatment quality assurance verification tool, the system could
be used to highlight calculation discrepancies (in a similar
way to IMRT, whereby plans are recalculated and delivered
to a phantom).
TREND IN ONCOLOGY?
With advances in technology in the external beam radiotherapy (EBRT) realm, the drive has been to deliver higher
doses in a conformal approach using available imaging
technology to ensure patient safety. HDR brachytherapy
treatment is inherently a highly conformal modality, but
it currently lacks the advanced treatment verification and
patient safety mechanisms available in EBRT. Implementing this system routinely in the clinic would push HDR
brachytherapy treatment verification forward and in line
with EBRT trends.
Figure 1. (a) The planned dose distribution after the delivery of 3 out of the planned 6 dwell positions. (b) The integrated EPID image for the delivered dwell
positions. (c) The difference between the planned dose and the measured dose in percentage.
35
2
3
HDR BRACHYTHERAPY DOSIMETRIC PREDICTORS OF BIOCHEMICAL
CONTROL OF PROSTATE CANCER
DOSE-RESPONSE FOR LOCAL CONTROL IN IMAGE GUIDED CERVIX
BRACHYTHERAPY IN THE RETROEMBRACE STUDY
By Peter Hoskin
By Kari Tanderup
Mount Vernon Hospital, UK
INFORMATION:
High Dose Rate brachytherapy is widely used for dose
escalation with external beam therapy. This study evaluates
the importance of implant quality as measured by the dose
to 90% of the tumour volume (D90) and volume receiving
100% dose (V100) in relation to biochemical relapse free
survival in a prospective cohort.
ABSTRACT OVERVIEW OF:
We have shown in a prospective randomised trial that dose
escalation in prostate cancer using HDR brachytherapy in
combination with external beam radiotherapy is effective
and results in improved biochemical relapse free survival
with no increase in toxicity. To determine whether implant
quality as measured by various dosimetric parameters,
in particular D90 and V100 are important in predicting
outcome in this setting we have evaluated the dosimetry of
implants performed in the brachytherapy boost arm of that
trial. Since the external beam component was homogenous
and constant (35.7Gy in 13 fractions) analysis of total dose
delivered including the implant component provides information on both the importance of good implant dosimetry
and the dose response for prostate cancer.
YOUR RESEARCH?
1. A progresssive, dose related increase in biochemical control of disease is seen with increasing D90 and
V100.
2. Based on 5 year biochemical RFS multivariate
analysis shows that the most predictive parameters
for biochemical control were implant D90 (p<0.004)
and V100 (p<0.0004). Presenting PSA and use of
ADT were two other factors which had a lesser but
significant, predictive effect.
3. A target D90 of 108% is recommended on the basis
of this data, representing the median value of the
distribution. This is equivalent to a total HDR dose of
17.6Gy (prescription isodose 17Gy) and when
converted to an equivalent dose in 2Gy per fraction (EQD2) including the external beam component
equates to a target dose of 104Gy EQD2.
36
Aarhus University Hospital, Denmark
HAVE?
This data highlights the importance of careful dosimetry when undertaking HDR prostate brachytherapy and
parallels the experience with low dose rate (LDR) seed
brachytherapy for prostate cancer. The flexibility of HDR
delivery with variable dwell times defined before exposure
gives greater opportunity to improve the dose delivered
and the target D90 of 108% should be attained wherever
possible. It also highlights the importance when using a
single step procedure under anaesthetic of correcting a
poor implant before proceeding to treat the patient.
The derivation of a threshold target dose of 104Gy is
in keeping with other data from the HDR literature
evaluating dose escalating schedules and suggests that
for localised prostate cancer a dose response up to and
beyond 100Gy exists. This then provides a rationale for all
techniques, whether brachytherapy, image guided external
beam therapy or stereotactic radiotherapy to aim for doses
in this range ensuring that tumour dose is not attained
at the expense of normal tissue constraints. This aim of
achieving maximum tumour control with acceptable toxicity is readily achieved with HDR brachytherapy.
INFORMATION:
Locally advanced cervical cancer is treated by external beam
radiochemotherapy followed by brachytherapy. During the
last decade, significant progress has been demonstrated with
integration of MRI in the brachytherapy planning procedure.
MRI is used to assess the tumour response after external beam
radiotherapy and to individualise the brachytherapy dose to
the individual patient according to size and response of the
tumour. Pioneering institutions started MRI guidance more
than 15 years ago and the GEC ESTRO gyn working group
was established in year 2000. Building on these efforts a core
group of European and international centers (GEC ESTRO
gyn network) was established in year 2005 with the aim of further development and promotion of MRI guided brachytherapy in research and through a multicentre clinical study,
EMBRACE (International study of MRI guided brachytherapy
in cervix cancer). RetroEMBRACE is a retrospective study
that has collected data from 12 institutions, from Europe and
Asia, who performed MRI guided brachytherapy previous to
2008 when the EMBRACE study was initiated.
ABSTRACT OVERVIEW:
Currently, there is no solid evidence for the optimal dose prescription in brachytherapy for cervical cancer, and there is a
wide variation of dose levels and brachytherapy fractionation
schedules applied. The retroEMBRACE dose response study
comprises data from 592 patients from 12 institutions. Dose
prescription varied significantly between institutions and
within each institution with a variation in prescribed dose of
14Gy (SD) with a mean of 87Gy. This significant heterogeneity in dose prescription allowed for an extensive analysis
of dose response. The purpose of this research project was to
evaluate dose response relationship for local control in locally advanced cervical cancer for the entire patient population
and for subgroups according to different risk criteria.
3. The finding of a dose response relationship demonstrates that the adaptive target concept (HR CTV),
which has been developed for MRI guided
brachytherapy, is highly relevant for local control and
is robust in a multicenter setting of centers
experienced in MRI guided brachytherapy
WHAT IMPACT COULD YOUR RESEARCH HAVE?
With the new retroEMBRACE evidence for dose response,
it will be possible for institutions to change their dose prescription in order to optimise the balance between local control and morbidity. The next logical step for future clinical
studies within locally advanced cervical cancer is to install
dose constraints which may lead to improved local control.
TREND IN ONCOLOGY?
There is currently a huge interest in adaptive radiotherapy.
MRI guided brachytherapy in cervix cancer is a very interesting adaptive model which directly takes into account the
response during radiotherapy. The upcoming ICRU report
on brachytherapy in cervix cancer introduces systematically
an adaptive CTV concept based on repeated imaging and
clinical examination during radiotherapy. This adaptive CTV
concept has much potential in other cancer sites, in particular those characterised by significant tumour regression during radiotherapy, such as head and neck, rectum and lung.
Furthermore, the application of highly focal boost doses to
a high risk CTV combined with administration of intermediate doses to an intermediate risk CTV has demonstrated
excellent local control in cervix cancer. Such a risk adapted
model with application of heterogeneous dose distributions
is also of great interest for other cancer sites.
YOUR RESEARCH?
The three main findings of the retroEMBRACE dose
response study are:
1. retroEMBRACE establishes evidence for a clear
dose response relationship in locally advanced
cervical cancer
2. retroEMBRACE demonstrates that a high local
control rate can be obtained with the use of MRI
guided brachytherapy: local control of >90% is possible with doses >90Gy to the high risk CTV.
Figure 1. Dose response relationship for local control.
37
4
BRACHYTHERAPY IN THE TREATMENT OF ANAL CANAL CANCERS: A
LARGE MONOCENTRIC RETROSPECTIVE SERIES.
By Laëtitia Lestrade
Centre Léon Bérard - Radiation Oncology Department, Lyon, France
INFORMATION:
Anal canal cancers are rare. External Beam Radiotherapy (EBRT), with concomitant chemotherapy (CT) for
advanced tumours, is the standard treatment for anal canal
carcinoma. Some retrospective studies have shown better
local control rates in patients receiving a total dose >5559Gy to the tumour bed. International guidelines support
the utility of a boost after the EBRT +/- CT. Brachytherapy (BRT) is considered a valuable technique to deliver
the boost to T1-2 and selected small T3 anal tumours
responding to EBRT+/-CT, but its role has still not been
well evaluated. Indeed, the number of patients treated by
BRT in the context of RCTs or in the retrospective series is
limited, with only 3 retrospective studies presenting results
from a little more than 200 patients.
ABSTRACT OVERVIEW:
We report data on 209 anal canal cancer (median age: 65
years; range: 26 – 89) patients treated in the period 05/1992
-12/2009 with EBRT (58/209) or EBRT+CT (151/209).
All patients underwent a boost delivered with a Low Dose
Rate (LDR, 151 patients) or a Pulse Dose Rate (PDR, 58
patients) BRT.
After a median follow-up time of 73 months, median
LC time was not reached, and 5- and 10- years LC rates
were 78.6% and 73.9%, respectively. G3-G4 acute and late
toxicity rates were 11.2% and 6.2%, respectively. Grade 3
CT related acute toxicities were recorded in 7/151 patients
(4.6%). After the longest follow-up available in the literature of the 4th larger population of anal cancer patients, our
data confirm the efficacy and the safety of BRT.
YOUR RESEARCH?
1. Benchmark data are strongly needed to evaluate different treatment techniques and modalities, particularly for rare cancers like anal canal cancer. The large
size of our series and our long follow-up make this
series one of the most important benchmark datasets
in this clinical and therapeutic setting.
2. This study is also an important benchmark showing
the safety of BRT with rates of 11.2% and 6.2% of
acute and late severe toxicity, respectively.
3. In our analysis, a statistical relationship exists
between the total BRT dose (<18Gy vs >18Gy) and
38
clinical response by digital rectal examination before
BRT, with higher doses delivered to patients showing
worse response (p = 0.001), but also with lower doses
showing better outcomes (p = 0.003). Moreover,
it should be noted that the risk of late toxicity was
influenced by the total dose of EBRT and the number
of implants, typically both larger in poorly-responding patients. These results could be interpreted as a
potential limit of BRT i.e., that BRT cannot compensate for a poor response to EBRT+/-CT, even using
higher doses, and moreover could be more toxic in
poorly-responding patients.
adopting new technologies to optimise economic resources
and, therefore, a clear knowledge of the benefits that new
and old technologies can provide to patients is strongly expected. BRT has been historically adopted in the treatment
of anal canal cancer patients, and our study is one of the
most important benchmark datasets on its role in this clinical and therapeutic setting. BRT in the treatment of anal
canal cancer should be evaluated and critically compared
to the new techniques of irradiation.
HAVE?
We confirm with long follow-up in a large population, the
role of BRT in the treatment of anal canal patients. We also
identify a potential limit of this technique that should be
further studied.
Finally, this study could be an important starting point for
several prospective studies:
A prospective randomised study using Health Technology Assessment parameters, comparing BRT and
External Beam Radiotherapy to deliver the boost on
the tumour bed.
Application of Artificial Intelligence and Machine
Learning to this large database in order to assess
relationships between the different variables. These
techniques would potentially offer a new, more
advanced way to identify patients that could take
advantage of BRT.
Feasibility study (phase I/II) to evaluate the potential
role of High Dose Rate BRT in this clinical context.
TREND IN ONCOLOGY?
The role of RT +/- CT in the treatment of anal canal cancer
patients has been definitively assessed, but some important
concerns still remain about dose and volume of irradiation.
Moreover, in the last decade, more advanced technologies have been extensively introduced in the daily clinical
practice, such as image-guided radiation therapy, intensity
modulated radiation therapy, several advanced dose modulation and delivery techniques. Because of the current
economic situation, special attention is required when
39
5
HDR BRACHYTHERAPY OF THE BASE OF TONGUE. TEN-YEAR RESULTS
OF A PROSPECTIVE STUDY
By Zoltán Takácsi-Nagy
Center of Radiotherapy, National Institute of Oncology, Budapest, Hungary
INFORMATION:
In the treatment of base of tongue cancer, definitive radiotherapy is largely used alone or combined with chemotherapy as an organ-preserving method instead of surgery,
which often results in poor quality of life due to impairment of speech and swallowing. Interstitial low-dose-rate
(LDR) brachytherapy (BT) has been applied for a long time
as a boost in the treatment of base of tongue tumors, but
only few detailed analyses can be found in the literature
about the application and efficacy of high-dose-rate (HDR)
BT.
ABSTRACT OVERVIEW:
We initiated a phase II, prospective investigation to study
the feasibility and efficacy of external beam irradiation
(EBI) + HDR BT. Between January 1992 and June 2011
sixty patients (mean age 57 years) with T1-4 and N0-3
carcinoma of the base of tongue were treated with HDR
BT boost (mean dose 17 Gy) after a mean dose of 62 Gy
locoregional EBI. The most frequent fractionation schedule
was 5x3 Gy and 5x4 Gy. In 10 cases rigid needles were
used, in 50 cases flexible tube technique was applied. Eight
patients underwent planned neck dissection.
YOUR RESEARCH?
survival was between 22 and 44%. With an LDR boost
local control at 5 years improved to 64-89%. Five-year
overall survival was between 35 and 72%. Severe grade 4
side-effects, soft-tissue necrosis occurred in 2,5-27% and
osteoradionecrosis in 0-6%. The five-year rate of local
tumor control in our T1-T4 patients treated with HDR
boost was 100%(T1), 75%(T2), 61%(T3) and 52%(T4), respectively, while in the boost LDR studies it was on average
85-93%(T1), 50-93%(T2) and 46-82% (T3-T4), respectively. Our results are similar to LDR results.
TREND IN ONCOLOGY?
The advantage of LDR is that continuous-low-dose irradiation allows redistribution of tumor cells into radiosensitive
portions of the cell cycle, prevents tumor repopulation and
exploits differential repair capacity between tumor cells
and normal tissues. This radiobiological “disadvantage” of
HDR BT can be eliminated usingtwice daily fractionation.
EBI combined with interstitial HDR BT boost can result
in acceptable local control and overall survival. The low
incidence of serious late side-effects in our series justifies
the use of HDR interstitial BT as a boost treatment. Combination with radiochemotherapy may improve results,
but further studies are needed to define the optimal dose
and fractionation of HDR BT in the treatment of base of
tongue cancer.
Implanted catheters into the base of tongue cancer
Dose distribution with the cross section of the catheters on CT slice
The mean follow-up time for surviving patients was 121
(range 20-229) months. Tumor response to treatment was
assessed 2-3 months after completion of the definitive
radiotherapy. The complete and partial local remission rate
was 77% (46/60) and 23% (14/60), respectively. The 5-year
actuarial rate of local-, locoregional control and overall
survival was 57%, 50% and 47%, respectively. Overall
survival was significantly better in patients receiving
radiochemotherapy (n=17) (69 vs. 39%; p=0.005). Delayed
soft tissue ulceration and osteoradionecrosis occurred in 8
(13%) patients. No permanent functional damage limiting
understandability of speech or normalcy of diet developed.
HAVE?
In the past base of tongue cancer has been treated exclusively with external beam irradiation with a five-year local
control rate was ranging from 28 to70 %. Five-year overall
40
41
RADIOBIOLOGY
OVERVIEW OF THE PREVENT MEETING COMPONENT
Radiotherapy is, after surgery, the second most important contributor to finding
a cancer cure. In the era of targeted therapies, radiotherapy is certainly one of
the best exemples of real and precise targeted treament, thanks to the recent
progress of physics and balistics. Today over fifty percent of cancer patients in
Europe are treated with radiation therapy. However, radiation therapy can still
cause disabling normal tissue injury in a subset long-term cancer survivors.
Introduction
OVERVIEW OF THE PREVENT MEETING COMPONENT
p 43
1_
SECOND CANCER RISKS AFTER RADIOTHERAPY FOR BREAST CANCER:
WHAT IS THE IMPACT OF ADVANCED TREATMENT TECHNIQUES?
p 44
2_
LET DEPENDENT RESPONSE OF THE RAT CERVICAL SPINAL CORD
AFTER CARBON ION IRRADIATION
p 45
3_
ACE-INHIBITION REDUCES ACUTE CARDIAC DAMAGE TO AMELIORATE
RADIATION-INDUCED LUNG DYSFUNCTION
p 46
Increasing normal tissue tolerance is therefore a worthwhile goal and a great challenge for modern radiation
therapy as exemplified in this third edition of PREVENT. In the next few years the development of individualized
treatment will enhance the safety and efficacy of radiation therapy and strong trans-disciplinary interactions
between clinicians, biologists, imaging specialists and physists is required to speed up the process. The three
selected abstracts use different and complementary approaches, which highlight the recent evolution of our
discipline.
The recent technical advances both in imaging and high precision dose delivery lead to the evolution of treatment planning toward hypofractionation schedules and safe reduction of targeted volume. While reduction in the irradiated volume
is thought to protect normal tissue, radiobiological investigation are required to understand the mechanisms involved and
to enhance safety. The study by E Donovan et al. is an example of interdisciplinary translational research where dose distribution, including imaging, was measured in breast cancer patients. It brings important new information, as no unacceptable increased risk of second cancers was predicted after the use of such advanced techniques. The study by Saager et al.
uses a well characterized model of late tissue damage of the CNS in rats to assess the accuracy and validity of mathematical
modeling and show different effects between high vs low LET irradiations. The last selected study, by Van der Veen et al.,
shows how precise balistics can affect the outcome in terms of physiopathological injury and shows the importance of irradiated volume, as well as demonstrating some specific interactions between organs included in the irradiation field (here
heart and lung). It stresses the importance of accurate targeting in experimental models and shows that personnalized
therapeutic modulation can then be successfully applied.
Marie-Catherine Vozenin and Jan Alsner
Chairs of the PREVENT Meeting
42
RADIOBIOLOGY | 2ND ESTRO FORUM - REPORT
2ND ESTRO FORUM - REPORT | RADIOBIOLOGY
43
1
2
SECOND CANCER RISKS AFTER RADIOTHERAPY FOR BREAST CANCER:
WHAT IS THE IMPACT OF ADVANCED TREATMENT TECHNIQUES?
LET DEPENDENT RESPONSE OF THE RAT CERVICAL SPINAL CORD AFTER
CARBON ION IRRADIATION
By Ellen Donovan*
By M. Saager
The Royal Marsden and the Institute of Cancer Research
INFORMATION:
Breast cancer is the most commonly diagnosed female
cancer and, with good survival rates, it is imperative that
any potential long term side effects from this effective
treatment are reduced. Radiotherapy deliveries specific to
patient cohorts with different risk factors for local recurrence are likely to be the new standard of care in breast
radiotherapy in 5 to 10 years. The radiotherapy beam
arrangements required will distribute the dose throughout
the body in a different pattern to the standard treatment,
as will the associated imaging at the time of treatment.
The aim of this work was to measure dose distributions
from these modern radiotherapy techniques (including the
imaging) and to use these data to predict the risk of second
cancer in a range of organs.
ABSTRACT OVERVIEW:
Five classes of radiotherapy plans used to treat the whole
breast, a partial breast and the whole breast plus the
tumour bed were created on a CT dataset. The plans were
transferred to a whole body phantom. Regions in the
phantom which represented radiosensitive organs were
delineated and thermoluminescent dosimeters (TLD) used
to measure the dose from the radiotherapy and its associated time-of-treatment imaging. These dose data were used
as input into the Biological Effects of Ionising Radiation
Report VII models of second cancer induction and lifetime
risks calculated for the five treatment classes and intensive
imaging regimes.
YOUR RESEARCH?
The modern complex radiotherapy techniques investigated
were not predicted to increase the theoretical risk of second cancer incidence in organs far from the treated breast.
Whilst increases in the lifetime risk of induced second
cancer in the lungs were predicted for some techniques,
these remained small compared to the large reduction
in local recurrence risk from receiving radiotherapy as a
component of curative treatment.
The use of image guidance is unlikely to result in an unacceptable increase in second cancer risk.
44
German Cancer Research Center (DKFZ), Heidelberg, Germany
HAVE?
INFORMATION:
* Ellen Donovan is funded by a National Institute for Health Research CSO
HealthCare Scientist award. This report presents independent research funded
by the National Institute for Health Research (NIHR). The views expressed are
those of the author(s) and not necessarily those of the NHS, the NIHR or the
Department of Health.
ABSTRACT OVERVIEW:
The work contributes to the understanding of the longterm implications of modern radiotherapy treatments on
normal tissues.
Is this research indicative of a bigger trend in oncology?
As the number of cancer survivors increases the long term
consequences of treatment, and their impact, will become
of greater importance.
Particle therapy is an advanced radiation strategy for
selected cancer patients. Beside a highly conformal dose
delivery, particles such as carbon ions have an increased
relative biological effectiveness (RBE), which depends on
the dose per fraction, the biological system, the selected
endpoint and the linear energy transfer (LET). LET is
defined as the energy deposition per unit length and increases along the beam path showing a profound increase
of RBE.
TREND IN ONCOLOGY?
Physical and biological advantages are the main reasons
why particle therapy has developed into a challenging
treatment option during the last decade. In spite of promising results, a concerted action of physical, biological and
clinical research is necessary to fully exploit the potential
capabilities of particle therapy in radio-oncology.
Tolerance doses of the rat cervical spinal cord after photon
and carbon ion irradiation were determined and used to
calculate RBEs. We conducted a systematic study on the
variation in RBE along the carbon ion depth-dose profile
using an established in vivo model for radiation induced
late normal tissue damage of the CNS. The obtained data
allowed us to study and assess accuracy and limitations
of a bio-mathematical model, which is used for treatment
planning to calculate the RBE. Additionally a MRI and
histology-based longitudinal study is ongoing to elucidate
the mechanisms of radiation induced myelopathy.
YOUR RESEARCH?
Compared to historical tolerance data measured in the entrance region of the beam, the irradiation method is stable
and reproducible. On the basis of the preliminary analysis
the LET effect is clearly visible, meaning that high LET
irradiations are more effective than low LET irradiations.
HAVE?
To include the RBE in particle treatment planning,
bio-mathematical models are required which rely on
biologically determined datasets. Systematic in vivo studies
on the relationship between the RBE and LET of carbon
ions at various positions along the depth-dose profiles may
not only be helpful to benchmark the RBE-models but may
also be used for the assessment of safety margins.
45
3
ACE-INHIBITION REDUCES ACUTE CARDIAC DAMAGE TO AMELIORATE
RADIATION-INDUCED LUNG DYSFUNCTION
S.J. van der Veen
University Medical Center, University of Groningen, The Netherlands
INFORMATION:
Thoracic tumors such as breast, esophagus, lung cancer
and Hodgkin’s lymphoma are among the most common
human malignancies. The treatment of choice is often radiation therapy. Unfortunately, the radiation dose that can be
administered safely is limited by the risk of radiation-induced lung toxicity (RILT), a potentially life-threatening
side effect of radiotherapy of thoracic tumors. As such,
mitigation of RILT would give opportunities to increase
tumor dose and improve local tumor control.
Treatment with ACE-inhibitors, commonly used drugs
to treat patients with cardiovascular diseases, has shown
to ameliorate RILT in rats although the exact mechanism
is not elucidated1. Recently, we found that in addition to
inflammation, pulmonary vascular remodeling plays an
important role in the development of RILT in rats, resulting in pulmonary hypertension, right ventricle hypertrophy and eventually to cardiopulmonary dysfunction2. ACE
inhibitors might attenuate these effects.
ABSTRACT OVERVIEW:
We hypothesized that the protective effect of ACE-inhibition on radiation-induced cardiopulmonary dysfunction
might be due to reduced vascular remodeling and pulmonary hypertension. Therefore, in this study we investigated
whether ACE-inhibition ameliorates early radiation-induced cardiopulmonary dysfunction by protection of pulmonary vascular remodeling. We excluded or included the
heart in the irradiated field to elucidate the exact protective
mechanism of ACE-inhibition on early radiation-induced
cardiopulmonary function loss.
YOUR RESEARCH?
At 8 weeks post-irradiation, the peak of early radiation-induced pulmonary/cardiac dysfunction, breathing rate
measurements showed that captopril administration significantly improved the rats’ cardiac/pulmonary function, but
only when the hearts were included in the radiation field.
This protective effect could not be explained by protection of the pulmonary vasculature or pulmonary artery
pressure changes, which were equally damaged with or
without captopril. Interestingly, besides decreased pleural
and pericardial effusion, captopril treated rats had better
cardiac function, as shown by left ventricle hemodynamic
46
measurements. In addition, captopril treatment reduced
perivascular and interstitial fibrosis in the irradiated
hearts indicating that captopril exerts a protective effect by
reducing direct acute heart damage and its effect on loss of
cardiopulmonary function.
HAVE?
The early effects of heart irradiation are recently getting
more attention in breast cancer and Hodgkin’s lymphoma
patients, since it is believed that they may predict late cardiac damage. Our preclinical studies showed that concomitant irradiation of the heart with the lungs enhanced the
risk of early radiation-induced pulmonary dysfunction3.
So, irradiation of the heart induces acute cardiac changes,
which may play an important role in the development of
the lung toxicity after thoracic irradiation. This research
shows that the clinically/FDA approved ACE-inhibitors
may be a promising strategy to reduce early cardio-pulmonary complications induced by radiotherapy to the
thoracic area in patients receiving a dose to the heart.
TREND IN ONCOLOGY?
Radiation treatment plays an important role in the treatment of thoracic tumors. The efficacy of the treatment
however, is limited by the sensitivity of unavoidably co-irradiated healthy tissues.
Therefore, new strategies are needed to decrease the
sensitivity of the co-irradiated healthy tissues and thereby
improve the effectiveness of thoracic radiotherapy.
In the current study, ACE-inhibition was found to decrease
acute radiation-induced cardiac damage. The early effects
of heart irradiation are recently getting more attention in
breast cancer and Hodgkin’s lymphoma patients, since it
is believed that they may predict late cardiac damage. Our
preclinical studies show that concomitant irradiation of
the heart with the lungs enhances the risk of early radiation-induced lung toxicity (RILT)4. Therefore, clinically/
FDA approved ACE-inhibitors might be useful to diminish
early radiation-induced cardiopulmonary toxicity in patients receiving a dose to the heart.
Ghosh et al. Int J Radiat Oncol Biol Phys 2009
Ghobadi et al. Thorax 2011
3
Van Luijk et al. Cancer Res 2005
4
Van Luijk et al. Cancer Res 2005
1
2
47
AWARDS
AWARDS
Dear colleagues,
At ESTRO we continue to find it important to recognise those whose work has an especial impact
on the field of radiation oncology, its advancement and thereby, inevitably, the care of our patients.
We bestow several types of Awards, ranging from Lifetime Achievement Awards, Award Lectures,
University Awards, and Company Awards.
Several of these Awards, in particular the Award Lectures, are a direct commemoration of our founding fathers and ESTRO’s history; receiving them is considered a great honour.
Introduction
AWARDS p 49
1_
ESTRO - VARIAN AWARD
MOTION SIMULATIONS WITH A STATISTICAL DEFORMATION MODEL TO EVALUATE
PTV MARGINS IN LOCALLY ADVANCED PROSTATE CANCER
During the 2nd ESTRO Forum we once again distinguished several colleagues for their noteworthy endeavours. The Award
Lecture and Lifetime achievement Awards have been highlighted for you on these pages. The following Awards section
report provides an overview of the work conducted by the recipients of the ESTRO-Jack Fowler University of Wisconsin
Award and the Company Awards.
I would like to once again congratulate all these praiseworthy individuals and thank them on behalf of the ESTRO community for their meaningful work. I would also like to extend a word of thanks to the Nominating Committee Members
and the Board for their work and the difficult decisions they had to make in regards to making a selection amongst so
many outstanding peers.
p 50
Vincenzo Valentini
President of ESTRO
2_
ESTRO - ACCURAY AWARD
RADIOBIOLOGICAL IMPLICATIONS OF RESPIRATORY MOTION IN THE TREATMENT
OF LUNG CANCER p 52
3_
ESTRO - NUCLETRON BRACHYTHERAPY AWARD
CORRELATION OF DOSE WITH VAGINAL MORBIDITY AFTER MRI-GUIDED
BRACHYTHERAPY FOR LOCALLY ADVANCED CERVICAL CANCER The Klaus Breur Award Lecture is the highest honour that can be conferred upon an ESTRO member and is
awarded in recognition of a major contribution to European radiotherapy. This annual Award is named after
Professor Breur – one of our most eminent founders – and is a tribute to his pioneering work. This year the Award
went to Vincent Grégoire from Belgium; he treated us to his lecture on ‘This is not an apple ...’
p 54
4_
ESTRO - JACK FOWLER UNIVERSITY OF WISCONSIN AWARD 2013
BEYOND VMAT - HIGH SPEED DELIVERY OF ROTATIONAL IMRT
WITH CONE-BEAM TOMOTHERAPY
The Emmanuel Van der Schueren Award Lecture is given in honour of a remarkable figure in ESTRO’s history; E.
Van der Schueren is considered by many as being the personification of ESTRO in its early years and his influence
on European multidisciplinary oncology made him unique. This year the Award went to Ben Mijnheer from
The Netherlands who presented us with his lecture on ‘The role of medical physicists in implementing advanced
technology in radiotherapy’.
p 56
5_
GEC-ESTRO BEST JUNIOR PRESENTATION SPONSORED BY NUCLETRON
MOTION SIMULATIONS WITH A STATISTICAL DEFORMATION MODEL
TO EVALUATE PTV MARGINS IN LOCALLY ADVANCED PROSTATE CANCER
The Irridium Award lecture is presented to a radiation oncologist or physicist who has made a major contribution
to the development of brachytherapy. This year we awarded Joseph Hammer from Austria who presented ‘From low
dose rate to high dose rate – a story of success’.
p 58
The Honorary Physicist Award Lecture is bestowed upon a non-physicist who has made an outstanding
contribution to the cause of physics in ESTRO and has thereby raised the profile of physics in the fields of radiation
oncology and clinical radiotherapy. This year Mary Coffey from Ireland received the Award; she presented her
lecture entitled ‘Collaboration supports success’.
The Lifetime Achievement Awards are handed out by the ESTRO Board to honour Society members who have
dedicated their professional life to Radiation Oncology and the work of ESTRO. This year they were conferred upon
four deserving individuals: Adrian Begg (The Netherlands), Albert J. van der Kogel (The Netherlands), Michael
Bamberg (Germany) and Mary Gospodarowicz (Canada.)
48
AWARDS | 2ND ESTRO FORUM - REPORT
2ND ESTRO FORUM - REPORT | AWARDS
49
1
ESTRO - VARIAN AWARD
This prize is awarded to a radiotherapy professional for research in the field of radiobiology, radiation physics, clinical radiotherapy or radiation technology.
MOTION SIMULATIONS WITH A STATISTICAL DEFORMATION MODEL TO
EVALUATE PTV MARGINS IN LOCALLY ADVANCED PROSTATE CANCER
By Sara Thörnqvist
Department of Medical Physics, Aarhus University Hospital, Aarhus, Denmark
INFORMATION:
residual target motion on dose escalations to both the
prostate and/or the elective targets. In this setting, the
accumulated target dose accounting for the most probable
motion patterns can be assessed as a function of heterogeneity of the dose prescription (i.e. dose painting). In
addition, the method can be applied to different treatment
sites involving irradiation of multiple targets or to further
analyse the motion patterns of targets and organs at risk
following the work of Söhn et al.
ABSTRACT OVERVIEW:
TREND IN ONCOLOGY?
Radiotherapy of several major tumour sites involves simultaneous treatment of multiple targets, typically occurring
when irradiation of both the primary and elective targets is
indicated. This study has evaluated the influence of target
movements on the required margins with a method allowing for both residual rigid motion as well as shape changes
of the targets.
In the treatment of locally advanced prostate cancer, the
dominating residual geometrical uncertainties following
image-guidance can be ascribed to deformations and
uncorrelated motion of the involved targets: the prostate
(CTV-p), the seminal vesicles (CTV-sv) and the pelvic
lymph nodes (CTV-ln). This is a challenge for simultaneous treatment delivery. In addition, the commonly applied
margin recipes do not explicitly accommodate deformations and partly correlated movement. The aim of this
study was therefore to use a statistical deformation motion
model to simulate target motion occurring throughout a
course of treatment, for the purpose of margin evaluations.
The current project fits the general trend of adaptively individualised radiotherapy. With the increased amount of volumetric imaging information available during radiotherapy, the method has potential to prospectively model and
adjust to patient specific motion patterns. The information
gained in the initial few fractions of the treatment could
thereby allow for modelling of the accumulated dose given
with the current treatment plan and adaptations of the plan
could further be made for improved target coverage or for
dose reduction to organs at risk.
YOUR RESEARCH?
The statistical motion model (Figure 1) revealed large
differences in the patterns of residual motion for the 19
patients included in the study. To account for the observed
motion patterns, margins around the elective targets
ranged from 3-15mm after image-guidance based on the
prostate. Applying similar criteria as for the conventional
margin recipes, 5mm margins were required around both
the CTV-p and CTV-ln whereas larger margins, 11mm
were needed for CTV-sv (Figure 2).
HAVE?
The model applied for margin evaluation in the current
study could form the basis for investigating the effect of
50
51
2
ESTRO - ACCURAY AWARD
The ESTRO – Accuray Award is handed out to a radiotherapy professional for research in the field of “High Precision Radiotherapy”.
RADIOBIOLOGICAL IMPLICATIONS OF RESPIRATORY MOTION IN THE
TREATMENT OF LUNG CANCER
By Dr Aidan J Cole
Queen’s University Belfast, Northern Ireland
INFORMATION:
Respiratory motion can affect many aspects of the staging,
planning and delivery of radiotherapy treatment in lung
cancer. Technological innovations in imaging (e.g PET
scanning/4-dimensional CT) enable clinicians to accurately determine the position of lung tumours in all parts
of the breathing cycle. Advances in radiotherapy delivery
techniques to improve dose delivery and account for
respiratory motion have been introduced without full concomitant understanding of the underlying radiobiological
response. To date in vitro studies examining such responses have been carried out exclusively under static conditions. The context of this study is to determine whether
tumour motion can impact on cancer cell survival when
exposed to clinically relevant radiotherapy treatments.
ABSTRACT OVERVIEW:
In this study we constructed a bespoke motor-driven
platform to replicate respiratory motion and study the consequences of tumour cell survival in vitro. (Figure 1) We
used a PMMA phantom which could accommodate flasks
containing non-small cell lung cancer cells. Using a 6MV
linear accelerator we delivered uniform and modulated
beams to the cells at varying doses and respiratory rates to
determine if tumour motion impacted on cell survival for
different conditions. Statistical comparisons were made between in and out of field regions for a number of different
experimental set-ups to investigate oscillatory type dose
delivery to tumour cells.
YOUR RESEARCH?
1. This is the first study in which respiratory motion
is applied to a novel in vitro set up to investigate lung
cancer cell survival.
2. The presence of respiratory motion in uniform
irradiation did not differ from static conditions for
cell survival.
3. When shielding was applied there was significantly
higher cell survival in-field and out-of-field with res-
52
piratory motion compared to a static set-up. To replicate the dose received by the tumour cells a moving
shield and manipulation of the multi-leaf collimators
(MLC’s) on the linear accelerator were also used and
confirmed these differences when compared with
static conditions. (Figure 2)
HAVE?
This work defines the need for further studies examining
the difference between motion management techniques
such as breath hold techniques, respiratory gating and
respiratory tracking. Selection of margins for treatment
planning volumes may also be influenced by the cell
survival patterns measured in this study indicating if
margins are too small efficacy may be affected. In addition,
modulated radiotherapy techniques such as IMRT/VMAT
deliver radiation with a complex relationship between time
and spatial dose which may significantly interact with respiratory motion in impacting on tumour cell survival. An
improved understanding of the radiobiological responses
of these treatments may help with treatment choice and
optimising dose delivery.
Figure 1 Moving platform set-up. a) Solid water b) Perspex phantom with flask/cells c) Motor unit d)
Rotational disc e) Treatment couch f) Linear accelerator g) Platform base h) (inset) lead shielding attached
to platform
TREND IN ONCOLOGY?
Motion management techniques in radiotherapy are becoming increasingly used, particularly in the era of stereotactic radiotherapy where accounting for tumour motion is
integral to safe delivery of high doses of radiotherapy with
concomitant sparing of normal tissue. Understanding the
interplay between irradiated and un-irradiated cancer and
normal tissue cells in the presence of motion may enable
us to harness delivery techniques to maximise the tumour
control probability and enhance the therapeutic ratio. In
vitro studies such as this can guide further investigation
into in vivo work to better evidence the introduction of
technological improvements in radiotherapy delivery.
Understanding the biology behind changes due to new
techniques can aid in the development of strategies to
target optimised dose delivery.
Figure 2 Region of interest for flask (top) and H460 clonogenic survival comparing uniform, static (Stat),
motion at respiratory rates (14,21) lateral (lat) motion, and lead shielding with motion (L 14, L21) for in- and
out-of-field regions. –IC (= no intercellular communication).
53
3
ESTRO - NUCLETRON BRACHYTHERAPY AWARD
This award is granted to the most innovative submitted paper. All abstracts that
were submitted and accepted for oral presentation at the GEC-ESTRO-ISIORT
Europe meeting, within the 2nd ESTRO forum, were automatically considered eligible for this award. The winning abstract was selected by the GEC-ESTRO-ISIORT
Europe meeting experts.
CORRELATION OF DOSE WITH VAGINAL MORBIDITY AFTER MRI-GUIDED
BRACHYTHERAPY FOR LOCALLY ADVANCED CERVICAL CANCER
By Kathrin Kirchheiner1, Remi A. Nout2, Kari Tanderup3
Department of Radiotherapy, Medical University Vienna; 2 Department of Clinical Oncology, Leiden University
Medical Center; 3 Department of Oncology, University Hospital Aarhus
1
INFORMATION:
Brachytherapy is an essential part of definitive radio-(chemo)therapy for locally advanced cervical cancer.
Recent advances such as the introduction of repetitive
volumetric imaging (CT, MRI) and concepts for definition
and delineation of target volumes and organs at risk, have
led to the concept of image guided adaptive brachytherapy
(IGABT). Several institutional series show that IGABT
leads to improved local control with simultaneous decrease
of treatment related side effects. Patient reported quality of
life studies point out that vaginal morbidity and associated
sexual dysfunction and symptoms are an important cause
of long-term distress in cervical cancer survivors.
The ongoing prospective observational EMBRACE study
(European and International study on MRI-guided
brachytherapy in locally advanced cervical cancer, www.
embracestudy.dk) implements IGABT in a multicenter
setting to establish a bench-mark for clinical outcome
regarding local control, survival, morbidity and quality
of life. Vaginal morbidity is prospectively assessed with
the Common Terminology Criteria for Adverse Events
(CTCAE v.3) in conjunction with dose volume parameters.
Follow-up is assessed three months after the end of the
treatment for the first year, every six months in the second
and third year and yearly thereafter.
Historically, in the radiographic era, bowel and bladder structures were dose-limiting organs at risk.
Few retrospective studies from this period have mainly
focused on severe (G3 or higher) vaginal morbidity, with
the aim to establish a maximum tolerance dose. No dose
volume response relationship for vaginal morbidity has
been established so far.
ABSTRACT OVERVIEW:
The aims of this analysis are:
1. to report on the vaginal morbidity, including single
54
endpoints of vaginal dryness, stenosis, mucositis,
bleeding, fistula and other vaginal symptoms (reported in free text field) during the first two years of
follow-up, in the ongoing EMBRACE study
2. to establish a dose response relationship. As no
specific vaginal dose points or contoured volume of
the vagina were assessed in the EMBRACE study, the
ICRU rectal point was chosen as most representative
surrogate marker for the delivered dose to the upper
part of the vaginal wall, because of its close proximity
and its defined relation to the vaginal wall and the
applicator.
of image guided adaptive brachytherapy, serves as a promising starting point for future research.
These results have led to the initiation of a vaginal
sub-study, which has started accrual in the frame of the
ongoing EMBRACE study. This research project refines the
assessment of vaginal side effects and dose assessment in
more specific vaginal points as well as patient reports about
the impact on sexuality.
TREND IN ONCOLOGY?
This approach will provide more precise information with
regard to the dose effect relationship of vaginal morbidity,
which can be taken into account during treatment optimization, i.e. with appropriate vaginal sparing techniques.
The overall goal is to reduce the dose to the non-involved
vagina in order to decrease these side effects and improve
patients’ quality of life.
With the possibility of dose adaption and optimization in
IGABT, a highly individualized and tailored treatment has
become possible, comparable to the targeted therapies in
medical oncology (“personalized medicine”).
WHAT WERE THE MAIN FINDINGS OF YOUR
RESEARCH?
Severe G3/G4 vaginal morbidity is rare, whereas the majority of patients are likely to experience mild to moderate
(G1/G2) vaginal morbidity in the first two years after end
of treatment. Most frequently reported symptom is vaginal
stenosis (narrowing and/or shortening of the vagina).
1. With increasing dose to the ICRU rectal point, the
probability for vaginal morbidity G≥2 increases
significantly (p=0.002).
2. With increasing dose to the ICRU rectal point, the
probability for vaginal morbidity G≥2 increases
significantly (p=0.002).
HAVE?
The main impact of this interim report is to raise awareness for the high frequency of mild to moderate vaginal
morbidity. In addition, a dose response relationship to
the ICRU rectal point is shown, which can be easily and
reproducibly assessed in patient images both with the use
of MRI/CT and radiographs. The fact that a single point
shows already a dose response effect within the framework
Figure 1 Dose response curve: Increasing dose to the ICRU rectal point
(“recto-vaginal point”) was associated with higher frequency of G≥2 vaginal
morbidity (p= 0.002). Patients were grouped according to 5Gy intervals for
better illustration; mean and standard deviation are shown.
55
4
ESTRO - JACK FOWLER UNIVERSITY
OF WISCONSIN AWARD 2013
This Award is conferred upon the best abstract in the field of radiation physics or
radiation technology,
BEYOND VMAT - HIGH SPEED DELIVERY OF ROTATIONAL IMRT WITH
CONE-BEAM TOMOTHERAPY
By Benjamin Sobotta
Section for Biomedical Physics, University Clinic for Radiooncology, Tuebingen, Germany
INFORMATION:
The fastest way to deliver photon radiotherapy arguably uses a rotating, modulated beam. Today’s treatment
machines are not optimised for this type of delivery. This
study aims to explore the quality and efficiency of radiotherapy treatments if these technological constraints are
removed, and replaced by a realistic, optimized design.
ABSTRACT OVERVIEW:
This study investigates the optimum design of a treatment
machine for intensity-modulated radiotherapy that allows
the fastest possible treatment delivery without reducing
quality compared with the current state-of-the-art. The
treatment machine was realistically modelled using a
dose-optimisation software. A variety of parameters, such
as beam rotation speed, collimator speeds and dose rates
were analysed. The most favourable design is a continuously rotating beam with a high rotation speed and a delivery
in 5-12 full rotations (compared to 1-2 today). This allows
the delivery of high-quality treatments about 3-5 times
faster than today.
YOUR RESEARCH?
1. The current design of treatment machines is not
optimum for the fast delivery of rotational intensity-modulated therapy.
2. The optimum design is a continuously rotating,
modulated cone-beam with a high rotation speed.
3. This delivery mode allows the application of higher
degrees of beam modulation in multiple passes of the
beam over the same angle than is currently possible.
56
HAVE?
A dedicated treatment machine for rotational intensity-modulated radiotherapy would allow very fast delivery
of treatments, thereby greatly reducing the risk of patient
movement and increasing patient comfort during irradiation. With overall treatment times of less than 1 minute,
even in complex situations, treatment uncertainties caused
by involuntary patient or organ movements would be
virtually eliminated.
TREND IN ONCOLOGY?
The technological advancement in radiotherapy enables a
much higher precision of dose delivery and thereby a lower
complication profile or more radical treatments, such as
stereotactic body radiotherapy. Driving forces of this development are imaging of the patient in the treatment position which allows repositioning of the target to the precise
treatment location, and rapid treatment delivery, which
reduces treatment uncertainties and patient discomfort.
This study proposes a design for treatment machines which
would further reduce irradiation time to an extent, that it
would be the shortest component of the treatment.
ESTRO
4 - 8 April 2014
Vienna, Austria
5
GEC-ESTRO BEST JUNIOR PRESENTATION
SPONSORED BY NUCLETRON
This Award is dedicated to ESTRO’s in-training members or members who are under 36 years of age. The winning abstract was selected by the GEC-ESTRO-ISIORT
Europe meeting experts.
MOTION SIMULATIONS WITH A STATISTICAL DEFORMATION MODEL TO
EVALUATE PTV MARGINS IN LOCALLY ADVANCED PROSTATE CANCER
By Isabelle Kindts
Department of Radiation-Oncology, University Hospital Leuven, Belgium
INFORMATION:
Whole breast radiotherapy followed by a boost irradiation
to the tumour bed is the standard treatment after breast
conserving surgery for early stage breast cancer patients.
Different techniques exist to perform a radiotherapy boost.
We compared three different boost techniques in terms of
local and loco-regional recurrences and overall survival.
ABSTRACT OVERVIEW:
The aim of the study is to compare three different radiotherapy boost techniques in women with early stage breast
cancer treated with breast conserving therapy (breast conserving surgery followed by whole breast radiotherapy), in
terms of differences in local and loco-regional recurrences
and overall survival. From 2000 to 2005, 1381 patients
were treated in our department with breast conserving
therapy for invasive breast cancer. An electron boost was
performed for a superficial boost volume (less the 29 mm
under the epidermis), in all other cases a brachytherapy boost was proposed. When patients refused or a
brachytherapy boost was not possible because of technical
reasons, a photon boost was performed.
YOUR RESEARCH?
1. No significant differences were found between the
three boost techniques with respect to local and
loco-regional recurrences. Five- and 10-years relapse
free survival rates were 98.8% and 96.9%. (figure 1)
2. No significant differences were found between the
three boost techniques with respect to overall survival. Five- and 10-years overall survival rates were
95.1% and 86.2%. (figure 2)
3. The metastasis-free survival was longer in the
electron boost group (90.7% at 10 years) and the
brachytherapy boost group (87.3% at 10 years) than
58
in the photon boost group (82.7% at 10 years). This
difference was not significant anymore after correction for tumour stage (pT) (p=0.09) and lymph node
stage (pN) (p=0.1). (figure 3)
Figure 1
HAVE?
We demonstrated very low local and loco-regional recurrences at 10 years in patients treated for invasive breast
cancer with breast conserving therapy followed by a boost
irradiation to the tumour bed. No difference in recurrence was observed comparing the three different boost
techniques. These observations indicate that the selection
criteria for the boost modality used in our department are
valid.
It would be interesting to validate our results in a prospective, multi-centric study. The results of this study can be
used to evaluate the results of newer boost techniques in
breast radiotherapy, such as Simultaneous Integrated Boost
(SIB) or intra-operative boost.
Figure 2
TREND IN ONCOLOGY?
This study has demonstrated excellent results with wellknown techniques and strict guidelines. In the last decade,
sophisticated and complex techniques in breast radiotherapy, such as partial breast irradiation, IMRT, arc therapy etc,
are booming. We should be aware that implementing new
techniques can only be defended in the presence of strong
evidence of improved outcome. Furthermore, in each
department the performance of new techniques should be
compared to the standard technique as well as to data in
the literature.
Figure 3
59
THANK YOU TO...
ESTRO would like to thank the authors of the abstracts
for taking the time to answer our questions about their
work, the chairpersons of the congress and of the scientific committees for having selected the most outstanding
abstracts and introducing each section, and also to Anne
Hansen Ree, Fiona Stewart, Ann Barrett, Michelle Leech
and Brendan McLean, who together with the Chairs took
the time to review the content of this report..
A special thank you goes out to the National Organising
Committee chairs, Jacques Bernier, Raymond Miralbell
and Raphaël Moeckli for having gracefully accepted to host
the 2nd ESTRO Forum.
CONTACT
ESTRO
Rue Martin V, 40
1200 Brussels - Belgium
Tel.: +32 2 775 93 40
[email protected]
www.estro.org

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HSS DoseMonitor:

RadPro International GmbH i

Bromo-DragonFly

Inhalation systems

mobileMOSFET Wireless Dose Verification System

Radiation Safety Issues for Radiologic Technologists Radiation

treatment of cancer with radiation theraphy

WHAT`S - SPI International