Innovation in Non Invasive Treatment

Innovation in Non Invasive Treatment
Dr.1 Roni Yagel
[email protected]
The Evolution of Surgery
2
What is ExAblate?
Non invasive tumor ablation
• Approved: Uterine fibroids, Bone mets, Brain dysfunction
• In Research: Cancer in Breast, Liver, Prostate, …
Awake patient
Next day return to normal life
No radiation
Image Guided by GE MRI
The only FDA approved Focused Ultrasound system
What is MR guided Focused Ultrasound (MRgFUS)?
Combination of two well known technologies:
High intensity focused
ultrasound to heat and
destroy targeted tissue
&
Magnetic resonance imaging (MRI)
for precise visualization, guidance and
real time treatment control
Focused Ultrasound generates heat by focusing
ultrasound waves, ablating tissue only at the focal
point, an effect similar to a magnifying glass used to
focus the sun’s energy on a single point.
4
Sharp Penumbra Achievable
Histology analysis shows a sharp
demarcation between treated and non
treated regions.
Coagulated and necrosed regions
seen in gross pathology image after
multiple sonications.
MRgFUS treated liver (pig)
0.1 mm
5
1.0 cm
Closed loop therapy:
Real Time MRI Guidance and Monitoring
Time Magazine: One of the 50 Best
Inventions
November 28, 2011
ExAblate System Configurations
ExAblate®O.R. Oncology and Women’s Health
Multiple indication platform
Can be purchased with any combination of
indications tailored to specific needs, and expanded
later for additional indications
Easily upgradeable to future configurations
Smartly-packed, small footprint, designed to use
existing MRI rooms
ExAblate®Neuro For treating functional CNS
disorders and brain tumors
8
ExAblate Indications
Commercial
Research
ExAblate O.R. Body System
Breast cancer *
Uterine fibroids
Phase II
ExAblate Neuro Brain system
Bone metastases
Liver cancer *
Phase I outside US
Brain treatments
Prostate cancer *
Phase I
9
* Investigational Device. Limited by United States Law to
Investigational Use.
9
ExAblate® for Treating
Uterine Fibroids & Adenomyosis
10
UF symptom relief after ExAblate treatment
Months
postprocedure
Patients
available for
follow-up
Symptom improvement
Improved
No relief
Worse
3
105
90
(85.7%)
14
(13.3%)
1
(1%)
6
99
92
(92.9%)
7 (7.1%)
0
12
89
78
(87.6%)
11
(12.4%)
0
Over 87% of patients experience sustained improvement in symptoms
Gorny KR, Woodrum DA et al. Magnetic resonance–guided focused ultrasound of uterine leiomyomas: review of a 12-month
outcome of 130 clinical patients. J Vasc Interv Radiol 2011
Durability vs Other Uterine Preserving Treatments
References:
1. Subramanian S, Clark MA, Isaacson K. Outcome and resource use associated with myomectomy. Obs & Gyn.2001; 98: 583-587
2. Nezhat FR, Roemisch M, et al. Recurrence rate after laparoscopic myomectomy. Am Assoc Gynecol Laparosc. 1998;5: 237-240
3. Rossseti et al. Long term results of laparoscopic myomectomy: recurrence rate in comparison with abdominal myomectomy. Hum Reprod.
2001:16:770-774
4. Doridot et al. Recurrence of leiomyomata after laparoscopic myomectomy. J Am Assoc Gynecol Laparosc. 2001;8: 495-500
5. Spies JB, Bruno J, et al. Long-term outcome of uterine artery embolization of leiomyomata. Obstet Gynecol. 2005; 106: 933-939
6. Goodwin SC, Spies JB, et al. Uterine artery embolization for treatment of leiomyomata: long-term outcomes from FIBROID registry. Obstet &
Gynecol. 2008; 111: 22-32
7. Sharp HT. Assessment of new technology in the treatment of idiopathic menorrhagia and uterine leiomyomata. Obstet Gynecol. 2006;108: 990–
1003
8. Stewart EA, Gostout B, Rabinovici J, et at. Sustained relief of leiomyoma symptoms by using focused ultrasound surgery. Obstet & Gynecol.
2007;110: 279-287
9. Morita Y, Ito N, Hikida H, Takeuchi S, Nakamura K, Ohashi H. Non-Invasive Magnetic Resonance Imaging Guided Focused Ultrasound Treatment
for Uterine Fibroids – Early Experience, Eur J Obstet Gynecol Reprod. Biol., 2008, 139(2):199-203
12
Clinical Case
Patient age: 47 years old
Fibroids volume: 130cc
Symptoms: Heavy menstrual bleeding, blood clots
and fluctuations in menstrual cycle.
Ability to perform fast
and effective treatment
with complete ablation
of fibroid in 1.4 hours
Treatment time: 1 hour ,
40 minutes
Results: 90% NPV with no
adverse effects
Courtesy of COGP, Moscow, Russia
13
Fibroid
Sagittal T2w
13
NPV
Sagittal T1+c Post treatment
Pregnancy after MRgFUS
41 yo. Nulligravida. 3 previous IVFs (the last one with oocytes from donor)
Previous myomectomy
Treated September 2010:
Intramural 130 cc-70 sonic.-NPV 80%
Pregnancy: 7 months after treatment (frozen embryo transference)
Courtesy of H. Millan, MD, Instituto Cartuja, Seville, Spain
14
Uterine Fibroids Patient Story
Used with permission from the Focused Ultrasound Surgery Foundation
15
Over 90 “focused ultrasound babies”…
ExAblate® for Treating
Bone Metastasis
16
Focused Ultrasound interaction with bone
Bone absorbs
acoustic energy
very efficiently
Broad surfaces can
be treated quickly
with low energy
levels
Denervation of
nerves provides
pain relief
Evidence of direct
damage to tumor
tissue and new
bone generation
Primary efficacy results:
Pain score improvement up to 90 days
Pivotal study: changes in NRS pain scores vs. time
8.0
TEST
SHAM
7.0
NRS scores (mean +/- 2xSEM)
7.0
5.7 5.5
6.0
5.8
5.6
5.8
6.1
5.0
4.7
4.2
4.0
3.0
3.7
3.2
3.3
3.2
2.0
1.0
0.0
0
10
20
30
40
50
Days post treatment
60
70
80
90
Clinical Case – Bone Metastases
65 year old male patient with primary thyroid cancer
Location: osteolytic bone metastasis in the right ilium
CT image pre- treatment
Ax T2w+FatSat MR image used for
treatment planning
Ax T1w+FatSat contrast-enhanced
subtraction image, acquired immediately
after MRgFUS treatment
Changes in pain level vs. time
10
Pre-treatment
pain score = 8
9
8
Patient’s pain level dropped from 8
before treatment to 0 (zero) at 1
week post treatment and remained
zero till 3m f/u
Pain level
7
6
5
4
3
2
1
0
0
0
0
0
0
0
10
20
30
40
50
60
70
80
90
Days post treatment
19
Courtesy of Y Inbar, MD, Sheba Medical Center, Ramat Gan, Israel
Clinical Case – Bone Metastases
61 year old male patient with primary lung cancer
Location: osteolytic bone metastasis in the right elbow
CT image pre- treatment
T1 + FatSat + contrast shows
enhancement in patient’s elbow 2 weeks
pre- treatment
Changes in pain level vs. time
T1 + FatSat + contrast acquired immediately
after MRgFUS treatment,
shows the ablated bone metastasis with no
enhancement
6
Pre-treatment pain score = 5
5
Pain level
Patient’s pain level dropped from 5
before treatment to 2 1 week post
treatment, then to zero at 1m f/u and
remained zero till 3m f/u
4
4
3
2
2
1
1
0
0
0
0
10
20
30
40
50
60
0
70
80
90
Days post treatment
20
Courtesy of V. Turkevich, MD, Petrov Oncology Institute, St. Petersburg, Russia
ExAblate® other Pain Palliation:
Osteoid Osteoma
Facet Rhizotomy
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Case Study – Osteoid Osteoma
Total of 31 sonications
Energy ranging from 700 to 1200 Joules. Sonication time 2 hours 10mins.
Prior to discharge next day, the patient’s visual analogue scale had reduced to
2/10.
At six months follow-up MRI, the size of the nidus had reduced from 5 mm to 2
mm in diameter.
Additionally, there was clinical moderate reduction of the soft tissue swelling.
Minimal bone marrow inflammation was still present. The visual analogue scale
was 3/10 with no oral medication (salicylates or NSAIDs).
Treatment planning and post contrast subtraction.
Images courtesy of University Malaysia Medical Centre – Kuala Lumpur
6 month follow up
ExAblate Facet Rhizotomy -Initial Experience
11 patients treated
2-6 facets treated in one session (mean 6)
Steady pain relief up to 6 Months (mean decrease 3.85)
No reported device related adverse events
Mean NRS 6.42 (before treatment) reduced to 3.87 after 6 months (60.2% reduction)
Worst NRS score 7.96 reduced to 4.08 after 6 months (51.5% reduction)
Weeks E. et al. MRI guided focused ultrasound to treat facet join osteoarthritis low back pain. Eur Rad. 2012
23
Caution: Investigational Device. Limited by United States Law to Investigational Use.
Clinical Case – Facet Rhizotomy
35 year old female patient
L4-L5, L5-S1 (bilateral) treated
Patient experienced significant pain relief following treatment
No adverse events were recorded
Axial PD planning image showing the targeted facet
joint in level L4-L5, marked in red arrows
Axial T1+c image showing the treatment results, red arrows
show hyper-intense areas in edges of L5-L4 facet joints
Courtesy of St. Mary’s, London
24
Caution: Investigational Device. Limited by United States Law to Investigational Use.
ExAblate Indications
Commercial
Research
ExAblate O.R. Body System
Breast cancer *
Uterine fibroids
Phase II
ExAblate Neuro Brain system
Bone metastases
Liver cancer *
Phase I outside US
Brain treatments
Prostate cancer *
Phase I
25
* Investigational Device. Limited by United States Law to
Investigational Use.
25
ExAblate® Research for Treating
Prostate Cancer
26
Real-time Treatment Monitoring and Control
Advantages of real time MR thermometry
closed-loop-feedback, allowing dose
adjustment during treatment, customized to
the patient
Immediate post-treatment Non Perfused
Volume (NPV) indicates the immediate
treatment outcome
Accumulated dose
27
During
treatment:
real time dose
measurement
Immediate Post-Tx NPV T1w subtraction
(*Based on: Sapareto-Dewey Equation, 1984)
Caution: Investigational Device. Limited by United States Law to Investigational Use.
ExAblate Initial Clinical Experience
31 patients with organ confined Low Risk PCa and
Intermediate-Low Risk PCa were treated under several
feasibility protocols:
focal therapy
near total gland
treat and resect
Endorectal treatment transducer
Up to 12 month follow-up
Pre-treatment prostate (Blue) and target (Yellow)
28
Non perfused volume (Green) post-treatment
28
ExAblate® Research for Treating
Breast Cancer
29
Breast Cancer– “Virtual” Lumpectomy
Non-invasive alternative to surgical “lumpectomy”
Ambulatory, single session procedure
Over 300 patients treated in Phase I/II trials, up
to 60 months follow-up
Patients treated with MRgFUS, followed by
adjuvant therapy
No recurrences; no severe adverse events
Pre-treatment
T1 contrast-enhanced
48 months post-treatment
T1 contrast-enhanced
Courtesy of Furusawa H MD, Breastopia, Japan
30
Caution: Investigational Device. Limited by United States Law to Investigational Use.
Clinical Case – Excision-less Study
Pre-Treatment
T1w+c
Post-Treatment
T1w+c
18M FU
T1w+c
Courtesy of Breastopia Namba Hospital, Miyazaki, Japan
31
Caution: Investigational Device. Limited by United States Law to Investigational Use.
30M FU
T1w+c
Significant Installed Base
InSightec Enjoys an installed base of >100 sites around the globe.
Customers include well-renowned centers of excellence.
AMERICAS 32
•
•
•
•
27USA
2 Canada
1 Mexico
2 Brazil
Selected Luminary Sites
EUROPE 38
•14 Russia
• 2 Israel
• 5 Germany
• 6 Italy
• 3 UK
• 1 Switzerland
• 1 Spain
• 2 France
• 1 Czech Republic
ASIA 31
•
•
•
•
•
•
•
•
•
•
12 Japan
6 India
3 Korea
2 China
2 Singapore
1 HK
1 Taiwan
1 Vietnam
1 Malaysia
2 Australia
PIROGOV NATIONAL
MEDICAL SURGICAL
CENTER
S.P. Botkin Moscow City
Clinical Hospital
Demonstrated Value to Hospitals
UF treatment at Shinsuma
Total: 117
120
# of UF patients
100
ExAblate
installed
Total: 102
11
6
16
20
10
80
LM
16
60
2
Total: 22
8
2
LH
AM
18
AH
15
40
20
27
Total: 50
MRgFUS
4
7
53
42
22
12
0
2003
2004
2005
2006
Courtesy of Shinsuma Hospital, Japan
for Functional Neuro-Surgery
• Non-invasive
• No ionizing radiation effects
• Highly localized sharp demarcation
• Immediate clinical effect
• No collateral or trajectory tissue damage
• CE approved. FDA Trial
Essential Tremor
T1W
POD 1
POD 7
POD 30
Neuropathic Pain Results
Daniel Jeanmonod et al
VAS (Scale up tp 100)
70.0
63.3 (n=11)
Mean Pain Relief
•
49% at 3 months (n=9)
•
57% at 1 year (n=8)
60.0
50.0
37.4
40.0
35.2
(n=11)
(n=8)
30.0
20.0
Average Pain Score Improvement (VAS) :
• 50% immediate
• 42% 3 months
• 51% at 1 year
10.0
0.0
-10
40
90
140
190
240
Days
Compares to long term pain relief of 42-50% after DBS1
1Levy
et. al. Pain Physician: March/April 2010; 13:157-165;
Rasche D et al. DBS for treatment of various chronic pain syndromes. Neurosurg. Focus Vol 21, Dec 2006
290
340
390
Case Study- Neuropathic Pain
48h
3m
1y
Axial T2
Photo courtesy of Zurich Univ. Hospital, Switzerland
Prof’ D. Jeanmonod, Prof’ E. Martin
CoronalT2
Axial T1
www.insightec.com
Thank you for your attention!
Dr. Roni Yagel
[email protected]