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MR Guided Focused Ultrasound (MRgFUS) Overview of Present and Future Clinical Research Studies
- 1. MR Guided FocusedUltrasound (MRgFUS) Overview of Present and Future Clinical Research Studies David Gianfelice MD University health Network Toronto, Canada Research Support Insightec Ltd.
- 2. Contents What isMR guided focused ultrasound surgery Clinical research : Pain palliation of bone metastases Breast cancer Prostate cancer Palliative treatments Clinical partners .
- 3. How does FocusedUltrasound work? Focused ultrasound generates heat, ablating tissue only at the focal point. Spot sizes Length: 10-45 mm Diameter: 2-10 mm Treatment illustration Perpendicular to beam Parallel to beam
- 4. Why is MRguidance and control important? 3D Imaging for precise tumor targeting Beam path visualization for controlled treatment MR thermometry for real-time temperature feedback Post treatment contrast imaging for precise treatment validation CLOSED LOOP THERAPY
- 5. Clinical applications andresearch* * All research studies under IDE - investigational use only Bone Tumors Liver Tumors Breast Cancer Uterine Fibroids Brain treatments Prostate
- 6. Pain Palliation ofBone Metastases* European CE mark received June 2007 FDA Phase I completed FDA Phase III IDE approved Nov 07 Next phase - MRgFUS treatment of Bone Mets with strappable bone system Started feasibility study at Sheba, Israel and Mt. Sinai General Hospital, Toronto IDE Caution-Investigational Device Limited by United States Law to Investigational Use.
- 7. Soft tissue: Narrow,point-shaped focus is required High energy density at focal point Bone : Wide Beam Approach Low energy usage Shorter Treatment Time MRgFUS for bone vs. tissue Acoustic Beam Transducer Bone Ablated Tissue Typical Sonication Energy – 2500J Typical Sonication Energy – 1000J Transducer
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- 9. Pain palliation ofbone metastases case CT before treatment Courtesy of Mt. Sinai Hospital, Toronto Patient with osteolytic breast cancer metastasis at right iliac bone Pain score of 5.5 before treatment reduced to 0 at 3M follow up CT after 3 months Note: At 3M new bone formation and thickening of cortical layer in treatment area IDE Caution-Investigational Device Limited by United States Law to Investigational Use.
- 10. Courtesy of Mt. Sinai Hospital, Toronto Clinical results – pain palliation of bone metastases case Clinical results: Patient VAS pain score dropped from 7 (severe) to 0 (no pain) Duration of treatment: 50 min Only 11 sonications required IDE Caution-Investigational Device Limited by United States Law to Investigational Use.
- 11. ExAblate work-in-progress: Strappable bone system Strappable bone applicator Access to more anatomical locations Improved patient comfort High density electronically steerable transducer IDE Caution-Investigational Device Limited by United States Law to Investigational Use.
- 12. Breast Cancer* *Investigational use ACRIN study: In submission - Extended Phase II with excision (up to 200 patients) Planned - Phase III excisionless IDE Caution-Investigational Device Limited by United States Law to Investigational Use.
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- 14. Breast cancer -phase II study results Objectives: Demonstrate feasibility to: Replace lumpectomy with non-invasive treatment of tumor Excise tumor and biopsy to verify over 95% necrosis Results: Total 193 patients treated, 66 in phase I & II protocols , 30 in Phase II with contrast enhanced planning images Results with contrast enhancement: 97% ± 4% tumor necrosis Study completed Courtesy of Breastopia Namba Medical Center, Miyazaki, Japan * Furusawa H, Namba K, Thomasen S, Akiyama F, Bendet A, Tanaka C, Yasuda Y, Nakahara H. Magnetic Resonance-Guided Focused Ultrasound Surgery of Breast Cancer: Reliability and Effectiveness , J Am Coll Surg, 2006, 203(1):54-63 T1w contrast enhanced subtracted images Hyperemia at edge of treated region IDE Caution-Investigational Device Limited by United States Law to Investigational Use.
- 15. Breast cancer -ACRIN study Objectives: To develop sufficient data to justify larger scale Phase III trial with MRgFUS as the non-invasive ablation alternative to lumpectomy for tumor de-bulking To prove that the combination of contrast enhanced MRI and biopsy (2 weeks after treatment) is a reliable predictor of treatment success Multiple sites in US Stages: Extended Phase II with excision (up to 200 patients) Phase III – excisionless (large scale study) IDE Caution-Investigational Device Limited by United States Law to Investigational Use.
- 16. Breast cancer –excisionless study Objective: Evaluate long term local recurrence of up to 1.5 cm MRgFUS treated breast carcinoma and evaluate safety of the procedure Design: Only patients with MR identified single focal lesion (up to 1.5 cm) of T1, N0, M0 disease will be treated Status: 44 patients treated, Max follow-up 36 months Average follow-up 18 months No recurrence cases Pre treatment T1w+CE MIP image 2 weeks post treatment T1w CE MIP image Location: Breastopia Namba Hospital, Miyazaki, Japan IDE Caution-Investigational Device Limited by United States Law to Investigational Use.
- 17. Prostate Cancer* *Investigational use Animal trials ongoing Clinical trials planned for end of 2008 IDE Caution-Investigational Device Limited by United States Law to Investigational Use.
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- 19. ExAblate for prostate– initial animal results Treatment effects in canine prostate The results show a good correlation between expected dose and NPV and similarity to the TTC stained tissue: WS expected dose: Non-perfused volume, T1w+contrast imaging: TTC stained tissue:
- 20. Uterine fibroids (leiomyomas)First FDA approved (Oct 2004) focused ultrasound application Symptomatic in 25% of women of childbearing age. Symptoms: excessive bleeding, pain, bloating, incontinence Up to 400,000 women in US undergo surgery each year More than 4000 symptomatic women treated around the world, up to 36 month follow-up 92% reported symptom relief Data shows most severely symptomatic patients return to near normal after MRgFUS treatment
- 21. Uterine fibroids casesCourtesy of Sheba Medical Center, Tel Aviv, Israel T1w contrast enhanced image before treatment T1w contrast enhanced image immediately post-treatment T2w planning image with dose overlay Outcome: Marked reduction in all symptoms. Fibroid reduced to 455 cc after one month and 298 cc after 36 months. 40 years old, 526cc fibroid Symptoms: heavy bleeding, cramps and dyspareunia. 49 year old, multiple fibroids Symptoms: pressure & frequent urination Outcome: Fibroids totally ablated, marked reduction in symptoms T2w image before treatment T1w contrast enhanced image one month after treatment T1w contrast enhanced image 36 months after treatment
- 22. Palliative Treatments* *Investigational use
- 23. Compassionate soft tissuetumor treatment Metastatic lesion secondary to primary lung cancer at Gluteous and Buttock muscles. Previous radiotherapy failed. 3 weeks after the pre-treatment screening the tumor has increased its volume by 40-50%. Treated with the regular ExAblate 2000 The untreated portions of tumor have all been treated in additional sessions. Pre Tx T2w Images Post Tx CE subtracted T1w Images Axial Coronal Pre Tx T2w Image Post Tx CE T1w Images Sagittal
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- 25. Brain tumors -closed skull safety study Axial temperature map of thermal spot Helmet shaped transducer Patient set up Patient entering MR
- 26. MRgFUS – valuein Oncology applications Local therapy Real time monitoring Non-invasive Treatments can be repeated No dose accumulation effects No long term toxicity Excellent soft tissue and soft tissue tumors imaging for detection
- 27. Kidney Pancreas BladderThyroid Lymph nodes Meningioma Epilepsy Vasculature Ovaries Targeted drug delivery Many potential applications
- 28. Total sites: 60 28 – Americas 17 – Europe 15 – Asia Clinical partners Place cursor on orange square to view site names Americas Europe Asia 28 sites 17 sites 15 sites
- 29. Click to returnto site map 31 sites Americas Research sites highlighted
- 30. Click to returnto site map Europe 17 sites Research sites highlighted
- 31. Click to returnto site map Asia 15 sites Research sites highlighted
- 32. « Today sciencefiction, tomorrow reality »
Editor's Notes
- #4 The focused ultrasound beam is generated by a phased array transducer which is located in the patient table and passes through a water bath and gel pad which create acoustic coupling with the patient. The effect of focusing ultrasound energy is similar to that of using a magnifying glass to focus the sun’s energy on a single point. However, unlike light, ultrasound energy can easily pass through the skin and propagate through tissue to converge to a focal point inside the body. The focal point has the shape of a small bean. In few seconds, the tissue at the focus reaches a temperature level that causes cell destruction. The system then moves to another spot to ablate it,until all the planned spots are treated. The size of the sonications can be varied, depending on the size and depth of the focal volume to be treated, ranging from 1x2mm to 10x30 mm.
- #5 Focused Ultrasound has been identified as the “ideal surgical tool” for over 40 years, however, without the ability to visualize or control the treatment, it was not accepted. The advent of Magnetic Resonance provided just such a tool: precise visualization of the tumor, other organs, and the beam path for exact targeting and to ensure that there are no unwanted structures or organs in the beam path; real time thermal imaging to evaluate if the beam actually reached the target and if so, if it reached coagulation temperatures. If it doesn’t reach the right temperature, then the physician has the ability to change the parameters. This closed loop therapy paradigm provides the ability to get immediate feedback, react to that feedback, and know immediately what the outcome is. All this provides the physician with much more information than traditional surgical procedures. This ensures efficacy and safety of the procedure.
- #6 Wide range of applications under development by InSightec. We have embarked on a very extensive clinical research program.
- #11 Also in the Inclusion: Bone metastasis are device accessible Also in the exclusion: Impending fracture or, at some sites, weight bearing bone Targeted tumor less then 10mm from skin, (avoid the risk of skin burn) Targeted tumor less then 10mm from major nerves, (avoid the risk of neural damage) Note: it is ok to have Mets in the spinal column as long as they are not the targeted ones
- #12 The illustration shows the usage of wide beam approach on a pelvic tumor. Difficult to see here but patient is not on back but somewhat tilted Details in the next slides
- #15 Breast cancer is the leading form of cancer among women, and ranks second among cancer deaths in women, behind lung cancer. 200,000 women are diagnosed with breast cancer annually and nearly 40,000 women die annually of breast cancer. The gold standard treatment is surgical removal of the tumor and a surrounding area of normal tissue, or lumpectomy, typically in combination with additional therapies such as radiation therapy or chemotherapy to prevent recurrence. InSightec has conducted several Phase I and Phase II studies with 120 patients. Early studies showed the importance of tumor margin delineation in order to totally treat tumors. We recently completed a Phase II study in Japan with contrast enhancement used in planning images, which enabled the physicians to clearly identify the borders of the lesions and identify small lesions that are often overlooked. These lesions were then excised with results of 97% necrosis. This pathology, which comes up after you click ones shows the slice by slice pathology of a biopsied tumor. You can see the ablated cancer, the boundary of the necrosis, to ensure that an appropriate margin is taken and the treatment boundary.
- #16 A press release on this topic has been issued prior to RSNA. This Phase II trial is intended to demonstrate that ExAblate 2000 can effectively and non-invasively serve at the method for destruction of the localized tumor versus conventional lumpectomy. The results of this study will provide the basis for a large scale excisionless pivotal study. For this study, MRgFUS will be used to treat the tumor plus a margin of normal tissue. A contrast MR will be performed 14-21 days later to assess the completeness of the treatment. Following this, a conventional lumpectomy will be performed and the cancerous growth will be excised for pathological evaluation, and the patient will receive the conventional standard of care therapy (radiation and/or chemotherapy). This study will use the pathology data to determine if ExAblate can destroy 95% of the tumor or more of the tumor volume. A secondary endpoint will be to evaluate the ability of contrast MR to identify those patients with residual tumor post MRgFUS treatment. The study will be involve 200 patients at up to 10 sites worldwide.
- #17 A trial is currently on-going in Japan to treat breast cancer without surgical removal of the treated lesion. Patients will be followed up for 5 years So far five women have been treated.
- #21 Uterine Fibroids are a very prevalent condition and occur in up to 80%, with 25% of women requiring some form of treatment to alleviate symptoms. UF are the leading cause of hysterectomy, with up to 1/3 of all hysterectomies performed for UF. Hyst. and Myomectomy, the leading treatment alternatives are both surgical treatments which require hospitalization and extensive recovery time. UAE, generally requires an overnight stay in the hospital and if often accompanied by significant pain and post-embolization syndrome. Drug therapy is a temporary measure, which is often a prelude to hysterectomy or myomectomy. Over 2200 women have been treated with ExAblate with close to 92% experiencing symptom relief.improvem
- #22 Upper case: 3 year follow-up without return of symptoms. The main shrinkage occurs in the months following the treatment. Lower case: Multiple fibroids can be treated using the ExAblate system. This example shows a patient with 2 fibroids treated successfully.
- #26 Our “closed-skull” protocol will treat up to 10 patients with brain tumors. The protocol does not require the participants to undergo a prior craniectomy procedure. To date, three patients have been treated at BWH with a protocol to demonstrate safety- meaning no skull heating, which might cause damage to the brain surface. The results were reported to the FDA and based on these results the FDA approved a continuation of the study with emphasis on efficacy.