1. ©2005 Surgical Planning Laboratory, ARR Slide 1 Magnetic Resonance Therapy: The Prostate program Clare Tempany MD Director, MRT Program leader & Core Leader

2. ©2005 Surgical Planning Laboratory, ARR Slide 2 Prostate cancer: Scope of the problem 1.5 million prostate biopsies per year 25 million men have had at least one negative biopsy 2003- 220,900 New cases were diagnosed 2015- 450,000 New cases will be diagnosed Approx 4-8% disease specific mortality rate How will we improve diagnosis and treat all these patients? Ideally –Non-invasive, low cost, effective therapy –Imaging Dx and Rx

3. ©2005 Surgical Planning Laboratory, ARR Slide 3 Staging/Treatment prostate cancer T1/T2 intra-glandular tumors –Treatment-goal-local cure Radical prostatectomy XRT Implant Watchful waiting T3 Extra-glandular –Through capsule –Into seminal vesicles Treatment-Radiation+/- Total androgen suppression

4. ©2005 Surgical Planning Laboratory, ARR Slide 4 BWH prostate program: Milestones 1991 Prostate MR Imaging (CT-BWH) –Urology (Jerome Richie)/Med Onc (Phil Kantoff) 1994 New collaboration –Prostate imaging/ Radiation Oncology collaboration began. ( Anthony D’Amico /CT ) CALGB trial Schering Oncology grant 1997 MRT brachytherapy program –1999 1 st NIH R01 grant (AG R01 19513) –8/05 427 men treated

5. ©2005 Surgical Planning Laboratory, ARR Slide 5 MR Appearance: Normal prostate Axial T2WSag T2W CG PZ E COIL

6. ©2005 Surgical Planning Laboratory, ARR Slide 6 Prostate MR image interpretation Tumor –T2W/T1W image: Low signal Capsule Neurovascular Bundles Seminal vesicles Nodes Bones

7. ©2005 Surgical Planning Laboratory, ARR Slide 7 Focal right sided tumor with ECP Axial T2W Sag T2W CG PZ Tumor

8. ©2005 Surgical Planning Laboratory, ARR Slide 8 1.5T normal prostate0.5T normal prostate 1997 state of the art Inc Clinical Cases QOL issues Morbidity IGT MR/TRUS Image quality IGT Neurosurgery program Clinical problems: rx of prostate Ca

9. ©2005 Surgical Planning Laboratory, ARR Slide 9 MR guided prostate interventions Two major clinical programs –Diagnostic biopsy –I-125 interstitial implant Brachytherapy/ Cancer treatment Pre intervention imaging-State of the art –1.5T endorectal coil MRI Open 0.5T MRT system- GE medical –Procedure guided with real time MR –Plan –Guide –Monitor

10. ©2005 Surgical Planning Laboratory, ARR Slide 10 Prostate cancer imaging and Brachytherapy program MR IMAGE TREATMENT PLANNING NEEDLE PLACEMENT Pre clinical testing, feasibility testing and Clinical trial, designed and established by Drs D’Amico & Tempany Pre clinical testing, feasibility testing and Clinical trial, designed and established by Drs D’Amico & Tempany 1997 First patient treated in MRT (GE Signa SP 0.5T) 1997 First patient treated in MRT (GE Signa SP 0.5T) Pt selection criteria- Pt selection criteria- T1C, PSA<10, GG< 3+4 Ecoil- no extra-glandular disease Ecoil- no extra-glandular disease

11. ©2005 Surgical Planning Laboratory, ARR Slide 11 Contouring PZ, urethra and rectum Axial T2W image Treatment plan

12. ©2005 Surgical Planning Laboratory, ARR Slide 12 Needle Placement Needle Insertion RT Imaging Cor,Sag,Ax Radio logic Evaluation Dosimetric Evaluation Place Seeds Dose Evaluation Plan Modification Reposition Needle Next Needle Additional Needles Necessary? Feedbacks:Anatomic Geometric Dosimetric Yes No

13. ©2005 Surgical Planning Laboratory, ARR Slide 13 Brachytherapy planning Software* * US PATENT OFFICE Radiation seed implant method and apparatus. JCR098-01pA: 2001, Nov 1.

14. ©2005 Surgical Planning Laboratory, ARR Slide 14 MR-guided prostate biopsy program –Clinical need TRUS high false negative MR Bx Target +Sextant/octant –Need target validation method –Need ‘free-hand’ or Robot assisted approach TARGET 3D-Slicer adapted for prostate procedures and target definition, trajectory planning and guidance

15. ©2005 Surgical Planning Laboratory, ARR Slide 15 MR guided biopsy protocol Pre-biopsy MR imaging Define any targets –T2W –Contrast –MRSI –LSDI –T2 maps Biopsy Open MRT Transperineal Targeted sampling Systematic sampling (Sextant/Octant) Site specific pathology

16. ©2005 Surgical Planning Laboratory, ARR Slide 16 MRI/MRSI : Data Summary Overlaid Choline/Citrate image Cancer Normal Overlaid Citrate Choline Images Up to 1024 Prostate spectra Data from UCSF Kurhanewicz et al

17. ©2005 Surgical Planning Laboratory, ARR Slide 17 Multi-parametric and multi- modal data problem

18. ©2005 Surgical Planning Laboratory, ARR Slide 18 [ 11 C] Choline PET/MRI PET FUSION MRI Courtesy of J. Czernin, MD Ahmanson Biological Imaging Center, David Geffen School of Medicine at UCLA

19. ©2005 Surgical Planning Laboratory, ARR Slide 19 Prostate IGT Research projects Registration & Segmentation –Multi-modal image display –Seed definition-seed based dosimetry Clinical outcomes –Cancer diagnosis, control, toxicity and QOL Target definition –Multi-parametric data analysis and summation Optimized biopsy –Davatzikos et al-mathematical statistical model Robotic assist device /closed bore systems –Fichtinger, Burdette et al MRg Prostate cancer FUS –Hynynen et al

20. ©2005 Surgical Planning Laboratory, ARR Slide 20 Interfractional Motion from Serial CT – Movement AP ~1cm* Courtesy of Andrew Zitman MD (MGH) IGT requires dynamic imaging to monitor delivery: Rapid image processing & registration

21. ©2005 Surgical Planning Laboratory, ARR Slide 21 Recent case: Rising PSA 4 years after brachytherapy

22. ©2005 Surgical Planning Laboratory, ARR Slide 22 MR/MRSI guided biopsy & Rx Adenocarcinoma Anterior TZ

23. ©2005 Surgical Planning Laboratory, ARR Slide 23 MR guided brachytherapy: Clinical validation / outcomes –Outcomes. Albert* et al Cancer (2003) Grade 3 rectal bleeding 8% vs. 30% (combined) 4yr freedom from Radiation cystitis: 100 vs. 95% No urethral strictures or TURP to date –Cancer control D’Amico et al (2003) 93% 5 yr PSA control, similar to a surgically managed population over the same time frame –QOL: Szot* et al RSNA 2004 Significant improvement over US in both GU and sexual function * R25 training grant fellows

24. ©2005 Surgical Planning Laboratory, ARR Slide 24 Non-invasive Focused ultrasound surgery High intensity FUS first proposed by Lele in 1962 –Sound waves heat tissue through molecular vibration –Delay due to lack of targeting, guidance and temperature monitoring –Tested in animals-nude mouse model- Vaezy S et al –Feasible for treating Breast Fibroadenomas-Hynenen K, et al –Feasible for treating uterine Leiomyomas-Tempany et al

25. ©2005 Surgical Planning Laboratory, ARR Slide 25 Future directions; MR guided Focused Ultrasound Surgery for Prostate cancer* FUS THERMO-COAGULATION necrosis Real time MR thermometry *R01: CA-109246-01 A1 Tempany