1. The Role of Cyberknife Stereotactic Body Radiation Therapy in the Treatment of Localized Prostate Cancer David M. Spellberg M.D., FACS

2. Radiation Options ConvenienceInvasiveToxicityEfficacy IMRTLowNoModHigh LDR BrachyTx HighYes X 1ModHigh HDR BrachyTx ModerateYes X 2ModHigh CKHighNoVery LowTBD

3. Frameless Radiosurgery Robotics Image Guidance Advanced Treatment Planning CyberKnife Technology

4. Patient lies comfortably on the couch while the CyberKnife robot moves, images and treats. Treatments typically last 1 hour Most patients require no sedation allowing them to depart at the completion of their treatment CyberKnife Treatment Delivery

5. Precise control limits dose to the rectal wall and urethra Prostate Radiosurgery Image courtesy of San Diego CyberKnife Center

6. Precise control limits dose to the rectal wall and urethra Automatic correction for target motion during treatment Prostate Radiosurgery Footage courtesy of St. Anthony’s Hospital

7. BED Calculations External Beam Radiation Therapy / HDR –BED = nd [ 1 + (d/ α/β) ] Low Dose Rate Permanent Decaying Implants –BED = (Ro/ λ) { 1 + [ Ro/(μ+ λ)(α/β)] } Definitions of parameters n = # fractions d = daily dose Ro = initial dose rate of implant λ = radioactive decay constant = 0.693/T 1/2 T 1/2 = radioactive half-life of isotope μ = repair rate constant = 0.693/t 1/2 t 1/2 = tissue repair half-time

8. Calculating BED For Low Risk CaP Monotherapy Treatment Regimens Biologically Equivalent Dose BED = D (1 + d/alpha beta ratio) D = total dose d = dose/fraction alpha/beta ratio = 1.5 for prostate 3 for late effects 10 for acute effects 81Gy IMRT/ 45fx / 9 weeks ( BED 1.5 = 178.2, BED 3 = 129.6 ) HDR monoTx @ 9.5Gy X 4fx ( BED 1.5 = 278.7, BED 3 = 158.3 ) HDR monoTx @ 8.55Gy X 4fx ( BED 1.5 = 229.1, BED 3 = 131.7 ) HDR monoTx @ 7.25Gy X 6fx ( BED 1.5 = 253.7, BED 3 = 148.6 ) Cyberknife monoTx @ 7Gy X 5fx ( BED 1.5 = 198.3, BED 3 = 116.7 ) Cyberknife monoTx @ 7.25Gy X 5fx ( BED 1.5 = 211.5, BED 3 = 123.9 ) NCH Hospital, Naples, FL

9. Dose Calculations for Cyberknife Stereotactic Body Radiation Therapy For CK, one can fractionate the therapy yet remain convenient and non-invasive for the patient CK doses are most like HDR, since the dose/fraction, total doses and time factors are similar SHARP trial from Virginia Mason Hospital with good results (33.5Gy/5fx) Thus, since we have intermediate and long term results with HDR, CK appears to be a well founded treatment option

10. Prostate PTV: gland expanded 5 mm in each direction except posteriorly where it is expanded 3 mm

11. Prostate comparison: axial & sagittal 40 and 25 mm colls40 mm coll

12. Prostate comparison: urethra 40 mm coll40 and 25 mm colls 18.7% vol at 90% dose 30.8% vol at 90% dose

13. Prostate comparison: bladder 12.2% vol at 60% dose 16.7% vol at 60% dose 40 mm coll 40 and 25 mm colls

14. Prostate comparison: rectum 40 mm coll40 and 25 mm colls 20.5% vol at 60% dose 11.2% vol at 60% dose

15. Basic Demographics Ages 62 to 85 Stage cT1cNoMo to cT2bNoMo All patients treated between 12/07/2004 and 5/25/2007 Total number of Patients = 162

16. Hormonal Therapy 135 Patients treated without Hormonal therapy 27 Patients treated with Neoadjuvant Hormonal Therapy

17. Histology Gleason grade 3 + 3 = 121 Patients Gleason grade 3 + 4 = 31 Patients Gleason grade 4 + 3 = 8 Patients Gleason grade 4 + 4 = 1 Patient Gleason grade 5 + 4 = 1 Patient

18. Prostate Volumes Range = 15.5cc to 109cc Mean initial volume = 45.7 cc Median initial volume = 46.1 cc

19. Prostate Cyberknife MonoTx Dose Mean Dose = 3503 cGy (n=162) Median Dose = 3500 cGy Range = 3500cGy to 3755 cGy Number of Fractions = 5

20. Initial PSA’s Range = 1.1 to 17.2 ng/ml Mean initial PSA = 5.87 ng/ml Median initial PSA = 5.75 ng/ml

21. PSA Response to Cyberknife

22. Acute Toxicity Urinary hesitancy, urgency, frequency (Day 3-10) Tenesmus/ rectal discomfort (Day 5-8) Diarrhea (Day 5-8) Rx: Flomax Lomotil Decadron Anusol-HC supp.

23. Acute Toxicity Scoring (IPSS/RAS/SHIM) Baseline, days 2 and 5, post-treatment day 10, 1 month and 4 months Acute effects generally return to baseline by 1 months Urinary symptoms more marked in patients with IPSS baseline scores >20 No urethral strictures/ persistent rectal bleeding observed

24. IPSS Scores After Cyberknife SBRT

25. RAS and SHIM Scores after Cyberknife SBRT

26. Summary Cyberknife is a new and innovative treatment delivery technique for prostate cancer. Cyberknife monotherapy produces an early decline of PSA’s in low risk patients. The acute toxicity of Cyberknife monotherapy is very minimal compared to other radiation treatments. Cyberknife therapy is a noninvasive and convenient treatment option for patients with early stage prostate cancer. Prostate cancer patients treated with Cyberknife should continued to be enrolled and followed in research protocols, and the data collectively analyzed.