1. 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

2. 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

3. 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 )

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

5. PSA Response to Cyberknife

6. IPSS Scores After Cyberknife SBRT

7. RAS and SHIM Scores after Cyberknife SBRT

8. 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.

9. 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

10. Acute Toxicity Overall (AUA/RAS/SHIM) Acute effects generally return to baseline by 4 months Urinary symptoms more marked in patients with AUA baseline scores >20 No urethral strictures/ persistent rectal bleeding observed

11. Rationale for Cyberknife SBRT Boost CK dosimetry is most like HDR, since the dose/fraction, total dose and time factors are similar With CK, one can fractionate the therapy yet remain convenient and non-invasive for the patient Published data supports HDR boost (Grills, Martinez)

12. Advanced Disease Demographics (n = 58) Age 54 to 88 Stage cT1cN0M0 to cT3cN0M0 Patients treated between 12/07/2004 and 12/31/2007

13. Hormonal Therapy 24 Patients treated without Hormonal therapy 34 Patients treated with Neoadjuvant Hormonal Therapy

14. Histology Gleason grade 3 + 3 = 8 Patients Gleason grade 3 + 4 = 24 Patients Gleason grade 4 + 3 = 14 Patients Gleason grade 4 + 4 = 7 Patients Gleason grade 4 + 5 = 3 Patients Gleason grade 5 + 3 = 2 Patients

15. Baseline Volume/PSA Initial prostate volume: range = 21.5cc to 77.5cc Initial PSA: mean = 10.2 range = 1.7cc – 80.1 cc

16. Dosing External beam (IMRT): 45Gy at 1.8Gy per fx Wait 1-2 weeks CK boost: 19.5Gy in 3 fx (median) range = 15Gy – 21.75Gy in 3 fx

17. PSA Response post-tx

18. GU Toxicity

19. GI Toxicity

20. SHIM Scores after CyberKnife SBRT

21. 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.

22. WHY SHOULD UROLOGISTS BE INVOLVED? A greater understanding of the anatomy We take care of the complications We keep control of our patients