1. Stereotactic Body Radiation Therapy: An Emerging Treatment Approach for Early Stage Prostate Cancer Stereotactic Body Radiation Therapy: An Emerging Treatment Approach for Early Stage Prostate Cancer Debra Freeman, MD David Spellberg, MD Naples Radiation Oncology, P.A. Naples Urology Associates, P.A.

2. Rationale for SBRT Biology of prostate cancer cells (alpha/beta < 2.0) favors hypofractionation Potential to improve therapeutic window Higher local control Reduced toxicity Shorter treatment course

3. BED for Prostate Monotherapy Treatment Regimens 81Gy IMRT/ 45fx / 9 weeks BED 1.5 = 178 BED 3 = 130 HDR monoTx @ 9.5Gy X 4fx BED 1.5 = 279 BED 3 = 158 HDR monoTx @ 8.55Gy X 4fx BED 1.5 = 229 BED 3 = 132 CK monoTx @ 7Gy X 5fx BED 1.5 = 198 BED 3 = 117 CK monoTx @ 7.25Gy X 5fx BED 1.5 = 212 BED 3 = 124 CK monoTx @ 9.5Gy X 4fx BED 1.5 = 279 BED 3 = 158

4. Preparation for SBRT

5. Fiducial Placement CyberKnife fiducials CyberKnife fiducials Stainless steel screws Stainless steel screws Gold seeds Gold seeds Our Prostate Fiducial Placement Our Prostate Fiducial Placement Use stranded gold seeds (2 seeds per needle, 2 cm spacing) Use stranded gold seeds (2 seeds per needle, 2 cm spacing) Patient in dorsal lithotomy position Patient in dorsal lithotomy position Place fiducials transperineally using TRUS and standard implant template Place fiducials transperineally using TRUS and standard implant template 2 needle sticks, drop off 4 seeds 2 needle sticks, drop off 4 seeds

6. Imaging Wait one week after fiducial placement for imaging Non-contrast CT and MRI planning scans 1.25-1.5mm slice thickness Feet first, flat board Minimal/no immobilization devices

7. Patient Prep Low residue diet before imaging and during treatment week (reduce bowel gas) Low residue diet before imaging and during treatment week (reduce bowel gas) Fleets enema 1 to 2 hours before imaging and treatment (decompress rectum) Fleets enema 1 to 2 hours before imaging and treatment (decompress rectum) Empty bladder 1 to 2 hours before treatment Empty bladder 1 to 2 hours before treatment

8. Clinical Example Treatment Planning CT CT at Time of Treatment

9. Treatment Planning

10. GTV to PTV: expand 5 mm anteriorly and laterally; 3mm posteriorly

11. Collimator Selection 12 collimators 12 collimators May use one or more collimators during a treatment session May use one or more collimators during a treatment session This study used 2 collimators for all prostate treatments This study used 2 collimators for all prostate treatments Large collimator to minimize tmt time Large collimator to minimize tmt time Small collimator to paint dose conformally at interfaces Small collimator to paint dose conformally at interfaces Dia. (mm) 5.0 7.5 10.0 12.5 15 20 25 30 35 40 50 60 The IRIS is here! Can change collimator size for every beam

12. 150 – 200 beams 35,000 – 45,000 mu’s prescribe to 85% isodose or higher Max / Min dose = 1.20 (mean) PTV coverage > 95% CI = 1.1 - 1.25 Treatment time: 45 - 60 minutes Typical Prostate Plan

13. Criteria of Acceptability: Rectum % RectumSuggested Dose Limit (Gy) (2 Gy/fx) Calculated Dose Limit (Gy) (7.25 Gy/fx, 5 fx, King) 604019.5 40 (50 RTOG) 60 (1) (2) 29 2570 (1) (2) 34 1575 (1) (2) 37 578 (1) (2) 38 1. Huang et al., Late Rectal Toxicity: Dose-Volume Effects of Conformal Radiotherapy for Prostate Cancer, IJROBP, Vol. 54, No. 5, 1314-1321, 2002 2. RTOG P-0126

14. CyberKnife Monotherapy: Clinical Experience

15. Stanford experience

16. T1c, T2a PSA ≤10 GS 3+3 or 3+4 (if ‘low’ volume) no TURP or other treatment low IPSS score (<20) Eligibility criteria

17. Published results 41 evaluable patients ▪ median FU of 33 months (6-45) ▪ median age 66 yrs ▪ median PSA 5.6 ng/mL (0.7 - 10) ▪ T1c (30 pts), T2a (10 pts), T2b (1 pt) ▪ 3+3 (29 pts), 3+4 (12 pts)

20. Naples experience

21. Accural to Date Accural to Date First patient treated in Jan. 2005 First patient treated in Jan. 2005 Initiated Monotherapy protocol in Feb. 2005 Initiated Monotherapy protocol in Feb. 2005 Total patients treated: 334 Monotherapy: 276 Boost: 58 (Jan. 2005-Apr. 2008) (Jan. 2005-Apr. 2008)

22. (n=201) Monotherapy Group (n=201) At least 6 months follow-up At least 6 months follow-up Stage T1cN0M0 to T2cN0M0 Stage T1cN0M0 to T2cN0M0 Mean age = 69.3 (49-87) Mean age = 69.3 (49-87) Mean prostate volume = 46.3cc Mean prostate volume = 46.3cc Mean initial PSA = 6.0 ng/ml Mean initial PSA = 6.0 ng/ml Gleason score (3+3) = 150 pts Gleason score (3+3) = 150 pts (3+4) = 39 pts (3+4) = 39 pts (4+3) = 8 pts (4+3) = 8 pts

23. Hormonal Therapy 174 Patients treated without hormonal therapy: 22% with Gleason score >7 mean prostate volume = 45cc 27 Patients treated with neoadjuvant hormonal therapy: 42% with Gleason score >7 mean prostate volume = 57cc

24. CyberKnife MonoTx Dose Feb 2005-Dec 2006: 7.0Gy X 5 fractions (35Gy) Feb 2005-Dec 2006: 7.0Gy X 5 fractions (35Gy) Jan 2007-present: 7.25Gy X 5 fractions (36.25Gy) Jan 2007-present: 7.25Gy X 5 fractions (36.25Gy)

25. PSA Response to CyberKnife

27. % achieving given PSA level by duration of follow-up PSA level1 Year (62 pts) 2 Years (54 pts) 3 Years (19 pts) ≤ 1.0 ng/ml56%84%95% ≤ 0.6 ng/ml39%54%68% ≤ 0.4 ng/ml19%43%53% ≤ 0.2 ng/ml6%14%32% PSA Response to CyberKnife

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

29. AUA Scores after CyberKnife SBRT

31. GI Toxicity RAS scores show pattern similar to AUA (minimal acute change with return to baseline by 4 months) Two pts. with documented radiation proctitis/rectal bleeding Developed <1yr post-tx Both pts. diabetic, on chronic Coumadin Treated with argon laser therapy; bleeding resolved

32. SHIM Scores After CyberKnife SBRT

34. E.D.(?) 82% of pts. maintained “erections sufficient for intercourse” at 3 yrs. (based on question #2 of SHIM)

35. Other data Katz, Winthrop (NY) >400pts treated; >200 monotherapy 35Gy/36.25Gy No local failures to date Accuray homogeneous trial (Meier) 159pts enrolled to date Accuray heterogenoeus trial (Fuller) 53pts enrolled to date

36. Summary CyberKnife monotherapy appears to produce a reasonable early decline of PSA in low risk patients. CyberKnife monotherapy appears to produce a reasonable early decline of PSA in low risk patients. The acute toxicity of CyberKnife monotherapy is acceptable. Late toxicity is thus far extremely low. The acute toxicity of CyberKnife monotherapy is acceptable. Late toxicity is thus far extremely low. CyberKnife is a noninvasive and convenient treatment option for patients with early stage prostate cancer. CyberKnife is a noninvasive and convenient treatment option for patients with early stage prostate cancer. Prostate cancer patients treated with CyberKnife should optimally be enrolled on clinical research protocols. Funded protocols are currently available. Prostate cancer patients treated with CyberKnife should optimally be enrolled on clinical research protocols. Funded protocols are currently available.

37. Reimbursement

38. Billable codes: Urologist Fiducial placement: 55876 fiducial insertion 76942 ultrasound-guidance Treatment: Previously 61793, stereotactic radiosurgery Currently 55899, “unlisted”

39. Billable codes: Rad Onc 77295 3D simulation 77263 Treatment planning 77470 Special treatment procedure 77435 Stereotactic radiation management

40. Be aware of CMS carrier policies for coverage of prostate SBRT in your geographic region!

41. The Balancing Act ConvenienceInvasiveToxicityEfficacy IMRTLowNoLowHigh LDRBrachyTxHigh Yes X 1 ModHigh HDRBrachyTxModerate Yes X 2 Low/Mod Very High SBRTHighNo Very Low TBD