1. Stereotactic Body Radiation Therapy for Early Stage Prostate Cancer: Outcomes from a Single Institution Study Stereotactic Body Radiation Therapy for Early Stage Prostate Cancer: Outcomes from a Single Institution Study Debra Freeman, MD Jay Friedland, MD Naples Radiation Oncology, PA

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

3. Experience to Date Experience 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)

4. (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

5. 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

6. 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)

7. 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

8. Patient Prep

9. 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

10. Patient Prep Low residue diet before imaging and during treatment week (bowel gas) Low residue diet before imaging and during treatment week (bowel gas) Fleet enema 1 to 2 hours before imaging and treatment Fleet enema 1 to 2 hours before imaging and treatment Empty bladder 1 to 2 hours before treatment, then drink specified volume of water Empty bladder 1 to 2 hours before treatment, then drink specified volume of water

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

12. Contouring

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

14. 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

15. 130 – 160 beams 35,000 – 45,000 mu’s prescribe to 85% isodose Max / Min dose = 1.20 (mean) PTV coverage > 95% CI = 1.1 - 1.25 Treatment time: 45 - 60 minutes Typical Prostate Plan: This Study

16. 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

17. Results

18. PSA Response to CyberKnife

20. % 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

21. 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

22. AUA Scores after CyberKnife SBRT

24. 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

25. SHIM Scores After CyberKnife SBRT

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

28. 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.