Stereotactic Body Radiation Therapy for Prostate Cancer Alexander R. Gottschalk, M.D., Ph.D. Associate Professor and Director of the CyberKnife Radiosurgery Program Department of Radiation Oncology University of California, San Francisco April 2, 2011 UC SF What is SBRT? Stereotactic body radiotherapy is not: 2D (AP/PA or postage-stamp field ) 3DCRT (4 fields) Intensity-modulated radiotherapy () Protons Stereotactic body radiotherapy is: Converging multiple beams on the tumor Resulting in a very conformal dose distribution Limiting dose to normal tissue Allowing for higher dose delivered to the tumor Delivered in a hypofractionated regimen (high-dose per fraction and few number of fractions) What is SBRT? SBRT is a treatment that couples a high degree of anatomic targeting accuracy and reproducibility with very high doses of extremely precise, externally generated, ionizing radiation, thereby maximizing the cell-killing effect on the target(s) while minimizing radiationrelated injury in adjacent normal tissues. The adjective stereotactic describes a procedure during which a target lesion is localized relative to a known three dimensional reference system that allows for a high degree of anatomic accuracy and precision. Examples of devices used in SBRT for stereotactic guidance may include a body frame with external reference markers in which a patient is positioned securely, a system of implanted fiducial markers that can be visualized with low-energy (kv) x-rays, and CT-imagingbased systems used to confirm the location of a tumor immediately prior to treatment. What is SBRT? All SBRT is performed with at least one form of image guidance to confirm proper patient positioning and tumor localization. To minimize intra-treatment tumor motion associated with respiration or other motion, some form of motion control or gating may be used. SBRT may be fractionated (up to 5 fractions). Each fraction requires an identical degree of precision, localization and image guidance. Since the goal of SBRT is to intensify the potency of the radiotherapy by completing an entire course of treatment within an extremely accelerated time frame, any course of radiation treatment extending beyond five fractions is not considered SBRT and is not to be billed using these codes. http://www.cms.gov/mcd http://www.cms.gov/mcd Page 1
Hypofractionation for Prostate Cancer Hypofractionation for Prostate Cancer Why hypofractionation? Shorter treatment More effective treatment? BED = nd[1 + d/(α/β)] Why hypofractionation? Shorter treatment More effective treatment? BED = nd[1 + d/(α/β)] BED Fractionation α/β = 10 α/β = 3 α/β = 1.5 1.8 Gy x 44 = 79.2 Gy 93 127 174 2 Gy x 39 = 78 Gy 94 130 182 6.7 Gy x 5 = 33.5 Gy 56 108 183 7.25 Gy x 5 = 36.25 Gy 63 124 211 9.5 Gy x 4 = 38 Gy 74 158 279 Hypofractionation for Prostate Cancer Hypofractionation for Prostate Cancer Are these dose for prostate cancer is new? Are these dose for prostate cancer is new? High dose per fraction has been use safely and effectively with brachytherapy (HDR) Page 2
HDR brachytherapy SBRT vs HDR brachytherapy 5-Year bdfs Outcomes for HDR-Monotherapy for Prostate Cancer HDR Details Institution # pts Medianf/u Phoenix ASTRO 6 7.25 Gy x 6 CA Endocurie 117 3.3 yrs 97% 9.5 Gy x 4 Beaumont 95 4.2 98% 7.5 Gy x 6 Texas Tech 145 5 90% 6.5 Gy x 6 Texas/Miami 209 1.2 96%* 99%* Gamma West SLC 119 1.2 89%* 89%* 6 Gy x 8-9 Osaka (Japan) 111 2.25 70% Totals 796 2.4 90% Toxicity review for HDR-Monotherapy for Prostate Cancer toxicity > Grade 2 HDR Details Institution # pts Median f/u GI (%) GU (%) 6 7.25Gy x 6 CA Endocurie 117 3.3 0 3 9.5Gy x 4 Beaumont 95 4.2 0 8 7.5Gy x 6 Texas Tech 145 5 1 4 7* 6.5Gy x 6 Gamma West (SLC) 328 1.2 0 1 6Gy x 8-9 Osaka (Japan) 111 2.25 1 6 Totals 796 2.4 0-1 5 Deliver high-dose per fraction Allows for hypofractionated treatment Treatment can be completed in 4-5 fractions SBRT compared to HDR Less invasive Less anesthesia Less risk of bleeding and infection Less requirement for pain medication No overnight stay in the hospital Analogy to HDR as a boost (following whole pelvis RT) HDR brachytherapy as boost High dose group Less biochemical failures Less distant mets Improved DFS, CSS and OS IJROBP 66:416, 2006 IJROBP 66: 416-423, 2006 Page 3
HDR brachytherapy as boost is a standard therapy RTOG 0321 (PI: I.C. Hsu) Phase II clinical trial of EBXRT + HDR boost EBXRT 45 Gy HDR boost 9.5 Gy x 2 112 patients Median f/u 29.6 m Grade 3 GI/GU toxicity in 2.5% Other grade 3 toxicities: hemorrhage, anemia, pylonephritis, proctalgia, ED Hsu IJROBP 78:751, 2010 HDR brachytherapy monotherapy N= 149 T1c/T2a, PSA < 10, GS < 7 103 Pd (120 Gy) vs HDR 9.5 Gy x 4 Median follow-up 35 m Similar biochemical control at 3 yrs HDR (98%) vs Pd (97%) J Urol 171: 1098-1104, 2004 Dosimetric Comparison between HDR and CK Dosimetric Comparison between HDR and CK IJROBP 70: 1588, 2008 Jabbari IJROBP Dec 21, 2010 Page 4
Dosimetric comparison of CyberKnife and Dosimetry of protons vs CTV Rectum 19Gy 14.2Gy CK 3DCPT 100 80 60 40 20 Bladder CK SBRT CTV Norm. Volume (%) 100 80 60 40 20 CK SBRT Rectum IMPT 0 0 20 40 60 80 100 120 0 0 20 40 60 80 100 120 Norm. Dose (%) Hossain IJROBP 78:58, 2010 IJROBP 69:444-453, 2007 40 patients 6.7 Gy x 5 fractions over consecutive days T1c-T2a, GS 6, PSA 10 6 non-coplanar beams with 4-5 mm margin Median follow-up 41 m No patients with grade 3 GI/GU toxicity 4-yr bned 70% (ASTRO) and 90% (nadir +2) 304 patients 7 Gy x 5 fractions (n=35) 7.25 Gy x 5 (n=254) T1c-T2a, GS 6, PSA 10 CyberKnife with 4-5 mm margin Median follow-up 30 m One patient grade 3 GU toxicity Follow-up too short to report bned Madsen IJROBP 67:1099, 2009 Katz BMC Urol 10:1, 2010 Page 5
41 patients (2003-2005 at Stanford and Naples, FL) 7-7.25 Gy x 5 fractions T1c-T2b, GS 6, PSA 10 Treatment volume = prostate + 5mm (3mm posterior) Median follow-up 5 years 1 patient with late grade 3 GU toxicity No patients with grade 3 GI toxicity 5-year bpfs 93% PSA nadir < 0.4 (78%) Stanford experience 67 patients 7.25 Gy x 5 fractions over 10 days T1c-T2b, GS 7, PSA 10 Treatment volume = prostate + 5mm (3mm posterior) Median follow-up 2.7 yrs Grade 3 GU toxicity in 2 patients (3%) No patients with grade 3 GI toxicity Median PSA at last follow-up 0.5 ng/ml 4-year brfs 94% Freeman Radiation Oncol 6:3, 2011 King IJROBP Feb 5, 2011 73 patients (41 intermediate and 32 high-risk) 45 Gy EBRT followed by SBRT boost 6 Gy x 3 fractions (n=28) 6.5 Gy x 3 (n=28) 7 Gy x 3 (n=17) Median follow-up 33 m One patient grade 3 GU toxicity No patients with grade 3 GI toxicity 3-year bned 89% (Int-risk) and 78% (high-risk) UCSF experience 38 patients with minimum f/u of 12 months (median 18.3, 12.6-43.5) 20 patients were treated CK monotherapy (9.5 Gy x 4) 18 patients were treated with EBRT (45-50Gy) CK boost (9.5Gy x 2) and 3-6 m of ADT. 44 HDR brachytherapy boost pts with PCa characteristics similar to the CK SBRT boost cohort was also analyzed as a descriptive comparison. Katz Tech Cancer Res 9:575, 2010 Jabbari IJROBP Dec, 2010 Page 6
CK for Prostate: UCSF experience No grade 3 or higher acute GU or GI toxicity. 2 patients (5%) with temporary late grade 3 GU toxicity No grade 3 late GI toxicity All pts are bned at last f/u CK monotherapy median f/u of 18.1 months median PSA nadir of 0.47 ng/ml (0.2-2.1). CK boost median f/u of 23.5 m median PSA nadir of 0.1 ng/ml (0.01-0.5) (post androgen recovery) HDR boost median f/u of 48.6 m median PSA nadir of 0.09 ng/ml (0.0 3.3) Jabbari IJROBP Dec, 2010 Conclusion SBRT for prostate cancer compared to /protons: Allows for a shorter course of therapy For low α/β delivers higher BED Similarly well tolerated with low toxicity Similar biochemical control rates (>90%) at 5 years Allows for less rectum in low dose range compared to Allows for less bladder, femoral head and penile bulb dose SBRT for prostate cancer compared to brachytherapy: Dose distribution is similar to HDR brachytherapy Less invasive than brachytherapy Similar biochemical control rates (>90%) at 5 years When uses as a boost, produces similar PSA nadirs to HDR Page 7