CyberKnife SBRT for Prostate Cancer

Transcription

1 CyberKnife SBRT for Prostate Cancer Robert Meier, MD Swedish Radiosurgery Center Swedish Cancer Institute Seattle, WA

2 2017 ESTRO Meeting, Vienna Austria 5-year safety, efficacy & quality of life outcomes from multicenter SBRT trial for prostate cancer R. Meier 1, A. Beckman 2, G. Henning 3, N. Mohideen 4, S. A. Woodhouse 5, C. Cotrutz 1, and I. D. Kaplan 6 1 Swedish Cancer Institute, Seattle, WA, 2 Central Baptist Hospital, Lexington, KY, 3 Huron River Radiation Oncology, Brighton, MI, 4 Northwest Community Hospital, Arlington Heights, IL, 5 Community Cancer Center, Normal, IL, 6 Beth Israel Deaconess Medical Center, Boston, MA

3 Disclosures ClinicalTrials.gov identifier NCT This study is supported by Accuray Inc. R. Meier: remuneration for speaking donated to charity The views expressed in this presentation are those of the presenter and do not reflect the views or policies of Accuray Incorporated or it s subsidiaries. No official endorsement by Accuray Incorporated or any of its subsidiaries of any vendor, products or services contained in this presentation is intended or should be inferred.

4 Dose-bDFS Relationship in Prostate Cancer Proportion of Patients Cancer-free (based on non-rising PSA) Fowler et al. IJROBP 56(4):

5 Randomized LDR+EBRT vs EBRT 398 Interm & high-risk 6.5 yrs median f/u Morris et al, ASCENDE-RT trial, IJROBP (in press)

6 SBRT: Theoretical Advantages Radiobiology of prostate CA may favor hypofractionation SBRT allows dose escalation to 100Gy (α/β=2gy) Improved dose conformality could spare adjacent normal tissues Brief treatment course offers convenience & cost saving

7 Background Single institution SBRT series have demonstrated Gy in 5 fractions using CyberKnife System is safe & effective Meta-analysis suggested trend in improved bdfs at 38-40Gy level Dose-escalation trial reported unacceptable toxicity with >45Gy

8 Hypotheses Across multiple community, regional and academic hospitals, precise delivery of SBRT at 8Gy x 5 level Is safe, with gr 3+ GU/GI toxicities 10% (a rate deemed excessive) In low-risk patients, would improve 5-year nadir + 2 bdfs, over 93% historical control rate expected w/ EBRT

9 Primary Safety Objective For both the low- and intermediate-risk groups: 101 pts required, for 90% power to identify excessive toxicity (one-sided 5% significance level) Accounting for ineligible pts, enrollment of 129 pts into each group was required

10 Primary Efficacy Objective: Low-risk Pts

11 Patient Eligibility Prostate adenocarcinoma, confirmed by central pathologic review Clinical staging stratified into risk groups: Low-risk: CS T1-T2a, Gleason 6, PSA<10ng/ml Intermediate-risk: CS T1-T2b, Gleason=7 & PSA<10ng/ml; or Gleason<6 & PSA 10-20ng/ml Other enrollment criteria: No previous treatment ECOG 0-1 No previous pelvic RT No concomitant or adjuvant hormone therapy Prostate volume 100 cc

12 Patient and Tumor Characteristic Entire Group Low-risk Interm-risk Evaluable patients Number Age (years) Median Prostate Volume (ml) Mean Clinical Stage T1b 3 (1%) 1 (0.6%) 2 (1%) T1c 244 (79%) 140 (81%) 104 (76%) T2a 53 (17%) 31 (18%) 22 (16%) T2b 9 (3%) 0 9 (7%) Initial PSA (ng/ml) Mean Gleason Score (65%) 172 (100%) 30 (22%)

13 SBRT Platform: CyberKnife System Real-time tracking implanted fiducials, correction for both translational & rotational motion Non-isocentric treatment, approx beams

14 Treatment Planning MRI fusion to assist target localization Prostate prescribed 8Gy x 5 = 40Gy: EQD 2,α/β=2 = 100Gy 2 nd Rx of 7.25Gy x 5 to: Low-risk: Prostate + 3-5mm Interm-risk pts: Prostate + 2cm seminal vesicles + 3-5mm

15 Normal Tissue Constraints Structure Constraint Revised Constraint Rectum V36Gy < 1cc Bowel V30Gy < 1cc Bladder V37Gy < 5-10cc V37Gy < 2cc Penile bulb D50 < 29.5Gy Prostatic urethra* D20 < 47Gy D20 < 42Gy Membranous urethra* D50 < 37Gy Neurovascular bundles* D50 < 38Gy D50 < 37.5Gy Testes no beams may traverse *if visualized

16 Assessments & Follow Up Toxicities were assessed using CTCAE v3 criteria Patient-reported quality of life outcomes were assessed with the EPIC-26 Actuarial survival outcomes were calculated using Kaplan Meier methods. Median follow-up was 61 months.

17 No Gr 4-5 toxicities RESULTS: Safety Five grade 3 side effects occurred in 4 pts, far below the 10% rate considered excessive: In low-risk group: Two pts (1.2%) had 3 Gr3 toxicities, p<0.001 In interm-risk group: Two pts (1.5%) had 2 Gr3 toxicities, p<0.001

18 Toxicities All grade 3 toxicities were GU and occurred between 11 and 51 months after treatment: Hematuria requiring cystoscopy in 2 pts Urinary obstruction & associated infection Bladder/ureter injury requiring ureteral stent Five patients (1.6%) developed urinary retention which required a temporary catheter placement. Seven patients were diagnosed with bladder cancers between 21 and 50 months after treatment.

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25 Patient-reported QoL Assessments Expanded Prostate Cancer Index Composite, short form (EPIC-26): a validated questionnaire for patient-reported QOL in multiple domains affected by prostate cancer treatment: Urinary (incontinence & irritation/obstruction) Bowel Sexual AUA Symptom Index

26 EPIC Urinary Incontinence Score 100 Mean EPIC Score Clinically relevant change: > ½ σ from baseline score NO clinically relevant changes Months # Responses

27 EPIC Urinary Irritative Score 100 Mean EPIC Score month & 1 year Clinically relevant Months # Responses

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29 Epic Bowel Score 100 Mean EPIC Score month: clinically relevant Months # Responses

30 EPIC Urinary Incontinence Score External Beam RT LDR Brachytherapy Sanda M. Quality of Life and Satisfaction with Outcome among Prostate-Cancer Survivors. N Engl J Med 2008;358:1250

31 EPIC Urinary Irritation or Obstruction Score External Beam RT LDR Brachytherapy Sanda M. Quality of Life and Satisfaction with Outcome among Prostate-Cancer Survivors. N Engl J Med 2008;358:1250

32 EPIC Bowel Score External Beam RT LDR Brachytherapy Sanda M. Quality of Life and Satisfaction with Outcome among Prostate-Cancer Survivors. N Engl J Med 2008;358:1250

33 All Patients: Overall Survival

34 All Patients: Relapse Free Survival (Nadir +2)

35 Low-risk Patients 5-yr Nadir+2 Disease-Free Survival 93% expected from EBRT historical controls 97.3% SBRT rate proved superior to historic comparison P=0.014 ASTRO definition = 92.3%

36 Intermediate-risk Patients 5-yr Nadir+2 Disease-Free Survival ASTRO definition = 91.3%

37 Conclusions Using the CyberKnife platform, dose-escalated prostate SBRT is safe, with a low rate of serious side effects. QOL outcomes show a brief acute effect on GI & GU QOL; Urinary irritative symptoms at 1 year resolve 5-year biochemical relapse rates following SBRT are very favorable compared to historical data CyberKnife SBRT is a suitable option for low- and intermediate-risk prostate cancer, and may be preferable to other treatment approaches.