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Five Year Results of a Randomized External Beam Radiotherapy Hypofractionation Trial for Prostate Cancer
Proceedings of the 53rd Annual ASTRO Meeting
SCIENTIFIC ABSTRACTS
1
Five Year Results of a Randomized External Beam Radiotherapy Hypofractionation Trial for Prostate Cancer
A. Pollack1, G. Walker1, M. Buyyounouski2, E. Horwitz2, R. Price2, S. Feigenberg3, A. Konski4, R. Stoyanova1, C. Ma2 1 University of Miami Miller School of Medicine, Miami, FL, 2Fox Chase Cancer Center, Philadelphia, PA, 3University of Maryland, Baltimore, MD, 4Wayne State University, Detroit, MI Purpose/Objective(s): Based on the assumption that the a/b ratio for prostate cancer is low at 1.5 Gy, a randomized trial was devised with a dose escalation strategy. We hypothesized that using hypofractionation to deliver the equivalent of an 8 Gy difference in 2 Gy fractions would significantly improve biochemical failure (BF) without increasing bladder or rectal side effects. The trial compared 76 Gy in conventional 2.0 Gy fractions (CIMRT) to 70.2 Gy in 2.7 Gy fractions (HIMRT), which was estimated to be equivalent to 84.4 Gy in 2.0 Gy fractions. The results of a planned analysis are described. Materials/Methods: There were 303 of 307 (goal 300) assessable patients entered between 2002 and 2006. Of these, 152 were assigned to receive CIMRT and 151 to receive HIMRT. Median follow-up for those alive is greater than 60 months in both arms. The rates of BF using the Nadir+2 ng/mL definition and clinical failure, consisting of either local-regional failure or distant metastasis (LRF/DM), and death without failure were estimated by the method of cumulative incidence (CI) allowing for competing risk. Patients without failure who died more than 6.5 months after last PSA assessment were censored at the time of last PSA follow-up. Only patients who died within 6.5 months of last the PSA assessment were treated as competing risk events at the time of death. Grey’s test was used to compare CI rates by treatment arm. Results: No significant differences were seen between the treatment arms in terms of the distribution of patients by T-category, Gleason score, pretreatment initial PSA, use of androgen deprivation therapy (ADT) or length of ADT. There were 41 BFs with 20 in the CIMRT group and 21 in the HIMRT group. Six BFs occurred within 6.5 months of either LRF or DM, with the earliest event time used as failure time. Competing risk events are comprised of 1 LRF, 2 DM, and 4 deaths. The 5-year CI rates of BF were 14.4% (95% CI, 8.8 – 21.5%) for CIMRT, and 13.9% (95% CI, 8.4 – 20.9%) for HIMRT. Rates for LRF/DM were 1.0% and 1.3% for CIMRT and HIMRT at 5 years. Considering any failure, the 5-year CI rates for CIMRT were 15.4% (95% CI, 9.5 – 22.7%) and 15.3% (95% CI, 9.5 – 22.4%) for HIMRT. There were no statistically significant differences in late toxicity between the arms. The Grade 2 or higher toxicities for the CIMRT and HIMRT arms were 8.9 and 13.8 (p = 0.2) for GU and 4.1 and 5.9% (p = 0.5) for GI. Conclusions: The anticipated failure rate of 15% in the HIMRT arm was accurate, but fewer failures were seen in the CIMRT arm at the time of this planned analysis. With a median follow-up of 5 years, there remain no statistically significant differences between the treatment arms in terms of BF, any failure, or late side effects. HIMRT is a reasonable option for men with intermediate to high-risk prostate cancer. Author Disclosure: A. Pollack: None. G. Walker: None. M. Buyyounouski: None. E. Horwitz: None. R. Price: None. S. Feigenberg: None. A. Konski: None. R. Stoyanova: None. C. Ma: None.
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Preliminary Analysis of 3D-CRT vs. IMRT on the High Dose Arm of the RTOG 0126 Prostate Cancer Trial: Toxicity Report
J. M. Michalski1, Y. Yan2, D. Watkins-Bruner3, B. Walter1, K. Winter2, J. M. Galvin4, J. Bahary5, G. C. Morton6, M. B. Parliament7, H. Sandler8 1 Washington University Medical Center, St. Louis, MO, 2RTOG Statistical Center, Philadelphia, PA, 3University of Pennsylvania School of Nursing, Philadelphia, PA, 4Thomas Jefferson University Hospital, Philadelphia, PA, 5Centre Hospitalier de l‘Universite de Montreal-Notre Dame, Montreal, QC, Canada, 6Toronto-Sunnybrook Regional Cancer Centre, Toronto, ON, Canada, 7Cross Cancer Institute, Edmonton, AB, Canada, 8Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA
Purpose/Objective(s): A preliminary analysis of clinical and treatment characteristics associated with acute and late toxicity in men receiving high dose RT on a Phase III RTOG dose escalation trial. Materials/Methods: The trial started with 3D-CRT and amended after 1 year to allow IMRT. Patients treated with 3D-CRT received 55.8 Gy to a PTV that included the prostate and proximal seminal vesicles (P+pSV) followed by a 23.4 Gy to prostate only. IMRT patients were treated to the P+pSV to 79.2 Gy. CTC v 2.0 and the RTOG/EORTC late morbidity scores were used for acute and late effects. Univariate and multivariate comparisons for acute effects were done with chi-squared and logistic regression; time to late effects with Gray’s test and the Fine-Gray method. Results: Seven hundred forty-eight of 763 patients randomized to the 79.2 Gy arm of RTOG 0126 were eligible and evaluable. Four hundred ninety-one and 257 patients were treated with 3D-CRT and IMRT, respectively. Median follow-up was 4.6 years and 3.5 years for 3D-CRT and IMRT patients. Median D98 delivered to the PTV7920 was 80 Gy for 3D-CRT and 79.2 Gy for IMRT. The median percentage of the bladder receiving at least x Gy (pVx) for pV65, pV70, and pV75 were 25.3%, 22.2%, and 17.7%, respectively, for 3D-CRT, and 19.7%, 16.6%, and 13.1%, respectively, for IMRT. The median rectum pV65, pV70, and pV75 were 27.4%, 21.7%, and 15.8% for 3D-CRT and 23.0%, 18.2%, and 13.0% for IMRT. For both bladder and rectum, the pVx was significantly lower with IMRT for 65, 70, and 75 Gy (all p \ 0.0001). Acute toxicity; there are 16.9% Grade (G2), 2.5% G3, and no G4 or 5 in the 3D-CRT group; there are 13.9% G2, 2.4% G3, 0.4% G4, and no G5 in the IMRT group. Late toxicity; there are 23.6% G2, 8.9% G3, 0.4% G4, and 0.2% G5 (1 death) with 3D-CRT group; there are 19.9% G2, 4.7% G3, 0.4% G4, and no G5 with IMRT. For G2+ acute GI/GU toxicity, both univariate and multivariate analyses show a statistically significant decrease in G2+ acute collective GI/GU toxicity for IMRT. There are no significant differences with 3D-CRT or IMRT for acute or late, G2+ or 3+ GU toxicities. Despite a small number of events, univariate analysis shows a statistically significant decrease in late G2+ GI toxicity for IMRT (p = 0.039). On multivariate analysis, IMRT shows a trend for a 26% reduction in G2+ late GI toxicity (p = 0.099). Acute G3+ toxicity was significantly associated with late G3+ toxicity. With DVH data in the multivariate analysis, RT modality is not significant whereas white race and a percentage of rectal V70 . = 15% are significantly associated with G2+ rectal toxicity.
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SCIENTIFIC ABSTRACTS
1
Five Year Results of a Randomized External Beam Radiotherapy Hypofractionation Trial for Prostate Cancer
A. Pollack1, G. Walker1, M. Buyyounouski2, E. Horwitz2, R. Price2, S. Feigenberg3, A. Konski4, R. Stoyanova1, C. Ma2 1 University of Miami Miller School of Medicine, Miami, FL, 2Fox Chase Cancer Center, Philadelphia, PA, 3University of Maryland, Baltimore, MD, 4Wayne State University, Detroit, MI Purpose/Objective(s): Based on the assumption that the a/b ratio for prostate cancer is low at 1.5 Gy, a randomized trial was devised with a dose escalation strategy. We hypothesized that using hypofractionation to deliver the equivalent of an 8 Gy difference in 2 Gy fractions would significantly improve biochemical failure (BF) without increasing bladder or rectal side effects. The trial compared 76 Gy in conventional 2.0 Gy fractions (CIMRT) to 70.2 Gy in 2.7 Gy fractions (HIMRT), which was estimated to be equivalent to 84.4 Gy in 2.0 Gy fractions. The results of a planned analysis are described. Materials/Methods: There were 303 of 307 (goal 300) assessable patients entered between 2002 and 2006. Of these, 152 were assigned to receive CIMRT and 151 to receive HIMRT. Median follow-up for those alive is greater than 60 months in both arms. The rates of BF using the Nadir+2 ng/mL definition and clinical failure, consisting of either local-regional failure or distant metastasis (LRF/DM), and death without failure were estimated by the method of cumulative incidence (CI) allowing for competing risk. Patients without failure who died more than 6.5 months after last PSA assessment were censored at the time of last PSA follow-up. Only patients who died within 6.5 months of last the PSA assessment were treated as competing risk events at the time of death. Grey’s test was used to compare CI rates by treatment arm. Results: No significant differences were seen between the treatment arms in terms of the distribution of patients by T-category, Gleason score, pretreatment initial PSA, use of androgen deprivation therapy (ADT) or length of ADT. There were 41 BFs with 20 in the CIMRT group and 21 in the HIMRT group. Six BFs occurred within 6.5 months of either LRF or DM, with the earliest event time used as failure time. Competing risk events are comprised of 1 LRF, 2 DM, and 4 deaths. The 5-year CI rates of BF were 14.4% (95% CI, 8.8 – 21.5%) for CIMRT, and 13.9% (95% CI, 8.4 – 20.9%) for HIMRT. Rates for LRF/DM were 1.0% and 1.3% for CIMRT and HIMRT at 5 years. Considering any failure, the 5-year CI rates for CIMRT were 15.4% (95% CI, 9.5 – 22.7%) and 15.3% (95% CI, 9.5 – 22.4%) for HIMRT. There were no statistically significant differences in late toxicity between the arms. The Grade 2 or higher toxicities for the CIMRT and HIMRT arms were 8.9 and 13.8 (p = 0.2) for GU and 4.1 and 5.9% (p = 0.5) for GI. Conclusions: The anticipated failure rate of 15% in the HIMRT arm was accurate, but fewer failures were seen in the CIMRT arm at the time of this planned analysis. With a median follow-up of 5 years, there remain no statistically significant differences between the treatment arms in terms of BF, any failure, or late side effects. HIMRT is a reasonable option for men with intermediate to high-risk prostate cancer. Author Disclosure: A. Pollack: None. G. Walker: None. M. Buyyounouski: None. E. Horwitz: None. R. Price: None. S. Feigenberg: None. A. Konski: None. R. Stoyanova: None. C. Ma: None.
2
Preliminary Analysis of 3D-CRT vs. IMRT on the High Dose Arm of the RTOG 0126 Prostate Cancer Trial: Toxicity Report
J. M. Michalski1, Y. Yan2, D. Watkins-Bruner3, B. Walter1, K. Winter2, J. M. Galvin4, J. Bahary5, G. C. Morton6, M. B. Parliament7, H. Sandler8 1 Washington University Medical Center, St. Louis, MO, 2RTOG Statistical Center, Philadelphia, PA, 3University of Pennsylvania School of Nursing, Philadelphia, PA, 4Thomas Jefferson University Hospital, Philadelphia, PA, 5Centre Hospitalier de l‘Universite de Montreal-Notre Dame, Montreal, QC, Canada, 6Toronto-Sunnybrook Regional Cancer Centre, Toronto, ON, Canada, 7Cross Cancer Institute, Edmonton, AB, Canada, 8Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA
Purpose/Objective(s): A preliminary analysis of clinical and treatment characteristics associated with acute and late toxicity in men receiving high dose RT on a Phase III RTOG dose escalation trial. Materials/Methods: The trial started with 3D-CRT and amended after 1 year to allow IMRT. Patients treated with 3D-CRT received 55.8 Gy to a PTV that included the prostate and proximal seminal vesicles (P+pSV) followed by a 23.4 Gy to prostate only. IMRT patients were treated to the P+pSV to 79.2 Gy. CTC v 2.0 and the RTOG/EORTC late morbidity scores were used for acute and late effects. Univariate and multivariate comparisons for acute effects were done with chi-squared and logistic regression; time to late effects with Gray’s test and the Fine-Gray method. Results: Seven hundred forty-eight of 763 patients randomized to the 79.2 Gy arm of RTOG 0126 were eligible and evaluable. Four hundred ninety-one and 257 patients were treated with 3D-CRT and IMRT, respectively. Median follow-up was 4.6 years and 3.5 years for 3D-CRT and IMRT patients. Median D98 delivered to the PTV7920 was 80 Gy for 3D-CRT and 79.2 Gy for IMRT. The median percentage of the bladder receiving at least x Gy (pVx) for pV65, pV70, and pV75 were 25.3%, 22.2%, and 17.7%, respectively, for 3D-CRT, and 19.7%, 16.6%, and 13.1%, respectively, for IMRT. The median rectum pV65, pV70, and pV75 were 27.4%, 21.7%, and 15.8% for 3D-CRT and 23.0%, 18.2%, and 13.0% for IMRT. For both bladder and rectum, the pVx was significantly lower with IMRT for 65, 70, and 75 Gy (all p \ 0.0001). Acute toxicity; there are 16.9% Grade (G2), 2.5% G3, and no G4 or 5 in the 3D-CRT group; there are 13.9% G2, 2.4% G3, 0.4% G4, and no G5 in the IMRT group. Late toxicity; there are 23.6% G2, 8.9% G3, 0.4% G4, and 0.2% G5 (1 death) with 3D-CRT group; there are 19.9% G2, 4.7% G3, 0.4% G4, and no G5 with IMRT. For G2+ acute GI/GU toxicity, both univariate and multivariate analyses show a statistically significant decrease in G2+ acute collective GI/GU toxicity for IMRT. There are no significant differences with 3D-CRT or IMRT for acute or late, G2+ or 3+ GU toxicities. Despite a small number of events, univariate analysis shows a statistically significant decrease in late G2+ GI toxicity for IMRT (p = 0.039). On multivariate analysis, IMRT shows a trend for a 26% reduction in G2+ late GI toxicity (p = 0.099). Acute G3+ toxicity was significantly associated with late G3+ toxicity. With DVH data in the multivariate analysis, RT modality is not significant whereas white race and a percentage of rectal V70 . = 15% are significantly associated with G2+ rectal toxicity.
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