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Outcomes in Men with Large Prostates (≥60 g) Treated with Definitive Proton Therapy for Prostate Cancer
I. J. Radiation Oncology d Biology d Physics
S210
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Volume 81, Number 2, Supplement, 2011
Outcomes in Men with Large Prostates ($60 g) Treated with Definitive Proton Therapy for Prostate Cancer
L. A. McGee1, B. S. Hoppe1, R. Henderson1, C. G. Morris1, R. Nichols1, R. B. Marcus1, Z. Li1, W. M. Mendenhall1, C. Williams2, N. P. Mendenhall1 1
University of Florida Proton Therapy Institute, Jacksonville, FL, 2University of Florida, Jacksonville, FL
Purpose/Objective(s): Men with large prostates are at high risk of genitourinary (GU) and gastrointestinal (GI) toxicities after definitive radiotherapy for prostate cancer. Therefore, they may undergo cytoreduction with androgen deprivation therapy (ADT) before treatment, which negatively impacts their quality of life. Proton therapy (PT) can reduce the radiation dose to the nontargeted rectum and bladder and may obviate the need for cytoreduction. This is a retrospective study of the toxicity profile of men with large prostates ($ 60 g) following definitive PT for prostate cancer. Materials/Methods: From 2006 to 2010, 190 men with prostates $ 60 g were treated with definitive PT (median dose, 78 CGE) for low- (46%), intermediate- (37%), and high-risk (17%) prostate cancer at our institution. The median age of patients was 70 years, the median prostate size was 76 g (range, 60 – 143g), and pretreatment International Prostate Symptom Score (IPSS) was . 15 in 27%. Before PT, 51% were treated for obstructive symptoms with $ 1 of the following: transurethral resection of the prostate (TURP; 9.5%) or medical management (MM) with a blockers (32%), 5 a-reductase inhibitors (15%), and/or saw palmetto (12%). Also, 33 men received ADT (14 for cytoreduction). Toxicity was assessed per CTCAE v3.0 weekly during PT and then every 6 months. Prostate-specific antigen (PSA) was evaluated every 3 months. Results: The median follow-up was 21 months and 2-year Phoenix-defined biochemical failure-free survival was 99%. Grade (GR) 3 GU toxicities occurred in 14 men, including temporary catheterization (n = 7), TURP (n = 6), and balloon dilation for urethral stricture (n = 1). The 6-, 12-, and 24-month cumulative incidence of GR 3 GU toxicity was 0.5%, 4.1%, and 7.2%. The median change in IPSS at 6, 12, and 24 months was 8, 11, and 7.5. On univariate analysis, prostate size . 76 g, pretreatment TURP, and pretreatment MM with a blockers or 5 a-reductase inhibitors were all associated with an increased risk of GR 3 GU toxicities. On multivariate analysis (MVA) of prostate size, dose, ADT, and pretreatment IPSS, MM, and TURP, only pretreatment MM (p = 0.0061) and pretreatment TURP (p = 0.0002) were significantly predictive of GR 3 GU toxicity during or after PT. In the cohort who did not receive neoadjuvant ADT or TURP, GR 3 late GU toxicity was 4%. One man experienced GR 3 GI toxicity and 12 men had GR 2 GI toxicities. The 6-, 12-, and 24-month incidence of GR 2+ GI toxicity was 0.5%, 6.2%, and 10.3%. On MVA, an association between dose . 78 CGE and an increased risk of Grade 2+ GI toxicities approached significance (p = 0.058). Conclusions: Cytoreduction with ADT in men with large prostates may not be necessary before PT treatment considering the acceptably low rates of GU and GI toxicities in this study. Longer follow-up is needed to confirm these results. Author Disclosure: L.A. McGee: None. B.S. Hoppe: None. R. Henderson: None. C.G. Morris: None. R. Nichols: None. R.B. Marcus: None. Z. Li: None. W.M. Mendenhall: None. C. Williams: None. N.P. Mendenhall: None.
1113
Predictors of Acute Toxicity after Stereotactic Body Radiation Therapy for Low and Intermediate-risk Prostate Cancer: Secondary Analysis of a Phase I Trial
D. S. Hong1, J. H. Heinzerling1, Y. Lotan1, L. C. Cho2, J. Brindle3, X. Xie1, D. Pistenmaa1, S. Cooley1, T. Boike1, R. D. Timmerman1 1 University of Texas Southwestern Medical Center, Dallas, TX, 2University of Minnesota, Minneapolis, MN, 3Prairie Lakes Hospital, Watertown, SD
Purpose/Objective(s): To evaluate patient and dosimetric factors associated with toxicity and quality of life after stereotactic body radiation therapy (SBRT) for treatment of low and intermediate-risk prostate cancer. Materials/Methods: Eligible patients for a Phase I dose escalation trial met the following criteria: Gleason score (GS) 2 – 6 with PSA # 20, GS 7 with PSA # 15, # T2b, prostate size #60 cc, AUA score #15. Forty-five patients were treated in 5 fractions over 2 weeks. Doses were escalated from 45 Gy in 15 patients to 47.5 Gy in 15 patients and finally 50 Gy in 15 patients. Patients underwent pretreatment enemas and rectal balloon placement. Treatment was delivered using image guidance and intensity modulation. Patients completed EPIC and AUA questionnaires at defined intervals and adverse events were graded according to CTCAEv3. After the primary endpoint was reported, regression models were developed to evaluate the correlation of patient and dosimetric parameters with incidence and duration of Grade $ 2 toxicity, increase in AUA score $ 3, and increase in global EPIC bowel and urinary function. Actuarial rates of toxicity-free survival were estimated using the Kaplan-Meier method. Results: Median follow-up was 30 months (range, 6 – 46). Patient characteristics included: T1c 69%, T2a 14.5%, T2b, 16.4%, GS = 6 45.4%, GS = 7 (3+4) 32.7%, GS = 7 (4+3) 21.8%, and mean pre-treatment PSA of 5.5. For all patients, GI Grade $ 2 and Grade $ 3 toxicity occurred in 18% and 2% respectively. GU Grade $ 2 and Grade $ 3 toxicity occurred in 31% and 4% respectively. Incidence of GI and GU toxicity Grade $ 2 plateaued at 70 and 360 days respectively. Older age correlated with GU toxicity Grade $ 2 (p \ 0.05). Longer duration of GI toxicity was associated with higher minimum anterior rectal wall (p \ 0.03) and higher mean (p \ 0.01), and maximum (p \ 0.02) anal canal dose. Three month EPIC urinary scores were associated with higher mean penile bulb dose (p \ 0.04). Higher mean dose to the anterior rectal wall was associated with several toxicity endpoints including incidence of GI toxicity Grade $ 2 (p \ 0.01), increase in 6 week (p \ 0.03) and 3 month (p\0.01) EPIC bowel scores, and earlier incidence of GI toxicity (p\0.01). Maximum urethral dose was associated with longer duration of GU toxicity (p\0.03). Higher minimum (p\0.03) and mean (p\0.01) bladder wall dose were associated with AUA increase from baseline $ 3. Conclusions: Patients with localized prostate cancer were treated with SBRT doses up to 50 Gy without DLT. Several dosimetric parameters shown above correlated with toxicity endpoints in these patients and will be analyzed for possible inclusion into dose constraints for future trials of prostate SBRT. The Phase II portion of this multicenter study is accruing patients with the primary endpoint of 18-month late toxicity. Author Disclosure: D.S. Hong: None. J.H. Heinzerling: None. Y. Lotan: None. L.C. Cho: None. J. Brindle: None. X. Xie: None. D. Pistenmaa: None. S. Cooley: None. T. Boike: None. R.D. Timmerman: None.
S210
1112
Volume 81, Number 2, Supplement, 2011
Outcomes in Men with Large Prostates ($60 g) Treated with Definitive Proton Therapy for Prostate Cancer
L. A. McGee1, B. S. Hoppe1, R. Henderson1, C. G. Morris1, R. Nichols1, R. B. Marcus1, Z. Li1, W. M. Mendenhall1, C. Williams2, N. P. Mendenhall1 1
University of Florida Proton Therapy Institute, Jacksonville, FL, 2University of Florida, Jacksonville, FL
Purpose/Objective(s): Men with large prostates are at high risk of genitourinary (GU) and gastrointestinal (GI) toxicities after definitive radiotherapy for prostate cancer. Therefore, they may undergo cytoreduction with androgen deprivation therapy (ADT) before treatment, which negatively impacts their quality of life. Proton therapy (PT) can reduce the radiation dose to the nontargeted rectum and bladder and may obviate the need for cytoreduction. This is a retrospective study of the toxicity profile of men with large prostates ($ 60 g) following definitive PT for prostate cancer. Materials/Methods: From 2006 to 2010, 190 men with prostates $ 60 g were treated with definitive PT (median dose, 78 CGE) for low- (46%), intermediate- (37%), and high-risk (17%) prostate cancer at our institution. The median age of patients was 70 years, the median prostate size was 76 g (range, 60 – 143g), and pretreatment International Prostate Symptom Score (IPSS) was . 15 in 27%. Before PT, 51% were treated for obstructive symptoms with $ 1 of the following: transurethral resection of the prostate (TURP; 9.5%) or medical management (MM) with a blockers (32%), 5 a-reductase inhibitors (15%), and/or saw palmetto (12%). Also, 33 men received ADT (14 for cytoreduction). Toxicity was assessed per CTCAE v3.0 weekly during PT and then every 6 months. Prostate-specific antigen (PSA) was evaluated every 3 months. Results: The median follow-up was 21 months and 2-year Phoenix-defined biochemical failure-free survival was 99%. Grade (GR) 3 GU toxicities occurred in 14 men, including temporary catheterization (n = 7), TURP (n = 6), and balloon dilation for urethral stricture (n = 1). The 6-, 12-, and 24-month cumulative incidence of GR 3 GU toxicity was 0.5%, 4.1%, and 7.2%. The median change in IPSS at 6, 12, and 24 months was 8, 11, and 7.5. On univariate analysis, prostate size . 76 g, pretreatment TURP, and pretreatment MM with a blockers or 5 a-reductase inhibitors were all associated with an increased risk of GR 3 GU toxicities. On multivariate analysis (MVA) of prostate size, dose, ADT, and pretreatment IPSS, MM, and TURP, only pretreatment MM (p = 0.0061) and pretreatment TURP (p = 0.0002) were significantly predictive of GR 3 GU toxicity during or after PT. In the cohort who did not receive neoadjuvant ADT or TURP, GR 3 late GU toxicity was 4%. One man experienced GR 3 GI toxicity and 12 men had GR 2 GI toxicities. The 6-, 12-, and 24-month incidence of GR 2+ GI toxicity was 0.5%, 6.2%, and 10.3%. On MVA, an association between dose . 78 CGE and an increased risk of Grade 2+ GI toxicities approached significance (p = 0.058). Conclusions: Cytoreduction with ADT in men with large prostates may not be necessary before PT treatment considering the acceptably low rates of GU and GI toxicities in this study. Longer follow-up is needed to confirm these results. Author Disclosure: L.A. McGee: None. B.S. Hoppe: None. R. Henderson: None. C.G. Morris: None. R. Nichols: None. R.B. Marcus: None. Z. Li: None. W.M. Mendenhall: None. C. Williams: None. N.P. Mendenhall: None.
1113
Predictors of Acute Toxicity after Stereotactic Body Radiation Therapy for Low and Intermediate-risk Prostate Cancer: Secondary Analysis of a Phase I Trial
D. S. Hong1, J. H. Heinzerling1, Y. Lotan1, L. C. Cho2, J. Brindle3, X. Xie1, D. Pistenmaa1, S. Cooley1, T. Boike1, R. D. Timmerman1 1 University of Texas Southwestern Medical Center, Dallas, TX, 2University of Minnesota, Minneapolis, MN, 3Prairie Lakes Hospital, Watertown, SD
Purpose/Objective(s): To evaluate patient and dosimetric factors associated with toxicity and quality of life after stereotactic body radiation therapy (SBRT) for treatment of low and intermediate-risk prostate cancer. Materials/Methods: Eligible patients for a Phase I dose escalation trial met the following criteria: Gleason score (GS) 2 – 6 with PSA # 20, GS 7 with PSA # 15, # T2b, prostate size #60 cc, AUA score #15. Forty-five patients were treated in 5 fractions over 2 weeks. Doses were escalated from 45 Gy in 15 patients to 47.5 Gy in 15 patients and finally 50 Gy in 15 patients. Patients underwent pretreatment enemas and rectal balloon placement. Treatment was delivered using image guidance and intensity modulation. Patients completed EPIC and AUA questionnaires at defined intervals and adverse events were graded according to CTCAEv3. After the primary endpoint was reported, regression models were developed to evaluate the correlation of patient and dosimetric parameters with incidence and duration of Grade $ 2 toxicity, increase in AUA score $ 3, and increase in global EPIC bowel and urinary function. Actuarial rates of toxicity-free survival were estimated using the Kaplan-Meier method. Results: Median follow-up was 30 months (range, 6 – 46). Patient characteristics included: T1c 69%, T2a 14.5%, T2b, 16.4%, GS = 6 45.4%, GS = 7 (3+4) 32.7%, GS = 7 (4+3) 21.8%, and mean pre-treatment PSA of 5.5. For all patients, GI Grade $ 2 and Grade $ 3 toxicity occurred in 18% and 2% respectively. GU Grade $ 2 and Grade $ 3 toxicity occurred in 31% and 4% respectively. Incidence of GI and GU toxicity Grade $ 2 plateaued at 70 and 360 days respectively. Older age correlated with GU toxicity Grade $ 2 (p \ 0.05). Longer duration of GI toxicity was associated with higher minimum anterior rectal wall (p \ 0.03) and higher mean (p \ 0.01), and maximum (p \ 0.02) anal canal dose. Three month EPIC urinary scores were associated with higher mean penile bulb dose (p \ 0.04). Higher mean dose to the anterior rectal wall was associated with several toxicity endpoints including incidence of GI toxicity Grade $ 2 (p \ 0.01), increase in 6 week (p \ 0.03) and 3 month (p\0.01) EPIC bowel scores, and earlier incidence of GI toxicity (p\0.01). Maximum urethral dose was associated with longer duration of GU toxicity (p\0.03). Higher minimum (p\0.03) and mean (p\0.01) bladder wall dose were associated with AUA increase from baseline $ 3. Conclusions: Patients with localized prostate cancer were treated with SBRT doses up to 50 Gy without DLT. Several dosimetric parameters shown above correlated with toxicity endpoints in these patients and will be analyzed for possible inclusion into dose constraints for future trials of prostate SBRT. The Phase II portion of this multicenter study is accruing patients with the primary endpoint of 18-month late toxicity. Author Disclosure: D.S. Hong: None. J.H. Heinzerling: None. Y. Lotan: None. L.C. Cho: None. J. Brindle: None. X. Xie: None. D. Pistenmaa: None. S. Cooley: None. T. Boike: None. R.D. Timmerman: None.