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Radiation Therapy-Induced Castration in Men With Advanced Prostate Cancer: Results of a Prospective Phase 1 Study
Poster Viewing Abstracts S457
Volume 90 Number 1S Supplement 2014 median d90, v150, v200, and R100 were 103.3%, 59.4%, 30.1%, and 0.5cc. Supplemental external beam radiation therapy (EBRT) was administered to 33.5% of patients before implant. The overall rates of grade 2 and 3 urinary toxicities were 23.2% and 0.4%, and grade 2 and 3 rectal toxicities were 6.9% and 2.9%, respectively. Six out of the 7 patients with a grade 3 rectal toxicity received EBRT. Severe radiation toxicities leading to an abdominoperineal resection and suprapubic catheter occurred in only one patient at 1.3 years, and another at 1.8 years, respectively. No patients required a cystectomy. After the initial 5 years, new grade 2 urinary and rectal toxicities occurred in 5.7% and 0.4% of patients, whereas there were no new grade 3 urinary or rectal toxicities. Conclusions: The Veterans Healthcare Administration CPRS captures indefinite follow-up clinical encounters for almost all patients treated in this integrated healthcare system. These records provide an accurate resource for studying late radiation toxicities. Beyond the typical 5 years of followup after prostate brachytherapy, grade 2 toxicities are rare, and grade 3 toxicities even less common. Author Disclosure: D. Asher: None. D. Moghanaki: None. N. Serrano: None. J. Karlin: None. M. Schutzer: None. M. Chang: None. M.P. Hagan: None.
2621 Radiation Therapy-Induced Castration in Men With Advanced Prostate Cancer: Results of a Prospective Phase 1 Study S. Faria, F. Cury, M. Duclos, and L. Souhami; McGill University, Montreal, QC, Canada Purpose/Objective(s): Testicles have a double function: production of spermatozoids (exocrine) and production of sexual hormones (endocrine). The exocrine function is sensitive to low doses of radiation, but the dose/ fractionation to stop the endocrine function is unknown. To our knowledge, there are no prospective studies on the use of radiation with the intent of castration in men. We present the results of a prospective phase I study where radiation was used to induce testicular castration in prostate cancer patients. Materials/Methods: Advanced prostate cancer patients with indication for long term castration were eligible. Treatment started with one LHRH injection followed by scrotal irradiation. Two regimens were initially designed to be tested: 17 Gy in 2 fractions (days 1 and 7), and 24 Gy in 3 fractions (days 1, 7 and 21). Radiation therapy was given with direct 6 MV photons to scrotum, with 0.5 cm bolus, at the given dose. Skin toxicity was prospectively scored according to CTCv3 system. Blood tests, performed before, one month and every 3 months after the scrotal irradiation included testosterone, FSH, LH, estradiol and PSA. All patients had at least one year of follow up after scrotal irradiation. This was an IRB approved study. All patients signed a consent form. Results: The first 3 patients treated in 2009 received 17 Gy/2 fractions, had median age of 65 years. None of them developed acute or late skin toxicity. None of them became castrated at 12, 24 and 36 months post-radiation therapy. Another 4 patients received 24 Gy/3 fractions in 2011. Their median age was 70 years. Two developed grade 1 dermatitis for few weeks. They were followed between 17 and 24 months and again none became castrated, presenting normal levels of testosterone during follow-up. Conclusions: Prospective studies on this topic are difficult and time consuming. The two RT regimens used in this study were well tolerated but not capable of causing castration at 12-36 months of follow up in men with prostate cancer. The optimal RT dose to induce castration in men remains to be determined. Author Disclosure: S. faria: None. F. Cury: None. M. Duclos: None. L. Souhami: None.
2622 Recently Updated Preliminary Results of an On-Going Phase 1/2 Trial Using Trimodality Therapy in Patients With Postprostatectomy High-Risk Pathologic (p) T2-3N0M0 Prostate Cancer P. Kumar,1 P.V. Veldhuizen,1 M. Thompson,1 X. Shen,1 J. Coster,1 and J. Pinski2; 1University of Kansas School of Medicine, Kansas City, KS,
2
University of Southern California Keck School of Medicine, Los Angeles, CA Purpose/Objective(s): We present the recently updated preliminary results of an on-going phase I / II trial with the purpose of determining the safety, feasibility and efficacy of post-prostatectomy radiation therapy (RT), hormonal therapy and concurrent docetaxel in patients with high risk pathologic (p) T2-3N0M0 prostate cancer. Materials/Methods: Post-prostatectomy high risk prostate cancer was defined as clinically non-metastatic disease with either an undetectable, persistent or rising PSA with 1 or more of the following clinical-pathologic features: (1) pT2-T3aN0 disease, positive or negative margins, with either (a) a gleason score (GS) of 8, and/or (b) a PSA doubling time of 10 months, and/or (c) with a pre-RT PSA of 1.0 ng/ml; and/or (2) pT3bN0 disease. The tri-modality treatment consisted of 6 months of hormonal therapy [Casodex (50 mg po daily), and Zoladex (10.8 mg sc q 3 mos x 2) or Lupron (22.5 mg im q 3 mos x 2)], RT to 66.0 Gy at 2.0 Gy/fraction (fx) once daily (50 Gy to the surgical bed followed by a 16 Gy Boost at 2.0 Gy/ fx using either 3-D conformal radiation therapy or IMRT, usually begun after 2 months of hormonal therapy), and concurrent weekly docetaxel at 20 mg/m2 x 7 infusions. Results: Between October 2008 and February 2014, a total of 26 patients have been enrolled to this on-going phase I/II clinical trial. The clinical and disease characteristics of these 26 patients are as follows: Median age, years (range) Z 63 (56 - 74); GS was as follows: 3+3 Z 6 in 1 patient, 3+4 Z 7 in 6 patients, 4+3 Z 7 in 5, 3+5 Z 8 in 3, 4+4 Z 8 in 3, 4+5 Z 9 in 5 and 5+4 Z 9 in 3; resection margin was negative in 10 patients, close in 2 and positive in 14; extracapsular extension was absent in 8 patients, and present in 18; seminal vesicle invasion was present in 12 patients and absent in 14; and pathologic T-stage was as follows: pT2a Z 2 patients, pT2c Z 5, pT3a Z 8 and pT3b Z 11. Nine patients are in the adjuvant RT category while the remaining 17 are in the salvage RT category. Eighteen of the 26 enrolled patients have completed their entire tri-modality therapy. All of these 18 patients completed their full dose of RT (66 Gy). These 18 patients also received a median of 7 weekly docetaxel infusions (range Z 5 - 8). Only 2 of these 18 patients experienced grade 3 GI possibly treatment-related acute toxicity, both of whom were on stool softners and / or laxatives preceding their grade 3 diarrhea. Among the 8 of 26 remaining patients, 2 of the 8 have completed their entire chemoradiation therapy treatments without any acute grade 3 GI / GU toxicity while the other 6 recently started their protocol therapy. Conclusions: The recently updated preliminary results of our on-going phase I/II clinical trial with an accrual goal of 40 patients indicate that our post-prostatectomy tri-modality therapy is well tolerated with a very high feasibility rate in patients with high risk pT2-3N0M0 prostate cancer. Author Disclosure: P. Kumar: None. P.V. Veldhuizen: None. M. Thompson: None. X. Shen: None. J. Coster: None. J. Pinski: None.
2623 Dosimetric Correlates for Acute Toxicity in Prostate Cancer Treated With Hypofractionated Radiation Therapy: Absolute Volumes Are Better Predictors Than Relative Volumes M. Arunsingh, S. Sarkar, S. Das, S. Prasath, P. Dharmendran, and I. Mallick; Tata Medical Centre, Kolkata, India Purpose/Objective(s): Hypofractionated radiation therapy is becoming a widely accepted approach in the treatment of prostate cancer. This retrospective study reports acute toxicity and the dosimetric correlates of a cohort of patients treated at a single centre in India. Materials/Methods: One hundred one patients with localized prostate cancer were treated with image guided intensity modulated radiation therapy (IG- IMRT) between July 2011 and Jan 2014. Two different fractionation schedules were used, with 65Gy/25Fr/ 5 weeks being used in the first 18 patients (EQD2 76Gy a/b Z 1.5) and the subsequent 83 being treated with 60Gy/20Fr/4 weeks schedule(77.2Gy a/b Z 1.5). Majority of them (n Z 83, 83.2%) had high risk or pelvic node positive disease and received elective pelvic nodal irradiation (44Gy/20Fr or 45 Gy/25Fr) using a single phase plan with simultaneous integrated boost to the prostate and
Volume 90 Number 1S Supplement 2014 median d90, v150, v200, and R100 were 103.3%, 59.4%, 30.1%, and 0.5cc. Supplemental external beam radiation therapy (EBRT) was administered to 33.5% of patients before implant. The overall rates of grade 2 and 3 urinary toxicities were 23.2% and 0.4%, and grade 2 and 3 rectal toxicities were 6.9% and 2.9%, respectively. Six out of the 7 patients with a grade 3 rectal toxicity received EBRT. Severe radiation toxicities leading to an abdominoperineal resection and suprapubic catheter occurred in only one patient at 1.3 years, and another at 1.8 years, respectively. No patients required a cystectomy. After the initial 5 years, new grade 2 urinary and rectal toxicities occurred in 5.7% and 0.4% of patients, whereas there were no new grade 3 urinary or rectal toxicities. Conclusions: The Veterans Healthcare Administration CPRS captures indefinite follow-up clinical encounters for almost all patients treated in this integrated healthcare system. These records provide an accurate resource for studying late radiation toxicities. Beyond the typical 5 years of followup after prostate brachytherapy, grade 2 toxicities are rare, and grade 3 toxicities even less common. Author Disclosure: D. Asher: None. D. Moghanaki: None. N. Serrano: None. J. Karlin: None. M. Schutzer: None. M. Chang: None. M.P. Hagan: None.
2621 Radiation Therapy-Induced Castration in Men With Advanced Prostate Cancer: Results of a Prospective Phase 1 Study S. Faria, F. Cury, M. Duclos, and L. Souhami; McGill University, Montreal, QC, Canada Purpose/Objective(s): Testicles have a double function: production of spermatozoids (exocrine) and production of sexual hormones (endocrine). The exocrine function is sensitive to low doses of radiation, but the dose/ fractionation to stop the endocrine function is unknown. To our knowledge, there are no prospective studies on the use of radiation with the intent of castration in men. We present the results of a prospective phase I study where radiation was used to induce testicular castration in prostate cancer patients. Materials/Methods: Advanced prostate cancer patients with indication for long term castration were eligible. Treatment started with one LHRH injection followed by scrotal irradiation. Two regimens were initially designed to be tested: 17 Gy in 2 fractions (days 1 and 7), and 24 Gy in 3 fractions (days 1, 7 and 21). Radiation therapy was given with direct 6 MV photons to scrotum, with 0.5 cm bolus, at the given dose. Skin toxicity was prospectively scored according to CTCv3 system. Blood tests, performed before, one month and every 3 months after the scrotal irradiation included testosterone, FSH, LH, estradiol and PSA. All patients had at least one year of follow up after scrotal irradiation. This was an IRB approved study. All patients signed a consent form. Results: The first 3 patients treated in 2009 received 17 Gy/2 fractions, had median age of 65 years. None of them developed acute or late skin toxicity. None of them became castrated at 12, 24 and 36 months post-radiation therapy. Another 4 patients received 24 Gy/3 fractions in 2011. Their median age was 70 years. Two developed grade 1 dermatitis for few weeks. They were followed between 17 and 24 months and again none became castrated, presenting normal levels of testosterone during follow-up. Conclusions: Prospective studies on this topic are difficult and time consuming. The two RT regimens used in this study were well tolerated but not capable of causing castration at 12-36 months of follow up in men with prostate cancer. The optimal RT dose to induce castration in men remains to be determined. Author Disclosure: S. faria: None. F. Cury: None. M. Duclos: None. L. Souhami: None.
2622 Recently Updated Preliminary Results of an On-Going Phase 1/2 Trial Using Trimodality Therapy in Patients With Postprostatectomy High-Risk Pathologic (p) T2-3N0M0 Prostate Cancer P. Kumar,1 P.V. Veldhuizen,1 M. Thompson,1 X. Shen,1 J. Coster,1 and J. Pinski2; 1University of Kansas School of Medicine, Kansas City, KS,
2
University of Southern California Keck School of Medicine, Los Angeles, CA Purpose/Objective(s): We present the recently updated preliminary results of an on-going phase I / II trial with the purpose of determining the safety, feasibility and efficacy of post-prostatectomy radiation therapy (RT), hormonal therapy and concurrent docetaxel in patients with high risk pathologic (p) T2-3N0M0 prostate cancer. Materials/Methods: Post-prostatectomy high risk prostate cancer was defined as clinically non-metastatic disease with either an undetectable, persistent or rising PSA with 1 or more of the following clinical-pathologic features: (1) pT2-T3aN0 disease, positive or negative margins, with either (a) a gleason score (GS) of 8, and/or (b) a PSA doubling time of 10 months, and/or (c) with a pre-RT PSA of 1.0 ng/ml; and/or (2) pT3bN0 disease. The tri-modality treatment consisted of 6 months of hormonal therapy [Casodex (50 mg po daily), and Zoladex (10.8 mg sc q 3 mos x 2) or Lupron (22.5 mg im q 3 mos x 2)], RT to 66.0 Gy at 2.0 Gy/fraction (fx) once daily (50 Gy to the surgical bed followed by a 16 Gy Boost at 2.0 Gy/ fx using either 3-D conformal radiation therapy or IMRT, usually begun after 2 months of hormonal therapy), and concurrent weekly docetaxel at 20 mg/m2 x 7 infusions. Results: Between October 2008 and February 2014, a total of 26 patients have been enrolled to this on-going phase I/II clinical trial. The clinical and disease characteristics of these 26 patients are as follows: Median age, years (range) Z 63 (56 - 74); GS was as follows: 3+3 Z 6 in 1 patient, 3+4 Z 7 in 6 patients, 4+3 Z 7 in 5, 3+5 Z 8 in 3, 4+4 Z 8 in 3, 4+5 Z 9 in 5 and 5+4 Z 9 in 3; resection margin was negative in 10 patients, close in 2 and positive in 14; extracapsular extension was absent in 8 patients, and present in 18; seminal vesicle invasion was present in 12 patients and absent in 14; and pathologic T-stage was as follows: pT2a Z 2 patients, pT2c Z 5, pT3a Z 8 and pT3b Z 11. Nine patients are in the adjuvant RT category while the remaining 17 are in the salvage RT category. Eighteen of the 26 enrolled patients have completed their entire tri-modality therapy. All of these 18 patients completed their full dose of RT (66 Gy). These 18 patients also received a median of 7 weekly docetaxel infusions (range Z 5 - 8). Only 2 of these 18 patients experienced grade 3 GI possibly treatment-related acute toxicity, both of whom were on stool softners and / or laxatives preceding their grade 3 diarrhea. Among the 8 of 26 remaining patients, 2 of the 8 have completed their entire chemoradiation therapy treatments without any acute grade 3 GI / GU toxicity while the other 6 recently started their protocol therapy. Conclusions: The recently updated preliminary results of our on-going phase I/II clinical trial with an accrual goal of 40 patients indicate that our post-prostatectomy tri-modality therapy is well tolerated with a very high feasibility rate in patients with high risk pT2-3N0M0 prostate cancer. Author Disclosure: P. Kumar: None. P.V. Veldhuizen: None. M. Thompson: None. X. Shen: None. J. Coster: None. J. Pinski: None.
2623 Dosimetric Correlates for Acute Toxicity in Prostate Cancer Treated With Hypofractionated Radiation Therapy: Absolute Volumes Are Better Predictors Than Relative Volumes M. Arunsingh, S. Sarkar, S. Das, S. Prasath, P. Dharmendran, and I. Mallick; Tata Medical Centre, Kolkata, India Purpose/Objective(s): Hypofractionated radiation therapy is becoming a widely accepted approach in the treatment of prostate cancer. This retrospective study reports acute toxicity and the dosimetric correlates of a cohort of patients treated at a single centre in India. Materials/Methods: One hundred one patients with localized prostate cancer were treated with image guided intensity modulated radiation therapy (IG- IMRT) between July 2011 and Jan 2014. Two different fractionation schedules were used, with 65Gy/25Fr/ 5 weeks being used in the first 18 patients (EQD2 76Gy a/b Z 1.5) and the subsequent 83 being treated with 60Gy/20Fr/4 weeks schedule(77.2Gy a/b Z 1.5). Majority of them (n Z 83, 83.2%) had high risk or pelvic node positive disease and received elective pelvic nodal irradiation (44Gy/20Fr or 45 Gy/25Fr) using a single phase plan with simultaneous integrated boost to the prostate and