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Prognostic Value of PSA Nadir in Patients Undergoing Definitive Radiation for Prostate Cancer
S456
International Journal of Radiation Oncology Biology Physics
2617
recognized but not well quantified. Prior studies of small bowel toxicity measure a heterogeneous patient population with a variety of different tumor types confounded by a variety of different treatments including prior surgeries and combined chemotherapy. The purpose of this study is to characterize the dose-volume relationship of small bowel toxicity during prostate radiation therapy in a homogenous Veterans Affairs population using modern IMRT/VMAT radiation techniques. Materials/Methods: All records of patients receiving radiation therapy for prostate cancer between 2009 and 2011 were analyzed. 73 patients met these inclusion criteria. Median age was 68. 35.6% were postoperative and 64% were definitive. 52% of patients received androgen deprivation therapy. Peritoneal space contents were contoured on each slice of the planning CT scan. A median dose of 75.6 Gy was delivered using either IMRT or VMAT. Small bowel constraint used was V45 < 200cc. Median follow up was 2.4 years. Toxicity was scored using CTCAE v4.0 to grade acute and late small bowel toxicity. Results: Seventeen patients (23%) experienced acute grade 1 small bowel toxicity. Twenty-six patients (36%) experienced acute grade 2 small bowel toxicity. There was 2% grade 1 chronic small bowel toxicity. There was 5% grade 2 chronic small bowel toxicity. There was no Grade 3 or higher acute or chronic bowel toxicity. The mean volume of small bowel receiving a dose of 45 Gy was 33 cc, range (0-193 cc). The mean volume of small bowel receiving a dose of 52 Gy was 4 cc, range (0-90 cc). 25 patients (34%) received greater than 52 Gy, range (52-80 Gy) and had no late small bowel toxicity. In a subset analysis, the mean volume of small bowel receiving a dose of 60 Gy was 10 cc, range (0 -34 cc). Median follow up for these high dose patients was 2.5 years. Conclusions: In this Veteran Affairs population of prostate cancer patients treated with radiation, we show that with modern VMAT/IMRT techniques there is a very low incidence of Grade 3+ acute and chronic small bowel toxicity. V45 < 200cc is a good constraint to follow to minimize small bowel toxicity. However, in certain situations this constraint can possibly be exceeded without significant short and long-term complications. While this study was not designed to determine maximum tolerated small bowel dose or volume, it is hypothesis generating given that no grade 3 toxicity was seen in our series. Further studies should explore maximum tolerated dose-volume relationship to maximize tumor control without increasing the small bowel toxicity profile. Author Disclosure: G. Green: None. R. Williams: None. J. Zhang: None. S. Azawi: None.
WITHDRAWN
2618 Prognostic Value of PSA Nadir in Patients Undergoing Definitive Radiation for Prostate Cancer A.N. Ram,1 S.P. Robertson,1 A.K. Narang,1 P. Hei,2 E. Griffith,1 H. Singh,1 T.A. DeWeese,1 S. Honig,1 T.R. McNutt,3 T.L. DeWeese,3 D.Y. Song,3 and P.T. Tran3; 1Johns Hopkins Hospital, Baltimore, MD, 2Stanford University, Palo Alto, MD, 3Johns Hopkins University, Baltimore, MD Purpose/Objective(s): In patients undergoing definitive radiation for localized prostate cancer, prognostic markers in the early post-treatment setting would be useful for identifying patients who may benefit from treatment intensification. Potential metrics that have been described include PSA nadir and time to PSA nadir, but the prognostic significance of these variables has thus far been mixed. Materials/Methods: We reviewed an IRB-monitored, prospectively acquired database of patients with prostate cancer from our institution with definitive radiation from 1993-2007 (n Z 890). Univariate analysis was performed to determine prognostic factors for biochemical failure-free survival (BFFS; Phoenix criteria) and overall survival (OS): age, race, initial PSA, clinical stage, Gleason score, radiation dose, use of IMRT, administration of androgen deprivation, PSA nadir, and time to PSA nadir, defined as time from end of radiation to lowest PSA value. Both PSA nadir and time to PSA nadir were examined as dichotomous variables with 0.5 ng/ml and 12 months used as cut points, respectively, based on definitions used in the literature. Significant factors on univariate analysis were included in multivariate analysis. Kaplan-Meier survival analysis was also performed for all endpoints. Results: Median age was 69 years, with an even distribution of low-risk (33.5%), intermediate-risk (34.0%), and high-risk (32.5%) patients. Median radiation dose was 7020 cGy, and 54% of patients were treated with androgen deprivation. Median follow-up of the entire cohort was 13.0 yrs, while median BFFS and OS were 11.4 yrs and 17.8 yrs, respectively. Median time to PSA nadir was 7.6 months with 28% achieving nadir at end of treatment and 57% achieving nadir by one year. Neither BFFS nor OS differed by time to nadir. However, on multivariate analysis, PSA nadir 0.5 ng/mL was significantly associated with worse BFFS (p<0.0001), which was true for low-, intermediate- and high-risk groups (all p<0.0001). On subset analysis, patients treated with radiation alone with a PSA nadir 0.5 ng/mL experienced worse BFFS (88.9 mos vs. 205.6 mos, p<0.0001). In patients treated with concurrent androgen deprivation, an undetectable PSA nadir (77% of all cases) was prognostic for BFFS (81.7 mos vs. 146.6 mos, p<0.0001). High-risk patients with an elevated PSA nadir also experienced worse overall survival (p<0.0001). Conclusions: PSA nadir 0.5 ng/mL in patients treated with radiation alone or a detectable PSA in patients treated with concurrent androgen suppression may both help identify patients at high risk of failure, which may be useful for determining strategies for close surveillance or more aggressive treatment. Prospective evaluation of the utility of PSA nadir should be further explored. Author Disclosure: A.N. Ram: None. S.P. Robertson: None. A.K. Narang: None. P. Hei: None. E. Griffith: None. H. Singh: None. T.A. DeWeese: None. S. Honig: None. T.R. McNutt: None. T.L. DeWeese: None. D.Y. Song: None. P.T. Tran: None.
2619 Dose-Volume Relationship of Acute and Late Small Bowel Toxicity From Radiation Therapy for Prostate Cancer: A Veteran Affairs Study G. Green,1 R. Williams,2 J. Zhang,2 and S. Azawi2; 1UC Irvine Medical Center, Orange, CA, 2VA Long Beach Healthcare System, Long Beach, CA Purpose/Objective(s): A direct relationship between the small bowel volume irradiated and the degree of acute and late small bowel toxicity experienced during radiation for adenocarcinoma of the prostate is well
2620 The Emergence of New Late Radiation Toxicities Beyond the Traditional 5 Years of Follow-Up After Low-Dose-Rate Prostate Brachytherapy D. Asher,1 D. Moghanaki,1,2 N. Serrano,1 J. Karlin,1 M. Schutzer,1 M. Chang,1,2 and M.P. Hagan1,2; 1Virginia Commonwealth University, Richmond, VA, 2Hunter Holmes McGuire VA Medical Center, Richmond, VA Purpose/Objective(s): Studies of late radiation toxicity beyond the typical 5 years of follow-up after prostate brachytherapy are often limited by a loss of patients to follow-up, dependence on mailed surveys, and/or reliance on billing codes that may not accurately capture clinical data. Since Veterans typically seek their care indefinitely within the Veterans Healthcare Administration, it was hypothesized that the availability of clinical encounters in the Computerized Patient Record System (CPRS) may detect a higher rate of late urinary and/or rectal toxicities, than previously believed, emerging only after this initial surveillance period. Materials/Methods: Individual patient records were reviewed in CPRS for a cohort of patients who underwent permanent low-dose rate brachytherapy between January 2004 and December 2007. The CTCAE v4.0 was used to score urinary and rectal toxicities. Results: A total of 245 patients were evaluated. Follow-up clinical records were available for 100%, including 95.1% of patients within one year of this study, or death. The median follow-up was 7.5 years, with 88.6% followed 5 years. Post-implant dosimetry was available for 95.5%. The
International Journal of Radiation Oncology Biology Physics
2617
recognized but not well quantified. Prior studies of small bowel toxicity measure a heterogeneous patient population with a variety of different tumor types confounded by a variety of different treatments including prior surgeries and combined chemotherapy. The purpose of this study is to characterize the dose-volume relationship of small bowel toxicity during prostate radiation therapy in a homogenous Veterans Affairs population using modern IMRT/VMAT radiation techniques. Materials/Methods: All records of patients receiving radiation therapy for prostate cancer between 2009 and 2011 were analyzed. 73 patients met these inclusion criteria. Median age was 68. 35.6% were postoperative and 64% were definitive. 52% of patients received androgen deprivation therapy. Peritoneal space contents were contoured on each slice of the planning CT scan. A median dose of 75.6 Gy was delivered using either IMRT or VMAT. Small bowel constraint used was V45 < 200cc. Median follow up was 2.4 years. Toxicity was scored using CTCAE v4.0 to grade acute and late small bowel toxicity. Results: Seventeen patients (23%) experienced acute grade 1 small bowel toxicity. Twenty-six patients (36%) experienced acute grade 2 small bowel toxicity. There was 2% grade 1 chronic small bowel toxicity. There was 5% grade 2 chronic small bowel toxicity. There was no Grade 3 or higher acute or chronic bowel toxicity. The mean volume of small bowel receiving a dose of 45 Gy was 33 cc, range (0-193 cc). The mean volume of small bowel receiving a dose of 52 Gy was 4 cc, range (0-90 cc). 25 patients (34%) received greater than 52 Gy, range (52-80 Gy) and had no late small bowel toxicity. In a subset analysis, the mean volume of small bowel receiving a dose of 60 Gy was 10 cc, range (0 -34 cc). Median follow up for these high dose patients was 2.5 years. Conclusions: In this Veteran Affairs population of prostate cancer patients treated with radiation, we show that with modern VMAT/IMRT techniques there is a very low incidence of Grade 3+ acute and chronic small bowel toxicity. V45 < 200cc is a good constraint to follow to minimize small bowel toxicity. However, in certain situations this constraint can possibly be exceeded without significant short and long-term complications. While this study was not designed to determine maximum tolerated small bowel dose or volume, it is hypothesis generating given that no grade 3 toxicity was seen in our series. Further studies should explore maximum tolerated dose-volume relationship to maximize tumor control without increasing the small bowel toxicity profile. Author Disclosure: G. Green: None. R. Williams: None. J. Zhang: None. S. Azawi: None.
WITHDRAWN
2618 Prognostic Value of PSA Nadir in Patients Undergoing Definitive Radiation for Prostate Cancer A.N. Ram,1 S.P. Robertson,1 A.K. Narang,1 P. Hei,2 E. Griffith,1 H. Singh,1 T.A. DeWeese,1 S. Honig,1 T.R. McNutt,3 T.L. DeWeese,3 D.Y. Song,3 and P.T. Tran3; 1Johns Hopkins Hospital, Baltimore, MD, 2Stanford University, Palo Alto, MD, 3Johns Hopkins University, Baltimore, MD Purpose/Objective(s): In patients undergoing definitive radiation for localized prostate cancer, prognostic markers in the early post-treatment setting would be useful for identifying patients who may benefit from treatment intensification. Potential metrics that have been described include PSA nadir and time to PSA nadir, but the prognostic significance of these variables has thus far been mixed. Materials/Methods: We reviewed an IRB-monitored, prospectively acquired database of patients with prostate cancer from our institution with definitive radiation from 1993-2007 (n Z 890). Univariate analysis was performed to determine prognostic factors for biochemical failure-free survival (BFFS; Phoenix criteria) and overall survival (OS): age, race, initial PSA, clinical stage, Gleason score, radiation dose, use of IMRT, administration of androgen deprivation, PSA nadir, and time to PSA nadir, defined as time from end of radiation to lowest PSA value. Both PSA nadir and time to PSA nadir were examined as dichotomous variables with 0.5 ng/ml and 12 months used as cut points, respectively, based on definitions used in the literature. Significant factors on univariate analysis were included in multivariate analysis. Kaplan-Meier survival analysis was also performed for all endpoints. Results: Median age was 69 years, with an even distribution of low-risk (33.5%), intermediate-risk (34.0%), and high-risk (32.5%) patients. Median radiation dose was 7020 cGy, and 54% of patients were treated with androgen deprivation. Median follow-up of the entire cohort was 13.0 yrs, while median BFFS and OS were 11.4 yrs and 17.8 yrs, respectively. Median time to PSA nadir was 7.6 months with 28% achieving nadir at end of treatment and 57% achieving nadir by one year. Neither BFFS nor OS differed by time to nadir. However, on multivariate analysis, PSA nadir 0.5 ng/mL was significantly associated with worse BFFS (p<0.0001), which was true for low-, intermediate- and high-risk groups (all p<0.0001). On subset analysis, patients treated with radiation alone with a PSA nadir 0.5 ng/mL experienced worse BFFS (88.9 mos vs. 205.6 mos, p<0.0001). In patients treated with concurrent androgen deprivation, an undetectable PSA nadir (77% of all cases) was prognostic for BFFS (81.7 mos vs. 146.6 mos, p<0.0001). High-risk patients with an elevated PSA nadir also experienced worse overall survival (p<0.0001). Conclusions: PSA nadir 0.5 ng/mL in patients treated with radiation alone or a detectable PSA in patients treated with concurrent androgen suppression may both help identify patients at high risk of failure, which may be useful for determining strategies for close surveillance or more aggressive treatment. Prospective evaluation of the utility of PSA nadir should be further explored. Author Disclosure: A.N. Ram: None. S.P. Robertson: None. A.K. Narang: None. P. Hei: None. E. Griffith: None. H. Singh: None. T.A. DeWeese: None. S. Honig: None. T.R. McNutt: None. T.L. DeWeese: None. D.Y. Song: None. P.T. Tran: None.
2619 Dose-Volume Relationship of Acute and Late Small Bowel Toxicity From Radiation Therapy for Prostate Cancer: A Veteran Affairs Study G. Green,1 R. Williams,2 J. Zhang,2 and S. Azawi2; 1UC Irvine Medical Center, Orange, CA, 2VA Long Beach Healthcare System, Long Beach, CA Purpose/Objective(s): A direct relationship between the small bowel volume irradiated and the degree of acute and late small bowel toxicity experienced during radiation for adenocarcinoma of the prostate is well
2620 The Emergence of New Late Radiation Toxicities Beyond the Traditional 5 Years of Follow-Up After Low-Dose-Rate Prostate Brachytherapy D. Asher,1 D. Moghanaki,1,2 N. Serrano,1 J. Karlin,1 M. Schutzer,1 M. Chang,1,2 and M.P. Hagan1,2; 1Virginia Commonwealth University, Richmond, VA, 2Hunter Holmes McGuire VA Medical Center, Richmond, VA Purpose/Objective(s): Studies of late radiation toxicity beyond the typical 5 years of follow-up after prostate brachytherapy are often limited by a loss of patients to follow-up, dependence on mailed surveys, and/or reliance on billing codes that may not accurately capture clinical data. Since Veterans typically seek their care indefinitely within the Veterans Healthcare Administration, it was hypothesized that the availability of clinical encounters in the Computerized Patient Record System (CPRS) may detect a higher rate of late urinary and/or rectal toxicities, than previously believed, emerging only after this initial surveillance period. Materials/Methods: Individual patient records were reviewed in CPRS for a cohort of patients who underwent permanent low-dose rate brachytherapy between January 2004 and December 2007. The CTCAE v4.0 was used to score urinary and rectal toxicities. Results: A total of 245 patients were evaluated. Follow-up clinical records were available for 100%, including 95.1% of patients within one year of this study, or death. The median follow-up was 7.5 years, with 88.6% followed 5 years. Post-implant dosimetry was available for 95.5%. The