Andrew Liman1, Rashmikant Shah1, Vida Passero1, Jocelyn Tan1, Hema Rai1, Laurie Harrold1, Joyce Tokarsky1, Agnes Liman1, Vidhi Gupta1, Kristina Gerszten1. 1. is Section Chief, Hematology/Oncology and is a Physician, Pathology and Laboratory Medicine, both at VA Central California Health Care System in Fresno. is Section Chief; , , and are Physicians; is a Nurse Practitioner, all in the Hematology/Oncology section at VA Pittsburgh Health Care System (VAPHCS) in Pennsylvania. , , and are Physicians in the Radiology and Radiation Oncology section at VAPHCS. Andrew Liman is an Assistant Clinical Professor of Medicine at the University of California San Francisco at Fresno. Vida Passero, Laurie Harrold, Jocelyn Tan, and Hema Rai are Assistant Clinical Professors of Medicine at University of Pittsburgh Cancer Institute in Pennsylvania.
Abstract
BACKGROUND: Radium-223 (Ra-223) radioisotope has been reported to increase median survival in bone metastatic prostate carcinoma. The addition of Ra-223 to abiraterone was associated with an increased risk of bone fractures. There has been no comprehensive data for using Ra-223 in veterans who were exposed to Agent Orange (AO+). METHODS: We present a retrospective study of veterans with bone metastatic castration-resistant prostate cancer (CRPC) who received standard doses of Ra-223 and other sequential therapies at US Department of Veterans Affairs Pittsburgh Healthcare System in Pennsylvania from January 2014 to January 2019. Veterans were divided into 2 groups: those who were exposed to Agent Orange (AO+) and those who had no exposure (AO-). Time to study was calculated from the initiation of Ra-223. Time to skeletal-related events (SRE), progression of prostate specific antigen (PSA), bone metastasis, and alkaline phosphatase (ALP) were calculated in months using unpaired t test with 2-tailed P values. Median survival was calculated by Kaplan Meier R log-rank test. RESULTS: There were 34 veterans with bone metastatic CRPC: 17 veterans (50%) were AO+ and 17 veterans (50%) were AO-. The mean age of diagnosis of AO+ veterans was 62 years and 69 years (P = .005) for AO- veterans (the mean Gleason score 8.2 and 8.0, respectively [P = .71]). The median number of Ra-223 cycles was 6 (60%). Ten veterans received Ra-223 as first line (29%) and 24 veterans received Ra-223 later (71%). There were 12 SREs with median survival of 15 months. There was no difference in mean time to SRE between AO+ (8 veterans, 10.6 months) and AO- (4 veterans, 10.3 months) (P = .93). The mean time to PSA progression for AO+ was 5.4 months and AO- was 6.8 months (P = .28). Mean time to bone progression for AO+ was 7.6 months and AO- was 10.1 months (P = .16). Mean time to ALP progression for AO+ and AO- was 6.3 months and 8.7 months, respectively (P = .05). Twenty veterans (58%) had died. Median survival for Ra-223 first was 32 months and for Ra-223 later was 15 months (P = .14; hazard ratio [HR] 0.48; 95% CI, 0.17-1.3). Median survival for AO+ and AO- veterans was 12 months and 18 months, respectively (P = .15; HR, 2.0; 95% CI, 0.77-5.0). CONCLUSIONS: There was no statistical difference between AO+ and AO- veterans in terms of time to SRE, PSA, bone and ALP progression, even though there was a trend of shorter duration in AO+ veterans. There was no median survival difference between Ra-223 first vs Ra-223 later as well as between AO+ and AO- but there is a trend of worse survival in AO+ veterans.
BACKGROUND: Radium-223 (Ra-223) radioisotope has been reported to increase median survival in bone metastatic prostate carcinoma. The addition of Ra-223 to abiraterone was associated with an increased risk of bone fractures. There has been no comprehensive data for using Ra-223 in veterans who were exposed to Agent Orange (AO+). METHODS: We present a retrospective study of veterans with bone metastatic castration-resistant prostate cancer (CRPC) who received standard doses of Ra-223 and other sequential therapies at US Department of Veterans Affairs Pittsburgh Healthcare System in Pennsylvania from January 2014 to January 2019. Veterans were divided into 2 groups: those who were exposed to Agent Orange (AO+) and those who had no exposure (AO-). Time to study was calculated from the initiation of Ra-223. Time to skeletal-related events (SRE), progression of prostate specific antigen (PSA), bone metastasis, and alkaline phosphatase (ALP) were calculated in months using unpaired t test with 2-tailed P values. Median survival was calculated by Kaplan Meier R log-rank test. RESULTS: There were 34 veterans with bone metastatic CRPC: 17 veterans (50%) were AO+ and 17 veterans (50%) were AO-. The mean age of diagnosis of AO+ veterans was 62 years and 69 years (P = .005) for AO- veterans (the mean Gleason score 8.2 and 8.0, respectively [P = .71]). The median number of Ra-223 cycles was 6 (60%). Ten veterans received Ra-223 as first line (29%) and 24 veterans received Ra-223 later (71%). There were 12 SREs with median survival of 15 months. There was no difference in mean time to SRE between AO+ (8 veterans, 10.6 months) and AO- (4 veterans, 10.3 months) (P = .93). The mean time to PSA progression for AO+ was 5.4 months and AO- was 6.8 months (P = .28). Mean time to bone progression for AO+ was 7.6 months and AO- was 10.1 months (P = .16). Mean time to ALP progression for AO+ and AO- was 6.3 months and 8.7 months, respectively (P = .05). Twenty veterans (58%) had died. Median survival for Ra-223 first was 32 months and for Ra-223 later was 15 months (P = .14; hazard ratio [HR] 0.48; 95% CI, 0.17-1.3). Median survival for AO+ and AO- veterans was 12 months and 18 months, respectively (P = .15; HR, 2.0; 95% CI, 0.77-5.0). CONCLUSIONS: There was no statistical difference between AO+ and AO- veterans in terms of time to SRE, PSA, bone and ALP progression, even though there was a trend of shorter duration in AO+ veterans. There was no median survival difference between Ra-223 first vs Ra-223 later as well as between AO+ and AO- but there is a trend of worse survival in AO+ veterans.
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