Thomas Eade1, Ananya Choudhury2, Alan Pollack3, Matthew Abramowitz3, Felix M Chinea3, Linxin Guo4, Jason Kennedy2, Sandra Louw5, George Hruby4, Andrew Kneebone4, Catharine West2. 1. Radiation Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, St. Leonards, New South Wales, Australia. Electronic address: Thomas.Eade@health.nsw.gov.au. 2. The University of Manchester and Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom. 3. Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida. 4. Radiation Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, St. Leonards, New South Wales, Australia. 5. McCloud Consulting Group, Belrose, New South Wales, Australia.
Abstract
PURPOSE: To test the hypothesis that increased acute toxicity, measured using subdomains reflective of epithelial cell damage, will be associated with reduced late biochemical failure, as a surrogate for tumor radiosensitivity. METHODS AND MATERIALS: The study design was retrospective, with discovery and validation cohorts involving routinely collected data. Eligible patients had prostate cancer, underwent radiation therapy with curative intent, and had acute toxicity assessed prospectively. The discovery cohort was from a single institution. Genitourinary and gastrointestinal acute toxicity related to epithelial cell damage (hematuria, dysuria, proctitis, or mucus) were related to freedom from late biochemical failure (FFBF; nadir + 2). The validation cohort was from two separate institutions. RESULTS: In all, 503 patients were included in the discovery cohort and 658 patients in the validation cohort. In the validation cohort, patients with acute radiation toxicity reflecting epithelial damage had a longer FFBF on both univariate (hazard ratio [HR] 0.37; P = .004) and multivariate (HR 0.45; P = .035) analysis. The impact of acute toxicity on late FFBF seemed to be greater in patients treated with androgen deprivation (HR 0.19) than in those without (HR 0.48). CONCLUSION: Patients reporting acute radiation toxicity reflective of epithelial cell damage during definitive radiation therapy for prostate cancer have significantly longer FFBF, consistent with an underlying genetic link between normal tissue and tumor radiosensitivity. Crown
PURPOSE: To test the hypothesis that increased acute toxicity, measured using subdomains reflective of epithelial cell damage, will be associated with reduced late biochemical failure, as a surrogate for tumor radiosensitivity. METHODS AND MATERIALS: The study design was retrospective, with discovery and validation cohorts involving routinely collected data. Eligible patients had prostate cancer, underwent radiation therapy with curative intent, and had acute toxicity assessed prospectively. The discovery cohort was from a single institution. Genitourinary and gastrointestinal acute toxicity related to epithelial cell damage (hematuria, dysuria, proctitis, or mucus) were related to freedom from late biochemical failure (FFBF; nadir + 2). The validation cohort was from two separate institutions. RESULTS: In all, 503 patients were included in the discovery cohort and 658 patients in the validation cohort. In the validation cohort, patients with acute radiation toxicity reflecting epithelial damage had a longer FFBF on both univariate (hazard ratio [HR] 0.37; P = .004) and multivariate (HR 0.45; P = .035) analysis. The impact of acute toxicity on late FFBF seemed to be greater in patients treated with androgen deprivation (HR 0.19) than in those without (HR 0.48). CONCLUSION:Patients reporting acute radiation toxicity reflective of epithelial cell damage during definitive radiation therapy for prostate cancer have significantly longer FFBF, consistent with an underlying genetic link between normal tissue and tumor radiosensitivity. Crown