TY - JOUR
T1 - Acute Epithelial Toxicity Is Prognostic for Improved Prostate Cancer Response to Radiation Therapy
T2 - A Retrospective, Multicenter, Cohort Study
AU - Eade, Thomas
AU - Choudhury, Ananya
AU - Pollack, Alan
AU - Abramowitz, Matthew
AU - Chinea, Felix M.
AU - Guo, Linxin
AU - Kennedy, Jason
AU - Louw, Sandra
AU - Hruby, George
AU - Kneebone, Andrew
AU - West, Catharine
N1 - Funding Information:
Conflict of interest: AC reports grants and personal fees from Bayer PLC, grants and personal fees from Elekta AB, grants from Astra Zeneca, grants from Cancer Research UK, grants from Prostate Cancer UK, and grants from the National Institute of Health Research, outside the submitted work. MA reports being a consultant for Varian and Bayer. SL reports personal fees from McCloud Consulting Group, during the conduct of the study.
Funding Information:
The work was supported by the Cancer Research UK Manchester Cancer Research Centre, the European Union's Seventh Framework Programme under grant agreement no. 601826 (REQUITE), and the Manchester Biomedical Research Centre.
Publisher Copyright:
© 2018
PY - 2018/7/15
Y1 - 2018/7/15
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ijrobp.2018.04.009
DO - 10.1016/j.ijrobp.2018.04.009
M3 - Article
C2 - 29976508
AN - SCOPUS:85048792733
VL - 101
SP - 957
EP - 963
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
SN - 0360-3016
IS - 4
ER -