Germline variants disrupting microRNAs predict long-term genitourinary toxicity after prostate cancer radiation.

The purpose of this study was to determine whether single nucleotide polymorphisms disrupting microRNA targets (mirSNPs) can serve as predictive biomarkers for toxicity after radiotherapy for prostate cancer and whether these may be differentially predictive depending on radiation fractionation.

We identified 201 men treated with two forms of definitive radiotherapy for prostate cancer at two institutions: 108 men received conventionally-fractionated radiotherapy (CF-RT) and 93 received stereotactic body radiotherapy (SBRT). Germline DNA was evaluated for the presence of functional mirSNPs. Random forest, boosted trees and elastic net models were developed to predict late grade≥2 GUtoxicity by the RTOG scale.

The crude incidence of late grade≥2 GU toxicitywas 16% after CF-RT and 15% after SBRT. An elastic net model based on 22 mirSNPs differentiated CF-RT patients at high risk (71.5%) versus low risk (7.5%) for toxicity, with an area under the curve (AUC) values of 0.76-0.81. An elastic net model based on 32 mirSNPs differentiated SBRT patients at high risk (64.7%) versus low risk (3.9%) for toxicity, with an area under the curve (AUC) values of 0.81-0.87. These models were specific to treatment type delivered. Prospective studies are warranted to further validate these results.

Predictive models using germline mirSNPs have high accuracy for predicting late grade≥2 GU toxicity after either CF-RT or SBRT, and are unique for each treatment, suggesting that germline predictors of late radiation sensitivity are fractionation-dependent. Prospective studies are warranted to further validate these results.

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2022 Jan 03 [Epub ahead of print]

Amar U Kishan, Nicholas Marco, Melanie-Birte Schulz-Jaavall, Michael L Steinberg, Phuoc T Tran, Jesus E Juarez, Audrey Dang, Donatello Telesca, Wolfgang A Lilleby, Joanne B Weidhaas

Department of Radiation Oncology, University of California, Los Angeles, California, United States; Department of Urology, University of California, Los Angeles, United States. Electronic address: ., Department of Biostatistics, University of California Los Angeles Fielding School of Public Health, Los Angeles, California, United States., Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway., Department of Radiation Oncology, University of California, Los Angeles, California, United States., Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.

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