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Prediction of poor response to neoadjuvant chemoradiation in patients with rectal cancer using a DNA repair deregulation score: Picking the losers instead of the winners

Diseases of the Colon and Rectum Feb 19, 2020

Jimenez L, Perez R, São Julião GP, et al. - As patients with rectal cancer could be provided neoadjuvant chemoradiation even in early stages in an attempt to attain complete clinical response and could undergo organ preservation, researchers identified accurate identification of poor responders as significant as it could spare patients with the early-stage disease from potentially unnecessary chemoradiation. They here focused on developing and testing a score based on DNA repair gene expression for predicting response to neoadjuvant chemoradiation in patients with rectal cancer. They collected pretreatment biopsy samples from patients with rectal cancer undergoing neoadjuvant chemoradiation and performed gene expression analysis on them using RNA-Seq (test cohort). Construction of a score was undertaken using 8 differentially expressed DNA repair genes between good (complete clinical) and poor responders (incomplete clinical) to treatment. Poor responders comprised patients with > 10% of residual cancer cells. In the test cohort, 25 patients (16 poor responders) were included. In the validation cohort 1, 28 patients (18 poor responders), and in the validation cohort 2, 46 patients (22 poor responders) were included. They observed significantly lower DNA repair scores in poor responders vs good responders across all 3 cohorts; this was observed regardless of the gene expression platform used. Correct prediction of poor response was made with a low score in 93%, 90%, and 71% in the test, validation 1, and validation 2 cohorts, respectively. These findings support the possible utility of a DNA repair gene score for predicting patients likely to have a poor response to chemoradiation.
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