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• W2897538922 abstract "Circulating microRNAs (c-miRNAs) have shown promise as biomarkers in non-small cell lung cancer (NSCLC) and cardiac disease. We sought to identify a c-miRNA signature prognostic for radiation-induced cardiac toxicity (RICT) in patients undergoing definitive radiotherapy (RT) for NSCLC. Data from 65 patients treated from 2004-2013 with definitive RT for stages II-III NSCLC on four consecutive prospective clinical trials were analyzed. The primary endpoint was time to first grade 3 or greater (G3+) cardiac event, as graded using Common Terminology Criteria for Adverse Events version 4.03. Pretreatment serum levels of 62 miRNA species were measured by quantitative reverse transcription polymerase chain reaction array. Prognostic models of G3+ RICT based on c-miRNA profile (“c-miRNA”), mean heart dose and baseline cardiac disease (“clinical”), and a combination of these (“c-miRNA + clinical”) were developed. Elastic net Cox regression was used for variable selection and parameter estimation. Model assessment and tuning parameter selection were performed through full cross validation. Area under the receiver operating curve (AUC) and C-index were used for comparison of model performance. The cumulative incidence of G3+ RICT was 16.9%. We identified 14 c-miRNA species prognostic for G3+ cardiac toxicity: miR-25, -34a, -100, -106b, -134, -145, -146a, -192, -195, -200b, -223, -574, -885, and let-7c. Two species previously shown to be associated with RICT in animal models, miR-15b and -21, were not significantly prognostic in this cohort and therefore not selected for the c-miRNA model. C-indices for the c-miRNA, clinical, and c-miRNA + clinical models were 0.701, 0.722, and 0.704, respectively. AUC values for these models were 0.643, 0.642, and 0.634, respectively. Hazard ratios for G3+ RICT in low- vs. high-risk patients, as defined using each model, were 0.25 (p=0.04, 95%CI 0.06-0.94) for the c-miRNA, 0.17 (p=0.02, 95%CI 0.04-0.76) for the clinical, and 0.29 (p=0.07, 95%CI 0.08-1.12) for the c-miRNA + clinical models. We identified a pretreatment c-miRNA signature that was prognostic for G3+ RICT in NSCLC. This signature performed similarly to a model based on dosimetric and clinical factors. This finding suggests that these c-miRNAs may represent biomarkers of underlying cardiac disease, which is consistent with the published literature regarding most of the identified species. It is therefore possible that midtreatment changes in these c-miRNAs could serve as an indicator of RT-induced worsening of cardiac function, which in turn could guide adaptation of therapy. Additionally, further investigation of these miRNAs may elucidate mechanisms of cardiac damage and protection." @default.
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• W2897538922 date "2018-11-01" @default.
• W2897538922 modified "2023-10-12" @default.
• W2897538922 title "Circulating microRNAs as Biomarkers of Radiation-Induced Cardiac Toxicity in Non-Small Cell Lung Cancer" @default.
• W2897538922 doi "https://doi.org/10.1016/j.ijrobp.2018.06.341" @default.
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