Abstract
Purpose
Radiation-induced cardiac toxicity (RICT) is an increasingly well-appreciated source of morbidity and mortality in patients receiving thoracic radiotherapy (RT). Currently available methods to predict RICT are suboptimal. We investigated circulating microRNAs (c-miRNAs) as potential biomarkers of RICT in patients undergoing definitive RT for non-small-cell lung cancer (NSCLC).
Methods
Data from 63 patients treated on institutional trials were analyzed. Prognostic models of grade 3 or greater (G3 +) RICT based on pre-treatment c-miRNA levels (‘c-miRNA’), mean heart dose (MHD) and pre-existing cardiac disease (PCD) (‘clinical’), and a combination of these (‘c-miRNA + clinical’) were developed. Elastic net Cox regression and full cross validation were used for variable selection, model building, and model evaluation. Concordance statistic (c-index) and integrated Brier score (IBS) were used to evaluate model performance.
Results
MHD, PCD, and serum levels of 14 c-miRNA species were identified as jointly prognostic for G3 + RICT. The ‘c-miRNA and ‘clinical’ models yielded similar cross-validated c-indices (0.70 and 0.72, respectively) and IBSs (0.26 and 0.28, respectively). However, prognostication was not improved by combining c-miRNA and clinical factors (c-index 0.70, IBS 0.28). The ‘c-miRNA’ and ‘clinical’ models were able to significantly stratify patients into high- and low-risk groups of developing G3 + RICT. Chi-square testing demonstrated a marginally significantly higher prevalence of PCD in patients with high- compared to low-risk c-miRNA profile (p = 0.09), suggesting an association between some c-miRNAs and PCD.
Conclusions
We identified a pre-treatment c-miRNA signature prognostic for G3 + RICT. With further development, pre- and mid-treatment c-miRNA profiling could contribute to patient-specific dose selection and treatment adaptation.
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This work was supported in part by R0 1CA142840 (Kong) and P01 CA059827 (Ten Haken and Lawrence).
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Hawkins, P.G., Sun, Y., Dess, R.T. et al. Circulating microRNAs as biomarkers of radiation-induced cardiac toxicity in non-small-cell lung cancer. J Cancer Res Clin Oncol 145, 1635–1643 (2019). https://doi.org/10.1007/s00432-019-02903-5
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DOI: https://doi.org/10.1007/s00432-019-02903-5