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Journal of Cancer Research and Clinical Oncology

Erschienen in:

28.03.2019 | Original Article – Clinical Oncology

Circulating microRNAs as biomarkers of radiation-induced cardiac toxicity in non-small-cell lung cancer

verfasst von: Peter G. Hawkins, Yilun Sun, Robert T. Dess, William C. Jackson, Grace Sun, Nan Bi, Muneesh Tewari, James A. Hayman, Gregory P. Kalemkerian, Shirish M. Gadgeel, Theodore S. Lawrence, Randall K. Ten Haken, Martha M. Matuszak, Feng-Ming (Spring) Kong, Matthew J. Schipper, Shruti Jolly

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 6/2019

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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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Titel: Circulating microRNAs as biomarkers of radiation-induced cardiac toxicity in non-small-cell lung cancer
verfasst von: Peter G. Hawkins
Yilun Sun
Robert T. Dess
William C. Jackson
Grace Sun
Nan Bi
Muneesh Tewari
James A. Hayman
Gregory P. Kalemkerian
Shirish M. Gadgeel
Theodore S. Lawrence
Randall K. Ten Haken
Martha M. Matuszak
Feng-Ming (Spring) Kong
Matthew J. Schipper
Shruti Jolly
Publikationsdatum: 28.03.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 6/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-02903-5

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Circulating microRNAs as biomarkers of radiation-induced cardiac toxicity in non-small-cell lung cancer

Abstract

Purpose

Methods

Results

Conclusions

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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