Telomere length dynamics and chromosomal instability for predicting individual radiosensitivity and risk via machine learning

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Abstract

The ability to predict a cancer patient’s response to radiotherapy and risk of developing adverse late health effects would greatly improve personalized treatment regimens and individual outcomes. Telomeres represent a compelling biomarker of individual radiosensitivity and risk, as exposure can result in dysfunctional telomere pathologies that coincidentally overlap with many radiation-induced late effects, ranging from degenerative conditions like fibrosis and cardiovascular disease to proliferative pathologies like cancer. Here, telomere length was longitudinally assessed in a cohort of fifteen prostate cancer patients undergoing Intensity Modulated Radiation Therapy (IMRT) utilizing Telomere Fluorescence in situ Hybridization (Telo-FISH). To evaluate genome instability and enhance predictions for individual patient risk of secondary malignancy, chromosome aberrations were assessed utilizing directional Genomic Hybridization (dGH) for high-resolution inversion detection. We present the first implementation of individual telomere length data in a machine learning model, XGBoost, trained on pre-radiotherapy (baseline) and in vitro exposed (4 Gy γ-rays) telomere length measurements, to predict post radiotherapy telomeric outcomes, which together with chromosomal instability provide insight into individual radiosensitivity and risk for radiation-induced late effects.

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APA

Luxton, J. J., McKenna, M. J., Lewis, A. M., Taylor, L. E., Jhavar, S. G., Swanson, G. P., & Bailey, S. M. (2021). Telomere length dynamics and chromosomal instability for predicting individual radiosensitivity and risk via machine learning. Journal of Personalized Medicine, 11(3). https://doi.org/10.3390/jpm11030188

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