Cardiovascular Morbidity Following Definitive Chemoradiotherapy for Lung Cancer in an Appalachian Population.

BACKGROUND/OBJECTIVES: Cardiovascular morbidity following definitive chemoradiotherapy (CRT) for lung cancer is a major concern in Appalachia due to high rates of smoking and pre-existing cardiovascular disease. This study characterized the cardiovascular burden following CRT in a real-world Appalachian population. METHODS: A retrospective study was conducted among Appalachian patients with lung cancer treated with definitive CRT from 2013 to 2025. Cardiovascular adverse event (CVAE) incidence, spectrum, and temporal distribution were characterized. Kaplan-Meier and Cox regression analyses evaluated time to CVAE and overall survival (OS). Exploratory machine-learning (ML) models assessed CVAE and mortality prediction. RESULTS: Fifty-one patients (59%) experienced a CVAE. NSTEMI (15/51, 29%) and pericardial disease (15/51, 29%) were most frequent, followed by arrhythmia (8/51, 16%). Ischemic events occurred predominantly within the first year, whereas pericardial events were concentrated within 2 years. Median CVAE-free survival was 22.6 months, with estimated cumulative CVAE occurrence of 28.3% at 1 year and 50.0% at 2 years. After adjustment for age, cardiovascular comorbidity, and M stage, heart V20 (HR, 1.024 per 1% increase; 95% CI, 1.005-1.044; p = 0.015) and V30 (HR, 1.031; 95% CI, 1.004-1.058; p = 0.025) were associated with increased CVAE hazard. Median OS was 29 months; pre-existing cardiovascular comorbidity was associated with mortality (HR range, 2.16-2.45). Exploratory ML showed limited CVAE prediction but moderate mortality discrimination after feature selection (maximum AUC, 0.71). CONCLUSIONS: Cardiovascular morbidity was common and accumulated over time following definitive CRT in this Appalachian cohort. These findings support attention to baseline cardiovascular risk, cardiac radiation exposure, and longitudinal cardiovascular surveillance.