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.