BACKGROUND : Radiotherapy (RT) associates with long-term cardiotoxicity. In preclinical models, RT-exposure induces early cardiotoxic arrhythmias including atrial fibrillation (AF). Yet, whether this occurs in patients is unknown.

METHODS : Leveraging a large cohort of consecutive esophageal cancer patients treated with thoracic-RT from 2007-2019, we assessed incidence and outcomes of incident-AF. Secondary outcomes included major adverse cardiovascular events (MACE), defined as AF, heart failure, ventricular-arrhythmias and sudden-death, by cardiac RT-dose. We also assessed the relationship between AF-development and progression-free and overall-survival. Observed incident-AF rates were compared with Framingham predicted-rates, and absolute-excess-risks (AER) were estimated. Multivariate-regression was used to define the relationship between clinical and RT-measures, and outcomes. Differences in outcomes, by AF-status, were also evaluated via 30-day landmark-analysis. Furthermore, we assessed the effect of cardiac substructure RT-dose (ex. left atrium, LA) on the risk of post RT-related outcomes.

RESULTS : Overall, from 238 RT-treated esophageal cancer patients, 21.4% developed incident-AF, and 33% developed MACE, with the majority (84%) of events occurring ≤2 years of RT-initiation; median time-to-AF, 4.1 months. Cumulative incidence of AF and MACE at 1-year was 19.5%, and 25.7%, respectively; translating into an observed incident-AF rate of 824 per 10,000 person-years, compared to the Framingham predicted-rate of 92 (RR 8.96, P<0.001, AER 732). Increasing LA dose strongly associated with incident-AF (P=0.001); and those with AF saw worse disease-progression (HR=1.54, P=0.03). In multivariate-models, outside of traditional cancer-related factors, increasing RT-dose to the LA remained associated with worse overall-survival.

CONCLUSIONS : Among esophageal cancer patients, radiotherapy increases AF-risk, and associates with worse long-term outcomes.