Electrocardiogram with Artificial Intelligence Assessment as a Predictor of Cardiac Events and Overall Survival in Patients Receiving Radiotherapy for Esophageal Cancer

Abstract

Neoadjuvant (chemo)radiotherapy (RT) has demonstrated an overall survival (OS) benefit in esophageal cancer and constitutes part of the standard of care trimodality therapy. Unfortunately, subsequent cardiac toxicity can reduce the benefit of treatment. Our group aimed to study whether data from electrocardiograms (ECGs) could predict clinical outcomes and cardiac events after RT for esophageal cancer, allowing for identification of and early intervention for patients at high risk for cardiac toxicity. Included patients received at least 41.4 Gy of pre-operative or definitive photon or proton RT for esophageal cancer from 2015 through July 2022. All ECGs were assessed using a previously validated artificial intelligence assessment for atrial fibrillation (AF) and reduced ejection fraction (rEF) (Noseworthy et al. Lancet 2022). The model determined propensities for the development of multiple cardiac events, including AF and heart failure (HF). Medical records were reviewed for cardiac events and conditions prior to and after RT. A cohort of 491 patients was assembled, with 301, 121, and 364 patients having an ECG prior to, during, and after RT, respectively. Of these, 84% had malignancy in the lower third of the esophagus and 48% underwent esophagectomy. At last follow-up relative to baseline assessment, patients had increased propensity for rEF (median 0.013, interquartile range (IQR): 0.001-0.038 vs. median 0.022, IQR: 0.011-0.074, p < 0.0001) and AF (median 0.16, IQR: 0.04-0.40 vs. median 0.048, IQR: 0.01-0.19, p < 0.0001). Increases in AF propensity were associated with reduced OS (hazard ratio (HR) = 1.10 per 0.1 increase, 95% confidence interval (CI): 1.03-1.17, p = 0.0071). Baseline rEF propensity was predictive of future HF events (HR = 1.14, 95% CI: 1.07-1.22, p < 0.001) for all patients or after excluding the 172 (35%) patients with baseline HF (HR = 1.45, 95% CI: 1.19-1.76, p < 0.001). Among patients who did not have HF prior to radiotherapy, the development of HF was associated with reduced OS (HR = 1.60, 95% CI: 1.10-2.32, p = 0.014). Currently available cardiac dosimetric parameters, including heart mean/max doses, did not significantly correlate with cardiac outcomes. Patients who underwent esophagectomy had improved OS (HR = 0.62, 95% CI: 0.47-0.82, p = 0.0008) and were not more likely to develop cardiac toxicity. This analysis suggests that chemoradiotherapy for esophageal cancer can have significant impacts on a patient's propensity for cardiac events, which are associated with reduced OS. ECGs carry the potential to identify patients at greater risk for such events, and baseline ECGs with artificial intelligence assessment could select patients for increased surveillance or early intervention to further optimize the therapeutic ratio of RT.