Association between radiation dose to pulmonary vein substructures and post-treatment atrial fibrillation following neoadjuvant chemoradiotherapy for esophageal squamous cell cancer.

Abstract

To determine whether incidental radiation dose to pulmonary vein (PV) substructures---known arrhythmogenic sites---was associated with increased risk of atrial fibrillation (AF) in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (nCRT). We conducted a retrospective analysis of 209 ESCC patients treated with nCRT. PV substructures (LSPV, LIPV, RSPV, RIPV) were contoured on radiotherapy planning scans, and dose-volume histogram parameters were extracted. AF events were ascertained through systematic cardiac monitoring. Multivariate competing risk regression was employed to assess associations between PV doses and AF, with adjustment for cardiovascular risk factors, surgical resection as a time-dependent covariate, and mortality as a competing risk. Among 209 patients (84.9% male; median age 66 years), the 2-year cumulative incidence of AF was 8.89%, with a median time to AF of 13 months. Among the 25 AF events, 15 (60%) occurred after esophagectomy, with a median time from surgery to AF of 2.1 months. On univariate analysis, age, hypertension, LIPV-∼Dmax∼, RSPV-∼Dmax∼, and coronary heart disease (CHD) were associated with AF. In the multivariable model, LIPV-∼Dmax remained an independent predictor (adjusted HR = 3.16, 95% CI: 1.19-8.42, p = 0.021) after adjustment for age (HR = 3.66, p = 0.009), CHD (HR = 2.59, p = 0.019), and surgical resection. Patients with LIPV-∼Dmax∼ >28.87 Gy had a significantly higher AF incidence (12.3%) than those below this threshold (p = 0.008). Moreover, AF was associated with inferior 2-year recurrence-free survival (36.9% vs. 78.6%, p = 0.0051) and inferior 2-year overall survival (58.3% vs. 82.1%, p = 0.012). Maximum dose to the LIPV was independently associated with increased AF risk and worse survival outcomes in ESCC patients receiving nCRT. These results highlighted the potential value of LIPV-sparing radiotherapy techniques and enhanced AF surveillance in this population. External validation in larger prospective cohorts was needed before firm clinical guidelines can be established.