Risk factors for esophageal fistula in patients with locally advanced esophageal carcinoma receiving chemoradiotherapy

Background: This study aimed to investigate risk factors for esophageal fistula in patients with locally advanced esophageal carcinoma receiving chemoradiotherapy. Subjects and methods: The study prospectively enrolled 212 esophageal carcinoma patients undergoing chemoradiotherapy and evaluated 16 clinical parameters. The best cut-off values were determined by receiver operating characteristics curves. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated by the Cox proportional hazards model. Kaplan–Meier analysis was used to evaluate the cumulative probability. Results: In total, 22 patients (10.38%) developed esophageal fistula, of whom 9 experienced fistula during treatment and the other 13 patients developed fistula after chemoradiotherapy. The median time until occurrence was 5.75 months (range 0.6–8 months). In univariate analysis, the evaluated significant factors were Karnofsky performance status, smoking status, esophageal stenosis, T stage, fraction dose, and carcinoembryonic antigen (CEA). In addition, esophageal stenosis (HR=4.089, 95% CI 1.451–11.527, p =0.008), T stage (HR=2.663, 95% CI 1.019–6.960, p =0.046), and CEA (HR=0.309, 95% CI 0.124–0.768, p =0.011) were revealed as risk parameters in further multivariate analysis. Conclusion: This is the first prospective study to evaluate factors associated with fistula formation in patients with esophageal carcinoma receiving chemoradiotherapy. More attention should be given to patients with esophageal stenosis, stage T4 disease, and high levels of CEA. Keywords: esophageal fistula, esophageal carcinoma, chemoradiotherapy, side effect, risk factors