Risk Factors Associated with Esophageal Fistula after Re-radiotherapy for Esophageal Cancer

Abstract

The purpose of this study was to investigate risk factors for esophageal fistula (EF) in patients with esophageal squamous cell carcinoma (ESCC) receiving re-radiotherapy (re-RT) with or without chemotherapy. We retrospectively analyzed 71 patients with recurrent ESCC were treated in Shandong Cancer Hospital and Institute from August 2014 to April 2019. The clinical characters and dosimetric parameters of patients during the initial diagnosis and treatment were recorded. Univariate and multivariate logistic regression analyses were provided to determine the risk factors associated with EF. Among the 71 patients included in the study, including 55 males and 16 females. The median age was 68 years old (51-89 years old). 26 patients were T4 staged EC (36.62%), 20 patients with ulcerative EC (28.17%), 18 patients received concurrent chemoradiotherapy (CRT) in primary RT (25.35%), 16 patients received concurrent CRT in re-RT (22.54%). In this study, 17 patients developed EF (23.94%). Of these, 2 patients developed EF during re-RT. 15 patients experienced EF after re-RT. The types of EF in this study included 8 patients with esophago-respiratory fistula, 9 patients with esophageal-mediastinum fistula. The median follow-up period was 12.75 months (range 0.33∼46.83 months). In univariate analysis, age, gender, T stage, total radiation dose, hyperfractionation RT, ulcerative EC, the maximum thickness of the tumor and the time interval had a correlation with the prevalence of EF. In addition, age, T stage, total radiation dose, and the time interval were significantly associated with EF in multivariate analysis. The incidence of EF was significantly increased in patients with EC who underwent re-RT. Patients with age <70 years old, T4 stage, higher total radiation dose, the shorter time interval was more likely to develop EF. Hyperfractionation RT could reduce the incidence of EF in patients undergoing re-RT. We should pay close attention to the patients with high risk factors of EF to prevent the occurrence of EF.