Risk Factors for Esophageal Fistula in Esophageal Cancer Patients Treated with Radiotherapy: A Systematic Review and Meta-Analysis

Abstract

Objective: Esophageal fistula is a critical and fatal complication of esophageal cancer. The aim of this meta-analysis was to explore the risk factors for esophageal perforation in esophageal cancer patients treated with radiotherapy. Methods: Data from the PubMed and Embase databases were retrieved for clinical research published between 1990 and 2018. The Newcastle-Ottawa Scale was used to evaluate the quality of the articles. A meta-analysis was performed using the RevMan 5.3 software provided by the Cochrane Collaboration Network. Results: Seventeen articles were eligible for the meta-analysis. In these articles, over 35 risk factors for esophageal fistula formation were described and 17 risk factors were analyzed. Significant differences in the odds of developing an esophageal perforation were found with regard to age (OR 2.34, 95% CI 1.08-5.03, p = 0.001), ulcerative type (OR 2.72, 95% CI 1.43-5.16, p = 0.002), histology (OR 4.16, 95% CI 1.14-15.12, p = 0.03), T stage (OR 2.66, 95% CI 1.44-4.91, p = 0.002), short-term response (OR 2.21, 95% CI 1.06-4.62, p = 0.03), chemotherapy regimen (OR 2.80, 95% CI 1.38-5.68, p = 0.005), and stenosis (OR 2.00, 95% CI 1.03-3.89, p = 0.04). Conclusions: An age of <60-65 years, ulcerative type, squamous cell cancer, T4 stage, incomplete response, fluorouracil-based regimen, and stenosis were associated with an increased risk of esophageal fistula during or after radiotherapy. However, further, large-scale prospective studies are needed to establish the validity of this associ-ation.