Risk Factors of Esophageal Fistula Associated with Volumetric Modulated Arc Therapy for Esophageal Squamous Cell Cancer

Purpose: To investigate risk factors for esophageal fistula in esophageal squamous cell cancer (ESCC) patients who treated with volumetric modulated arc therapy (VMAT).

Patients and methods: A retrospective analysis was performed on 171 ESCC patients treated with VMAT at Hefei Cancer Hospital, Chinese Academy of Sciences, from February 2017 to February 2021. Clinical and dosimetric parameters, including age, gender, feeding channel, tumor location, T stage, ulcerative tumor, were recorded. Univariate and multivariate logistic regression were used to determine risk factors for esophageal fistula. The predictive accuracy of the constructed nomogram was assessed using a receiver operating characteristic (ROC) curve and calibration curves.

Results: Esophageal fistula occurred in 12.87% (22/171) of all the patients. Univariate analysis showed that gender, age, diabetes, T4 stage, ulcerative tumor, total radiation dose, maximum gross tumor volume (GTV) diameter, and GTV length correlated with the incidence of esophageal fistula. Multivariable analysis highlighted gender, age, diabetes, T4 stage, and total radiation dose as significant predictors. A predictive nomogram including these five factors was developed and showed an AUC of 0.876 (95% CI 0.807-0.946), a C-index of 0.847, and a corrected C-index of 0.833.

Conclusion: Gender, age, diabetes, T4 stage, and total radiation dose emerged as significant risk factors for esophageal fistula in ESCC patients undergoing VMAT. The developed nomogram provides a reliable tool to predict the risk of esophageal fistula risk in this cohort.