Esophageal fistula after definitive concurrent chemotherapy and intensity modulated radiotherapy for esophageal squamous cell carcinoma

Abstract

Background The literature regarding esophageal fistula after definitive concurrent chemotherapy and intensity modulated radiotherapy (IMRT) for esophageal squamous cell carcinoma (ESCC) remains lacking. We aimed to investigate the risk factors of esophageal fistula among ESCC patients undergoing definitive concurrent chemoradiotherapy (CCRT) via IMRT technique. Methods A total of 129 consecutive ESCC patients receiving definitive CCRT with IMRT between 2008 and 2018 were reviewed. The cumulative incidence of esophageal fistula and survival of patients were estimated by the Kaplan–Meier method and compared between groups by the log-rank test. The risk factors of esophageal fistula were determined with multivariate Cox proportional hazards regression analysis. Results Median follow-up was 14.9 months (IQR, 7.0–28.8). Esophageal perforation was identified in 20 (15.5%) patients, resulting in esophago-pleural fistula in nine, esophago-tracheal fistula in seven, broncho-esophageal fistula in two, and aorto-esophageal fistula in two patients. The median interval from IMRT to the occurrence of esophageal fistula was 4.4 months (IQR, 3.3–10.1). Patients with esophageal fistula had an inferior median overall survival (10.0 vs. 17.2 months, p = 0.0096). T4 (HR, 3.776; 95% CI, 1.383–10.308; p = 0.010) and esophageal stenosis (HR, 2.601; 95% CI, 1.053–6.428; p = 0.038) at baseline were the independent risk factors for esophageal fistula. The cumulative incidence of esophageal fistula was higher in patients with T4 (p = 0.018) and pre-treatment esophageal stenosis (p = 0.045). There was a trend toward better survival after esophageal fistula among patients receiving repair or stenting for the fistula than those only undergoing conservative treatments (median survival, 5.9 vs. 0.9 months, p = 0.058). Conclusions T4 and esophageal stenosis at baseline independently increased the risk of esophageal fistula in ESCC treated by definitive CCRT with IMRT. There existed a trend toward improved survival after the fistula among patients receiving repair or stenting for esophageal perforation.

Incorporation of PET Metabolic Parameters With Clinical Features Into a Predictive Model for Radiotherapy-Related Esophageal Fistula in Esophageal Squamous Cell Carcinoma

“…There was no significant correlation between the development of EF and tumor with ulceration or esophageal stenosis in the regression equation. This result is inconsistent with those of other studies ( 7 – 9 , 12 – 14 , 16 ). This finding may be due to the different assessment methods used in our study.…”

“…However, reports on the effects of diabetes on EF are rare. Some studies tracking risk factors in EF did not show an effect of diabetes status ( 7 , 9 ), while our study found that diabetes increases the risk of RT-related EF by more than seven times in ESCC.…”

“…EF is an adverse event of ESCC that develops due to tumor progression or therapeutic intervention. As one of the most serious complications of RT for EC, the incidence of EF is 1.01%–22.1% ( 7 – 15 ), which is 14.6%–30.5% in T4 stage patients ( 16 – 19 ). The clinical application of oral meglumine diatrizoate esophagogram enables early detection of EF ( 20 ), and some salvage strategies are used such as stents or bypass surgery ( 21 , 22 ).…”

“…However, the prognosis of EF in patients with ESCC receiving RT remains poor. The median interval from initiation of RT to the occurrence of EF was 1.3–5.75 months ( 7 – 11 , 13 – 19 ), and the median post-fistula survival time is only 3.1–3.63 months ( 6 , 7 , 13 ). Therefore, early prediction of radiotherapy-related EF could have a significant impact on the outcome of patients with ESCC.…”

A Nomogram for Predicting the Risk of Radiotherapy-Related Esophageal Fistula in Esophageal Cancer Patients

“…Previous literature ( 6 , 8 , 12 ) described that several clinical parameters are closely correlated with the occurrence of EF, including age, T stage, N stage, stenosis, ulceration, low serum cholesterol level, and body mass index (BMI). However, a unified diagnosis criterion for esophageal stenosis has not been unified, and the majority of studies defined stenosis solely based on symptoms ( 4 , 8 , 13 ).…”