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

Abstract

<b><i>Objective:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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, <i>p</i> = 0.001), ulcerative type (OR 2.72, 95% CI 1.43–5.16, <i>p</i> = 0.002), histology (OR 4.16, 95% CI 1.14–15.12, <i>p</i> = 0.03), T stage (OR 2.66, 95% CI 1.44–4.91, <i>p</i> = 0.002), short-term response (OR 2.21, 95% CI 1.06–4.62, <i>p</i> = 0.03), chemotherapy regimen (OR 2.80, 95% CI 1.38–5.68, <i>p</i> = 0.005), and stenosis (OR 2.00, 95% CI 1.03–3.89, <i>p</i> = 0.04). <b><i>Conclusions:</i></b> 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 associ­ation.

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.…”

“…Patients who received the same dose of RT and the same intensity of chemotherapy sometimes had different outcomes of EF. This variation might be due to patient status, treatment-related factors, or tumor characteristics ( 12 ). As a functional imaging method, PET/CT can construct biological tumor volume, which could reflect cell metabolism, proliferation, hypoxia, apoptosis, and even phenotype ( 23 ).…”

Addition of camrelizumab to docetaxel, cisplatin, and radiation therapy in patients with locally advanced esophageal squamous cell carcinoma: a phase 1b study

“…T4 stage and ulcerative ESCC were risk factors associated with esophageal fistula. 32 , 33 High esophageal fistula rates of 22% (31/140), 34 24% (28/116) 35 and 30.1% (41/136) 36 were reported in patients with ESCC and receiving definitive chemoradiotherapy, which accounted for 76%, 34 100% 35 and 100% 36 in all patients with T4 or T4b tumors, individually. Relative low rate of 10.38% (22/212) was also reported in ESCC patients who received definitive chemoradiotherapy, which accounted for 15.09% in T4 patients.…”

“… 37 Combined chemoradiotherapy and anti-PD-1 antibody did not increased the occurrence of esophageal fistula (10% vs 5–24%). 32 We found more frequent radiation esophagitis compared with concurrent chemoradiotherapy (40% vs 16.9–32.7% in grade 2; 20% vs 3.2–5.6% in grade 3), 4 , 5 , 31 which might be due to the relatively higher radiation dose per fraction (2 Gy vs 1.8 Gy), 4 , 5 , 31 total radiation dose (60 Gy vs 54 Gy), 5 , 31 and incorporation of the anti-PD-1 antibody in the present trial.…”

Rehabilitation Nursing Intervention Can Improve Dysphagia and Quality of Life of Patients Undergoing Radiotherapy for Esophageal Cancer

“…However, most patients lose the chance of operation because of the location of tumor or the rapid progress of disease, so radiotherapy needs to be given to patients with advanced disease. However, the spread of cancer cells cannot be controlled when the radiotherapy measures are implemented, so the incidence of adverse reactions is higher after treatment [ 13 , 14 ], which leads to greater psychological pressure of patients, directly affects their psychological state and quality of life, and has a certain negative impact on the therapeutic effect [ 15 , 16 ]. Moreover, radiation injury to esophageal mucosa is one of the most common side effects of radiotherapy, which can lead to mucosal edema, congestion, ulcer, and erosion causing patients to feel esophageal burning, esophageal swelling and pain, and then suffering from dysphagia, swallowing pain, pain behind the sternum, and other symptoms when eating [ 17 – 19 ].…”