Development and validation of a risk prediction model for radiotherapy-related esophageal fistula in esophageal cancer

Abstract

ObjectivesWe aimed to identify the risk factors and provide a nomogram for the prediction of radiotherapy-related esophageal fistula in patients with esophageal cancer (EC) using a case-control study.Patients and methodsPatients with esophageal fistula who received radiotherapy or chemoradiotherapy between 2003 and 2017 were retrospectively collected in two institutions. In the training cohort (TC), clinical, pathologic, and serum data of 136 patients (cases) who developed esophageal fistula during or after radiotherapy were enrolled and compared with 272 controls (1:2 matched with the diagnosis time of EC, sex, marriage, and race). After the univariable and multivariable logistic regression analyses, the independent risk factors were identified and incorporated into a nomogram. Then the nomogram for the risk prediction was externally validated in the validation cohort (VC; 47 cases and 94 controls) using bootstrap resampling.ResultsMultivariable analyses demonstrated that ECOG PS, BMI, T4, N2/3 and re-radiotherapy were independent factors for esophageal fistula. Then a nomogram was constructed with the C-index of 0.805 (95% CI, 0.762–0.848) for predicting the risk of developing esophageal fistula in EC patients receiving radiotherapy. Importantly, the C-index maintained 0.764 (95% CI, 0.683–0.845) after the external validation.ConclusionsWe created and externally validated the first risk nomogram of esophageal fistula associated with radiotherapy. This will aid individual risk stratification of patients with EC developing esophageal fistula.

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

“…Moreover, consistent with the earlier researches [ 5 , 10 ], esophageal stenosis independently increased the risk of esophageal fistula in the present study. But, the other studies did not observe the similar finding [ 6 , 7 , 20 ]. These discrepant results possibly derived from various definitions of esophageal stenosis used in the published literature and a limited sample size of each study.…”

“…To begin with, IMRT was utilized in the present study while conventional technique or 3DCRT were used in the earlier researches [5][6][7][8][9]. In addition, all patients underwent definitive CCRT in the current cohort whereas the previous reports included cases treated with radiotherapy alone [6,14,15], sequential chemoradiotherapy [10], brachytherapy [16,17], or salvage radiotherapy [15,[18][19][20]. Furthermore, the current cohort only included patients with ESCC, but patients with ESCC and esophageal adenocarcinoma were combined for analysis in some earlier studies [14,17,21].…”

Efficacy and toxicity of re-irradiation for esophageal cancer patients with locoregional recurrence: a retrospective analysis

“…There is no prediction of risk factors for EP caused by re-RT in the past, but the risk factors were similar to patients who received radiotherapy for the first time [ 18 , 33 ]. Other risk factors for EP in patients undergoing RT for the first time have also been reported [ 34 – 36 ], further study on the risk of EP in re-RT is expected to be included in analysis. Patients with esophageal stenosis might be treated with stenting/bouginage, which is a risk factor for EP especially in patients who underwent RT [ 37 ].…”

High incidence of esophageal fistula on patients with clinical T4b esophageal squamous cell carcinoma who received chemoradiotherapy: A retrospective analysis

“…In the present study, 41 (30.1%) patients developed esophageal fistula, which accounts for 80.4% of all cases with severe complications. Since T4 refers to tumor invasion of surrounding tissues, the rate of fistula in T4 ESCC is much higher than in early T stages [15][16][17]. A list of studies reporting the rates of esophageal fistula in locally advanced ESCC patients was provided in Table 6.…”