title: Risk Factors for Esophageal Fistula Associated With Chemoradiotherapy for Locally Advanced Unresectable Esophageal Cancer: A Supplementary Analysis of JCOG0303.
abstract: Esophageal fistula is a critical adverse event in patients treated with chemoradiotherapy (CRT) for locally advanced esophageal cancer. However, risk factors associated with esophageal fistula formation in patients receiving CRT have not yet been elucidated.We retrospectively analyzed data obtained from 140 patients who were enrolled in a phase II/III trial comparing low-dose cisplatin with standard-dose cisplatin administered in combination with 5-flurouracil and concomitant radiotherapy. Inclusion criteria were performance status (PS) 0 to 2 and histologically proven thoracic esophageal cancer clinically diagnosed as T4 and/or unresectable lymph node metastasis for which definitive CRT was applicable. Risk factors for esophageal fistula were examined with univariate analysis using Fisher exact test and multivariate analysis using logistic regression models.Esophageal fistula was observed in 31 patients (22%). Of these, 6 patients developed fistula during CRT. Median time interval between the date of CRT initiation and that of fistula diagnosis was 100 days (inter quartile range, 45-171). Esophageal stenosis was the only significant risk factor for esophageal fistula formation both in univariate (P = 0.026) and in multivariate analyses (odds ratio, 2.59; 95% confidence interval, 1.13-5.92, P = 0.025). Other clinicopathological factors, namely treatment arm, age, sex, PS, primary tumor location, T stage, lymph node invasion to adjacent organs, blood cell count, albumin level, and body mass index, were not risk factors fistula formation.Esophageal stenosis was a significant risk factor for esophageal fistula formation in patients treated with CRT for unresectable locally advanced thoracic esophageal squamous cell carcinoma.
authors.affiliation: From the Division of Gastrointestinal Oncology (TT) and Division of Esophageal Surgery (YT), Shizuoka Cancer Center, Sunto-gun, Shizuoka; JCOG Data Center/Operation Office, National Cancer Center (JM, KN, HF); Gastrointestinal Medical Oncology Division (KS, YH, KK) and Division of Esophageal Surgery (HI), National Cancer Center Hospital; Department of Thoracic Surgery, Aichi Cancer Center (MS); and Department of Surgery, Keio University School of Medicine (YK) Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tsushima
authors.forename: Junki
authors.initials: J
authors.lastname: Mizusawa
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sudo
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Honma
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Igaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsubosa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shinoda
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Fukuda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004937:Esophageal Fistula / Q000209:etiology*; D004938:Esophageal Neoplasms / Q000628:therapy*; D004940:Esophageal Stenosis / Q000150:complications*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D002945:Cisplatin; D005472:Fluorouracil