Gastrointestinal/genitourinary perforation and fistula formation with or without bevacizumab in patients with previously irradiated recurrent cervical cancer: a Korean multicenter retrospective study of the Gynecologic Oncology Research Investigators Collaboration (GORILLA) group (GORILLA-1001)

Abstract

Background This study aims to evaluate the incidence of and identify risk factors for gastrointestinal (GI) and genitourinary (GU) fistula or perforation formation with or without bevacizumab in patients with recurrent cervical cancer who underwent pelvic radiation therapy (RT). Methods Medical records of patients with recurrent cervical cancer who previously underwent pelvic RT between 2007 and 2020 were retrospectively reviewed. Clinicopathological factors were compared between groups that are stratified according to: 1) fistula/perforation (+) versus (-); and 2) bevacizumab plus conventional chemotherapy (BC) versus chemotherapy alone (C). Univariate and multivariate regression analyses were performed to identify risk factors for fistula/perforation. Overall survival (OS) was compared between the different groups. Results Of 219 participants, fistula/perforation of any grade occurred in 36 patients (16.4%); 27 fistulas and 9 perforations. Bevacizumab was more frequently used in Bevacizumab was more frequently used ( +) group than fistula/perforation (-) group (p = 0.015). Multivariate analysis showed that bevacizumab administration was the only independent risk factor for fistula or perforation (HR, 3.27; 95% CI, 1.18–9.10; P = 0.023). F/P was observed more frequently in women receiving BC (n = 144) than those receiving C (n = 75) (20.8% vs. 8.0%; P = 0.019). During median follow-up of 33.7 months (1.2–185.6 months), no significant OS difference was observed between fistula/perforation ( +) vs. (-) (hazards ratio [HR], 1.78; median 84.2 months [95% CI, 59.3–109.0] vs. 129.5 months [95% CI, 114.1–144.9]; P = 0.065) or BC vs. C (HR, 1.03; median 119.8 months [95% CI, 97.3–142.3] vs. 115.7 months [95% CI, 96.0–135.4]; P = 0.928). Conclusions This study suggests that incorporation of bevacizumab in chemotherapy regimens for treating recurrent cervical cancer in patients who underwent pelvic RT incurs considerable risk for GI/GU fistula or perforation. There were no other independent risk factors for developing GI/GU fistula or perforation in this study population.

Gastrointestinal perforation after bevacizumab: a multi-site, single-institution study with a focus on survival

“…Other studies that had examined such overall survival outcomes included only small numbers of patients—24 and 7 patients, respectively, thus highlighting the importance of the current study [ 9 , 10 ]. Other such studies examined perforation and fistula formation together and included only a small number of patients with a perforation ( n < 10) [ 20 ]. Similarly, although the large database study from Wichelmann and others included 1375 patients with gastrointestinal perforation, these investigators reported only death rates, not overall survival and not whether surgery was undertaken [ 8 ].Thus, the overall survival data reported here provide a contemporary experience that enables patients, their families, and their healthcare providers to make better-informed management decisions and better informed expectations after the occurrence of this devastating drug-induced complication.…”