RT Journal Article
SR Electronic
T1 Use of bevacizumab before or after radiotherapy increases the risk of fistula formation in patients with cervical cancer
JF International Journal of Gynecologic Cancer
JO Int J Gynecol Cancer
FD BMJ Publishing Group Ltd
SP ijgc-2020-002031
DO 10.1136/ijgc-2020-002031
A1 Nalee Kim
A1 Seo Hee Choi
A1 Jee Suk Chang
A1 Young-Tae Kim
A1 Sang Wun Kim
A1 Gun Min Kim
A1 Yong Bae Kim
YR 2020
UL http://ijgc.bmj.com/content/early/2020/12/02/ijgc-2020-002031.abstract
AB Objective Several reports have documented the risk of fistula formation after bevacizumab in patients previously treated with radiation therapy. The aim of this study was to investigate the risk of fistula formation with bevacizumab and radiotherapy compared with radiotherapy alone.Methods We retrospectively analyzed patients with stage I–IV cervical cancer between January 2013 and December 2018. Patients who had a history of pelvic radiotherapy, who were treated with intracavitary brachytherapy alone, received radiotherapy at another hospital, received concurrent bevacizumab and radiotherapy, or had missing follow-up data or a short follow-up period (<6 months) were excluded. The fistula rates were compared between the groups using the Cox proportional hazards model and propensity score analyses.Results A total of 302 patients were included in the study: 249 patients were treated with definitive or adjuvant radiotherapy, and 53 patients were treated with radiotherapy before or after bevacizumab. With a median follow-up of 35.9 (IQR 22.8–53.5) months, the 3 year cumulative fistula incidence rate was significantly higher in the radiotherapy + bevacizumab group than in the radiotherapy group (27.0% vs 3.0%, p<0.001). Bevacizumab administration was significantly associated with fistula formation in the multivariable adjusted model (HR 4.76, 95% CI 1.71 to 13.23) and three propensity score adjusted model (all p<0.05). Biologically equivalent dose in 2 Gy fractions for 2 cc of the rectum more than 76 Gy was also associated with fistula formation (HR 4.30, 95% CI 1.52 to 12.18). Additionally, a 10 month interval between radiotherapy and bevacizumab reduced the incidence of fistula formation in the radiotherapy + bevacizumab group (p=0.032).Conclusions In patients with cervical cancer treated with pelvic radiotherapy, the addition of bevacizumab substantially increased the risk of fistula formation. Physicians should perform pelvic radiotherapy in combination with bevacizumab with caution; moreover, close monitoring for fistula formation is warranted in these patients.