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Use of bevacizumab before or after radiotherapy increases the risk of fistula formation in patients with cervical cancer

Authors
 Nalee Kim  ;  Seo Hee Choi  ;  Jee Suk Chang  ;  Young-Tae Kim  ;  Sang Wun Kim  ;  Gun Min Kim  ;  Yong Bae Kim 
Citation
 INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol.31(1) : 59-65, 2021-01 
Journal Title
 INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 
ISSN
 1048-891X 
Issue Date
2021-01
Keywords
cervical cancer ; radiotherapy ; rectovaginal fistula ; vaginal fistula
Abstract
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.
Full Text
https://ijgc.bmj.com/content/31/1/59.long
DOI
10.1136/ijgc-2020-002031
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Gun Min(김건민) ORCID logo https://orcid.org/0000-0001-9167-8682
Kim, Nalee(김나리) ORCID logo https://orcid.org/0000-0003-4742-2772
Kim, Sang Wun(김상운) ORCID logo https://orcid.org/0000-0002-8342-8701
Kim, Young Tae(김영태) ORCID logo https://orcid.org/0000-0002-7347-1052
Kim, Yong Bae(김용배) ORCID logo https://orcid.org/0000-0001-7573-6862
Chang, Jee Suk(장지석) ORCID logo https://orcid.org/0000-0001-7685-3382
Choi, Seo Hee(최서희) ORCID logo https://orcid.org/0000-0002-4083-6414
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182076
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