Toxicity Related Patients Factors and Bevasizumab Use in Patients With Locally Advanced Cervical Cancer Treated With Definitive Chemoradiation and HDR Brachytherapy Boost

Abstract

The purpose of this study is to identify factors associated with severe late toxicity and prognosis in women with locally advanced cervical cancer treated with definitive chemoradiation (CRT) and high dose rate (HDR) radiation therapy boost. An increased rate of GI toxicity when Bevacizumab is administered in combination with high doses of abdominal radiation therapy such as stereotactic body radiotherapy (SBRT) has been demonstrated in other malignancies. Our aim is to compare the risk of Grade 3+ toxicity in patients who receive Bevacizumab after HDR brachytherapy in comparison with other risk factors.Patients with locally advanced cervical cancer treated with CRT from 2010-2019 in a single academic institution were included. Records were reviewed for demographic information, treatment details, toxicities, and outcomes. Patients with and those without severe late gastrointestinal (GI) toxicity and severe late genitourinary (GU) toxicity were compared. Progression free-survival (PFS) was also compared between groups. Smoking status was classified as current smokers, former smokers and non-smokers. Statistical comparisons were performed using t-tests and ANOVA tests.Of 101 patients identified, 10.9% had severe grade 3+ GI toxicity, and 9.1% had severe grade 3+ GU toxicity. Mean duration to follow up was 30 months (range 1-124 months). In patients who received Bevacizumab after completion of definitive treatment, there was a significantly higher rate of Grade 3+ GI or GU toxicity (50% versus 16%, P = 0.005). 83% of Grade 3+ toxicity in the Bevacizumab group was GI related. There was no correlation between the time interval between radiation and Bevacizumab initiation to toxicity. Age was also significantly associated with toxicity, patients 55 and younger had a 10% rate of Grade 3+ toxicity while patients older than 55 had a 28% rate (P = 0.02). Patient who received interstitial versus intracavitary brachytherapy technique also demonstrated high rates of toxicity (30% vs. 8%, P = 0.002). PFS was similar among patients with severe toxicities compared to those without toxicity. In regards to smoking status, there was no significant difference in toxicity. Risk of recurrence was higher in the current smokers and former smokers (40% and 31% respectively) but did not reach statistical significance when compared to non-smokers (25%).In patients with locally advanced cervical cancer, the use of Bevacizumab is significantly associated with increased toxicity after definitive chemoradiation. Similar data has been shown in patients who receive Bevacizumab and abdominal SBRT. Given that the addition of Bevacizumab is first-line therapy and improves survival for recurrent cervical cancer, further investigation is warranted to determine how to optimize the risk-benefit ratio.S. Azghadi: None. P.L. Beagen: None. A. Ahmed: None. R.K. Valicenti: None. R.A. Brooks: None. X. Zhao: None.