Risk factors and dose-effects for bladder fistula, bleeding and cystitis after radiotherapy with imaged-guided adaptive brachytherapy for cervical cancer: An EMBRACE analysis.

Abstract

PURPOSE\nTo identify patient- and treatment-related risk factors for fistula, bleeding, cystitis, pain and difficulty in voiding in locally advanced cervical cancer patients treated with radio(chemo)therapy and image-guided adaptive brachytherapy (IGABT).\n\n\nMATERIAL AND METHODS\nMorbidity within the EMBRACE-I study was prospectively reported for physician-assessed (CTCAE) fistula, bleeding and cystitis and patient-reported (EORTC) pain and difficulty in voiding. Analysis of risk factors was performed in patients without bladder infiltration. Risk factors were tested with Cox regression for grade (G)\xa0≥\xa03 cystitis, for G\xa0≥\xa02 fistula, bleeding and cystitis, and for EORTC very much and quite a bit or worse.\n\n\nRESULTS\nOf 1416 patients enrolled, 1153 and 884 patients without bladder infiltration were evaluable for the analysis of CTCAE and EORTC items, respectively. Median follow-up was 48[3-120] months. Crude incidence rates for G\xa0≥\xa02 fistula, bleeding and cystitis were 0.7%, 2.7% and 8.8%, respectively, and 16% and 14% for quite a bit or worse pain and difficulty in voiding, respectively. Baseline urinary morbidity and overweight/obesity were significant risk factors for most endpoints. Bladder D2cm3 correlated with G\xa0≥\xa02 fistula, bleeding and cystitis, while ICRU bladder point dose correlated with EORTC pain quite a bit or worse. An increase from 75\xa0Gy to 80\xa0Gy in bladder D2cm3 resulted in an increase from 8% to 13% for 4-year actuarial estimate of G\xa0≥\xa02 cystitis.\n\n\nCONCLUSION\nClinical and treatment-related risk factors for bladder fistula, bleeding and cystitis were identified within a prospective and multi-institutional setting. A dose-effect was established with bladder D2cm3, reinforcing the importance of continued optimization during individualized IGABT planning.