Dose-Volume Effects and Risk Factors for Late Diarrhea in Cervix Cancer Patients After Radiochemotherapy With Image Guided Adaptive Brachytherapy in the EMBRACE I Study

Purpose: To evaluate patient- and treatment-related risk factors associated with incidence and persistence of late diarrhea after radiochemotherapy and image guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer. Materials and Methods: Of 1416 patients from the EMBRACE I study, 1199 were prospectively evaluated using physician-reported (Common Terminology Criteria for Adverse Events version 3 [CTCAEv3]) assessment for diarrhea; median follow-up 48 months. Patient-reported outcome (EORTC) was available in 900 patients. Incidence of CTCAE G >= 2, G >= 3, and EORTC very much diarrhea was analyzed with Cox proportional hazards regression. Binary logistic regression was used for analysis of persistent G >= 1 and EORTC quite a bit - very much (>=quite a bit) diarrhea, defined if present in at least half of all follow-ups. Results: Crude incidences of G >= 2 and G >= 3 diarrhea were 8.3% and 1.5%, respectively, and 8% of patients reported very much diarrhea. Persistent G >= 1 and >=quite a bit diarrhea was present in 16% and 7%, respectively. Patient-related risk factors were baseline diarrhea, smoking, and diabetes with hazard ratios of 1.4 to 7.3. Treatment-related risk factors included prescribed dose, V43 Gy, V57 Gy (lymph node boost), and para-aortic irradiation for external beam radiation therapy (EBRT). G >= 2 diarrhea at 3 years increased from 9.5% to 19.9% with prescribed dose 45 Gy versus 50 Gy, 8.7% to 14.0% with V43 Gy <2500 cm(3) versus >3000 cm(3) and 9.4% to 19.0% with V57 Gy <165 cm(3) versus >= 165 cm(3). Brachytherapy-related bowel and rectum D-2cm3 were also associated with diarrhea. Conclusion: Dose and volume effects have been established for late diarrhea after radiochemotherapy and IGABT in both CTCAE and EORTC reporting. The risk of diarrhea was lower with a pelvic EBRT prescription of 45 Gy, and higher with larger lymph node boosts volumes (ie, >= 165 cm(3)). The importance of EBRT volumes as determinants of late toxicity underline the need for continuous quality assurance of target contouring, dose planning, and conformity. The findings of brachytherapy dosimetric factors related to the intestines may become more important with highly conformal EBRT. (C) 2020 Elsevier Inc. All rights reserved.

Automated summary

The study evaluated patient- and treatment-related risk factors associated with late diarrhea after radiochemotherapy and image guided adaptive brachytherapy in locally advanced cervical cancer. Dose and volume effects were established for late diarrhea, with the importance of EBRT volumes as determinants of late toxicity emphasized.