Severity and Persistency of Late Gastrointestinal Morbidity in Locally Advanced Cervical Cancer: Lessons Learned From EMBRACE-I and Implications for the Future

Authors Sofia Spampinato, Nina B K Jensen, Richard Pötter, Lars U Fokdal, Cyrus Chargari, Jacob C Lindegaard, Maximilian P Schmid, Alina Sturdza, Ina M Jürgenliemk-Schulz, Umesh Mahantshetty, Peter Hoskin, Barbara Segedin, Bhavana Rai, Kjersti Bruheim, Ericka Wiebe, Elzbieta Van der Steen-Banasik, Rachel Cooper, Erik Van Limbergen, Marit Sundset, Bradley R Pieters, Ludy C H W Lutgens, Li Tee Tan, Elena Villafranca, Stéphanie Smet, Noha Jastaniyah, Remi A Nout, Christian Kirisits, Supriya Chopra, Kathrin Kirchheiner, Kari Tanderup, Embrace Collaborative Group

Source Int J Radiat Oncol Biol Phys. 2022 Mar 1;112(3):681-693 Publicationdate 20 Oct 2021

Abstract

Purpose: The purpose was to evaluate patient- and treatment-related risk factors for physician-assessed and patient-reported gastrointestinal (GI) symptoms after radio(chemo)therapy and image guided adaptive brachytherapy in locally advanced cervical cancer.

Methods and materials: Of 1416 patients from the EMBRACE-I study, 1199 and 1002 were prospectively evaluated using physician-assessed (Common Terminology Criteria for Adverse Events [CTCAE]) and patient-reported (European Organization for Research and Treatment of Cancer [EORTC]) GI symptoms, respectively. CTCAE severe grade (grade [G] ≥3) events were pooled according to the location in the GI tract (anus/rectum, sigmoid, and colon/small bowel). CTCAE G ≥2 and EORTC "very much" and "quite a bit" plus "very much" scores (≥ "quite a bit") were analyzed for individual symptoms with Cox regression. Logistic regression was used for persistent G ≥1 and EORTC ≥ "quite a bit" symptoms, defined if present in at least half of follow-ups.

Results: The incidence of G ≥3 events was 2.8%, 1.8%, and 2.3% for G ≥3 anus/rectum, sigmoid, and colon/small bowel events, respectively. Among G ≥2 symptoms, diarrhea and flatulence were the most prevalent (8.5% and 9.9%, respectively). Among patient-related factors, baseline morbidity, increasing age, smoking status, and low body mass index were associated with GI symptoms to varying degrees. Among treatment-related factors, rectum D_2cm3 and the International Commission on Radiation Units and Measurements recto-vaginal reference point (ICRU RV-RP) correlated with G ≥3 anus/rectum events and moderate/persistent diarrhea, proctitis, bleeding, abdominal cramps, and difficulty in bowel control. Bowel D_2cm3 correlated with G ≥3 sigmoid and colon/small bowel events and moderate/persistent diarrhea and flatulence. For external beam radiation therapy (EBRT), prescription dose correlated with G ≥3 anus/rectum, diarrhea, and difficulty in bowel control. Patients with large lymph-node boost (V57Gy) were at higher risk for G ≥3 sigmoid events, moderate/persistent diarrhea, proctitis, and cramps.

Conclusions: The analysis showed that both EBRT and image guided adaptive brachytherapy contribute to GI symptoms after locally advanced cervical cancer treatment. Rectum D_2cm3, ICRU RV-RP , and bowel D_2cm3 are risk factors for GI morbidity. The risk for various symptoms was lower with an EBRT prescription of 45 Gy than 50 Gy and increased with larger V57Gy.