ESTRO 2025 - Abstract Book

S1156

Clinical – Lower GI

ESTRO 2025

479

Proffered Paper NTCP models for acute bowel toxicity and chemotherapy compliance based on LARC patients treated with 5x5 Gy and chemotherapy in the RAPIDO trial Max D. Tanaka 1 , Tomas M. Janssen 1 , Bas W.K. Schipaanboord 1 , Ane L. Appelt 2,3 , Boudewijn van Etten 4 , Geke A.P. Hospers 5 , Corrie A.M. Marijnen 1,6 , Elma Meershoek-Klein Kranenbarg 7 , Per J. Nilsson 8 , Annet G.H. Roodvoets 7 , Cornelis J.H. van de Velde 7 , Alexander Valdman 9,10 , Bengt Glimelius 11 , Alice M. Couwenberg 1 1 Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands. 2 Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom. 3 Department of Medical Physics, Leeds Cancer Centre, St James's University Hospital, Leeds, United Kingdom. 4 Department of Surgery, University Medical Center Groningen, Groningen, Netherlands. 5 Department of Medical Oncology, University Medical Center Groningen, Groningen, Netherlands. 6 Department of Radiation Oncology, Leiden University Medical Center, Leiden, Netherlands. 7 Department of Surgery, Leiden University Medical Center, Leiden, Netherlands. 8 Department of Pelvic Cancer, Karolinska University Hospital, Stockholm, Sweden. 9 Department of Radiation Oncology, Karolinska University Hospital, Stockholm, Sweden. 10 Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden. 11 Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden Purpose/Objective: Short-course radiotherapy (SCRT) is used in total neoadjuvant treatment (TNT) for locally advanced rectal cancer (LARC). Robust dose-constraints for acute bowel toxicity after SCRT are lacking, especially in the TNT setting, where toxicity could compromise chemotherapy compliance. We aimed to develop normal tissue complication probability (NTCP) models that predict acute bowel toxicity and non-compliance with chemotherapy during TNT for patients with LARC treated in the RAPIDO trial. Material/Methods: High-risk LARC patients treated with TNT (5x5 Gy and 6xCAPOX/9xFOLFOX4) in the RAPIDO trial were included if original DICOM data were available. The CTV consisted of the GTV, mesorectum, pre-sacral/internal iliac lymph nodes, and other regional lymph nodes based on tumor location/growth. Included patients were treated supine. A ‘bowelbag’ according to RTOG-guidelines 1 , and a smaller ‘bowelloop’ contour according to EMBRACE-guidelines 2 , were retrospectively delineated using in-house trained auto-segmentation models, followed by manual revisions. Binary outcomes of interest were (1) acute diarrhea grade >2 (hereafter ‘diarrhea’) vs. grade 0-1 (CTCAEv.4), which included the highest grade recorded during the entire TNT period; and (2) non-compliance with preoperative chemotherapy, defined as failure to receive more than 2/3 of prescribed courses (dose-reductions were allowed). The association between the bowelbag/-loop V 10Gy , V 15Gy and V 20Gy (cc) and outcomes was evaluated with univariable and multivariable logistic regression models, adjusted for baseline diarrhea, BMI, ECOG performance status, and radiation technique (IMRT/VMAT vs. 3D-CRT). Odds ratios were calculated for each 100cc increase in irradiated volume-of-interest (OR 100cc ). Discrimination was measured with the area-under-the-curve (AUC) and calibration by visual inspection of calibration plots. Results: Data were currently available from sixteen radiation centers for 160/468 patients allocated to the TNT arm. All patients completed SCRT and 21% were non-compliant with preoperative chemotherapy. Acute diarrhea was observed in 43% of patients. Bowelbag and bowelloop models demonstrated AUCs ranging from 0.58-0.63 for acute diarrhea and 0.56-0.62 for non-compliance. For both outcomes, the strongest association was observed for the bowelbag V 20Gy model, with p -values of 0.03/0.05 (univariable/multivariable) for acute diarrhea and 0.03/0.03, respectively, for non-compliance. Good calibration was observed for all models. Other covariables were not associated with either outcome. Fig.1&2 show dose-response curves of the univariable bowelbag V 20Gy model for acute diarrhea (OR 100cc =1.20 [95%CI 1.01-1.43]) and non-compliance (OR 100cc =1.24 [95%CI 1.02-1.50]).