NTCP Models Predicting Bowel Toxicity After Total Neoadjuvant Treatment or Chemoradiation for Rectal Cancer in the...

Radiation-induced bowel toxicity is a frequently observed adverse event after rectal cancer treatment. In the phase 3 Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial, patients with locally advanced rectal cancer received either short-course radiation therapy (SCRT, 5 × 5 Gy) with consolidation chemotherapy (total neoadjuvant treatment [TNT] arm) or chemoradiation (CRT) with optional postoperative chemotherapy (CRT arm). We developed normal tissue complication probability models for bowel toxicity after SCRT-based TNT and CRT, using 2 different bowel contour definitions.

Normal tissue complication probability models were developed for each arm separately using the Image guided intensity modulated External beam radiochemotherapy and MRI based adaptive BRAchytherapy in locally advanced CErvical cancer (EMBRACE) and Radiation Therapy Oncology Group (RTOG) bowel contours. Evaluated dose-parameters were the V_10Gy, V_15Gy, and V_20Gy in the TNT and V_15Gy, V_30Gy, and V_40Gy in the CRT arm. Endpoints included acute diarrhea grade ≥2, noncompliance with preoperative chemotherapy, late diarrhea grade ≥1, and patient-reported late diarrhea. Associations were assessed with uni- and multivariable logistic regression models, and model performance with the area-under-the-curve (AUC) and calibration plots.

The numbers of eligible patients in the TNT arm were 309 (acute toxicity), 221 (late diarrhea grade ≥1), and 209 (patient-reported late diarrhea), whereas in the CRT arm respective numbers were 279, 191, and 190. Acute diarrhea grade ≥2 was reported in 38% (TNT) and 28% (CRT) of the patients. All dose-parameters (from both bowel contours) showed comparable associations with the endpoint acute diarrhea grade ≥2. In the TNT arm, P-values ranged from .003 to .08 and cross-validated AUCs from 0.48 to 0.61. In the CRT arm, P-values ranged from <.001 to .03 and cross-validated AUCs from 0.56 to 0.67. All models were reasonably well calibrated. In addition, associations were observed between dose-parameters and late diarrhea grade ≥1 in the CRT arm.

The evaluated dose-parameters were able to predict acute diarrhea after SCRT-based TNT and CRT, and late diarrhea after CRT. Model performance was better in the CRT arm than the TNT arm. Both the EMBRACE bowel loop and RTOG bowel bag contour can be used to guide treatment plan optimization.