Evaluation of CITOR NTCP models in HNC patients treated at MDACC

<b>Background and purpose:</b> Normal tissue complication probability (NTCP) models can be used to guide radiation therapy (RT) treatment planning and select the optimal technique to minimize side-effects. The comprehensive individual toxicity risk (CITOR) profile encompasses NTCP models for 22 common side-effects experienced by head and neck cancer (HNC) patients. To investigate the generalizability of these models, even with different side-effect assessments, and to promote integration into clinical practice, this study aimed to evaluate the performance of several CITOR models in HNC patients treated with RT at the MD Anderson Cancer Center (MDACC).<b>Material/methods:</b> In total, 407 patients from a prospective registry study with oropharyngeal cancer or an unknown primary HNC tumor treated with definitive RT with or without systemic therapy between 2015 and 2022 were included. NTCP models predicting dysphagia, aspiration, xerostomia, sticky saliva, taste loss, speech problems, oral pain, and fatigue at 6 and 12 months after RT were evaluated. All side-effects were patient-rated using the MDASI-HN, except dysphagia which was reported by clinicians using PSS-HN diet normalcy score. Model performance was appraised by discrimination (area under the curve (AUC)), calibration, and explained variance (R²).<b>Results</b>: CITOR models showed moderate-to-high performance in the MDACC cohort (mean AUC=0.67, often slight overestimation of the predicted risk, range R²=0.02-0.28). NTCP models for dysphagia, xerostomia, sticky saliva, and fatigue were the top performing models. Models for aspiration, taste loss and speech problems performed moderately well, which was partly explained by lower incidences.<b>Conclusion: </b>Despite differences between the CITOR development and MDACC validation cohorts, including use of different side-effect assessment tools, most models exhibited moderate-to-high performance, demonstrating that the dose-effect relations as described in the models were generalizable. Therefore, this study supports further integration of these NTCP models in clinical practice, especially of the NTCP models predicting dysphagia, xerostomia, sticky saliva, and fatigue.