Evaluation of a comprehensive set of normal tissue complication probability models for patients with head and neck cancer in an international cohort

Background/purpose: Normal tissue complication probability (NTCP) models can be used to guide radiation therapy (RT) decisions by estimating side-effect risks pretreatment to minimize (late) side-effects. Recently, a comprehensive individual toxicity risk (CITOR) profile of NTCP models addressing common side-effects in head and neck cancer (HNC) patients was developed. This study investigates the generalizability of these models in an international setting, with different treatment approaches and side-effect assessments, promoting their integration into more widespread clinical practice. Materials/methods: From a prospective registry study, 407 HNC patients were included who were treated with definitive RT with or without systemic therapy between 2015 and 2022. 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 the PSS-HN diet normalcy score. Model performance was appraised by discrimination (area under the curve [AUC]) and calibration. Results: CITOR models showed moderate-to-high performance in this cohort (mean AUC = 0.67[range = 0.55-0.80], moderate-to-good calibration). 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. Conclusion: Despite differences between the CITOR development and this evaluation cohort, including use of different side-effect scoring systems, most models exhibited moderate-to-high performance. This demonstrated that the dose-effect relations were generalizable. Therefore, this study supports further integration of these NTCP models in clinical practice.