A low skeletal muscle index (SMI), defined with cut-off values, is a promising predictor for adverse events (AEs) in head and neck squamous cell cancer (HNSCC) patients. The aim was to generate sex-specific SMI cut-off values based on AE to diagnose low SMI and to analyse the relationship between low SMI and AEs in HNSCC patients. In this present study, HNSCC patients were prospectively included in a large oncological data-biobank and SMI was retrospectively measured using baseline neck scans. In total, 193 patients were included and were stratified according to treatment modality: (chemo-)radiotherapy ((C)RT) (n = 135) and surgery (n = 61). AE endpoints were based on the occurrence of clinically relevant toxicities (Common Terminology Criteria for Adverse Events grade ≥ III) and postoperative complications (Clavien–Dindo Classification grade ≥ II). Sex-specific SMI cut-off values were generated with receiver operating characteristic curves, based on the AE endpoints. The relationship of the baseline characteristics and AEs was analysed with logistic regression analysis, with AEs as the endpoint. Multivariable logistic analysis showed that low SMI (OR 3.33, 95%CI 1.41–7.85) and tumour stage (OR 3.45, 95%CI 1.28–9.29) were significantly and independently associated to (C)RT toxicity. Low SMI was not related to postoperative complications. To conclude, sex-specific SMI cut-off values, were generated based on the occurrence of AEs. Low SMI and tumour stage were independently related to (C)RT toxicity in HNSCC patients.

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. 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. 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. 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.

Background/Objectives: Studies have shown that dose to the parotid gland stem cell rich (SCR) regions should be reduced to lower the risk of xerostomia after radiotherapy (RT). This study aimed to assess whether stem cell sparing (SCS)-RT can be adopted in routine clinical practice. Methods: Multiple planning studies were performed to compare SCS-RT with standard (ST)-RT using 30 head and neck cancer patients. Shifts in mean dose to the SCR regions (D_mean,SCR) and other organs at risk and their estimated impact on normal tissue complication probability (NTCP) for side-effects were compared using Wilcoxon signed-rank test. A multicenter study was performed (eight institutions, three patients) to test the generalizability of SCS-RT using the Friedman test. Results: Using photons, D_mean,SCR was reduced with median 4.1/3.5 Gy for ipsilateral/contralateral (p < 0.001). The largest reductions were when the SCR regions overlapped less with target volumes. Subsequently, NTCPs for xerostomia decreased (p < 0.001). Using protons, D_mean,SCR was also reduced (2.2/1.9 Gy for ipsilateral/contralateral, p < 0.002). Nevertheless, SCS-RT did not further decrease NTCPs for xerostomia (p > 0.17). Target coverage and prevention of other side-effects were not compromised. However, increased mean oral cavity dose was observed in some patients. Lastly, in the multicenter study D_mean,SCR could be reduced by slightly adjusting the standard optimization. Contralateral D_mean,SCR reductions differed between centers (p = 0.01), which was attributed to differences in ST-RT plans. Conclusions: Stem cell sparing radiotherapy can be clinically introduced by making small adjustments to the optimization strategy and can reduce the risk of xerostomia.