Normal tissue complication probability modeling of radiation-induced neck fibrosis in head and neck Cancer survivors: a patient-reported outcome–based analysis

Purpose Skin and soft tissue fibrosis of the neck is a common late toxicity after head and neck radiotherapy (Muehlebach et al., 2025; Ramia et al., 2022; Strojan et al., 2017 [1–3]), yet no dedicated patient-reported outcome (PRO) instrument exists to capture its specific functional and quality-of-life (QOL) impact. Renslo et al. (2024), Shaw et al. (2016) [4–6] This study evaluates a fibrosis-directed PRO adapted from scleroderma research and explores dosimetric correlates and normal tissue complication probability (NTCP) relationships for neck fibrosis. [7] Materials and Methods In an IRB-approved prospective trial, 95 patients in remission after curative-intent head and neck radiotherapy completed the EORTC QLQ-C30, QLQ-H&N43, and the 22-item Scleroderma Skin Patient-Reported Outcome (SSPRO) instrument. [7–9] Neck organs at risk (OARs) constituting skin, subcutaneous tissue, and sternocleidomastoid (SCM) muscle were retrospectively contoured; dose–volume metrics are analyzed using Lyman–Kutcher–Burman (LKB) NTCP modeling. Results All 95 patients completed SSPRO, QLQ-C30, and QLQ-H&N43. Correlation analyses showed moderate-to-strong associations between SSPRO and established QOL instruments. SSPRO total scores categorized using pre-specified thresholds (mild 0–20, moderate 21–40, severe ≥41) showed 64.4% mild, 20.0% moderate, and 15.6% severe fibrosis-related symptom burden. In non-surgical patients, higher mean dose and selected V_x metrics to skin, SCM, and subcutaneous tissue were positively associated with worsening SSPRO scores, whereas no robust dose–response was seen in surgically treated patients. Conclusions SSPRO captures neck fibrosis–related QOL impairment that is incompletely reflected by standard head and neck QOL instruments. PRO-anchored NTCP modeling suggests that dose to skin, SCM, and subcutaneous tissue predicts fibrosis-related PRO deterioration in non-surgical patients. Eisbruch et al. (1999, 2004), Murdoch-Kinch et al. (2008), Nutting et al. (2011) [10–14] Exploratory replanning analyses suggest these candidate constraints may be technically achievable and warrant prospective validation before clinical implementation.