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], [2], [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], [5], [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], [8], [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], [11], [12], [13], [14] Exploratory replanning analyses suggest these candidate constraints may be technically achievable and warrant prospective validation before clinical implementation.