Chronic Radiation-Associated Dysphagia in Oropharyngeal Cancer Survivors: Towards Age-Adjusted Dose Constraints for Deglutitive Muscles

Objectives: We sought to model chronic radiation-associated dysphagia (RAD) in patients given intensity-modulated radiation therapy (IMRT) for oropharyngeal squamous cell cancer (OPSCC) as a function of age and dose to non-target swallowing muscles. Methods: We reviewed 300 patients with T1-T4 N0-3 M0 OPSCC given definitive IMRT with concurrent chemotherapy. Chronic RAD was defined as aspiration or stricture on videoflouroscopy/endoscopy, gastrostomy tube, or aspiration pneumonia at >= 12 months after IMRT. Doses to autosegmented regions of interest (ROIs; inferior, middle and superior constrictors, anterior and posterior digastrics, mylo/geniohyoid complex, intrinsic tongue, and gengioglossus) were obtained from DICOM-RT plans and dose-volume histograms. The probability of chronic RAD as a function of mean ROI dose, stratified by age (<50, 50-59, 60-69, or >70 years), was estimated with logistic probability models and subsequent unsupervised nonlinear curves. Results: Chronic RAD was observed in 34 patients (11%). Age was a significant correlate of chronic RAD, both independently and with dose for all muscle groups examined. Distinct muscle-specific dose-response profiles were observed as a function of age (e.g., 5% of patients in their 50 s [but 20% of those 70 +] who received 60 Gy to the superior constrictor had chronic RAD). This effect was stable across all observed muscle ROIs, with a false discovery rate-corrected p < 0.05, for all dose/muscle/age models, suggesting that including age as a covariate improves modeling of chronic RAD. Conclusions: Age at treatment moderates the probability of chronic RAD after chemo-IMRT for OPSCC, with aging muscles showing lower dose thresholds. Uniform dose constraints may not predict toxicity in older patients. (C) 2019 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.