Description: Publication date: Available online 28 June 2018 Source: Radiotherapy and Oncology Author(s): Mona Kamal, Abdallah S.R. Mohamed, Stefania Volpe, Jhankruti Zaveri, Martha Portwood Barrow, G. Brandon Gunn, Stephen Y. Lai, Renata Ferrarotto, Jan S. Lewin, David I. Rosenthal, Amit Jethanandani, Mohamed Ahmed Mohamed Meheissen, Samuel L. Mulder, Carlos E. Cardenas, Clifton D. Fuller, Katherine A. Hutcheson Purpose Our primary aim was to prospectively validate retrospective dose–response models of chronic radiation-associated dysphagia (RAD) after intensity modulated radiotherapy (IMRT) for oropharyngeal cancer (OPC). The secondary aim was to validate a grade ≥2 cut-point of the published videofluoroscopic dysphagia severity (Dynamic Imaging Grade for Swallowing Toxicity, DIGEST) as radiation dose-dependent. Material and methods Ninety-seven patients enrolled on an IRB-approved prospective registry protocol with stage I–IV OPC underwent pre- and 3–6 month post-RT videofluoroscopy. Dose–volume histograms (DVH) for swallowing regions of interest (ROI) were calculated. Dysphagia severity was graded per DIGEST criteria (dichotomized with grade ≥2 as moderate/severe RAD). Recursive partitioning analysis (RPA) and Bayesian Information Criteria (BIC) were used to identify dose–volume effects associated with moderate/severe RAD. Results 31% developed moderate/severe RAD (i.e. DIGEST grade ≥2) at 3–6 months after RT. RPA found DVH-derived dosimetric parameters of geniohyoid/mylohyoid (GHM), superior pharyngeal constrictor (SPC), and supraglottic region were associated with DIGEST grade ≥2 RAD. V61 ≥ 18.57% of GHM demonstrated optimal model performance for prediction of DIGEST grade ≥2. Conclusion The findings from this prospective longitudinal registry validate prior observations that dose to submental musculature predicts for increased burden of dysphagia after oropharyngeal IMRT. Findings also support dichotomization of DIGEST grade ≥2 as a dose-dependent split for use as an endpoint in trials or predictive dose–response analysis of videofluoroscopy results.