Radiotherapy dose-volume parameters predict videofluoroscopy-detected dysphagia per DIGEST after IMRT for oropharyngeal cancer: Results of a prospective registry

Abstract

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.

Keywords: DIGEST; Dose–volume; Dysphagia; Intensity-modulated radiation therapy; Oropharyngeal cancer; Radiotherapy.

Figure 1.

Distribution of videofluoroscopic dysphagia grade pre and post-RT (per DIGEST) (n=97). Abbreviations: DIGEST; Dynamic Imaging Grade for Swallowing Toxicity, RT; Radiotherapy.

Figure 2.

Mean dose for all ROIs by dysphagia status (per DIGEST grade) 3–6 months post-RT (n=97). ★Statistically Significant after Bonferroni correction. Abbreviations: ROIs; region of interests, (S/M/IPC); Superior/ middle/inferior pharyngeal constrictors, ITM; intrinsic tongue muscle, Ant; anterior.

Figure 3.

Dose volume histograms stratified by dysphagia classification (per DIGEST) 3–6 months after RT (n=97). Abbreviations: ROIs; region of interests, ADM; anterior digastrics muscle, CPM; cricopharyngeal muscle, GGM genioglossus muscle, GHM geniohyoid muscle, (S/M/IPC); Superior/ middle/inferior pharyngeal constrictors, MHM; mylohyoid, ITM; intrinsic tongue muscle. Heatmap of statistical significance for utilized analyses, is displayed below each ROI DVH to quantify the magnitude of p-values for each 1-Gy bin, allowing visual representation of Bonferroni correction. Solid blue squares denote lack of statistical significance, while solid red squares indicate statistical significance under strict multiple-comparison correction.