Beyond mean pharyngeal constrictor dose for beam path toxicity in non-target swallowing muscles: Dose-volume correlates of chronic radiation-associated dysphagia (RAD) after oropharyngeal intensity modulated radiotherapy

Abstract

Purpose/objective(s): We sought to identify swallowing muscle dose-response thresholds associated with chronic radiation-associated dysphagia (RAD) after IMRT for oropharyngeal cancer.

Materials/methods: T1-4 N0-3 M0 oropharyngeal cancer patients who received definitive IMRT and systemic therapy were examined. Chronic RAD was coded as any of the following ⩾12months post-IMRT: videofluoroscopy/endoscopy detected aspiration or stricture, gastrostomy tube and/or aspiration pneumonia. DICOM-RT plan data were autosegmented using a custom region-of-interest (ROI) library and included inferior, middle and superior constrictors (IPC, MPC, and SPC), medial and lateral pterygoids (MPM, LPM), anterior and posterior digastrics (ADM, PDM), intrinsic tongue muscles (ITM), mylo/geniohyoid complex (MHM), genioglossus (GGM), masseter (MM), buccinator (BM), palatoglossus (PGM), and cricopharyngeus (CPM), with ROI dose-volume histograms (DVHs) calculated. Recursive partitioning analysis (RPA) was used to identify dose-volume effects associated with chronic-RAD, for use in a multivariate (MV) model.

Results: Of 300 patients, 34 (11%) had chronic-RAD. RPA showed DVH-derived MHM V69 (i.e. the volume receiving⩾69Gy), GGM V35, ADM V60, MPC V49, and SPC V70 were associated with chronic-RAD. A model including age in addition to MHM V69 as continuous variables was optimal among tested MV models (AUC 0.835).

Conclusion: In addition to SPCs, dose to MHM should be monitored and constrained, especially in older patients (>62-years), when feasible.

Keywords: Dose–volume; Dysphagia; Geniohyoid; Intensity-modulated radiation therapy; Mylohyoid; Oropharyngeal cancer.

Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Figures

Figure 1. Exemplar swallow-related ROI

Axial, coronal, and sagittal images of the contoured segments. Abbreviations: GGM – Genioglossus Muscle; HP – Hard Palate; IPC – Inferior Pharyngeal Constrictor; ITM – Intrinsic Tongue Muscles; LPM – Lateral Pterygoid Muscle; MHM – Mylo/geniohyoid Complex; MM – Masseter Muscle; MPM – Medial Pterygoid Muscle; PDM – Posterior Dygastric Muscle; SP – Soft Palate; SPC – Superior Pharyngeal Constrictor, R.-right, L.-left.

Figure 2. Swallow-related ROI DVH stratified by chronic-RAD

Note non-overlapping confidence intervals of dose in 1-Gy bins visually suggests a magnitude difference of p

Figure 3. Observed and Predicted probabilities of chronic-RAD by age and MHMV69

Observed nominal logistic continuous variable regressor-response plots for age (3a) and MHM V69 (3b). Bootstrap estimated population probability of Chronic-RAD plots for age (3c) and MHM V69 (3d); points are shown in 5 Gy/5-year “bins” with gray lines representing unsupervised fits across 104 resampled distribution, indicative of the expected range of uncertainty attributable to differentials between the observed sample and the parent oropharyngeal cancer patient true population.

Figure 4. Chronic RAD as a function MHM V69 by Age

Composite plot of MHM V69 (as a continuous variable) and age cohort (green shading denotes the observed whole population; red identifies patients over 62 years of age; blue indicates patients less than 62 years old). Smoothed fits are shown with color-specific ellipses covering 95% of observed values for each cohort as a visual uncertainty estimator.