Dysphagia at 1 year is associated with mean dose to the inferior section of the brainstem

Abstract

Purpose: Dysphagia is a common toxicity after head and neck (HN) radiotherapy that negatively affects quality of life. We explored the relationship between radiotherapy dose to normal HN structures and dysphagia one year after treatment using image-based datamining (IBDM), a voxel-based analysis technique. Materials and methods: We used data from 104 oropharyngeal cancer patients treated with definitive (Chemo)RT. Swallow function was assessed pre-treatment and 1 year after treatment using three validated measures: M.D. Anderson Dysphagia Inventory (MDADI), performance status scale for normalcy of diet (PSS-HN), and water swallowing test (WST). For IBDM, we spatially normalised all patients' planning dose matrices to three reference anatomies. Regions where the dose was associated with dysphagia measures at 1 year were found by performing voxel-wise statistics and permutation testing. Clinical factors, treatment variables and pre-treatment measures were used in multivariable analysis to predict each dysphagia measure at 1 year. Clinical baseline models were found using backward stepwise selection. Improvement in model discrimination after adding the mean dose to the identified region was quantified using Akaike information criterion. We also compared the prediction performance of the identified region to a well-established association: mean doses to the pharyngeal constrictor muscles. Results: IBDM revealed highly significant associations between dose to distinct regions and the three outcomes. These regions overlapped around the inferior section of the brainstem. All clinical models were significantly improved by including mean dose to the overlap region (p≤0.006). Including pharyngeal dosimetry only significantly improved WST (p=0.04), but not PSS-HN nor MDADI (p≥0.06). Conclusions: In this hypothesis-generating study, we found that mean dose to the inferior section of the brainstem is strongly associated with dysphagia 1 year after treatment. The identified region includes the swallowing centres in the medulla oblongata, providing a possible mechanistic explanation. Further work including validation in an independent cohort is required.