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Purpose: Dysphagia is a common toxicity after head and neck (HN) radiation therapy that negatively affects quality of life. We explored the relationship between radiation therapy dose to normal HN structures and dysphagia 1 year after treatment using image-based datamining (IBDM), a voxel-based analysis technique., Methods and Materials: We used data from 104 patients with oropharyngeal cancer treated with definitive (chemo)radiation therapy. Swallow function was assessed pretreatment and 1 year posttreatment using 3 validated measures: MD Anderson Dysphagia Inventory (MDADI), performance status scale for normalcy of diet (PSS-HN), and water swallowing test (WST). For IBDM, we spatially normalized all patients' planning dose matrices to 3 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 pretreatment 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 the Akaike information criterion. We also compared the prediction performance of the identified region with a well-established association: mean doses to the pharyngeal constrictor muscles., Results: IBDM revealed highly significant associations between dose to distinct regions and the 3 outcomes. These regions overlapped around the inferior section of the brain stem. All clinical models were significantly improved by including mean dose to the overlap region (P ≤ .006). Including pharyngeal dosimetry significantly improved WST (P = .04) but not PSS-HN or MDADI (P ≥ .06)., Conclusions: In this hypothesis-generating study, we found that mean dose to the inferior section of the brain stem is strongly associated with dysphagia 1 year posttreatment. The identified region includes the swallowing centers in the medulla oblongata, providing a possible mechanistic explanation. Further work including validation in an independent cohort is required., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: For patients with lung cancer treated with radiation therapy, a dose to the heart is associated with excess mortality; however, it is often not feasible to spare the whole heart. Our aim is to define cardiac substructures and dose thresholds that optimally reduce early mortality., Methods and Materials: Fourteen cardiac substructures were delineated on 5 template patients with representative anatomies. One thousand one hundred sixty-one patients with non-small cell lung cancer were registered nonrigidly to these 5 template anatomies, and their radiation therapy doses were mapped. Mean and maximum dose to each substructure were extracted, and the means were evaluated as input to prediction models. The cohort was bootstrapped into 2 variable reduction techniques: elastic net least absolute shrinkage and selection operator and the random survival forest model. Each method was optimized to extract variables contributing most to overall survival, and model coefficients were evaluated to select these substructures. The most important variables common to both models were selected and evaluated in multivariable Cox-proportional hazard models. A threshold dose was defined, and Kaplan-Meier survival curves plotted., Results: Nine hundred seventy-eight patients remained after visual quality assurance of the registration. Ranking the model coefficients across the bootstraps selected the maximum dose to the right atrium, right coronary artery, and ascending aorta as the most important factors associated with survival. The maximum dose to the combined cardiac region showed significance in the multivariable model, a hazard ratio of 1.01/Gy, and P = .03 after accounting for tumor volume (P < .001), N stage (P < .01), and performance status (P = .01). The optimal threshold for the maximum dose, equivalent dose in 2-Gy fractions, was 23 Gy. Kaplan-Meier survival curves showed a significant split (log-rank P = .008)., Conclusions: The maximum dose to the combined cardiac region encompassing the right atrium, right coronary artery, and ascending aorta was found to have the greatest effect on patient survival. A maximum equivalent dose in 2-Gy fractions of 23 Gy was identified for consideration as a dose limit in future studies., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)