Dosimetric Predictors of Patient-Reported Xerostomia and Dysphagia With Deintensified Chemoradiation Therapy for HPV-Associated Oropharyngeal Squamous Cell Carcinoma

Purpose/Objective(s) To estimate the association between different dose-volume metrics of the salivary glands and pharyngeal constrictors with patient reported severity of xerostomia/dysphagia in the setting of deintensified chemoradiation therapy (CRT). Methods and Materials Forty-five patients were treated on a phase 2 study assessing the efficacy of deintensified CRT for favorable-risk, HPV-associated oropharyngeal squamous cell carcinoma. Patients received 60 Gy intensity modulated radiation therapy with concurrent weekly cisplatin (30 mg/m²), and reported the severity of their xerostomia/dysphagia (before and after treatment) using the patient-reported outcome version of the Common Terminology Criteria for Adverse Events (CTCAE) (PRO-CTCAE). Individual patient dosimetric data of the contralateral parotid and submandibular glands and pharyngeal constrictors were correlated with changes in PRO-CTCAE severity. A change in severity (from baseline) of ≥2 was considered clinically meaningful. Associations between dose-volume metrics and patient outcomes were assessed with receiver operating characteristic (ROC) curve and logistic regression model. Results Six months after CRT, patients reporting <2 change in xerostomia severity (n=14) had an average D_mean = 22 ± 9 Gy to the sum of the contralateral glands (parotid + submandibular) compared with the patients reporting ≥2 change (n=21), who had an average D_mean = 34 ± 8 Gy. V15 to V55 for the combined contralateral glands showed the strongest association with xerostomia (area under the curve [AUC] = 0.83-0.86). Based on the regression analysis, a 20% risk of toxicity was associated with V15 = 48%, V25 = 30%, and D_mean=21 Gy. Six months after CRT, patients reporting <2 change in dysphagia severity (n=26) had an average V55 = 76 ± 13 (%) to the superior pharyngeal constrictor compared with the patients reporting ≥2 change in severity (n=9), who had average V55 = 89 ± 13 (%). V55to V60 had the strongest association with dysphagia (AUC = 0.70-0.75). Based on the regression analysis, a 20% risk of toxicity was associated with V55 = 78%, V60 = 40%. The findings at 12 months were similar. Conclusions After deintensified CRT, the rate of patient-reported xerostomia/dysphagia appears to be associated with the V15 of the combined contralateral salivary glands and V55 to V60 of the superior pharyngeal constrictors.