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ObjectiveThis study aimed to develop a least absolute shrinkage and selection operator (LASSO)-based multivariable normal tissue complication probability (NTCP) model to predict radiation-induced xerostomia in patients with nasopharyngeal carcinoma (NPC) treated with comprehensive salivary gland–sparing helical tomotherapy technique.Methods and MaterialsLASSO with the extended bootstrapping technique was used to build multivariable NTCP models to predict factors of patient-reported xerostomia relieved by 50% and 80% compared with the level at the end of radiation therapy within 1 year and 2 years, R50-1year and R80-2years, in 203 patients with NPC. The model assessment was based on 10-fold cross-validation and the area under the receiver operating characteristic curve (AUC).ResultsThe prediction model by LASSO with 10-fold cross-validation showed that radiation-induced xerostomia recovery could be predicted by prognostic factors of R50-1year (age, gender, T stage, UICC/AJCC stage, parotid Dmean, oral cavity Dmean, and treatment options) and R80-2years (age, gender, T stage, UICC/AJCC stage, oral cavity Dmean, N stage, and treatment options). These prediction models also demonstrated a good performance by the AUC.ConclusionThe prediction models of R50-1year and R80-2years by LASSO with 10-fold cross-validation were recommended to validate the NTCP model before comprehensive salivary gland–sparing radiation therapy in patients with NPC.