ObjectiveThe early response to concurrent chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) is closely correlated with prognosis. In this study, we aimed to predict early response using a combined model that combines sub-regional radiomics features from multi-sequence MRI with clinically relevant factors. MethodsA total of 104 patients with LA-NPC were randomly divided into training and test cohorts at a ratio of 3:1. Radiomic features were extracted from subregions within the tumor area using the K-means clustering method, and feature selection was performed using LASSO regression. Four models were established: a radiomics model, a clinical model, an Intratumor Heterogeneity (ITH) score-based model and a combined model that integrates the ITH score with clinical factors. The predictive performance of these models was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). ResultsAmong the models, the combined model incorporating the ITH score and clinical factors exhibited the highest predictive performance in the test cohort (AUC=0.838). Additionally, the models based on ITH score showed superior prognostic value in both the training cohort (AUC=0.888) and the test cohort (AUC=0.833). ConclusionThe combined model that integrates the ITH score with clinical factors exhibited superior performance in predicting early response following concurrent chemoradiotherapy in patients with LA-NPC.