AbstractBackgroundEndoscopic ultrasonography (EUS) is recommended as the best tool for evaluating gastric subepithelial lesions (SELs); nonetheless, it has difficulty distinguishing gastrointestinal stromal tumors (GISTs) from leiomyomas and schwannomas. GISTs have malignant potential, whereas leiomyomas and schwannomas are considered benign.PurposeThis study aimed to establish a combined radiomic model based on EUS images for distinguishing GISTs from leiomyomas and schwannomas in the stomach.MethodsEUS images of pathologically confirmed GISTs, leiomyomas, and schwannomas were collected from five centers. Gastric SELs were divided into training and testing datasets based on random split‐sample method (7:3). Radiomic features were extracted from the tumor and muscularis propria regions. Principal component analysis, least absolute shrinkage, and selection operator were used for feature selection. Support vector machine was used to construct radiomic models. Two radiomic models were built: the conventional radiomic model included tumor features alone, whereas the combined radiomic model incorporated features from the tumor and muscularis propria regions.ResultsA total of 3933 EUS images from 485 cases were included. For the differential diagnosis of GISTs from leiomyomas and schwannomas, the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve were 74.5%, 72.2%, 78.7%, and 0.754, respectively, for the EUS experts; 76.8%, 74.4%, 81.0%, and 0.830, respectively, for the conventional radiomic model; and 90.9%, 91.0%, 90.6%, and 0.953, respectively, for the combined radiomic model. For gastric SELs <20 mm, the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of the combined radiomic model were 91.4%, 91.6%, 91.1%, and 0.960, respectively.ConclusionsWe developed and validated a combined radiomic model to distinguish gastric GISTs from leiomyomas and schwannomas. The combined radiomic model showed better diagnostic performance than the conventional radiomic model and could assist EUS experts in non‐invasively diagnosing gastric SELs, particularly gastric SELs <20 mm.