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BackgroundTo investigate the value of computed tomography (CT)-based radiomics signatures in combination with clinical and CT morphological features to identify epidermal growth factor receptor (EGFR)-mutation subtypes in lung adenocarcinoma (LADC).MethodsFrom February 2012 to October 2019, 608 patients were confirmed with LADC and underwent chest CT scans. Among them, 307 (50.5%) patients had a positive EGFR-mutation and 301 (49.5%) had a negative EGFR-mutation. Of the EGFR-mutant patients, 114 (37.1%) had a 19del -mutation, 155 (50.5%) had a L858R-mutation, and 38 (12.4%) had other rare mutations. Three combined models were generated by incorporating radiomics signatures, clinical, and CT morphological features to predict EGFR-mutation status. Patients were randomly split into training and testing cohorts, 80% and 20%, respectively. Model 1 was used to predict positive and negative EGFR-mutation, model 2 was used to predict 19del and non-19del mutations, and model 3 was used to predict L858R and non-L858R mutations. The receiver operating characteristic curve and the area under the curve (AUC) were used to evaluate their performance.ResultsFor the three models, model 1 had AUC values of 0.969 and 0.886 in the training and validation cohorts, respectively. Model 2 had AUC values of 0.999 and 0.847 in the training and validation cohorts, respectively. Model 3 had AUC values of 0.984 and 0.806 in the training and validation cohorts, respectively.ConclusionCombined models that incorporate radiomics signature, clinical, and CT morphological features may serve as an auxiliary tool to predict EGFR-mutation subtypes and contribute to individualized treatment for patients with LADC.