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Objectives:  To predict the anaplastic lymphoma kinase (ALK) mutations in lung adenocarcinoma patients non-invasively with machine learning models that combine clinical, conventional CT and radiomic features.   Methods:  This retrospective study included 335 lung adenocarcinoma patients who were randomly divided into a primary cohort (268 patients; 90 ALK-rearranged; and 178 ALK wild-type) and a test cohort (67 patients; 22 ALK-rearranged; and 45 ALK wild-type). One thousand two hundred and eighteen quantitative radiomic features were extracted from the semi-automatically delineated volume of interest (VOI) of the entire tumor using both the original and the pre-processed non-enhanced CT images. Twelve conventional CT features and seven clinical features were also collected. Normalized features were selected using a sequential of the F-test-based method, the density-based spatial clustering of applications with noise (DBSCAN) method, and the recursive feature elimination (RFE) method. Selected features were then used to build three predictive models (radiomic, radiological, and integrated models) for the ALK-rearranged phenotype by a soft voting classifier. Models were evaluated in the test cohort using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity, and the performances of three models were compared using the DeLong test.   Results:  Our results showed that the addition of clinical information and conventional CT features significantly enhanced the validation performance of the radiomic model in the primary cohort (AUC = 0.83–0.88,  P  = 0.01), but not in the test cohort (AUC = 0.80–0.88,  P  = 0.29). The majority of radiomic features associated with ALK mutations reflected information around and within the high-intensity voxels of lesions. The presence of the cavity and left lower lobe location were new imaging phenotypic patterns in association with ALK-rearranged tumors. Current smoking was strongly correlated with non-ALK-mutated lung adenocarcinoma.   Conclusions:  Our study demonstrates that radiomics-derived machine learning models can potentially serve as a non-invasive tool to identify ALK mutation of lung adenocarcinoma.

Clinical, Conventional CT and Radiomic Feature-Based Machine Learning Models for Predicting ALK Rearrangement Status in Lung Adenocarcinoma Patients