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Purpose  To establish a non-invasive diagnostic model based on convolutional neural networks (CNNs) to distinguish benign from malignant lesions manifesting as a solid, indeterminate solitary pulmonary nodule (SPN) or mass (SPM) on computed tomography (CT).    Method  A total of 459 patients with solid indeterminate SPNs/SPMs on CT were ultimately included in this retrospective study and assigned to the train (n=366), validation (n=46), and test (n=47) sets. Histopathologic analysis was available for each patient. An end-to-end CNN model was proposed to predict the natural history of solid indeterminate SPN/SPMs on CT. Receiver operating characteristic curves were plotted to evaluate the predictive performance of the proposed CNN model. The accuracy, sensitivity, and specificity of diagnoses by radiologists alone were compared with those of diagnoses by radiologists by using the CNN model to assess its clinical utility.    Results  For the CNN model, the AUC was 91% (95% confidence interval [CI]: 0.83–0.99) in the test set. The diagnostic accuracy of radiologists with the CNN model was significantly higher than that without the model (89  vs.  66%, P&amp;lt;0.01; 87  vs.  61%, P&amp;lt;0.01; 85  vs.  66%, P=0.03, in the train, validation, and test sets, respectively). In addition, while there was a slight increase in sensitivity, the specificity improved significantly by an average of 42% (the corresponding improvements in the three sets ranged from 43, 33, and 42% to 82, 78, and 84%, respectively; P&amp;lt;0.01 for all).    Conclusion  The CNN model could be a valuable tool in non-invasively differentiating benign from malignant lesions manifesting as solid, indeterminate SPNs/SPMs on CT.

Convolutional Neural Network-Based Diagnostic Model for a Solid, Indeterminate Solitary Pulmonary Nodule or Mass on Computed Tomography