Abstract

To develop and validate a radiomics-clinical nomogram for the detection of the acquired T790M mutation in patients with advanced non-small cell lung cancer (NSCLC) with resistance after the duration of first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment. Thoracic CT was collected from 120 advanced NSCLC patients who suffered progression on first- or second-generation TKIs. Radiomics signatures were retrieved from the entire tumor. Pearson correlation and the least absolute shrinkage and selection operator (LASSO) regression method were adopted to choose the most suitable radiomics features. Clinical and radiological factors were assessed using univariate and multivariate analysis. Three Machine Learning (ML) models were constructed according to three classifiers, including Logistic Regression (LR), Support Vector Machine (SVM), and RandomForest (RF), combining clinical and radiomic features. A nomogram combining clinical features and the rad score signature was built. The predictive ability of the nomogram was assessed by the ROC curve, calibration curve, and decision curve analysis (DCA). Multivariate regression analysis showed that two clinicopathological characteristics and two radiological features were highly correlated with the acquired T790M mutation, including the progression-free survival (PFS) of first-line EGFR TKIs (P = 0.029), the initial EGFR profile (P = 0.01), vascular convergence (P = 0.043), and air bronchogram (P = 0.030). The AUCs of clinical, radiomics, and combined models using RF classifiers for T790M mutation detection were 0.951 (95% confidence interval [CI] 0.911,0.991), 0.917 (95%CI 0.856,0.978), and 0.961 (95%CI 0.927,0.995) in the training cohort, respectively, higher than those of other classifier models.The calibration curve and Hosmer-Lemeshow Test showed good calibration power, and the DCA demonstrated a significant net benefit. A radiomics-clinical nomogram based on CT radiomics proved valuable in non-invasively and efficiently predicting the acquired T790M mutation in patients who suffered progression on first-line TKIs.

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