PET/CT Radiomic Features: A Potential Biomarker for EGFR Mutation Status and Survival Outcome Prediction in NSCLC Patients Treated With TKIs

BACKGROUNDS: Epidermal growth factor receptor (EGFR) mutation profiles play a vital role in treatment strategy decisions for non–small cell lung cancer (NSCLC). The purpose of this study was to evaluate the predictive efficacy of baseline (18)F-FDG PET/CT-based radiomics analysis for EGFR mutation status, mutation site, and the survival benefit of targeted therapy. METHODS: A sum of 313 NSCLC patients with pre-treatment (18)F-FDG PET/CT scans and genetic mutations detection were retrospectively studied. Clinical and PET metabolic parameters were incorporated into independent predictors of determining mutation status and mutation site. The dataset was randomly allocated into the training and the validation sets in a 7:3 ratio. Three-dimensional (3D) radiomics features were extracted from each PET- and CT-volume of interests (VOI) singularly, and then a radiomics signature (RS) associated with EGFR mutation profiles is built by feature selection. Three different prediction models based on support vector machine (SVM), decision tree (DT), and random forest (RF) classifiers were established. Furthermore, nomograms for estimation of overall survival (OS) and progression-free survival (PFS) were established by integrating PET/CT radiomics score (Rad-score), metabolic parameters, and clinical factors. Predictive performance was assessed by the receiver operating characteristic (ROC) analysis and the calibration curve analysis. The decision curve analysis (DCA) was applied to estimate and compare the clinical usefulness of nomograms. RESULTS: Three hundred thirteen NSCLC patients were classified into a training set (n=218) and a validation set (n=95). Multivariate analysis demonstrated that SUVmax and sex were independent indicators of EGFR mutation status and mutation site. Eight CT-derived RS, six PET-derived RS, and two clinical factors were retained to develop integrated models, which exhibited excellent ability to distinguish between EGFR wild type (EGFR-WT), EGFR 19 mutation type (EGFR-19-MT), and EGFR 21 mutation type (EGFR-21-MT). The SVM model outperformed the RF model and the DT model, yielding training area under the curves (AUC) of EGFR-WT, EGFR-19-WT, and EGFR-21-WT, with 0.881, 0.851, and 0.849, respectively, and validation AUCs of 0.926, 0.805 and 0.859, respectively. For prediction of OS, the integrated nomogram is superior to the clinical nomogram and the radiomics nomogram, with C-indexes of 0.80 in the training set and 0.83 in the validation set, respectively. CONCLUSIONS: The PET/CT-based radiomics analysis might provide a novel approach to predict EGFR mutation status and mutation site in NSCLC patients and could serve as useful predictors for the patients’ survival outcome of targeted therapy in clinical practice.