Next Generation Radiogenomics Sequencing for Prediction of EGFR and KRAS Mutation Status in NSCLC Patients Using Multimodal Imaging and Machine Learning Approaches

Aim: In the present work, we aimed to evaluate a comprehensive radiomics framework that enabled prediction of EGFR and KRAS mutation status in NSCLC cancer patients based on PET and CT multi-modalities radiomic features and machine learning (ML) algorithms. Methods: Our study involved 211 NSCLC cancer patient with PET and CTD images. More than twenty thousand radiomic features from different image-feature sets were extracted Feature value was normalized to obtain Z-scores, followed by student t-test students for comparison, high correlated features were eliminated and the False discovery rate (FDR) correction were performed Six feature selection methods and twelve classifiers were used to predict gene status in patient and model evaluation was reported on independent validation sets (68 patients). Results: The best predictive power of conventional PET parameters was achieved by SUVpeak (AUC: 0.69, P-value = 0.0002) and MTV (AUC: 0.55, P-value = 0.0011) for EGFR and KRAS, respectively. Univariate analysis of radiomics features improved prediction power up to AUC: 75 (q-value: 0.003, Short Run Emphasis feature of GLRLM from LOG preprocessed image of PET with sigma value 1.5) and AUC: 0.71 (q-value 0.00005, The Large Dependence Low Gray Level Emphasis from GLDM in LOG preprocessed image of CTD sigma value 5) for EGFR and KRAS, respectively. Furthermore, the machine learning algorithm improved the perdition power up to AUC: 0.82 for EGFR (LOG preprocessed of PET image set with sigma 3 with VT feature selector and SGD classifier) and AUC: 0.83 for KRAS (CT image set with sigma 3.5 with SM feature selector and SGD classifier). Conclusion: We demonstrated that radiomic features extracted from different image-feature sets could be used for EGFR and KRAS mutation status prediction in NSCLC patients, and showed that they have more predictive power than conventional imaging parameters.

PET/CT Radiomic Sequencer for Prediction of EGFR and KRAS Mutation Status in NSCLC Patients

The aim of this study was to develop radiomic models using PET/CT radiomic features with different machine learning approaches for finding best predictive epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) mutation status. Patients images including PET and CT [diagnostic (CTD) and low dose CT (CTA)] were pre-processed using wavelet (WAV), Laplacian of Gaussian (LOG) and 64 bin discretization (BIN) (alone or in combinations) and several features from images were extracted. The prediction performance of model was checked using the area under the receiver operator characteristic (ROC) curve (AUC). Results showed a wide range of radiomic model AUC performances up to 0.75 in prediction of EGFR and KRAS mutation status. Combination of K-Best and variance threshold feature selector with logistic regression (LREG) classifier in diagnostic CT scan led to the best performance in EGFR (CTD-BIN+B-KB+LREG, AUC: mean 0.75 sd 0.10) and KRAS (CTD-BIN-LOG-WAV+B-VT+LREG, AUC: mean 0.75 sd 0.07) respectively. Additionally, incorporating PET, kept AUC values at ~0.74. When considering conventional features only, highest predictive performance was achieved by PET SUVpeak (AUC: 0.69) for EGFR and by PET MTV (AUC: 0.55) for KRAS. In comparison with conventional PET parameters such as standard uptake value, radiomic models were found as more predictive. Our findings demonstrated that non-invasive and reliable radiomics analysis can be successfully used to predict EGFR and KRAS mutation status in NSCLC patients.