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Objectives  This project aimed to construct an individualized PET/CT prognostic biomarker to accurately quantify the progression risk of patients with stage IIIC-IV epidermal growth factor receptor (EGFR)-mutated Non-small cell lung cancer (NSCLC) after first-line first and second generation EGFR- tyrosine kinase inhibitor (TKI) drug therapy and identify the first and second generation EGFR-TKI treatment-sensitive population.    Methods  A total of 250 patients with stage IIIC-IV EGFR-mutated NSCLC underwent first-line first and second generation EGFR-TKI drug therapy were included from two institutions (140 patients in training cohort; 60 patients in internal validation cohort, and 50 patients in external validation cohort). 1037 3D radiomics features were extracted to quantify the phenotypic characteristics of the tumor region in PET and CT images, respectively. A four-step feature selection method was performed to enable derivation of stable and effective signature in the training cohort. According to the median value of radiomics signature score (Rad-score), patients were divided into low- and high-risk groups. The progression-free survival (PFS) behaviors of the two subgroups were compared by Kaplan–Meier survival analysis.    Results  Our results shown that higher Rad-scores were significantly associated with worse PFS in the training ( p  < 0.0001), internal validation ( p  = 0.0153), and external validation ( p  = 0.0006) cohorts. Rad-score can effectively identify patients with a high risk of rapid progression. The Kaplan–Meier survival curves of the three cohorts present significant differences in PFS between the stratified slow and rapid progression subgroups.    Conclusion  The PET/CT-derived Rad-score can realize the precise quantitative stratification of progression risk after first-line first and second generation EGFR-TKI drug therapy for NSCLC and identify EGFR-mutated NSCLC populations sensitive to targeted therapy, which might help to provide precise treatment options for NSCLC.

frontiers in oncology

Identification of Stage IIIC/IV EGFR-Mutated Non-Small Cell Lung Cancer Populations Sensitive to Targeted Therapy Based on a PET/CT Radiomics Risk Model