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

Background: To address the clinical challenges that the progression risk of patients with stage IIIC-IV EGFR-mutated Non-small cell lung cancer (NSCLC) is difficult to accurately quantify and stratify after first-line EGFR-TKI targeted drug therapy, we aimed to construct an individualized PET/CT prognostic biomarker to accurately quantify the progression risk of patients and identify the EGFR-TKI treatment-sensitive population. Methods: 250 patients with stage IIIC-IV EGFR-mutated NSCLC underwent first-line 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). 64 patients in the chemotherapy group. 1037 3D radiomics features were extracted to quantify the phenotypic characteristics of the tumor region in PET and CT images. 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 with the chemotherapy group by Kaplan–Meier survival analysis.  Findings: 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, and for these patients.  Interpretation: The PET/CT-derived Rad-score can realize the precise quantitative stratification of progression risk after first-line EGFR-TKI drug therapy and identify EGFR-mutated NSCLC populations sensitive to targeted therapy. Funding: National Natural Science Foundation of China; Guangdong Basic and Applied Basic Research Foundation; Science and Technology Planning Project of Guangdong Province. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The Research Ethics Committee of Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences approved this retrospective study and waived the requirement for informed consent from the patients. The approval ID was GDREC2019154H(R1).