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

Dan Shao,Wenbing Lv,Lijun Lu,Haiping Liu,Jieqin Lv,You Cheng,Hao Zhang,Dongyang Du,Shuxia Wang

doi:10.3389/fonc.2021.721318

Abstract

ObjectivesThis 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.MethodsA 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.ResultsOur 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.ConclusionThe 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.

Highlights

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide [1]
tyrosine kinase inhibitor (TKI) group patients were treated with first-line first and second generation epidermal growth factor receptor (EGFR)-TKI according to the criteria established by the National Comprehensive Cancer Network (NCCN) until disease progression, with doses appropriately reduced if severe adverse events occurred; and 4. pretherapy PET/CT was acquired two weeks before the initiation of EGFR-TKI therapy
The baseline characteristics of the three patient cohorts with stage IIIC-IV EGFR-mutant NSCLC from two institutions are summarized in Table 1. 250 patients received first and second generation EGFR-TKI therapy (140 patients, 60 patients, and 50 patients in three cohorts), and 243 of the 250 (97.2%) patients suffered NSCLC progression during the follow-up period

Summary

Introduction

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide [1]. The onset of NSCLC is insidious, and most patients present at an advanced stage. For advanced NSCLC, platinum-based combination chemotherapy has reached a bottleneck, with suboptimal efficacy. In patients with NSCLC, especially in East Asian populations, the mutation rate of human epidermal growth factor receptor (EGFR) is as high as 40%~55% [2]. Researchers have developed small-molecule tyrosine kinase inhibitor (TKI) drugs that target EGFR in EGFR gene mutation therapy, which have subsequently been found to prolong progression-free survival (PFS) in such patients when compared with chemotherapy in clinical application [3], extend the median PFS of patients to 9~11 months [4]

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