Circulating Tumor Cell-based Molecular Responses Stratify EGFR-TKI Efficacy in Patients with EGFR-Mutant Lung Cancer

Circulating tumor cell (CTC) is a promising minimally invasive biomarker for EGFR-mutant non-small cell lung cancer (NSCLC). However, the rarity of CTCs and limitations in their isolation and molecular characterization hinder their clinical utility, particularly in predicting treatment outcomes. This study evaluates the potential of CTC molecular response to predict treatment efficacy and guide therapy in patients with EGFR-mutant NSCLC undergoing EGFR-tyrosine kinase inhibitors (TKI) therapy.

Seventy-seven patients with EGFR-mutant NSCLC treated with EGFR-TKIs were enrolled. CTCs were isolated using continuous centrifugal microfluidic technology (CCM-CTCD) and compared with ctDNA and tissue biopsy for EGFR mutation analysis. Patients were categorized as CTC molecular responders or non-responders based on a ≥ 44.4% reduction in CTC count from baseline. Progression-free survival (PFS) and tumor burden changes were evaluated.

CTC responders had significantly longer PFS (46.3 vs. 13.6 months, p=0.007) and greater tumor burden reduction (-37.7% vs. -35.2%, p=0.218) compared to non-responders. The CCM-CTCD demonstrated concordance with the cobas test while exhibiting higher sensitivity for EGFR mutation detection among 46 patients who underwent both tests simultaneously. Mutational discordance among tissue, ctDNA, and CTCs highlighted tumor heterogeneity. CTC profiling complemented traditional methods for identifying genomic alterations and predicting early progression.

CTC analysis using CCM-CTCD shows potential as a biomarker for predicting treatment response and prognosis in EGFR-mutant NSCLC. Stratification by CTC molecular response may inform risk-adapted treatment; however, its clinical utility remains to be established. Prospective studies are warranted to validate these findings and determine the role of CTC-guided decision-making.