Telomerase-based circulating tumor cell detection for treatment response prediction in patients with non-small-cell lung cancer

Background: Monitoring circulating tumor cells (CTCs) using a non-invasive liquid biopsy might provide valuable information for predicting ongoing therapeutic responses. Methods: We developed and adapted a highly sensitive/specific CTC detection system using TelomeScan® (OBP-401). We evaluated CTC subtypes with programmed death-ligand 1 (PD-L1), an immune checkpoint molecule, and vimentin, an epithelial–mesenchymal transition (EMT) marker, using a multi-fluorescent color microscope reader. We evaluated the prognostic value of CTCs and predicted the therapeutic response by dynamically monitoring CTC counts in patients with advanced non-small-cell lung cancer (NSCLC). Results: In this cohort study, a highly sensitive/specific CTC detection system using TelomeScan ^® (OBP-401) was developed, and CTC subtypes with programmed death-ligand 1 (PD-L1) and vimentin expression were evaluated as epithelial–mesenchymal transition (EMT) markers. CTC counts of 99 patients with advanced non-small-cell lung cancer (NSCLC) were dynamically monitored to evaluate the prognostic value and predict the therapeutic response. The sensitivity and specificity of TelomeScan ^® -guided total CTC (≥3 cells) and PD-L1 ⁽⁺⁾ CTC (≥1 cell) measurements were 63.0%/75.0% and 75.0%/100%, respectively, indicating high diagnostic value. Baseline CTC counts (≥3 cells) were independent poor prognostic factors. PD-L1 ⁽⁺⁾ CTCs and EMT ⁽⁺⁾ CTCs were detected in 75% and 12% of patients, respectively. Declined and inclined PD-L1 ⁽⁺⁾ CTC counts after two cycles were significantly associated with a partial response ( p = 0.032) and progressive disease ( p = 0.023), respectively. Conclusions: TelomeScan ^® -guided CTC measurements are recommended as an early and sensitive predictor of poor prognosis in patients with NSCLC. PD-L1 ⁽⁺⁾ CTC detection could help predict the response or resistance to frontline treatment in patients with advanced NSCLC, helping optimize the choice of precision medicines.