Messaritakis I, Nikolaou M, Koinis F, et al. - In small cell lung cancer (SCLC) patients receiving front-line chemotherapy, researchers described and assessed the presence of DLL3-positive Circulating Tumor Cells (CTCs) and evaluated their clinical relevance. Peripheral blood was obtained after one etoposide/platinum cycle (n = 68 patients) and on disease progression (n = 48 patients) from treatment-naïve patients with SCLC (n = 108 patients). For the detection and characterization of CTCs, immunofluorescence staining using antibodies against the DLL3, cytokeratins (CK), CD45 and vimentin (Vim) was used. Data reported that 74.1% of patients had detectable DLL3⁺/CD45⁻ CTCs before treatment. The one-treatment cycle reduced both the detection rate and the absolute number of DLL3⁺/CD45⁻ CTCs significantly. In multivariate analysis, detection of baseline DLL3⁺/CD45⁻ CTCs was significantly correlated with reduced progression-free survival while their detection of disease progression was related to reduced overall survival. These results show a significant heterogeneity of CTCs in patients with SCLC, based on the expression of CK, Vim and DLL3, and changes in DLL3⁺/CD45⁻ CTCs during therapy appear to be a dynamic biomarker connected with the clinical outcome of patients.