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Quantifying EpCAM heterogeneity of circulation-tumor-cells (CTCs) from small cell lung cancer (SCLC) patients.

H.Sorotsky, M.Aparanthi, D.Z.Wang, F.McFadden, S.N.Popescu, R.M.Mohamadi, M.Pereira, J.Weiss, D.Patel, S.Majeed, M.Cabanero, A.G.Sacher, P.A.Bradbury, N.B.Leighl, F.A.Shepherd, M.S.Tsao, G.Lui, S.O.Kelly, B.H.Lok


Objectives: To investigate the effect of pazopanib on different CTCs subpopulations in patients with recurrent SCLC and evaluate their clinical relevance.

Methods: Peripheral blood was obtained before the administration of pazopanib (n=56 patients), after the first cycle (n=35 patients) and at disease progression (n=45 patients). CTCs were detected by CellSearch and double immunofluorescent staining using antibodies against the cytokeratins (CK), TTF-1, CD56 and VEGFR2.

Results: Before treatment, CTCs could be detected in 50% of patients by CellSearch; phenotypic characterization of CTCs demonstrated that 50%, 46.6% and 27.6% of patients had CD45-/TTF1+, CD45-/CD56+ and TTF-1+/CD56+ CTCs, respectively. Additionally, 59% of CTCs were TTF-1+/VEGFR2+ and 53% CK+/VEGFR2+. One pazopanib cycle resulted to a significant decrease of the number of CTCs (CellSearch: p=0.043) and CK+/VEGFR2+ cells (p=0.027). At the time of PD, both the total number of CTCs (p=0.027) and the number of the different subpopulations were significantly increased compared to post-1st cycle values; this increased CTCs number was associated with a significant increase of TTF-1+/VEGFR2+ (p=0.028) and CK+/VEGFR2+ CTCs (p=0.018). In multivariate analysis, only the number of CTCs as assessed by CellSearch after one treatment cycle was significantly associated with OS (HR: 0.21; p=0.005).

Conclusions: Pazopanib has a significant effect on different subpopulations of CTCs in patients with relapsed SCLC; the detection of VEGFR2+ CTCs during treatment could be a surrogate marker associated with resistance to pazopanib.

Keywords: CD56; CTCs; CellSearch; Immunofluorescence; Pazopanib; SCLC; TTF-1; VEGFR2.

Original research paper :


2nd Summer School on Complex Fluid-Flows in Microfluidics


Single-cell mRNA cytometry via sequence-specific nanoparticle clustering and trapping