Enumeration and Molecular Characterization of Tumor Cells in Lung Cancer Patients Using a Novel In Vivo Device for Capturing Circulating Tumor Cells

• Published in: Clinical cancer research 2016-05, Vol.22 (9), p.2197-2206
• Main Authors: Gorges, Tobias M, Penkalla, Nicole, Schalk, Thomas, Joosse, Simon A, Riethdorf, Sabine, Tucholski, Johannes, Lücke, Klaus, Wikman, Harriet, Jackson, Stephen, Brychta, Nora, von Ahsen, Oliver, Schumann, Christian, Krahn, Thomas, Pantel, Klaus
• Format: Article
• Language: English
• Subjects: A549 Cells; Cell Count - methods; Cell Line, Tumor; Humans; Lung Neoplasms - blood; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Mutation - genetics; Neoplastic Cells, Circulating - metabolism; Neoplastic Cells, Circulating - pathology; Prospective Studies; Proto-Oncogene Proteins p21(ras) - metabolism; Receptor, Epidermal Growth Factor - metabolism
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-15-1416

The use of circulating tumor cells (CTC) as "liquid biopsy" is limited by the very low yield of CTCs available for subsequent analyses. Most in vitro approaches rely on small sample volumes (5-10 mL). Here, we used a novel approach, the GILUPI CellCollector, which enables an in vivo isolation of CTCs from peripheral blood. In total, 50 lung cancer patients were screened in two subsequent device applications before and after therapy (n = 185 applications). By in vivo isolation, 58% (108/185) of the patients were positive for ≥1 CTC (median, 5 CTCs; range, 1-56 cells) as compared with 27% (23/84; range, 1-300 cells) using the FDA-cleared CellSearch system. Furthermore, we could show that treatment response during therapy was associated with significant decreases in CTC counts (P = 0.001). By dPCR, mutations in the KRAS and EGFR genes relevant for treatment decisions could be detected in CTCs captured by in vivo isolation and confirmed in the primary tumors of the same patients. In vivo isolation of CTCs overcomes blood volume limitations of other approaches, which might help to implement CTC-based "liquid biopsies" into clinical decision making. Clin Cancer Res; 22(9); 2197-206. ©2015 AACR.