Toward a real liquid biopsy in metastatic breast and prostate cancer: Diagnostic LeukApheresis increases CTC yields in a European prospective multicenter study (CTCTrap)

Kiki C Andree, Anouk Mentink, Leonie L Zeune, Leon W M M Terstappen, Nikolas H Stoecklein, Rui P Neves, Christiane Driemel, Rita Lampignano, Liwen Yang, Hans Neubauer, Tanja Fehm, Johannes C Fischer, Elisabetta Rossi, Mariangela Manicone, Umberto Basso, Piero Marson, Rita Zamarchi, Yohann Loriot, Valerie Lapierre, Vincent FaugerouxMarianne Oulhen, Françoise Farace, Gemma Fowler, Mariane Sousa Fontes, Berni Ebbs, Maryou Lambros, Mateus Crespo, Penny Flohr, Johann S de Bono

Research output: Contribution to journalArticle

Abstract

Frequently, the number of circulating tumor cells (CTC) isolated in 7.5 mL of blood is too small to reliably determine tumor heterogeneity and to be representative as a "liquid biopsy". In the EU FP7 program CTCTrap, we aimed to validate and optimize the recently introduced Diagnostic LeukApheresis (DLA) to screen liters of blood. Here we present the results obtained from 34 metastatic cancer patients subjected to DLA in the participating institutions. About 7.5 mL blood processed with CellSearch® was used as "gold standard" reference. DLAs were obtained from 22 metastatic prostate and 12 metastatic breast cancer patients at four different institutions without any noticeable side effects. DLA samples were prepared and processed with different analysis techniques. Processing DLA using CellSearch resulted in a 0-32 fold increase in CTC yield compared to processing 7.5 mL blood. Filtration of DLA through 5 μm pores microsieves was accompanied by large CTC losses. Leukocyte depletion of 18 mL followed by CellSearch yielded an increase of the number of CTC but a relative decrease in yield (37%) versus CellSearch DLA. In four out of seven patients with 0 CTC detected in 7.5 mL of blood, CTC were detected in DLA (range 1-4 CTC). The CTC obtained through DLA enables molecular characterization of the tumor. CTC enrichment technologies however still need to be improved to isolate all the CTC present in the DLA.

Original languageEnglish
Pages (from-to)2584-2591
Number of pages8
JournalInternational Journal of Cancer
Volume143
Issue number10
DOIs
Publication statusPublished - Nov 15 2018

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  • Cite this

    Andree, K. C., Mentink, A., Zeune, L. L., Terstappen, L. W. M. M., Stoecklein, N. H., Neves, R. P., Driemel, C., Lampignano, R., Yang, L., Neubauer, H., Fehm, T., Fischer, J. C., Rossi, E., Manicone, M., Basso, U., Marson, P., Zamarchi, R., Loriot, Y., Lapierre, V., ... de Bono, J. S. (2018). Toward a real liquid biopsy in metastatic breast and prostate cancer: Diagnostic LeukApheresis increases CTC yields in a European prospective multicenter study (CTCTrap). International Journal of Cancer, 143(10), 2584-2591. https://doi.org/10.1002/ijc.31752