Towards a real liquid biopsy in metastatic breast and prostate cancer: Diagnostic LeukApheresis increases CTC yields in a European prospective multi-center study (CTCTrap)

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. 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 5µm pores microsieves was accompanied by large CTC losses. Leukocyte depletion of 18mL followed by CellSearch yielded an increase of the number of CTC but a relative decrease in yield (37%) versus CellSearch DLA. In 4 out of 7 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. This article is protected by copyright. All rights reserved.

International journal of cancer. 2018 Jul 14 [Epub ahead of print]

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 Faugeroux, Marianne Oulhen, Françoise Farace, Gemma Fowler, Mariane Sousa Fontes, Berni Ebbs, Maryou Lambros, Mateus Crespo, Penny Flohr, Johann S de Bono

Department of Medical Cell BioPhysics, University of Twente, Enschede, the Netherlands., Department of General, Visceral and Pediatric Surgery, University Hospital of the Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Department of Gynecology and Obstetrics, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., IOV-IRCC, Padova, Italy., Apheresis Unit, Blood Transfusion Service, University Hospital of Padova, Padova, Italy., Department of Medicine, Gustave Roussy, Université Paris-Saclay, Villejuif, France., INSERM U981 'Identification of molecular predictors and new targets for cancer treatment', Gustave Roussy, Villejuif, France., 'Circulating Tumor Cells' Translational Platform, CNRS UMS3655 - INSERM US23 Ammica, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Cancer Biomarkers, Institute of Cancer Research, Sutton, UK., Prostate Cancer Targeted Therapies Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.