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

Fingerprint

Leukapheresis
Circulating Neoplastic Cells
Multicenter Studies
Prostatic Neoplasms
Prospective Studies
Breast Neoplasms
Biopsy
Neoplasms
Prostate
Leukocytes
Technology

Cite this

Toward a real liquid biopsy in metastatic breast and prostate cancer : Diagnostic LeukApheresis increases CTC yields in a European prospective multicenter study (CTCTrap). / Andree, Kiki C; Mentink, Anouk; Zeune, Leonie L; Terstappen, Leon W M M; Stoecklein, Nikolas H; Neves, Rui P; Driemel, Christiane; Lampignano, Rita; Yang, Liwen; Neubauer, Hans; Fehm, Tanja; Fischer, Johannes C; Rossi, Elisabetta; Manicone, Mariangela; Basso, Umberto; Marson, Piero; Zamarchi, Rita; Loriot, Yohann; Lapierre, Valerie; Faugeroux, Vincent; Oulhen, Marianne; Farace, Françoise; Fowler, Gemma; Sousa Fontes, Mariane; Ebbs, Berni; Lambros, Maryou; Crespo, Mateus; Flohr, Penny; de Bono, Johann S.

In: International Journal of Cancer, Vol. 143, No. 10, 15.11.2018, p. 2584-2591.

Research output: Contribution to journalArticle

Andree, KC, Mentink, A, Zeune, LL, Terstappen, LWMM, Stoecklein, NH, Neves, RP, Driemel, C, Lampignano, R, Yang, L, Neubauer, H, Fehm, T, Fischer, JC, Rossi, E, Manicone, M, Basso, U, Marson, P, Zamarchi, R, Loriot, Y, Lapierre, V, Faugeroux, V, Oulhen, M, Farace, F, Fowler, G, Sousa Fontes, M, Ebbs, B, Lambros, M, Crespo, M, Flohr, P & de Bono, JS 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, vol. 143, no. 10, pp. 2584-2591. https://doi.org/10.1002/ijc.31752
Andree, Kiki C ; Mentink, Anouk ; Zeune, Leonie L ; Terstappen, Leon W M M ; Stoecklein, Nikolas H ; Neves, Rui P ; Driemel, Christiane ; Lampignano, Rita ; Yang, Liwen ; Neubauer, Hans ; Fehm, Tanja ; Fischer, Johannes C ; Rossi, Elisabetta ; Manicone, Mariangela ; Basso, Umberto ; Marson, Piero ; Zamarchi, Rita ; Loriot, Yohann ; Lapierre, Valerie ; Faugeroux, Vincent ; Oulhen, Marianne ; Farace, Françoise ; Fowler, Gemma ; Sousa Fontes, Mariane ; Ebbs, Berni ; Lambros, Maryou ; Crespo, Mateus ; Flohr, Penny ; de Bono, Johann S. / Toward a real liquid biopsy in metastatic breast and prostate cancer : Diagnostic LeukApheresis increases CTC yields in a European prospective multicenter study (CTCTrap). In: International Journal of Cancer. 2018 ; Vol. 143, No. 10. pp. 2584-2591.
@article{0d1f4ffd52074f11a9a0f591d24b6442,
title = "Toward a real liquid biopsy in metastatic breast and prostate cancer: Diagnostic LeukApheresis increases CTC yields in a European prospective multicenter study (CTCTrap)",
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{\circledR} 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.",
author = "Andree, {Kiki C} and Anouk Mentink and Zeune, {Leonie L} and Terstappen, {Leon W M M} and Stoecklein, {Nikolas H} and Neves, {Rui P} and Christiane Driemel and Rita Lampignano and Liwen Yang and Hans Neubauer and Tanja Fehm and Fischer, {Johannes C} and Elisabetta Rossi and Mariangela Manicone and Umberto Basso and Piero Marson and Rita Zamarchi and Yohann Loriot and Valerie Lapierre and Vincent Faugeroux and Marianne Oulhen and Fran{\cc}oise Farace and Gemma Fowler and {Sousa Fontes}, Mariane and Berni Ebbs and Maryou Lambros and Mateus Crespo and Penny Flohr and {de Bono}, {Johann S}",
note = "{\circledC} 2018 UICC.",
year = "2018",
month = "11",
day = "15",
doi = "10.1002/ijc.31752",
language = "English",
volume = "143",
pages = "2584--2591",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "10",

}

TY - JOUR

T1 - Toward a real liquid biopsy in metastatic breast and prostate cancer

T2 - Diagnostic LeukApheresis increases CTC yields in a European prospective multicenter study (CTCTrap)

AU - Andree, Kiki C

AU - Mentink, Anouk

AU - Zeune, Leonie L

AU - Terstappen, Leon W M M

AU - Stoecklein, Nikolas H

AU - Neves, Rui P

AU - Driemel, Christiane

AU - Lampignano, Rita

AU - Yang, Liwen

AU - Neubauer, Hans

AU - Fehm, Tanja

AU - Fischer, Johannes C

AU - Rossi, Elisabetta

AU - Manicone, Mariangela

AU - Basso, Umberto

AU - Marson, Piero

AU - Zamarchi, Rita

AU - Loriot, Yohann

AU - Lapierre, Valerie

AU - Faugeroux, Vincent

AU - Oulhen, Marianne

AU - Farace, Françoise

AU - Fowler, Gemma

AU - Sousa Fontes, Mariane

AU - Ebbs, Berni

AU - Lambros, Maryou

AU - Crespo, Mateus

AU - Flohr, Penny

AU - de Bono, Johann S

N1 - © 2018 UICC.

PY - 2018/11/15

Y1 - 2018/11/15

N2 - 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.

AB - 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.

U2 - 10.1002/ijc.31752

DO - 10.1002/ijc.31752

M3 - Article

C2 - 30006930

VL - 143

SP - 2584

EP - 2591

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 10

ER -