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Cells. 2019 May 28;8(6). pii: E516. doi: 10.3390/cells8060516.

Circulating Tumor Cells and Circulating Tumor DNA Detection in Potentially Resectable Metastatic Colorectal Cancer: A Prospective Ancillary Study to the Unicancer Prodige-14 Trial.

Author information

1
Department of Medical Oncology, Institut Curie, PSL Research University, 75005 Paris, France. francois-clement.bidard@curie.fr.
2
Circulating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, France. francois-clement.bidard@curie.fr.
3
UVSQ, Paris Saclay University, 92210 Saint Cloud, France. francois-clement.bidard@curie.fr.
4
Department of Medical Oncology, Institut Curie, PSL Research University, 75005 Paris, France. nicolas.kiavue@curie.fr.
5
Department of Digestive Oncology, ICM Regional Cancer Institute of Montpellier, 34298 Montpellier, France. marc.ychou@icm.unicancer.fr.
6
Department of Oncology, Montpellier University, 34000 Montpellier, France. marc.ychou@icm.unicancer.fr.
7
Department of Medical Oncology, Institut Curie, PSL Research University, 75005 Paris, France. luc.cabel@curie.fr.
8
Circulating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, France. luc.cabel@curie.fr.
9
UVSQ, Paris Saclay University, 92210 Saint Cloud, France. luc.cabel@curie.fr.
10
INSERM U830, Institut Curie, PSL Research University, 75005 Paris, France. marc-henri.stern@curie.fr.
11
Circulating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, France. jordan.madic@curie.fr.
12
Circulating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, France. adrien.saliou@curie.fr.
13
Circulating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, France. aurore.rampanou@curie.fr.
14
Circulating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, France. charles.decraene@curie.fr.
15
CNRS UMR144, Institut Curie, PSL Research University, 75005 Paris, France. charles.decraene@curie.fr.
16
Department of Medical Oncology, Hôpital Robert Debré, Reims University Hospital, 51100 Reims, France. obouche@chu-reims.fr.
17
Department of Digestive Oncology, Centre Léon Bérard, 69008 Lyon, France. michel.rivoire@lyon.unicancer.fr.
18
INSERM U866, Centre Georges-François Leclerc, 21000 Dijon, France. fghiringhelli@cgfl.fr.
19
Department of Medical Oncology, Centre Antoine Lacassagne, 06189 Nice, France. eric.francois@nice.unicancer.fr.
20
Department of Digestive Oncology, CHU de Toulouse, 31059 Toulouse, France. guimbaudr@chu-toulouse.fr.
21
Department of Digestive Oncology, Institut Sainte Catherine, 84000 Avignon, France. l.mineur@isc84.org.
22
Department of Gastroenterology, Hôpital Saint Jean, 66000 Perpignan, France. faiza.khemissa@ch-perpignan.fr.
23
Department of Digestive Oncology, ICM Regional Cancer Institute of Montpellier, 34298 Montpellier, France. t-mazard@chu-montpellier.fr.
24
Department of Gastroenterology, CHRU de Tours, 37044 Tours, France. guimbaudr@chu-toulouse.fr.
25
Circulating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, France. charlotte.proudhon@curie.fr.
26
Department of Medical Oncology, Institut Curie, PSL Research University, 75005 Paris, France. jean-yves.pierga@curie.fr.
27
Circulating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, France. jean-yves.pierga@curie.fr.
28
Université Paris Descartes, 75270 Paris, France. jean-yves.pierga@curie.fr.
29
UCGI Group, R&D UNICANCER, 75654 Paris, France. t-stanbury@unicancer.fr.
30
Biometrics Unit, ICM Regional Cancer Institute of Montpellier, 34298 Montpellier, France. simon.thezenas@icm.unicancer.fr.
31
Department of Surgical Oncology, Institut Curie, PSL Research University, 75005 Paris, France. pascale.mariani@curie.fr.

Abstract

The management of patients with colorectal cancer (CRC) and potentially resectable liver metastases (LM) requires quick assessment of mutational status and of response to pre-operative systemic therapy. In a prospective phase II trial (NCT01442935), we investigated the clinical validity of circulating tumor cell (CTC) and circulating tumor DNA (ctDNA) detection. CRC patients with potentially resectable LM were treated with first-line triplet or doublet chemotherapy combined with targeted therapy. CTC (Cellsearch®) and Kirsten RAt Sarcoma (KRAS) ctDNA (droplet digital polymerase chain reaction (PCR)) levels were assessed at inclusion, after 4 weeks of therapy and before LM surgery. 153 patients were enrolled. The proportion of patients with high CTC counts (≥3 CTC/7.5mL) decreased during therapy: 19% (25/132) at baseline, 3% (3/108) at week 4 and 0/57 before surgery. ctDNA detection sensitivity at baseline was 91% (N=42/46) and also decreased during treatment. Interestingly, persistently detectable KRAS ctDNA (p=0.01) at 4 weeks was associated with a lower R0/R1 LM resection rate. Among patients who had a R0/R1 LM resection, those with detectable ctDNA levels before liver surgery had a shorter overall survival (p<0.001). In CRC patients with limited metastatic spread, ctDNA could be used as liquid biopsy tool. Therefore, ctDNA detection could help to select patients eligible for LM resection.

KEYWORDS:

FOLFIRINOX; circulating tumor DNA; circulating tumor cells; liquid biopsy; metastatic colorectal cancer

PMID:
31142037
DOI:
10.3390/cells8060516
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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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