Circulating Tumor Cells and Circulating Tumor DNA Detection in Potentially Resectable Metastatic Colorectal Cancer: A Prospective Ancillary Study to the Unicancer Prodige-14 Trial
François-Clément Bidard,
Nicolas Kiavue,
Marc Ychou,
Luc Cabel,
Marc-Henri Stern,
Jordan Madic,
Adrien Saliou,
Aurore Rampanou,
Charles Decraene,
Olivier Bouché,
Michel Rivoire,
François Ghiringhelli,
Eric Francois,
Rosine Guimbaud,
Laurent Mineur,
Faiza Khemissa-Akouz,
Thibault Mazard,
Driffa Moussata,
Charlotte Proudhon,
Jean-Yves Pierga,
Trevor Stanbury,
Simon Thézenas,
Pascale Mariani
Affiliations
François-Clément Bidard
Department of Medical Oncology, Institut Curie, PSL Research University, 75005 Paris, France
Nicolas Kiavue
Department of Medical Oncology, Institut Curie, PSL Research University, 75005 Paris, France
Marc Ychou
Department of Digestive Oncology, ICM Regional Cancer Institute of Montpellier, 34298 Montpellier, France
Luc Cabel
Department of Medical Oncology, Institut Curie, PSL Research University, 75005 Paris, France
Marc-Henri Stern
INSERM U830, Institut Curie, PSL Research University, 75005 Paris, France
Jordan Madic
Circulating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, France
Adrien Saliou
Circulating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, France
Aurore Rampanou
Circulating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, France
Charles Decraene
Circulating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, France
Olivier Bouché
Department of Medical Oncology, Hôpital Robert Debré, Reims University Hospital, 51100 Reims, France
Michel Rivoire
Department of Digestive Oncology, Centre Léon Bérard, 69008 Lyon, France
François Ghiringhelli
INSERM U866, Centre Georges-François Leclerc, 21000 Dijon, France
Eric Francois
Department of Medical Oncology, Centre Antoine Lacassagne, 06189 Nice, France
Rosine Guimbaud
Department of Digestive Oncology, CHU de Toulouse, 31059 Toulouse, France
Laurent Mineur
Department of Digestive Oncology, Institut Sainte Catherine, 84000 Avignon, France
Faiza Khemissa-Akouz
Department of Gastroenterology, Hôpital Saint Jean, 66000 Perpignan, France
Thibault Mazard
Department of Digestive Oncology, ICM Regional Cancer Institute of Montpellier, 34298 Montpellier, France
Driffa Moussata
Department of Gastroenterology, CHRU de Tours, 37044 Tours, France
Charlotte Proudhon
Circulating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, France
Jean-Yves Pierga
Department of Medical Oncology, Institut Curie, PSL Research University, 75005 Paris, France
Trevor Stanbury
UCGI Group, R&D UNICANCER, 75654 Paris, France
Simon Thézenas
Biometrics Unit, ICM Regional Cancer Institute of Montpellier, 34298 Montpellier, France
Pascale Mariani
Department of Surgical Oncology, Institut Curie, PSL Research University, 75005 Paris, France
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.
