Circulating Tumor Cells and Circulating Tumor DNA Detection in Potentially Resectable Metastatic Colorectal Cancer: A Prospective Ancillary Study to the Unicancer Prodige-14 Trial
- Creators
- Bidard, François-Clément
- Kiavue, Nicolas
- Ychou, Marc
- Cabel, Luc
- Stern, Marc-Henri
- Madic, Jordan
- Saliou, Adrien
- Rampanou, Aurore
- Decraene, Charles
- Bouché, Olivier
- Rivoire, Michel
- Ghiringhelli, Francois
- François, Eric
- Guimbaud, Rosine
- Mineur, Laurent
- Khemissa-Akouz, Faiza
- Mazard, Thibault
- Moussata, Driffa
- Proudhon, Charlotte
- Pierga, Jean-Yves
- Stanbury, Trevor
- Thezenas, Simon
- Mariani, Pascale
- Others:
- Institut Curie [Paris]
- Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
- Université Paris-Saclay
- Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM) ; CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
- Unité de génétique et biologie des cancers (U830) ; Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Compartimentation et dynamique cellulaires (CDC) ; Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
- Centre Hospitalier Universitaire de Reims (CHU Reims)
- Centre Léon Bérard [Lyon]
- Lipides - Nutrition - Cancer (U866) (LNC) ; Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)
- Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL) ; UNICANCER
- Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL) ; UNICANCER-Université Côte d'Azur (UCA)
- CHU Toulouse [Toulouse]
- Institut Sainte Catherine [Avignon]
- Centre Hospitalier Saint Jean de Perpignan
- Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours] ; CHU Trousseau [APHP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
- Université Paris Descartes - Paris 5 (UPD5)
- R&D Unicancer [Paris]
- CRLCC Val d'Aurelle - Paul Lamarque
Description
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.
Abstract
International audience
Additional details
- URL
- https://hal.umontpellier.fr/hal-02419551
- URN
- urn:oai:HAL:hal-02419551v1
- Origin repository
- UNICA