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

被引：89

作者：

Bidard, Francois-Clement ^{[1
,2
,3
]}

Kiavue, Nicolas ^{[1
]}

Ychou, Marc ^{[4
,5
]}

Cabel, Luc ^{[1
,2
,3
]}

Stern, Marc-Henri ^{[6
]}

Madic, Jordan ^{[2
]}

Saliou, Adrien ^{[2
]}

Rampanou, Aurore ^{[2
]}

Decraene, Charles ^{[2
,7
]}

Bouche, Olivier ^{[8
]}

Rivoire, Michel ^{[9
]}

Ghiringhelli, Francois ^{[10
]}

Francois, Eric ^{[11
]}

Guimbaud, Rosine ^{[12
]}

Mineur, Laurent ^{[13
]}

Khemissa-Akouz, Faiza ^{[14
]}

Mazard, Thibault ^{[4
]}

Moussata, Driffa ^{[15
]}

Proudhon, Charlotte ^{[2
]}

Pierga, Jean-Yves ^{[1
,2
,16
]}

Stanbury, Trevor ^{[17
]}

Thezenas, Simon ^{[18
]}

Mariani, Pascale ^{[19
]}

机构：

[1] PSL Res Univ, Inst Curie, Dept Med Oncol, F-75005 Paris, France

[2] PSL Res Univ, Inst Curie, Circulating Tumor Biomarkers Lab, F-75005 Paris, France

[3] Paris Saclay Univ, UVSQ, F-92210 St Cloud, France

[4] ICM Reg Canc Inst Montpellier, Dept Digest Oncol, F-34298 Montpellier, France

[5] Montpellier Univ, Dept Oncol, F-34000 Montpellier, France

[6] PSL Res Univ, Inst Curie, INSERM U830, F-75005 Paris, France

[7] PSL Res Univ, Inst Curie, CNRS UMR144, F-75005 Paris, France

[8] Reims Univ Hosp, Hop Robert Debre, Dept Med Oncol, F-51100 Reims, France

[9] Ctr Leon Berard, Dept Digest Oncol, F-69008 Lyon, France

[10] Ctr Georges Francois Leclerc, INSERM U866, F-21000 Dijon, France

[11] Ctr Antoine Lacassagne, Dept Med Oncol, F-06189 Nice, France

[12] CHU Toulouse, Dept Digest Oncol, F-31059 Toulouse, France

[13] Inst St Catherine, Dept Digest Oncol, F-84000 Avignon, France

[14] Hop St Jean, Dept Gastroenterol, F-66000 Perpignan, France

[15] CHRU Tours, Dept Gastroenterol, F-37044 Tours, France

[16] Univ Paris 05, F-75270 Paris, France

[17] R&D UNICANCER, UCGI Grp, F-75654 Paris, France

[18] ICM Reg Canc Inst Montpellier, Biometr Unit, F-34298 Montpellier, France

[19] PSL Res Univ, Inst Curie, Dept Surg Oncol, F-75005 Paris, France

来源：

CELLS | 2019年 / 8卷 / 06期

关键词：

circulating tumor cells; circulating tumor DNA; liquid biopsy; metastatic colorectal cancer; FOLFIRINOX; 1ST-LINE TREATMENT; PROGRESSION-FREE; CHEMOTHERAPY; MUTATIONS; KRAS; RESECTION; SURVIVAL; BLOOD;

D O I：

10.3390/cells8060516

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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((R))) 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.

引用

页数：13

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