J. Ferlay, M. Colombet, I. Soerjomataram, T. Dyba, G. Randi et al., Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018, Eur. J. Cancer (Internet), vol.103, pp.356-387, 2018.

J. F. Seligmann, D. Fisher, C. G. Smith, S. D. Richman, F. Elliott et al., Investigating the poor outcomes of BRAF -mutant advanced colorectal cancer: Analysis from 2530 patients in randomised clinical trials, Ann. Oncol, vol.28, pp.562-568, 2016.

H. Davies, G. R. Bignell, C. Cox, P. Stephens, S. Edkins et al., Mutations of the BRAF gene in human cancer, Nature, vol.417, pp.949-954, 2002.

C. P. Vaughn, S. D. Zobell, L. V. Furtado, C. L. Baker, and W. S. Samowitz, Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer, Genes Chromosomes Cancer, vol.50, pp.307-312, 2011.

P. T. Wan, M. J. Garnett, S. M. Roe, S. Lee, D. Niculescu-duvaz et al., Mechanism of Activation of the RAF-ERK Signaling Pathway by Oncogenic Mutations of B-RAF, Cell, vol.116, pp.855-867, 2004.

B. Tran, S. Kopetz, J. Tie, P. Gibbs, Z. Q. Jiang et al., Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer: Metastatic Pattern in BRAF Mutant CRC, Cancer, vol.117, pp.4623-4632, 2011.

T. Yokota, T. Ura, N. Shibata, D. Takahari, K. Shitara et al., BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer, Br. J. Cancer, vol.104, pp.856-862, 2011.

C. Cremolini, F. Loupakis, C. Antoniotti, C. Lupi, E. Sensi et al., Folfoxiri plus bevacizumab versus Folfiri plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: Updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study, Lancet Oncol, vol.16, pp.1306-1315, 2015.

E. Cutsem, A. Cervantes, R. Adam, A. Sobrero, J. H. Krieken et al., ESMO consensus guidelines for the management of patients with metastatic colorectal cancer, Ann. Oncol, vol.27, pp.1386-1422, 2016.

S. Kopetz, J. Desai, E. Chan, J. R. Hecht, P. J. Dwyer et al., Phase II Pilot Study of Vemurafenib in Patients with Metastatic BRAF -Mutated Colorectal Cancer, J. Clin. Oncol, vol.33, pp.4032-4038, 2015.

C. A. Gomez-roca, J. Delord, C. Robert, M. Hidalgo, V. R. Moos et al., 535Pencorafenib (LGX818), an oral braf inhibitor, in patients (pts) with braf v600e metastatic colorectal cancer (MCRC): Results of Dose Expansion in an Open-Label, phase 1 study, Ann. Oncol, vol.25, pp.182-183, 2014.

R. B. Corcoran, C. E. Atreya, G. S. Falchook, E. L. Kwak, D. P. Ryan et al., Combined BRAF and MEK Inhibition with Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer, J. Clin. Oncol, vol.33, pp.4023-4031, 2015.

D. S. Hong, V. K. Morris, B. Osta, A. V. Sorokin, F. Janku et al., Phase IB Study of Vemurafenib in Combination with Irinotecan and Cetuximab in Patients with Metastatic Colorectal Cancer with BRAFV600E Mutation, Cancer Discov, vol.6, pp.1352-1365, 2016.

R. B. Corcoran, T. André, C. E. Atreya, J. H. Schellens, T. Yoshino et al., Combined BRAF, EGFR, and MEK Inhibition in Patients with BRAF V600E -Mutant Colorectal Cancer, Cancer Discov, vol.8, pp.428-443, 2018.

C. E. Van, S. Huijberts, A. Grothey, R. Yaeger, P. J. Cuyle et al., Encorafenib, and Cetuximab Triplet Therapy for Patients with BRAF V600E-Mutant Metastatic Colorectal Cancer: Safety Lead-In Results from the Phase III BEACON Colorectal Cancer Study, J. Clin. Oncol, vol.18, p.2459, 2019.

A. Lièvre, J. L. Merlin, J. C. Sabourin, P. Artru, S. Tong et al., RAS mutation testing in patients with metastatic colorectal cancer in French clinical practice: A status report in 2014, Dig. Liver Dis, vol.50, pp.507-512, 2018.

F. Garlan, P. Laurent-puig, D. Sefrioui, N. Siauve, A. Didelot et al., Early Evaluation of Circulating Tumor DNA as Marker of Therapeutic Efficacy in Metastatic Colorectal Cancer Patients (PLACOL Study), Clin. Cancer Res, vol.23, pp.5416-5425, 2017.

N. Boeckx, K. Beeck, M. Beyens, V. Deschoolmeester, C. Hermans et al., Mutation and Methylation Analysis of Circulating Tumor DNA Can Be Used for Follow-up of Metastatic Colorectal Cancer Patients, Clin. Colorectal Cancer, vol.17, pp.369-379, 2018.

P. Laurent-puig, D. Pekin, C. Normand, S. K. Kotsopoulos, P. Nizard et al., Clinical Relevance of KRAS-Mutated Subclones Detected with Picodroplet Digital PCR in Advanced Colorectal Cancer Treated with Anti-EGFR Therapy. Clin. Cancer Res, vol.21, pp.1087-1097, 2015.

T. Reinert, T. V. Henriksen, E. Christensen, S. Sharma, R. Salari et al., Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients with Stages I to III Colorectal Cancer, JAMA Oncol

Y. Wang, L. Li, J. D. Cohen, I. Kinde, J. Ptak et al., Prognostic Potential of Circulating Tumor DNA Measurement in Postoperative Surveillance of Nonmetastatic Colorectal Cancer, JAMA Oncol

J. Y. Douillard, G. Ostoros, M. Cobo, T. Ciuleanu, R. Cole et al., Gefitinib Treatment in EGFR Mutated Caucasian NSCLC: Circulating-Free Tumor DNA as a Surrogate for Determination of EGFR Status, J. Thorac. Oncol, vol.9, pp.1345-1353, 2014.

J. B. Bachet, O. Bouché, J. Taieb, O. Dubreuil, M. L. Garcia et al., RAS mutation analysis in circulating tumor DNA from patients with metastatic colorectal cancer: The AGEO RASANC prospective multicenter study, Ann. Oncol, vol.29, pp.1211-1219, 2018.

C. Bettegowda, M. Sausen, R. J. Leary, I. Kinde, Y. Wang et al., Detection of Circulating Tumor DNA in Early-and Late-Stage Human Malignancies, Sci. Transl. Med, vol.6, 2014.

J. Grasselli, E. Elez, G. Caratù, J. Matito, C. Santos et al., Concordance of blood-and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer, Ann. Oncol, vol.28, pp.1294-1301, 2017.

E. Van-cutsem, K. Lesniewski-kmak, M. P. Saunders, H. Wasan, G. Argiles et al., 542PDroplet digital PCR of circulating tumour DNA for the detection of RAS/BRAF mutation in metastatic colorectal cancer, Ann. Oncol

A. R. Thierry, S. Messaoudi, C. Mollevi, J. L. Raoul, R. Guimbaud et al., Clinical utility of circulating DNA analysis for rapid detection of actionable mutations to select metastatic colorectal patients for anti-EGFR treatment, Ann. Oncol, vol.28, pp.2149-2159, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01682168

S. Kato, M. C. Schwaederlé, P. T. Fanta, R. Okamura, L. Leichman et al., Genomic Assessment of Blood-Derived Circulating Tumor DNA in Patients with Colorectal Cancers: Correlation with Tissue Sequencing, Therapeutic Response, and Survival, JCO Precis. Oncol, 2019.

A. Mcree, C. E. Atreya, E. Elez, V. E. Cutsem, F. Rangwala et al., Efficacy and circulating tumor DNA (ctDNA) analysis of the BRAF inhibitor dabrafenib (D), MEK inhibitor trametinib (T), and anti-EGFR antibody panitumumab (P) in patients (pts) with BRAF V600E-mutated (BRAFm) metastatic colorectal cancer (mCRC), Ann. Oncol

J. C. Jones, L. A. Renfro, H. O. Al-shamsi, A. B. Schrock, A. Rankin et al., Non-V600 BRAF Mutations Define a Clinically Distinct Molecular Subtype of Metastatic Colorectal Cancer, J. Clin. Oncol, vol.35, pp.2624-2630, 2017.

A. Ohtsu, D. Kotani, H. Bando, T. Yoshino, S. Fujii et al., 607TiPBIG BANG study: A multicenter phase II study of the MEK inhibitor binimetinib + BRAF inhibitor encorafenib + anti-EGFR antibody cetuximab in patients with BRAF non-V600E mutated metastatic colorectal cancer (EPOC 1703), Ann. Oncol

N. Pécuchet, Y. Rozenholc, E. Zonta, D. Pietrasz, A. Didelot et al., Analysis of Base-Position Error Rate of Next-Generation Sequencing to Detect Tumor Mutations in Circulating DNA, Clin. Chem, vol.62, pp.1492-1503, 2016.

S. Garrigou, G. Perkins, F. Garlan, C. Normand, A. Didelot et al., A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker, Clin. Chem, vol.62, pp.1129-1139, 2016.
URL : https://hal.archives-ouvertes.fr/hal-02295782

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