P. Rawla, T. Sunkara, and V. Gaduputi, Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors, World Journal of Oncology, vol.10, issue.1, pp.10-27, 2019.

A. Bouvier, Z. Uhry, V. Jooste, A. Drouillard, L. Remontet et al., Focus on an unusual rise in pancreatic cancer incidence in France, International Journal of Epidemiology, vol.46, issue.6, pp.1764-1772, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01541663

J. Ferlay, C. Partensky, and F. Bray, More deaths from pancreatic cancer than breast cancer in the EU by 2017, Acta Oncologica, vol.55, issue.9-10, pp.1158-1160, 2016.

T. Conroy, F. Desseigne, M. Ychou, O. Bouché, R. Guimbaud et al., FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer, New England Journal of Medicine, vol.364, issue.19, pp.1817-1825, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00598658

T. Conroy, P. Hammel, M. Hebbar, M. Ben-abdelghani, A. C. Wei et al., FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer, New England Journal of Medicine, vol.379, issue.25, pp.2395-2406, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02281628

U. K. Ballehaninna and R. S. Chamberlain, Serum CA 19-9 as a Biomarker for Pancreatic Cancer?A Comprehensive Review, Indian Journal of Surgical Oncology, vol.2, issue.2, pp.88-100, 2011.

C. Chang, S. Huang, and H. Chiu, Low efficacy of serum levels of CA 19-9 in prediction of malignant diseases in asymptomatic population in Taiwan, Hepatogastroenterology, vol.53, issue.67, pp.1-4, 2006.

J. Kim, K. T. Lee, J. K. Lee, S. W. Paik, J. C. Rhee et al., Clinical usefulness of carbohydrate antigen 19-9 as a screening test for pancreatic cancer in an asymptomatic population, Journal of Gastroenterology and Hepatology, vol.19, issue.2, pp.182-186, 2004.

C. Neuzillet, S. Gaujoux, N. Williet, J. Bachet, L. Bauguion et al., Pancreatic cancer: French clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, AFC), Digestive and Liver Disease, vol.50, issue.12, pp.1257-1271, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02143547

M. Distler, E. Pilarsky, S. Kersting, and R. Grützmann, Preoperative CEA and CA 19-9 are prognostic markers for survival after curative resection for ductal adenocarcinoma of the pancreas ? A retrospective tumor marker prognostic study, International Journal of Surgery, vol.11, issue.10, pp.1067-1072, 2013.

N. Kondo, Y. Murakami, K. Uemura, N. Nakagawa, S. Takahashi et al., Comparison of the prognostic impact of pre- and post-operative CA19-9, SPan-1, and DUPAN-II levels in patients with pancreatic carcinoma, Pancreatology, vol.17, issue.1, pp.95-102, 2017.

M. G. Schlieman, H. S. Ho, and R. J. Bold, Utility of Tumor Markers in Determining Resectability of Pancreatic Cancer, Archives of Surgery, vol.138, issue.9, p.951, 2003.

H. Ishii, S. Okada, H. Nose, M. Yoshimori, K. Aoki et al., Prognostic Factors in Patients with Advanced Pancreatic Cancer Treated with Systemic Chemotherapy, Pancreas, vol.12, issue.3, pp.267-271, 1996.

J. C. Wan, C. Massie, J. Garcia-corbacho, F. Mouliere, J. D. Brenton et al., Liquid biopsies come of age: towards implementation of circulating tumour DNA, Nature Reviews Cancer, vol.17, issue.4, pp.223-238, 2017.

D. A. Haber and V. E. Velculescu, Blood-Based Analyses of Cancer: Circulating Tumor Cells and Circulating Tumor DNA, Cancer Discovery, vol.4, issue.6, pp.650-661, 2014.

C. Almoguera, D. Shibata, K. Forrester, J. Martin, N. Arnheim et al., Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes, Cell, vol.53, issue.4, pp.549-554, 1988.

Y. E. , Cancer biomarkers: Written in blood, 2003.

M. Strijker, E. C. Soer, M. Pastena, A. Creemers, A. Balduzzi et al., Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma, International Journal of Cancer, vol.146, issue.5, pp.1445-1456, 2019.

D. Pietrasz, N. Pécuchet, F. Garlan, A. Didelot, O. Dubreuil et al., Plasma Circulating Tumor DNA in Pancreatic Cancer Patients Is a Prognostic Marker, Clinical Cancer Research, vol.23, issue.1, pp.116-123, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01458933

V. Taly, D. Pekin, A. E. Abed, and P. Laurent-puig, Detecting biomarkers with microdroplet technology, Trends in Molecular Medicine, vol.18, issue.7, pp.405-416, 2012.
URL : https://hal.archives-ouvertes.fr/inserm-02299585

T. Forshew, M. Murtaza, C. Parkinson, D. Gale, D. W. Tsui et al., Noninvasive Identification and Monitoring of Cancer Mutations by Targeted Deep Sequencing of Plasma DNA, Science Translational Medicine, vol.4, issue.136, pp.136ra68-136ra68, 2012.

D. K. Owens, K. W. Davidson, A. H. Krist, M. J. Barry, M. Cabana et al., Screening for Pancreatic Cancer, JAMA, vol.322, issue.5, p.438, 2019.

S. Yachida, S. Jones, I. Bozic, T. Antal, R. Leary et al., Distant metastasis occurs late during the genetic evolution of pancreatic cancer, Nature, vol.467, issue.7319, pp.1114-1117, 2010.

H. Algül, M. Treiber, M. Lesina, and R. M. Schmid, Mechanisms of Disease: chronic inflammation and cancer in the pancreas?a potential role for pancreatic stellate cells?, Nature Clinical Practice Gastroenterology & Hepatology, vol.4, issue.8, pp.454-462, 2007.

F. Le-calvez-kelm, M. Foll, M. B. Wozniak, T. M. Delhomme, G. Durand et al., KRAS mutations in blood circulating cell-free DNA: a pancreatic cancer case-control, Oncotarget, vol.7, issue.48, pp.78827-78840, 2016.

J. D. Cohen, A. A. Javed, C. Thoburn, F. Wong, J. Tie et al., Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers, Proceedings of the National Academy of Sciences, vol.114, issue.38, pp.10202-10207, 2017.

E. Takai, Y. Totoki, H. Nakamura, M. Kato, T. Shibata et al., Clinical Utility of Circulating Tumor DNA for Molecular Assessment and Precision Medicine in Pancreatic Cancer, Advances in Experimental Medicine and Biology, vol.924, pp.13-17, 2016.

N. Brychta, T. Krahn, and O. Von-ahsen, Detection of KRAS Mutations in Circulating Tumor DNA by Digital PCR in Early Stages of Pancreatic Cancer, Clinical Chemistry, vol.62, issue.11, pp.1482-1491, 2016.

K. Allenson, J. Castillo, F. A. San-lucas, G. Scelo, D. U. Kim et al., High prevalence of mutantKRAS in circulating exosome-derived DNA from early-stage pancreatic cancer patients, Annals of Oncology, vol.28, issue.4, pp.741-747, 2017.

M. Sausen, J. Phallen, V. Adleff, S. Jones, R. J. Leary et al., Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients, Nature Communications, vol.6, issue.1, p.7686, 2015.

A. R. Thierry, F. Mouliere, S. El-messaoudi, C. Mollevi, E. Lopez-crapez et al., Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA, Nature Medicine, vol.20, issue.4, pp.430-435, 2014.
URL : https://hal.archives-ouvertes.fr/hal-02362372

M. B. Freidin, D. V. Freydina, M. Leung, A. Montero-fernandez, A. G. Nicholson et al., Circulating Tumor DNA Outperforms Circulating Tumor Cells for KRAS Mutation Detection in Thoracic Malignancies, Clinical Chemistry, vol.61, issue.10, pp.1299-1304, 2015.

P. Adamo, C. M. Cowley, C. P. Neal, V. Mistry, K. Page et al., Profiling tumour heterogeneity through circulating tumour DNA in patients with pancreatic cancer, Oncotarget, vol.8, issue.50, pp.87221-87233, 2017.

M. A. Eissa, L. Lerner, E. Abdelfatah, N. Shankar, J. K. Canner et al., Promoter methylation of ADAMTS1 and BNC1 as potential biomarkers for early detection of pancreatic cancer in blood, Clinical Epigenetics, vol.11, issue.1, p.59, 2019.

L. L. Fujii and M. J. Levy, Basic techniques in endoscopic ultrasound-guided fine needle aspiration for solid lesions: Adverse events and avoiding them, Endosc. Ultrasound, vol.3, issue.1, pp.35-45, 2014.

A. M. Alizadeh, S. Shahrokh, M. Hadizadeh, M. Padashi, and M. Zali, Diagnostic potency of EUS-guided FNA for the evaluation of pancreatic mass lesions, Endoscopic Ultrasound, vol.5, issue.1, p.30, 2016.

C. Luchini, N. Veronese, A. Nottegar, V. Cappelletti, M. G. Daidone et al., Liquid Biopsy as Surrogate for Tissue for Molecular Profiling in Pancreatic Cancer: A Meta-Analysis Towards Precision Medicine, Cancers, vol.11, issue.8, p.1152, 2019.

C. Bettegowda, M. Sausen, R. J. Leary, I. Kinde, N. Agrawal et al., DETECTION OF CIRCULATING TUMOR DNA IN EARLY AND LATE STAGE HUMAN MALIGNANCIES, Neuro-Oncology, vol.16, issue.suppl 3, pp.iii7-iii7, 2014.

S. Ako, K. Nouso, H. Kinugasa, C. Dohi, H. Matushita et al., Utility of serum DNA as a marker for KRAS mutations in pancreatic cancer tissue, Pancreatology, vol.17, issue.2, pp.285-290, 2017.

H. Patel, R. Okamura, P. Fanta, C. Patel, R. B. Lanman et al., Clinical correlates of blood-derived circulating tumor DNA in pancreatic cancer, Journal of Hematology & Oncology, vol.12, issue.1, p.130, 2019.

V. Bernard, D. U. Kim, F. A. San-lucas, J. Castillo, K. Allenson et al., Circulating Nucleic Acids Are Associated With Outcomes of Patients With Pancreatic Cancer, Gastroenterology, vol.156, issue.1, pp.108-118.e4, 2019.

I. Chen, V. M. Raymond, J. A. Geis, E. A. Collisson, B. V. Jensen et al., Ultrasensitive plasma ctDNA KRAS assay for detection, prognosis, and assessment of therapeutic response in patients with unresectable pancreatic ductal adenocarcinoma, Oncotarget, vol.8, issue.58, pp.97769-97786, 2017.

M. K. Kim, S. M. Woo, B. Park, K. Yoon, Y. K. Kim et al., Prognostic Implications of Multiplex Detection of KRAS Mutations in Cell-Free DNA from Patients with Pancreatic Ductal Adenocarcinoma, Clinical Chemistry, vol.64, issue.4, pp.726-734, 2018.

Z. Wang, X. Ding, and H. Zhu, RAS mutation analysis in circulating tumor DNA from patients with metastatic colorectal cancer: the AGEO RASANC prospective multicenter study, Ann. Oncol. Off. J. Eur. Soc. Med. Oncol, vol.9, issue.5, pp.1211-1219, 2018.

M. Sugimori, K. Sugimori, H. Tsuchiya, Y. Suzuki, S. Tsuyuki et al., Quantitative monitoring of circulating tumor DNA in patients with advanced pancreatic cancer undergoing chemotherapy, Cancer Science, vol.111, issue.1, pp.266-278, 2019.

V. P. Groot, S. Mosier, A. A. Javed, J. A. Teinor, G. Gemenetzis et al., Circulating Tumor DNA as a Clinical Test in Resected Pancreatic Cancer, Clinical Cancer Research, vol.25, issue.16, pp.4973-4984, 2019.

M. J. Pishvaian, R. J. Bender, L. M. Matrisian, L. Rahib, A. Hendifar et al., A pilot study evaluating concordance between blood-based and patient-matched tumor molecular testing within pancreatic cancer patients participating in the Know Your Tumor (KYT) initiative, Oncotarget, vol.8, issue.48, pp.83446-83456, 2016.

A. A. Melnikov, D. Scholtens, M. S. Talamonti, D. J. Bentrem, and V. V. Levenson, Methylation profile of circulating plasma DNA in patients with pancreatic cancer, Journal of Surgical Oncology, vol.99, issue.2, pp.119-122, 2009.

A. W. Berger, D. Schwerdel, T. J. Ettrich, A. Hann, S. A. Schmidt et al., Targeted deep sequencing of circulating tumor DNA in metastatic pancreatic cancer, Oncotarget, vol.9, issue.2, pp.2076-2085, 2017.

G. Park, J. K. Park, D. Son, S. Shin, Y. J. Kim et al., Utility of targeted deep sequencing for detecting circulating tumor DNA in pancreatic cancer patients, Scientific Reports, vol.8, issue.1, p.11631, 2018.

X. Liu, L. Liu, Y. Ji, C. Li, T. Wei et al., Enrichment of short mutant cell-free DNA fragments enhanced detection of pancreatic cancer, EBioMedicine, vol.41, pp.345-356, 2019.

E. D. Pratt, R. W. Cowan, S. L. Manning, E. Qiao, H. Cameron et al., Multiplex Enrichment and Detection of Rare KRAS Mutations in Liquid Biopsy Samples using Digital Droplet Pre-Amplification, Analytical Chemistry, vol.91, issue.12, pp.7516-7523, 2019.

H. Kinugasa, K. Nouso, K. Miyahara, Y. Morimoto, C. Dohi et al., Detection ofK-rasgene mutation by liquid biopsy in patients with pancreatic cancer, Cancer, vol.121, issue.13, pp.2271-2280, 2015.

S. Rashid, N. Singh, S. Gupta, S. Rashid, N. Nalika et al., Progression of Chronic Pancreatitis to Pancreatic Cancer, Pancreas, vol.47, issue.2, pp.227-232, 2018.

D. Sefrioui, F. Blanchard, E. Toure, P. Basile, L. Beaussire et al., Diagnostic value of CA19.9, circulating tumour DNA and circulating tumour cells in patients with solid pancreatic tumours, British Journal of Cancer, vol.117, issue.7, pp.1017-1025, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02377819

A. W. Berger, D. Schwerdel, A. Reinacher-schick, W. Uhl, H. Algül et al., A Blood-Based Multi Marker Assay Supports the Differential Diagnosis of Early-Stage Pancreatic Cancer, Theranostics, vol.9, issue.5, pp.1280-1287, 2019.

S. D. Henriksen, P. H. Madsen, A. C. Larsen, M. B. Johansen, A. M. Drewes et al., Cell-free DNA promoter hypermethylation in plasma as a diagnostic marker for pancreatic adenocarcinoma, Clinical Epigenetics, vol.8, issue.1, p.117, 2016.

T. Liggett, A. Melnikov, Q. Yi, C. Replogle, R. Brand et al., Differential methylation of cell-free circulating DNA among patients with pancreatic cancer versus chronic pancreatitis, Cancer, vol.116, issue.7, pp.1674-1680, 2010.

J. Lee, T. Rhee, D. Pietrasz, J. Bachet, P. Laurent-puig et al., Circulating tumor DNA as a prognostic indicator in resectable pancreatic ductal adenocarcinoma: A systematic review and meta-analysis, Scientific Reports, vol.9, issue.1, 2019.
URL : https://hal.archives-ouvertes.fr/hal-02408835

F. Watanabe, K. Suzuki, S. Tamaki, I. Abe, Y. Endo et al., Longitudinal monitoring of KRAS-mutated circulating tumor DNA enables the prediction of prognosis and therapeutic responses in patients with pancreatic cancer, PLOS ONE, vol.14, issue.12, p.e0227366, 2019.

B. Lee, L. Lipton, J. Cohen, J. Tie, A. A. Javed et al., Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer, Annals of Oncology, vol.30, issue.9, pp.1472-1478, 2019.

Y. Nakano, M. Kitago, S. Matsuda, Y. Nakamura, Y. Fujita et al., KRAS mutations in cell-free DNA from preoperative and postoperative sera as a pancreatic cancer marker: a retrospective study, British Journal of Cancer, vol.118, issue.5, pp.662-669, 2018.

H. Chen, H. Tu, Z. Q. Meng, Z. Chen, P. Wang et al., K-ras mutational status predicts poor prognosis in unresectable pancreatic cancer, European Journal of Surgical Oncology (EJSO), vol.36, issue.7, pp.657-662, 2010.

K. Tjensvoll, M. Lapin, T. Buhl, S. Oltedal, K. Steen-ottosen-berry et al., Clinical relevance of circulating KRAS mutated DNA in plasma from patients with advanced pancreatic cancer, Molecular Oncology, vol.10, issue.4, pp.635-643, 2015.

L. Chen, Y. Zhang, Y. Cheng, D. Zhang, S. Zhu et al., Prognostic value of circulating cell-free DNA in patients with pancreatic cancer: A systemic review and meta-analysis, Gene, vol.679, pp.328-334, 2018.

J. Van-laethem, J. Jassem, V. Heinemann, C. D. Weekes, J. A. Bridgewater et al., Phase II study of refametinib (BAY 86-9766), an allosteric dual MEK 1/2 inhibitor, and gemcitabine in patients with unresectable, locally advanced, or metastatic pancreatic cancer., Journal of Clinical Oncology, vol.32, issue.15_suppl, pp.4025-4025, 2014.

G. J. Ullenhag, F. Mozaffari, M. Broberg, H. Mellstedt, and M. Liljefors, Clinical and Immune Effects of Lenalidomide in Combination with Gemcitabine in Patients with Advanced Pancreatic Cancer, PLOS ONE, vol.12, issue.1, p.e0169736, 2017.

T. Semrad, A. Barzi, H. Lenz, I. M. Hutchins, E. J. Kim et al., Pharmacodynamic separation of gemcitabine and erlotinib in locally advanced or metastatic pancreatic cancer: therapeutic and biomarker results, International Journal of Clinical Oncology, vol.20, issue.3, pp.518-524, 2014.

R. Perets, O. Greenberg, T. Shentzer, V. Semenisty, R. Epelbaum et al., Mutant KRAS Circulating Tumor DNA Is an Accurate Tool for Pancreatic Cancer Monitoring, The Oncologist, vol.23, issue.5, pp.566-572, 2018.

R. Perets, O. Greenberg, T. Shentzer, V. Semenisty, R. Epelbaum et al., Mutant KRAS Circulating Tumor DNA Is an Accurate Tool for Pancreatic Cancer Monitoring, The Oncologist, vol.23, issue.5, pp.566-572, 2018.

H. Cheng, C. Liu, J. Jiang, G. Luo, Y. Lu et al., Analysis of ctDNA to predict prognosis and monitor treatment responses in metastatic pancreatic cancer patients, International Journal of Cancer, vol.140, issue.10, pp.2344-2350, 2017.

S. Mohan, M. Ayub, D. G. Rothwell, S. Gulati, B. Kilerci et al., Analysis of circulating cell-free DNA identifies KRAS copy number gain and mutation as a novel prognostic marker in Pancreatic cancer, Scientific Reports, vol.9, issue.1, 2019.

M. Lapin, S. Oltedal, K. Tjensvoll, T. Buhl, R. Smaaland et al., Fragment size and level of cell-free DNA provide prognostic information in patients with advanced pancreatic cancer, Journal of Translational Medicine, vol.16, issue.1, p.300, 2018.

N. Singh, S. Gupta, R. M. Pandey, S. S. Chauhan, and A. Saraya, High Levels of Cell-Free Circulating Nucleic Acids in Pancreatic Cancer are Associated With Vascular Encasement, Metastasis and Poor Survival, Cancer Investigation, vol.33, issue.3, pp.78-85, 2015.

D. Pietrasz, S. Wang-renault, L. Dahan, J. Taieb, K. Le-malicot et al., Methylated circulating tumor DNA (Met-DNA) as an independent prognostic factor in metastatic pancreatic adenocarcinoma (mPAC) patients., Journal of Clinical Oncology, vol.37, issue.15_suppl, pp.4136-4136, 2019.
URL : https://hal.archives-ouvertes.fr/inserm-02413138

S. D. Henriksen, P. H. Madsen, A. C. Larsen, M. B. Johansen, I. S. Pedersen et al., Promoter hypermethylation in plasma-derived cell-free DNA as a prognostic marker for pancreatic adenocarcinoma staging, International Journal of Cancer, vol.141, issue.12, pp.2489-2497, 2017.

S. D. Henriksen, P. H. Madsen, A. C. Larsen, M. B. Johansen, I. S. Pedersen et al., Cell-free DNA promoter hypermethylation in plasma as a predictive marker for survival of patients with pancreatic adenocarcinoma, Oncotarget, vol.8, issue.55, pp.93942-93956, 2017.

M. Del-re, C. Vivaldi, E. Rofi, E. Vasile, M. Miccoli et al., Early changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer, Scientific Reports, vol.7, issue.1, p.7931, 2017.

S. Kruger, V. Heinemann, and C. Ross, Repeated mutKRAS ctDNA measurements represent a novel and promising tool for early response prediction and therapy monitoring in advanced pancreatic cancer, Ann. Oncol. Off. J. Eur. Soc. Med. Oncol, vol.29, issue.12, pp.39-50, 2017.

Z. I. Hu, J. Shia, Z. K. Stadler, A. M. Varghese, M. Capanu et al., Evaluating Mismatch Repair Deficiency in Pancreatic Adenocarcinoma: Challenges and Recommendations, Clinical Cancer Research, vol.24, issue.6, pp.1326-1336, 2018.

A. Marabelle, D. T. Le, and P. A. Ascierto, Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study, J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol, vol.38, issue.1, pp.317-327, 2019.

M. R. Jones, L. M. Williamson, J. T. Topham, M. K. Lee, A. Goytain et al., NRG1 gene fusions are recurrent, clinically actionable gene rearrangements in KRAS wild-type pancreatic ductal adenocarcinoma, Clinical Cancer Research, vol.25, issue.15, p.clincanres.0191.2019, 2019.

H. Moriyama, N. Matsubara, T. Kanbara, M. Mori, J. Matsuoka et al., Allelic imbalance and microsatellite instability in plasma DNA released from polyclonal pancreatic adenocarcinoma, International Journal of Oncology, vol.21, issue.5, pp.949-956, 2002.

H. Terasawa, H. Kinugasa, S. Ako, M. Hirai, H. Matsushita et al., Utility of liquid biopsy using urine in patients with pancreatic ductal adenocarcinoma, Cancer Biology & Therapy, vol.20, issue.10, pp.1348-1353, 2019.

N. Hadano, Y. Murakami, K. Uemura, Y. Hashimoto, N. Kondo et al., Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer, British Journal of Cancer, vol.115, issue.1, pp.59-65, 2016.

F. Maire, S. Micard, P. Hammel, H. Voitot, P. Lévy et al., Differential diagnosis between chronic pancreatitis and pancreatic cancer: value of the detection of KRAS2 mutations in circulating DNA, British Journal of Cancer, vol.87, issue.5, pp.551-554, 2002.