title: Plasma Circulating Tumor DNA in Pancreatic Cancer Patients Is a Prognostic Marker.
abstract: OBJECTIVE
  Despite recent therapeutic advances, prognosis of patients with pancreatic adenocarcinoma remains poor. Analyses from tumor tissues present limitations; identification of informative marker from blood might be a promising alternative. The aim of this study was to assess the feasibility and the prognostic value of circulating tumor DNA (ctDNA) in pancreatic adenocarcinoma.
  
  
  METHODS
  From 2011 to 2015, blood samples were prospectively collected from all consecutive patients with pancreatic adenocarcinoma treated in our center. Identification of ctDNA was done with next-generation sequencing targeted on referenced mutations in pancreatic adenocarcinoma and with picoliter droplet digital PCR.
  
  
  RESULTS
  A total of 135 patients with resectable (n = 31; 23%), locally advanced (n = 36; 27%), or metastatic (n = 68; 50%) pancreatic adenocarcinoma were included. In patients with advanced pancreatic adenocarcinoma (n = 104), 48% (n = 50) had ctDNA detectable with a median mutation allelic frequency (MAF) of 6.1%. The presence of ctDNA was strongly correlated with poor overall survival (OS; 6.5 vs. 19.0 months; P < 0.001) in univariate and multivariate analyses (HR = 1.96; P = 0.007). To evaluate the impact of ctDNA level, patients were grouped according to MAF tertiles: OS were 18.9, 7.8, and 4.9 months (P < 0.001). Among patients who had curative intent resection (n = 31), 6 had ctDNA detectable after surgery, with an MAF of 4.4%. The presence of ctDNA was associated with a shorter disease-free survival (4.6 vs.17.6 months; P = 0.03) and shorter OS (19.3 vs. 32.2 months; P = 0.027).
  
  
  CONCLUSIONS
  ctDNA is an independent prognostic marker in advanced pancreatic adenocarcinoma. Furthermore, it arises as an indicator of shorter disease-free survival in resected patients when detected after surgery. Clin Cancer Res; 23(1); 116-23. ©2016 AACR.
authors.affiliation: Department of Digestive and Hepatobiliary Surgery, Pitié-Salpêtrière Hospital, Paris, France.|Université Paris Sorbonne Cité, INSERM UMR-S1147 MEPPOT, CNRS SNC5014, Centre Universitaire des Saints-Péres, Paris, France. Equipe labélisée Ligue contre le Cancer.|Sorbonne University, UPMC University, Paris 06, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pietrasz
authors.affiliation: Université Paris Sorbonne Cité, INSERM UMR-S1147 MEPPOT, CNRS SNC5014, Centre Universitaire des Saints-Péres, Paris, France. Equipe labélisée Ligue contre le Cancer.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pécuchet
authors.affiliation: Université Paris Sorbonne Cité, INSERM UMR-S1147 MEPPOT, CNRS SNC5014, Centre Universitaire des Saints-Péres, Paris, France. Equipe labélisée Ligue contre le Cancer.
authors.forename: Fanny
authors.initials: F
authors.lastname: Garlan
authors.affiliation: Université Paris Sorbonne Cité, INSERM UMR-S1147 MEPPOT, CNRS SNC5014, Centre Universitaire des Saints-Péres, Paris, France. Equipe labélisée Ligue contre le Cancer.
authors.forename: Audrey
authors.initials: A
authors.lastname: Didelot
authors.affiliation: Gastroenterology and Digestive Oncology Department, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Dubreuil
authors.affiliation: Gastroenterology and Digestive Oncology Department, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Solène
authors.initials: S
authors.lastname: Doat
authors.affiliation: Department of Metabolic Biochemistry, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Francoise
authors.initials: F
authors.lastname: Imbert-Bismut
authors.affiliation: Department of Digestive and Hepatobiliary Surgery, Pitié-Salpêtrière Hospital, Paris, France.|Sorbonne University, UPMC University, Paris 06, France.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Karoui
authors.affiliation: Department of Digestive and Hepatobiliary Surgery, Pitié-Salpêtrière Hospital, Paris, France.|Sorbonne University, UPMC University, Paris 06, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Vaillant
authors.affiliation: Université Paris Sorbonne Cité, INSERM UMR-S1147 MEPPOT, CNRS SNC5014, Centre Universitaire des Saints-Péres, Paris, France. Equipe labélisée Ligue contre le Cancer.
authors.forename: Valérie
authors.initials: V
authors.lastname: Taly
authors.affiliation: Université Paris Sorbonne Cité, INSERM UMR-S1147 MEPPOT, CNRS SNC5014, Centre Universitaire des Saints-Péres, Paris, France. Equipe labélisée Ligue contre le Cancer.
authors.forename: Pierre
authors.initials: P
authors.lastname: Laurent-Puig
authors.affiliation: Université Paris Sorbonne Cité, INSERM UMR-S1147 MEPPOT, CNRS SNC5014, Centre Universitaire des Saints-Péres, Paris, France. Equipe labélisée Ligue contre le Cancer. jean-baptiste.bachet@aphp.fr.|Sorbonne University, UPMC University, Paris 06, France.|Gastroenterology and Digestive Oncology Department, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Bachet
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D000074141:Circulating Tumor DNA; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D014408:Biomarkers, Tumor; D000074141:Circulating Tumor DNA