title: Clinical value of chip-based digital-PCR platform for the detection of circulating DNA in metastatic colorectal cancer.
abstract: BACKGROUND
  The detection of circulating DNA is considered a promising strategy in cancer patients. Digital PCR has emerged as a sensitive method able to quantify both circulating free and tumour DNA.
  
  
  OBJECTIVE
  The aim of this study was to prospectively evaluate the clinical value of a chip-based digital PCR for the detection of circulating DNA.
  
  
  METHODS
  Digital PCR was used in 34 metastatic colorectal cancer patients to detect and quantify circulating free and tumour DNA based on K-ras mutational status. Clinical outcomes were analyzed according to circulating DNA measurements.
  
  
  RESULTS
  Digital PCR yielded a detection rate of 69% for circulating tumour DNA. The median concentrations of circulating free and tumour DNA were 20 and 6.8 ng/mL, respectively, with significant correlation between both biomarkers (p<0.001). Median overall survival was 4.8 months in patients with high circulating free DNA (>75% quartile) versus not reached in patients with a low level (<25% quartile) (p=0.029). Moreover, median overall survival was significantly decreased in patients with detectable circulating tumour DNA compared to those without (respectively 11.8 months versus not reached, p=0.04).
  
  
  CONCLUSIONS
  Chip-based digital PCR is a simple and non-invasive method allowing the efficient detection of circulating DNA. Our results highlight that levels of these circulating markers may have a potential prognostic value.
authors.affiliation: Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen Cedex, France; EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen Cedex, France. Electronic address: david.sefrioui@chu-rouen.fr.
authors.forename: David
authors.initials: D
authors.lastname: Sefrioui
authors.affiliation: EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen Cedex, France.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Sarafan-Vasseur
authors.affiliation: Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen Cedex, France; EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen Cedex, France; Cancer Center, Humanitas Cinical and Research Center, Rozzano, Milano, Italy; Department of Pathology, Rouen University Hospital, Rouen Cedex, France; Department of Medical Oncology, Centre Henri Becquerel, Rouen Cedex 1, France.
authors.forename: Ludivine
authors.initials: L
authors.lastname: Beaussire
authors.affiliation: Cancer Center, Humanitas Cinical and Research Center, Rozzano, Milano, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Baretti
authors.affiliation: Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen Cedex, France; EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Gangloff
authors.affiliation: EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Department of Pathology, Rouen University Hospital, Rouen Cedex, France.
authors.forename: France
authors.initials: F
authors.lastname: Blanchard
authors.affiliation: EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Department of Medical Oncology, Centre Henri Becquerel, Rouen Cedex 1, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Clatot
authors.affiliation: EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen Cedex, France; Department of Pathology, Rouen University Hospital, Rouen Cedex, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Sabourin
authors.affiliation: EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen Cedex, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Sesboüé
authors.affiliation: EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen Cedex, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Frebourg
authors.affiliation: Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen Cedex, France; EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen Cedex, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Michel
authors.affiliation: Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen Cedex, France; EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen Cedex, France; Department of Medical Oncology, Centre Henri Becquerel, Rouen Cedex 1, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Di Fiore
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D004273:DNA, Neoplasm / Q000097:blood / Q000302:isolation & purification*; D005260:Female; D011905:Genes, ras; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction / Q000379:methods*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
keywords: Circulating tumour DNA; K-ras mutation; Prognostic value; Ultrasensitive detection method