title: Circulating Cell-Free Tumor DNA Analysis of 50 Genes by Next-Generation Sequencing in the Prospective MOSCATO Trial.
abstract: Liquid biopsies based on circulating cell-free DNA (cfDNA) analysis are described as surrogate samples for molecular analysis. We evaluated the concordance between tumor DNA (tDNA) and cfDNA analysis on a large cohort of patients with advanced or metastatic solid tumor, eligible for phase I trial and with good performance status, enrolled in MOSCATO 01 trial (clinical trial NCT01566019).
  
  
  
  Blood samples were collected at inclusion and cfDNA was extracted from plasma for 334 patients. Hotspot mutations were screened using next-generation sequencing for 50 cancer genes.
  
  
  
  Among the 283 patients with tDNA-cfDNA pairs, 121 had mutation in both, 99 in tumor only, 5 in cfDNA only, and for 58 patients no mutation was detected, leading to a 55.0% estimated sensitivity [95% confidence interval (CI), 48.4%-61.6%] at the patient level. Among the 220 patients with mutations in tDNA, the sensitivity of cfDNA analysis was significantly linked to the number of metastatic sites, albumin level, tumor type, and number of lines of treatment. A sensitivity prediction score could be derived from clinical parameters. Sensitivity is 83% in patients with a high score (≥8). In addition, we analyzed cfDNA for 51 patients without available tissue sample. Mutations were detected for 22 patients, including 19 oncogenic variants and 8 actionable mutations.
  
  
  
  Detection of somatic mutations in cfDNA is feasible for prescreening phase I candidates with a satisfactory specificity; overall sensitivity can be improved by a sensitivity score allowing to select patients for whom cfDNA constitutes a reliable noninvasive surrogate to screen mutations. Clin Cancer Res; 22(12); 2960-8. ©2016 AACR.
authors.affiliation: Laboratoire de Recherche Translationnelle et Centre de RessourcesBiologiques, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy, Villejuif, France. cecile.jovelet@gustaveroussy.fr.
authors.forename: Cécile
authors.initials: C
authors.lastname: Jovelet
authors.affiliation: Laboratoire de Recherche Translationnelle et Centre de RessourcesBiologiques, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy, Villejuif, France. Département d'Innovation Thérapeutique et d'Essais Précoces, Gustave Roussy, Villejuif, France.
authors.forename: Ecaterina
authors.initials: E
authors.lastname: Ileana
authors.affiliation: Département de Biostatistiques et Epidémiologie, Gustave Roussy, Villejuif, France. INSERM U1018, Gustave Roussy, Villejuif, France. Faculté de Médecine, Université Paris Sud, Le Kremlin-Bicêtre, Orsay, France.
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Le Deley
authors.affiliation: Laboratoire de Recherche Translationnelle et Centre de RessourcesBiologiques, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy, Villejuif, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Motté
authors.affiliation: Département de Biostatistiques et Epidémiologie, Gustave Roussy, Villejuif, France.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rosellini
authors.affiliation: Laboratoire de Recherche Translationnelle et Centre de RessourcesBiologiques, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy, Villejuif, France.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Romero
authors.affiliation: INSERM U981, Gustave Roussy, Villejuif, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Lefebvre
authors.affiliation: INSERM U981, Gustave Roussy, Villejuif, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Pedrero
authors.affiliation: Plateforme de Génomique Fonctionnelle, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy, Villejuif, France.
authors.forename: Noémie
authors.initials: N
authors.lastname: Pata-Merci
authors.affiliation: Plateforme de Génomique Fonctionnelle, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy, Villejuif, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Droin
authors.affiliation: Plateforme de bioinformatique, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy, Villejuif, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Deloger
authors.affiliation: Département d'Innovation Thérapeutique et d'Essais Précoces, Gustave Roussy, Villejuif, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.affiliation: Département d'Innovation Thérapeutique et d'Essais Précoces, Gustave Roussy, Villejuif, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Hollebecque
authors.affiliation: Département d'Oncologie Médicale, Gustave Roussy, Villejuif, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Ferté
authors.affiliation: Laboratoire de Recherche Translationnelle et Centre de RessourcesBiologiques, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy, Villejuif, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Boichard
authors.affiliation: Département d'Innovation Thérapeutique et d'Essais Précoces, Gustave Roussy, Villejuif, France. INSERM U981, Gustave Roussy, Villejuif, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Postel-Vinay
authors.affiliation: Département d'Innovation Thérapeutique et d'Essais Précoces, Gustave Roussy, Villejuif, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Ngo-Camus
authors.affiliation: Département de Radiologie, Gustave Roussy, Villejuif, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: De Baere
authors.affiliation: Département de Biologie et Pathologie Médicales, Gustave Roussy, Villejuif, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Vielh
authors.affiliation: Laboratoire de Recherche Translationnelle et Centre de RessourcesBiologiques, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy, Villejuif, France. Faculté de Médecine, Université Paris Sud, Le Kremlin-Bicêtre, Orsay, France. Département de Biologie et Pathologie Médicales, Gustave Roussy, Villejuif, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Scoazec
authors.affiliation: Direction de la Recherche Clinique, Gustave Roussy, Villejuif, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Vassal
authors.affiliation: Faculté de Médecine, Université Paris Sud, Le Kremlin-Bicêtre, Orsay, France. Département d'Oncologie Médicale, Gustave Roussy, Villejuif, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Eggermont
authors.affiliation: Faculté de Médecine, Université Paris Sud, Le Kremlin-Bicêtre, Orsay, France. INSERM U981, Gustave Roussy, Villejuif, France. Département d'Oncologie Médicale, Gustave Roussy, Villejuif, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: André
authors.affiliation: Département d'Innovation Thérapeutique et d'Essais Précoces, Gustave Roussy, Villejuif, France. Faculté de Médecine, Université Paris Sud, Le Kremlin-Bicêtre, Orsay, France. INSERM U981, Gustave Roussy, Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.affiliation: Laboratoire de Recherche Translationnelle et Centre de RessourcesBiologiques, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy, Villejuif, France. INSERM U981, Gustave Roussy, Villejuif, France. Département de Biologie et Pathologie Médicales, Gustave Roussy, Villejuif, France. Faculté de Pharmacie, Université Paris Sud, Châtenay-Malabry, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lacroix
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D000074141:Circulating Tumor DNA / Q000235:genetics*; D017321:Clinical Trials, Phase I as Topic; D004252:DNA Mutational Analysis / Q000379:methods*; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000097:blood / Q000235:genetics*; D018579:Patient Selection; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D000074141:Circulating Tumor DNA; D004273:DNA, Neoplasm