Circulating Cell-Free Tumor DNA Analysis of 50 Genes by Next-Generation Sequencing in the Prospective MOSCATO Trial.

Abstract

PURPOSE:

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).

EXPERIMENTAL DESIGN:

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.

RESULTS:

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.

CONCLUSIONS:

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: Cécile Jovelet, Ecaterina Ileana, Marie-Cécile Le Deley, Nelly Motté, Silvia Rosellini, Alfredo Romero, Celine Lefebvre, Marion Pedrero, Noémie Pata-Merci, Nathalie Droin, Marc Deloger, Christophe Massard, Antoine Hollebecque, Charles Ferté, Amélie Boichard, Sophie Postel-Vinay, Maud Ngo-Camus, Thierry De Baere, Philippe Vielh, Jean-Yves Scoazec, Gilles Vassal, Alexander Eggermont, Fabrice André, Jean-Charles Soria, Ludovic Lacroix
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 22 Issue 12 Pg. 2960-8 (06 15 2016) ISSN: 1557-3265 [Electronic] United States
• PMID: 26758560 (Publication Type: Evaluation Study, Journal Article)
• Copyright: ©2016 American Association for Cancer Research.

Chemical References

• Biomarkers, Tumor
• Circulating Tumor DNA
• DNA, Neoplasm

Topics

• Adolescent
• Adult
• Aged
• Biomarkers, Tumor (blood, genetics)
• Circulating Tumor DNA (genetics)
• Clinical Trials, Phase I as Topic
• DNA Mutational Analysis (methods)
• DNA, Neoplasm (blood, genetics)
• Female
• High-Throughput Nucleotide Sequencing
• Humans
• Male
• Middle Aged
• Molecular Targeted Therapy
• Mutation
• Neoplasms (blood, genetics)
• Patient Selection
• Prospective Studies
• Young Adult