Open AccessReal-World Utility of an Amplicon-Based Next-Generation Sequencing Liquid Biopsy for Broad Molecular Profiling in Patients With Advanced Non–Small-Cell Lung Cancer
Author(s) -
Jordi Remón,
Ludovic Lacroix,
Cécile Jovelet,
Caroline Caramella,
Karen Howarth,
Vincent Plagnol,
Nitzan Rosenfeld,
Clive Morris,
Laura Mezquita,
Chloé Pannet,
Maud Ngo-Camus,
C. Le Péchoux,
Julien Adam,
A.M. Grecea,
David Planchard,
Gilles Vassal,
José Carlos Benítez,
Anas Gazzah,
Emma Green,
JeanCharles Soria,
Benjamin Besse
Publication year - 2019
Publication title -
jco precision oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.405
H-Index - 22
ISSN - 2473-4284
DOI - 10.1200/po.18.00211
Subject(s) - liquid biopsy , concordance , amplicon , lung cancer , medicine , oncology , circulating tumor dna , amplicon sequencing , biopsy , molecular diagnostics , ros1 , pathology , cancer , bioinformatics , polymerase chain reaction , gene , biology , adenocarcinoma , genetics , 16s ribosomal rna
PURPOSE To assess the feasibility and utility of circulating tumor DNA (ctDNA) by amplicon-based next-generation sequencing (NGS) analysis in the daily clinical setting in a cohort of patients with advanced non–small-cell lung cancer (NSCLC), as an alternative approach to tissue molecular profiling.PATIENTS AND METHODS In this single-center prospective study, treatment-naïve and previously treated patients with advanced NSCLC were enrolled. Clinical validation of ctDNA using amplicon-based NGS analysis (with a 36-gene panel) was performed against standard-of-care tissue molecular analysis in treatment-naïve patients. The feasibility, utility, and prognostic value of ctDNA as a dynamic marker of treatment efficacy was evaluated. Results of tissue molecular profile were blinded during ctDNA analysis.RESULTS Of 214 patients with advanced NSCLC who were recruited, 156 were treatment-naïve patients and 58 were pretreated patients with unknown tissue molecular profile. ctDNA screening was successfully performed for 91% (n = 194) of all patients, and mutations were detected in 77% of these patients. Tissue molecular analysis was available for 111 patients (52%), and tissue somatic mutations were found for 78% (n = 87) of patients. For clinically relevant variants, concordance agreement between ctDNA and tumor tissue analysis was 95% among 94 treatment-naïve patients who had concurrent liquid and tumor biopsy molecular profiles. Sensitivity and specificity were 81% and 97%, respectively. Of the 103 patients with no tissue available, ctDNA detected potential actionable mutations in 17% of patients; of these, 10% received personalized treatment. ctDNA kinetics correlated with response rate and progression-free survival in 31 patients treated with first-line platinum-based chemotherapy.CONCLUSION These real-world data from a prospective study endorse ctDNA molecular profile by amplicon-based NGS as an accurate and reliable tool to detect and monitor clinically relevant molecular alterations in patients with advanced NSCLC.