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Publication

Real-World Utility of an Amplicon-Based Next-Generation Sequencing Liquid Biopsy for Broad Molecular Profiling in Patients With Advanced Non-Small-Cell Lung Cancer.

Journal : JCO precision oncology
Authors : Remon J, Lacroix L, Jovelet C, Caramella C, Howarth K, Plagnol V, Rosenfeld N, Morris C, Mezquita L, Pannet C, Ngocamus M, Le Pechoux C, Adam J, Grecea AM, Planchard D, Vassal G, Benitez JC, Gazzah A, Green E, Soria JC, Besse B

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Open in PubMed
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10.1200/PO.18.00211 : DOI
32914037 : PMID
PMC7446523 : PMC-ID

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.