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. 2020 Jun 24:4:15.
doi: 10.1038/s41698-020-0118-x. eCollection 2020.

Liquid biopsy mutation panel for non-small cell lung cancer: analytical validation and clinical concordance

Lee S Schwartzberg  1 , Hidehito Horinouchi  2 , David Chan  3 , Sara Chernilo  4 , Michaela L Tsai  5 , Dolores Isla  6 , Carles Escriu  7 , John P Bennett  8 , Kim Clark-Langone  8 , Christer Svedman  8 , Pascale Tomasini  9 ; Oncotype SEQ® Study Investigators and Program Team
Collaborators, Affiliations

Liquid biopsy mutation panel for non-small cell lung cancer: analytical validation and clinical concordance

Lee S Schwartzberg et al. NPJ Precis Oncol. .

Abstract

Molecular testing for genomic variants is recommended in advanced non-small cell lung cancer (NSCLC). Standard tissue biopsy is sometimes infeasible, procedurally risky, or insufficient in tumor tissue quantity. We present the analytical validation and concordance study of EGFR variants using a new 17-gene liquid biopsy assay (NCT02762877). Of 144 patients enrolled with newly diagnosed or progressive stage IV nonsquamous NSCLC, 140 (97%) had liquid assay results, and 117 (81%) had both EGFR blood and tissue results. Alterations were detected in 58% of liquid samples. Overall tissue-liquid concordance for EGFR alterations was 94.0% (95% CI 88.1%, 97.6%) with positive percent agreement of 76.7% (57.7%, 90.1%) and negative percent agreement of 100% (95.8%, 100%). Concordance for ALK structural variants was 95.7% (90.1%, 98.6%). This assay detected alterations in other therapeutically relevant genes at a rate similar to tissue analysis. These results demonstrate the analytical and clinical validity of this 17-gene assay.

Keywords: Cancer genomics.

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Conflict of interest statement

Competing interestsL.S.S: Consultant for Inivata and Caris Life Sciences. H.H.: None. D.C.: None. S.C.: Received fees from Pfizer for working on their protocols. M.L.T.: None. D.I.: None. C.E.: Consultant fees from Merck Sharp & Dohme, Boehringer Ingelheim, and AstraZeneca; and lecture fees from Bristol-Myers Squibb and Pfizer. J.P.B.: Current employment at and stock ownership in Genomic Health, Inc. (now Exact Sciences Corp.). K.C.-L.: Current employment at and stock ownership in Genomic Health, Inc. (now Exact Sciences Corp.). C.S.: Previous employment at Genomic Health, Inc. (now Exact Sciences Corp.) during this work; consultant for Precision Medicine Asia Co Ltd and Cantargia AB. P.T.: None. G.A.: Previous employment at and stock ownership in Genomic Health, Inc. (now Exact Sciences Corp.). F.L.B.: Current employment at and stock ownership in Genomic Health, Inc. (now Exact Sciences Corp.). T.B.: None. A.B.: Previous employment at and stock ownership in Genomic Health, Inc. (now Exact Sciences Corp.). J.C.: Reports grants from Genomic Health, during the conduct of the study; personal fees from Genomic Health, outside the submitted work; and Genomic Health provided speakers for educational activities. D.D.: Previous employment at and stock ownership in Genomic Health, Inc. (now Exact Sciences Corp.). D.A.E.: Previous employment at and stock ownership in Genomic Health, Inc. (now Exact Sciences Corp.). N.G.: None. J.H.: Previous employment at and stock ownership in Genomic Health, Inc. (now Exact Sciences Corp.). W.I.,Jr.: None. M.L.: Previous employment at and stock ownership in Genomic Health, Inc. (now Exact Sciences Corp.). J.O.,Jr.: None. B.T.S: None.

Figures

Fig. 1
Fig. 1. Number of alterations by gene reported in the liquid biopsy assay for 140 patients in cohorts A and B.
CNV copy number variant, SNV single-nucleotide variant, SV structural variant.
Fig. 2
Fig. 2. Alterations detected in liquid biopsy in cohorts A and B, by gene and patient (n = 81 patients with at least one alteration detected).
Each row represents a gene and each column represents an individual patient. CNV copy number variant, SNV single-nucleotide variant, SV structural variant.
See this image and copyright information in PMC

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