%0 Journal Article
%A Romero, Atocha
%A Jantus-Lewintre, Eloisa
%A García-Peláez, Beatriz
%A Royuela, Ana
%A Insa, Amelia
%A Cruz, Patricia
%A Collazo, Ana
%A Pérez Altozano, Javier
%A Vidal, Oscar Juan
%A Diz, Pilar
%A Cobo, Manuel
%A Hernández, Berta
%A Vázquez Estevez, Sergio
%A Benítez, Gretel
%A Guirado, Maria
%A Majem, Margarita
%A Bernabé, Reyes
%A Ortega, Ana Laura
%A Blasco, Ana
%A Bosch-Barrera, Joaquim
%A Jurado, Jose M
%A García González, Jorge
%A Viteri, Santiago
%A Garcia Giron, Carlos
%A Massutí, Bartomeu
%A Lopez Martín, Ana
%A Rodriguez-Festa, Alejandro
%A Calabuig-Fariñas, Silvia
%A Molina-Vila, Miguel Ángel
%A Provencio, Mariano
%T Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing: results of the RING observational trial.
%D 2020
%U http://hdl.handle.net/10668/16484
%X Several platforms for noninvasive EGFR testing are currently used in the clinical setting with sensitivities ranging from 30% to 100%. Prospective studies evaluating agreement and sources for discordant results remain lacking. Herein, seven methodologies including two next-generation sequencing (NGS)-based methods, three high-sensitivity PCR-based platforms, and two FDA-approved methods were compared using 72 plasma samples, from EGFR-mutant non-small-cell lung cancer (NSCLC) patients progressing on a first-line tyrosine kinase inhibitor (TKI). NGS platforms as well as high-sensitivity PCR-based methodologies showed excellent agreement for EGFR-sensitizing mutations (K = 0.80-0.89) and substantial agreement for T790M testing (K = 0.77 and 0.68, respectively). Mutant allele frequencies (MAFs) obtained by different quantitative methods showed an excellent reproducibility (intraclass correlation coefficients 0.86-0.98). Among other technical factors, discordant calls mostly occurred at mutant allele frequencies (MAFs) ≤ 0.5%. Agreement significantly improved when discarding samples with MAF ≤ 0.5%. EGFR mutations were detected at significantly lower MAFs in patients with brain metastases, suggesting that these patients risk for a false-positive result. Our results support the use of liquid biopsies for noninvasive EGFR testing and highlight the need to systematically report MAFs.
%K NGS
%K circulating free DNA
%K epidermal growth factor receptor
%K non-small-cell lung cancer
%K osimertinib
%K tyrosine kinase inhibitor
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