Comprehensive cross‐platform comparison of methods for non‐invasive EGFR mutation testing: results of the RING observational trial

Autor: Atocha Romero, Eloisa Jantus‐Lewintre, Beatriz García‐Peláez, Ana Royuela, Amelia Insa, Patricia Cruz, Ana Collazo, Javier Pérez Altozano, Oscar Juan Vidal, Pilar Diz, Manuel Cobo, Berta Hernández, Sergio Vázquez Estevez, Gretel Benítez, Maria Guirado, Margarita Majem, Reyes Bernabé, Ana Laura Ortega, Ana Blasco, Joaquim Bosch‐Barrera, Jose M. Jurado, Jorge García González, Santiago Viteri, Carlos Garcia Giron, Bartomeu Massutí, Ana Lopez Martín, Alejandro Rodriguez‐Festa, Silvia Calabuig‐Fariñas, Miguel Ángel Molina‐Vila, Mariano Provencio
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Molecular Oncology, Vol 15, Iss 1, Pp 43-56 (2021)
Druh dokumentu: article
ISSN: 1878-0261
1574-7891
DOI: 10.1002/1878-0261.12832
Popis: 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.
Databáze: Directory of Open Access Journals
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