Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing : results of the RING observational trial
Romero, Atocha (Hospital Universitario Puerta de Hierro Majadahonda (Madrid))
Jantus-Lewintre, Eloisa (Universitat Politècnica de València)
García-Peláez, Beatriz (Hospital Universitari Dexeus (Barcelona, Catalunya))
Royuela, Ana (Hospital Universitario Puerta de Hierro Majadahonda (Madrid))
Insa, Amelia (Hospital Clínic Universitari (València))
Cruz Castellanos, Patricia (Hospital Universitario La Paz (Madrid))
Collazo-Lorduy, Ana (Hospital Universitario HM Sanchinarro (Madrid))
Pérez Altozano, Javier (Hospital Virgen de los Lirios)
Vidal, Oscar Juan (Hospital Universitari i Politècnic La Fe (València))
Diz Taín, Pilar (Complejo Asistencial Universitario de León)
Cobo, Manuel (Hospital Regional Universitario de Málaga)
Hernández, Berta (Complejo Hospitalario de Navarra)
Vázquez Estevez, Sergio (Hospital Universitario Lucus Augusti (Lugo))
Benítez, Gretel (Complejo Hospitalario Universitario Insular de Gran Canaria)
Guirado, Maria (Hospital General Universitario de Elche)
Majem, Margarita (Institut d'Investigació Biomèdica Sant Pau)
Bernabé, Reyes (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Ortega Granados, Ana Laura (Complejo Hospitalario de Jaén)
Blasco, Ana (Centro de Investigación Biomédica en Red de Cáncer)
Bosch-Barrera, J (Institut d'Investigació Biomèdica de Girona)
Jurado, Jose M. (Hospital Universitario San Cecilio (Granada))
García González, Jorge (Hospital Clínico Universitario (Santiago de Compostela, Galícia))
Viteri, Santiago (Instituto Oncológico Dr. Rosell. Hospital Universitario Dexeus. Grupo Quiron Salud)
Garcia Giron, Carlos (Hospital Universitario de Burgos)
Massuti, Bartomeu (Hospital General Universitario de Alicante (Alacant, País Valencià))
Lopez Martín, Ana (Hospital Universitario Severo Ochoa)
Rodriguez-Festa, Alejandro (Fundación de Investigación Biomédica del H.U. Puerta de Hierro Majadahonda)
Calabuig-Fariñas, Silvia (Universitat de València. Departament de Patologia)
Molina-Vila, Miguel Ángel (Hospital Universitari Dexeus (Barcelona, Catalunya))
Provencio, Mariano (Hospital Universitario Puerta de Hierro Majadahonda (Madrid))

Date:	2021
Abstract:	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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Circulating free DNA ; Epidermal growth factor receptor ; NGS ; Non-small-cell lung cancer ; Osimertinib ; Tyrosine kinase inhibitor
Published in:	Molecular Oncology, Vol. 15 Núm. 1 (january 2021) , p. 43-56, ISSN 1878-0261

DOI: 10.1002/1878-0261.12832
PMID: 33107189

14 p, 586.6 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles