RT Journal Article
T1 Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing: results of the RING observational trial.
A1 Romero, Atocha
A1 Jantus-Lewintre, Eloisa
A1 García-Peláez, Beatriz
A1 Royuela, Ana
A1 Insa, Amelia
A1 Cruz, Patricia
A1 Collazo, Ana
A1 Pérez Altozano, Javier
A1 Vidal, Oscar Juan
A1 Diz, Pilar
A1 Cobo, Manuel
A1 Hernández, Berta
A1 Vázquez Estevez, Sergio
A1 Benítez, Gretel
A1 Guirado, Maria
A1 Majem, Margarita
A1 Bernabé, Reyes
A1 Ortega, Ana Laura
A1 Blasco, Ana
A1 Bosch-Barrera, Joaquim
A1 Jurado, Jose M
A1 García González, Jorge
A1 Viteri, Santiago
A1 Garcia Giron, Carlos
A1 Massutí, Bartomeu
A1 Lopez Martín, Ana
A1 Rodriguez-Festa, Alejandro
A1 Calabuig-Fariñas, Silvia
A1 Molina-Vila, Miguel Ángel
A1 Provencio, Mariano
K1 NGS
K1 circulating free DNA
K1 epidermal growth factor receptor
K1 non-small-cell lung cancer
K1 osimertinib
K1 tyrosine kinase inhibitor
AB 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.
YR 2020
FD 2020-11-13
LK http://hdl.handle.net/10668/16484
UL http://hdl.handle.net/10668/16484
LA en
DS RISalud
RD Apr 5, 2025