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Title: Optimization of RAS/BRAF Mutational Analysis Confirms Improvement in Patient Selection for Clinical Benefit to Anti-EGFR Treatment in Metastatic Colorectal Cancer.
Authors: Santos, Cristina
Azuara, Daniel
Garcia-Carbonero, Rocio
Alfonso, Pilar Garcia
Carrato, Alfredo
Elez, Mª Elena
Gomez, Auxiliadora
Losa, Ferran
Montagut, Clara
Massuti, Bartomeu
Navarro, Valenti
Varela, Mar
Lopez-Doriga, Adriana
Moreno, Victor
Valladares, Manuel
Manzano, Jose Luis
Vieitez, Jose Maria
Aranda, Enrique
Sanjuan, Xavier
Tabernero, Josep
Capella, Gabriel
Salazar, Ramon
metadata.dc.subject.mesh: Adult
Aged, 80 and over
Antineoplastic Agents
Antineoplastic Combined Chemotherapy Protocols
Biomarkers, Tumor
Colorectal Neoplasms
DNA Mutational Analysis
ErbB Receptors
Middle Aged
Molecular Targeted Therapy
Neoplasm Metastasis
Neoplasm Staging
Protein Kinase Inhibitors
Proto-Oncogene Proteins B-raf
Retrospective Studies
Treatment Outcome
Young Adult
ras Proteins
Issue Date: 16-Jun-2017
Abstract: In metastatic colorectal cancer (mCRC), recent studies have shown the importance to accurately quantify low-abundance mutations of the RAS pathway because anti-EGFR therapy may depend on certain mutation thresholds. We aimed to evaluate the added predictive value of an extended RAS panel testing using two commercial assays and a highly sensitive and quantitative digital PCR (dPCR). Tumor samples from 583 mCRC patients treated with anti-EGFR- (n = 255) or bevacizumab- (n = 328) based therapies from several clinical trials and retrospective series from the TTD/RTICC Spanish network were analyzed by cobas, therascreen, and dPCR. We evaluated concordance between techniques using the Cohen kappa index. Response rate, progression-free survival (PFS), and overall survival (OS) were correlated to the mutational status and the mutant allele fraction (MAF). Concordance between techniques was high when analyzing RAS and BRAF (Cohen kappa index around 0.75). We observed an inverse correlation between MAF and response in the anti-EGFR cohort (P
metadata.dc.identifier.doi: 10.1158/1535-7163.MCT-17-0153
Appears in Collections:Producción 2020

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