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Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer
Grasselli, J (Institut Català d'Oncologia)
Élez Fernández, Mª Elena (Universitat Autònoma de Barcelona)
Caratù, G (Vall d'Hebron Institut d'Oncologia)
Matito, J (Vall d'Hebron Institut d'Oncologia)
Santos, C (Institut Català d'Oncologia)
Macarulla Mercadé, Teresa (Universitat Autònoma de Barcelona. Hospital Universitari de la Vall d'Hebron)
Vidal, J (Hospital del Mar. Departament d'Oncologia)
Garcia, M (Institut Català d'Oncologia)
Viéitez, J M (Hospital Universitario de Asturias. Departamento de Oncologia Médica)
Paéz, D (Institut d'Investigació Biomèdica Sant Pau)
Falcó, E (Hospital Universitari Son Llatzer. Departament d'Oncologia Mèdica)
Lopez Lopez, C (Hospital Universitario Marqués de Valdecilla. Departamento de Oncología Médica)
Aranda, E (Hospital Universitario Reina Sofía (Córdoba). Departamento de Oncología Médica)
Jones, F (Sysmex Inostics, Mundelein, USA)
Sikri, V (Sysmex Inostics, Mundelein, USA)
Nuciforo, Paolo (Vall d'Hebron Institut d'Oncologia)
Fasani, R (Vall d'Hebron Institut d'Oncologia)
Tabernero Caturla, Josep (Universitat Autònoma de Barcelona)
Montagut, C (Hospital del Mar. Departament d'Oncologia)
Azuara, D (Institut Català d'Oncologia)
Dienstmann, Rodrigo (Vall d'Hebron Institut d'Oncologia)
Salazar, R (Institut Català d'Oncologia)
Vivancos, A (Vall d'Hebron Institut d'Oncologia)

Date: 2017
Abstract: Circulating tumor DNA (ctDNA) is a potential source for tumor genome analysis. We explored the concordance between the mutational status of RAS in tumor tissue and ctDNA in metastatic colorectal cancer (mCRC) patients to establish eligibility for anti-epidermal growth factor receptor (EGFR) therapy. A prospective-retrospective cohort study was carried out. Tumor tissue from 146 mCRC patients was tested for RAS status with standard of care (SoC) PCR techniques, and Digital PCR (BEAMing) was used both in plasma and tumor tissue. ctDNA BEAMing RAS testing showed 89. 7% agreement with SoC (Kappa index 0. 80; 95% CI 0. 71 − 0. 90) and BEAMing in tissue showed 90. 9% agreement with SoC (Kappa index 0. 83; 95% CI 0. 74 − 0. 92). Fifteen cases (10. 3%) showed discordant tissue-plasma results. ctDNA analysis identified nine cases of low frequency RAS mutations that were not detected in tissue, possibly due to technical sensitivity or heterogeneity. In six cases, RAS mutations were not detected in plasma, potentially explained by low tumor burden or ctDNA shedding. Prediction of treatment benefit in patients receiving anti-EGFR plus irinotecan in second- or third-line was equivalent if tested with SoC PCR and ctDNA. Forty-eight percent of the patients showed mutant allele fractions in plasma below 1%. Plasma RAS determination showed high overall agreement and captured a mCRC population responsive to anti-EGFR therapy with the same predictive level as SoC tissue testing. The feasibility and practicality of ctDNA analysis may translate into an alternative tool for anti-EGFR treatment selection.
Note: Número d'acord de subvenció ISCIII/FIS PI12-01589
Note: Número d'acord de subvenció MINECO/SPI-2885-2011
Note: Número d'acord de subvenció ISCIII/PI15/00457
Note: Número d'acord de subvenció ISCIII/DTS15/00048
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. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Anti-EGFR therapy ; Circulating tumor DNA ; Metastatic colorectal cancer ; RAS analysis
Published in: Annals of Oncology, Vol. 28 (march 2017) , p. 1294-1301, ISSN 1569-8041

PMID: 28368441
DOI: 10.1093/annonc/mdx112

8 p, 357.7 KB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació Biomèdica Sant Pau
Articles > Research articles
Articles > Published articles

 Record created 2018-03-26, last modified 2019-06-27

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