Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer

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....

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Detalles Bibliográficos
Autores: Grasselli, Julieta|||0000-0002-6313-3033, Elez, Elena|||0000-0002-4653-6324, Caratù, Ginevra|||0000-0003-1085-8062, Matito, Judit|||0000-0001-7560-7737, Santos Vivas, Cristina|||0000-0002-9854-5097, Macarulla Mercadé, Teresa|||0000-0002-5856-4082, Vidal, J., García, Montserrat|||0000-0002-3437-3185, Viéitez, J. M., Paez, David|||0000-0002-5596-6588, Falcó, Esther, Lopez Lopez, C., Aranda Aguilar, Enrique|||0000-0002-5471-2842, Jones, F., Sikri, V., Nuciforo, Paolo|||0000-0003-1380-0990, Fasani, Roberta|||0000-0003-1630-9988, Tabernero, Josep|||0000-0002-2495-8139, Montagut, Clara, Azuara, D., Dienstmann, Rodrigo|||0000-0001-5997-318X, Salazar, Ramón, Vivancos, Ana|||0000-0003-2888-6512
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:188579
Acceso en línea:https://ddd.uab.cat/record/188579
https://dx.doi.org/urn:doi:10.1093/annonc/mdx112
Access Level:acceso abierto
Palabra clave:Anti-EGFR therapy
Circulating tumor DNA
Metastatic colorectal cancer
RAS analysis
Descripción
Sumario: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.

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