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| Pàgina inicial > Articles > Articles publicats > Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer |
(Institut Català d'Oncologia) (Universitat Autònoma de Barcelona) (Vall d'Hebron Institut d'Oncologia) (Vall d'Hebron Institut d'Oncologia) (Institut Català d'Oncologia) (Hospital Universitari Vall d'Hebron) (Institut d'Investigació Biomèdica Sant Pau) (Hospital Universitario Reina Sofía (Còrdova, Espanya)) (Vall d'Hebron Institut d'Oncologia) (Universitat Autònoma de Barcelona) (Vall d'Hebron Institut d'Oncologia) (Vall d'Hebron Institut d'Oncologia)| Data: | 2017 |
| Resum: | 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. |
| Ajuts: | Instituto de Salud Carlos III FIS PI12-01589 Ministerio de Economía y Competitividad SPI-2885-2011 Instituto de Salud Carlos III PI15/00457 Instituto de Salud Carlos III DTS15/00048 |
| Drets: | 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.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Anti-EGFR therapy ; Circulating tumor DNA ; Metastatic colorectal cancer ; RAS analysis |
| Publicat a: | Annals of oncology, Vol. 28 (march 2017) , p. 1294-1301, ISSN 1569-8041 |
