Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients

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• dc.contributor.author Vidal Barrull, Joana
• dc.contributor.author Albanell Mestres, Joan
• dc.contributor.author Montagut Viladot, Clara
• dc.date.accessioned 2025-01-21T07:37:47Z
• dc.date.available 2025-01-21T07:37:47Z
• dc.date.issued 2017
• dc.description.abstract Background. RAS assessment is mandatory for therapy decision in metastatic colorectal cancer (mCRC) patients. This determination is based on tumor tissue, however, genotyping of circulating tumor (ct)DNA offers clear advantages as a minimally invasive method that represents tumor heterogeneity. Our study aims to evaluate the use of ctDNA as an alternative for determining baseline RAS status and subsequent monitoring of RAS mutations during therapy as a component of routine clinical practice. Patients and methods. RAS mutational status in plasma was evaluated in mCRC patients by OncoBEAM™ RAS CRC assay. Concordance of results in plasma and tissue was retrospectively evaluated.RAS mutations were also prospectively monitored in longitudinal plasma samples from selected patients. Results. Analysis of RAS in tissue and plasma samples from 115 mCRC patients showed a 93% overall agreement. Plasma/tissue RAS discrepancies were mainly explained by spatial and temporal tumor heterogeneity. Analysis of clinico-pathological features showed that the site of metastasis (i.e. peritoneal, lung), the histology of the tumor (i.e. mucinous) and administration of treatment previous to blood collection negatively impacted the detection of RAS in ctDNA. In patients with baseline mutant RAS tumors treated with chemotherapy/antiangiogenic, longitudinal analysis of RAS ctDNA mirrored response to treatment, being an early predictor of response. In patients RAS wt, longitudinal monitoring of RAS ctDNA revealed that OncoBEAM was useful to detect emergence of RAS mutations during anti-EGFR treatment. Conclusion. The high overall agreement in RAS mutational assessment between plasma and tissue supports blood-based testing with OncoBEAM™ as a viable alternative for genotyping RAS of mCRC patients in routine clinical practice. Our study describes practical clinico-pathological specifications to optimize RAS ctDNA determination. Moreover, OncoBEAM™ is useful to monitor RAS in patients undergoing systemic therapy to detect resistance and evaluate the efficacy of particular treatments.en
• dc.format.mimetype application/pdf
• dc.identifier.citation Vidal J, Muinelo L, Dalmases A, Jones F, Edelstein D, Iglesias M, et al. Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients. Ann Oncol. 2017 Jun;28(6):1325-32. DOI: 10.1093/annonc/mdx125
• dc.identifier.doi http://dx.doi.org/10.1093/annonc/mdx125
• dc.identifier.issn 0923-7534
• dc.identifier.uri http://hdl.handle.net/10230/69212
• dc.language.iso eng
• dc.publisher Kluwer Academic Publishers
• dc.relation.ispartof Annals of Oncology. 2017 Jun;28(6):1325-32
• dc.rights © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword ctDNAen
• dc.subject.keyword RAS mutationsen
• dc.subject.keyword Colorectal canceren
• dc.subject.keyword Liquid biopsyen
• dc.subject.keyword Tumor dynamicsen
• dc.subject.keyword Heterogeneityen
• dc.title Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patientsen
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion