2026-07-16T10:44:53Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/204322024-11-29T00:41:55Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Grasselli, J author Elez, Elena author Caratu, G author Matito, J author Santos, C author Macarulla, T author Vidal, J author Garcia, M author Vieitez, J. M author Paez, D author Falcó, Esther author Lopez Lopez, C author Aranda, E author Jones, F author Sikri, V author Nuciforo, P author Fasani, Roberta author Tabernero, J author Montagut, C author Azuara, D author Dienstmann, R author Salazar, R author Vivancos, A author 2017-06 Background: 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. Patients and methods: 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. Results: 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%. Conclusions: 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. Grasselli J, Elez E, Caratu G, Matito J, Santos C, Macarulla T, et al. Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer. Ann Oncol. 2017 Jun;28(6):1294-301. 10.1093/annonc/mdx112 1569-8041 0923-7534 Annals of Oncology http://hdl.handle.net/20.500.13003/9802 28368441 L616918819 2-s2.0-85021127627 http://hdl.handle.net/20.500.12105/20432 402861900017 anti-EGFR therapy Circulating tumor DNA Metastatic colorectal cancer RAS analysis Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer