Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer
Por:
Grasselli, J, Elez, E, Caratu, G, Matito, J, Santos, C, Macarulla, T, Vidal, J, Garcia, M, Vieitez, JM, Paez, D, Falco, E, Lopez, CL, Aranda, E, Jones, F, Sikri, V, Nuciforo, P, Fasani, R, Tabernero, J, Montagut, C, Azuara, D, Dienstmann, R, Salazar, R, Vivancos, A
Publicada:
1 jun 2017
Resumen:
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.
Filiaciones:
Grasselli, J:
Vall dHebron Inst Oncol, Dept Med Oncol, Barcelona, Spain
Univ Barcelona, Catalan Inst Oncol, Dept Med Oncol, Barcelona, Spain
Elez, E:
Vall dHebron Inst Oncol, Dept Med Oncol, Barcelona, Spain
Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Dept Med Oncol, Barcelona, Spain
Caratu, G:
Vall dHebron Inst Oncol, Canc Genom Grp, Barcelona, Spain
Matito, J:
Vall dHebron Inst Oncol, Canc Genom Grp, Barcelona, Spain
Santos, C:
Univ Barcelona, Catalan Inst Oncol, Dept Med Oncol, Barcelona, Spain
Macarulla, T:
Vall dHebron Inst Oncol, Dept Med Oncol, Barcelona, Spain
Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Dept Med Oncol, Barcelona, Spain
Vidal, J:
Del Mar Univ Hosp, Dept Med Oncol, Barcelona, Spain
Garcia, M:
Univ Barcelona, Catalan Inst Oncol, Dept Med Oncol, Barcelona, Spain
Vieitez, JM:
Asturias Univ Hosp, Dept Med Oncol, Oviedo, Spain
Paez, D:
Santa Creu & St Pau Univ Hosp, Dept Med Oncol, Barcelona, Spain
Falco, E:
Son Llatzer Univ Hosp, Dept Med Oncol, Palma De Mallorca, Spain
Lopez, CL:
Marques de Valdecilla Univ Hosp, Dept Med Oncol, Santander, Spain
Aranda, E:
Reina Sofia Univ Hosp, Dept Med Oncol, Cordoba, Spain
Jones, F:
Sysmex Inost, Mundelein, IL USA
Sikri, V:
Sysmex Inost, Mundelein, IL USA
Nuciforo, P:
Vall dHebron Inst Oncol, Mol Oncol Grp, Barcelona, Spain
Fasani, R:
Vall dHebron Inst Oncol, Mol Oncol Grp, Barcelona, Spain
Tabernero, J:
Vall dHebron Inst Oncol, Dept Med Oncol, Barcelona, Spain
Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Dept Med Oncol, Barcelona, Spain
Montagut, C:
Del Mar Univ Hosp, Dept Med Oncol, Barcelona, Spain
Azuara, D:
Catalan Inst Oncol, Traslat Res Lab, Barcelona, Spain
Dienstmann, R:
Vall dHebron Inst Oncol, Dept Med Oncol, Barcelona, Spain
Vall dHebron Inst Oncol, Oncol Data Sci Grp, Barcelona, Spain
Salazar, R:
Univ Barcelona, Catalan Inst Oncol, Dept Med Oncol, Barcelona, Spain
Vivancos, A:
Vall dHebron Inst Oncol, Canc Genom Grp, Barcelona, Spain
Hybrid Gold, Green Published
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