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

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.

Transformed world of industrial infrared analysis.

Infrared spectroscopy is a widely used industrial tool for the structural and compositional analysis of organic, inorganic, or polymeric samples and for quality control of raw materials and commercial products. The increased sensitivity of Fourier transform infrared has greatly enhanced the problem-solving opportunities for infrared in research and development laboratories. Examples are given where FT-IR has been particularly effective in the rapid identification of very small quantities of product from unusual chemical reactions without the necessity of separating the product from the reactants. The good SNR attainable with FT-IR, with the data processing capability, has increased the ability to observe very small differences between the spectra of supposedly similar polymers. These differences have been related to changes in processing conditions and polymer physical properties. FT-IR has been used successfully to characterize structural changes in petroleum products, which may occur as a result of chemical and physical treatment. FT-IR spectra of a series of acrylonitrile-containing copolymers have also been correlated with NMR monomer sequence data to delineate sequence-sensitive infrared bands.