Search

Background: Tumor genomic profiling has a significant impact on the selection of targeted therapy. Circulating tumor DNA (ctDNA) has emerged as a noninvasive, and reproducible assay compared with tissue biopsy. We aimed to evaluate its utility in identifying mutations and guiding targeted therapy for lung cancer. Methods: A total of 173 lung cancer patients underwent next-generation sequencing (NGS) using a targeted enrichment panel covering 20 lung cancer-related genes. The performance of the ctDNA NGS assay in identifying genetic mutations or alterations was compared with tissue biopsy and droplet digital PCR (ddPCR). The treatment response to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapies based on the ctDNA assay results was also assessed. Results: The ctDNA was detected in 61.85% of patients. Tissue mutations were detected in paired ctDNA in 38.57% of cases, while ctDNA mutations were detected in paired tissues in 89.1% of cases. The ctDNA increased the number of advanced non-small cell lung cancer (NSCLC) patients who received NCCN-recommended genetic testing by 12%. The concordance between ddPCR and ctDNA was relatively high reaching 99.43%. EGFR T790M/C797S c.G2390C and EGFR T790M/C797S c.T2389A were detected in tissue and ctDNA, respectively, in patient 01015. Moreover, ctDNA assay identified the EGFR T790M mutation, which was missed by tissue biopsy in patient 01149, who developed drug resistance after 1 year of EGFR-TKI therapy. Of the 17 patients who received EGFR-TKI targeted therapies based on the ctDNA NGS results, 12 patients achieved a partial response and two patients had stable disease. Conclusions: The results demonstrated that the ctDNA assay could partially overcome tumor heterogeneity in detecting mutations and provide complementary information on tumor genomic profiles. Moreover, the presence of EGFR mutations in ctDNA could offer valuable guidance for selecting appropriate EGFR-TKI treatment for advanced lung cancer patients. However, it is important to note that the ctDNA NGS assay has certain limitations in fully identifying all genomic alterations present in the tumor. [ABSTRACT FROM AUTHOR]

Large volume of multidimensional data can be summarised, both in terms of tabulated statistics, and as graphic geospatial visualisations. The latter approach allows rapid interpretation and communication of complex information to stake-holders such as regulators, risk assessors and policy makers. In the main study on polychlorinated naphthalene (PCN), individual samples representing different edible fish species were analysed from around the UK. PCNs were observed in all samples with nearly all of the twelve measured congeners being detected. Summed congener concentrations ranged from 0.7 ng/kg ww (turbot) to 265 ng/kg ww (sprats). The highest contamination levels were recorded for sprats and mackerel with mean summed concentrations of 67 ng/kg ww and 68 ng/kg ww respectively. Two ancillary studies, on potentially toxic elements (PTEs) in crabs from China and aflatoxin in children's blood from Tanzania, demonstrate the wide applicability of this approach. The PTE contents in crab showed strong dependence on the tested tissues and elements, and crabs from Tai and Yangcheng Lakes showed obviously higher PTE levels than the other lakes. Geospatial distribution of the aflatoxin biomarker AF-alb in children's serum from 3 locations showed how individual anthropometric or socio-economic data reveals the relationship between family size, socio-economic score and magnitude of serum aflatoxin levels. In addition to facilitating the flow of interpreted data to stakeholders, these techniques can direct the formulation of risk mitigation activities and help with the identification of data gaps. When combined with hierarchical cluster analyses, correlations within the data can also be predicted., (Copyright © 2019. Published by Elsevier Ltd.)