Molecular profiling and feasibility using a comprehensive hybrid capture panel on a consecutive series of non-small-cell lung cancer patients from a single centre.

BACKGROUND: Targeted next-generation sequencing (NGS) is recommended to screen actionable genomic alterations (GAs) in patients with non-small-cell lung cancer (NSCLC). We determined the feasibility to detect actionable GAs using TruSight™ Oncology 500 (TSO500) in 200 consecutive patients with NSCLC. MATERIALS AND METHODS: DNA and RNA were sequenced on an Illumina® NextSeq 550 instrument and processed using the TSO500 Docker pipeline. Clinical actionability was defined within the molecular tumour board following European Society for Medical Oncology (ESMO) guidelines for oncogene-addicted NSCLC. Overall survival (OS) was estimated as per the presence of druggable GAs and treatment with targeted therapy. RESULTS: Most patients were males (69.5%) and former or current smokers (86.5%). Median age was 64 years. The most common histological type and tumour stage were lung adenocarcinoma (81%) and stage IV (64%), respectively. Sequencing was feasible in most patients (93.5%) and actionable GAs were found in 26.5% of patients. A high concordance was observed between single-gene testing and TSO500 NGS panel. Patients harbouring druggable GAs and receiving targeted therapy achieved longer OS compared to patients without druggable GAs. Conversely, patients with druggable GAs not receiving targeted therapy had a trend toward shorter OS compared with driver-negative patients. CONCLUSIONS: Hybrid capture sequencing using TSO500 panel is feasible to analyse clinical samples from patients with NSCLC and is an efficient tool for screening actionable GAs.

Impact of antibiotic therapy on systemic cytokine expression in pneumococcal pneumonia.

The aim of this study was to compare the evolution of systemic cytokine levels over time in patients with pneumococal pneumonia treated either with ß-lactam monotherapy or with combination therapy (ß-lactam plus fluoroquinolone). Prospective observational study of hospitalized non-immunocompromised adults with PP. Concentrations of IL-6, IL-8, IL-10, and TNF-α were determined on days 0, 1, 2, 3, 5, and 7. Patients on ß-lactam monotherapy were compared with those receiving combination therapy. Fifty-two patients were enrolled in the study. Concentrations of IL-6, IL-8, and IL-10 decreased rapidly in the first days after admission, in accordance with the mean time to defervescence. High levels of IL-6 were found in patients with the worst outcomes, measured by the need for intensive care unit admission and mortality. No major differences in demographic or clinical characteristics or severity of disease were found between patients treated with ß-lactam monotherapy and those treated with combination therapy. IL-6 levels fell more rapidly in patients with combination therapy in the first 48 h (p = 0.016). Our data suggest that systemic expression of IL-6 production in patients with PP correlates with prognosis. Initial combination antibiotic therapy produces a faster decrease in this cytokine in the first 48 h.