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Background: Neurogenic differentiation factor 1 (NEUROD1) is frequently overexpressed in small‐cell lung cancer (SCLC). NEUROD1 plays an important role in promoting malignant behavior and survival. Methods: In this study, we evaluated the association between putative functional polymorphisms in 45 NEUROD1 target genes and chemotherapy response and survival outcomes in 261 patients with SCLC. Among the 100 single nucleotide polymorphisms (SNPs) studied, two were significantly associated with both chemotherapy response and overall survival (OS) of patients with SCLC. Results: The SNP rs3806915C>A in semaphorin 6A (SEMA6A) gene was significantly associated with better chemotherapy response and OS (p = 0.04 and p = 0.04, respectively). The SNP rs11265375C>T in nescient helix–loop helix 1 (NHLH1) gene was also associated with better chemotherapy response and OS (p = 0.04 and p = 0.02, respectively). Luciferase assay showed a significantly higher promoter activity of SEMA6A with the rs3806915 A allele than C allele in H446 lung cancer cells (p = 4 × 10−6). The promoter activity of NHLH1 showed a significantly higher with the rs11265375 T allele than C allele (p = 0.001). Conclusion: These results suggest that SEMA6A rs3806915C>A and NHLH1 rs11265375C>T polymorphisms affect the promoter activity and expression of the genes, which may affect the survival outcome of patients with SCLC. [ABSTRACT FROM AUTHOR]

Objective: ASTRIS is a large real-world, open-label, multinational clinical study of osimertinib in patients with epidermal growth factor receptor (EGFR) T790M mutation-positive advanced non-small cell lung cancer (NSCLC) who have previously received a tyrosine kinase inhibitor (TKI). We report data from the Korean ASTRIS subgroup.Methods: Adult patients with locally advanced or metastatic NSCLC with a confirmed T790M mutation, WHO performance status of 0-2 and prior EGFR-TKI therapy, received osimertinib 80 mg once daily. Efficacy outcomes were overall survival (OS), investigator-assessed response rate (RR) and progression-free survival (PFS), and time to treatment discontinuation (TTD).Results: At data cut-off (20 October 2017), 466 Korean patients were enrolled. Baseline EGFR molecular testing was mainly performed on biopsied tissue (75.1%). Baseline mutations co-occurring with T790M included exon 19 deletions (60.7%) and L858R (32.8%). 1-year OS was 82.7% (OS data not matured at data cut-off). Overall, RR was 71.0%, median PFS was 12.4 months and median TTD was 15.0 months. In patients with/without CNS metastases, RR was 68.0% and 79.6%, respectively; median PFS, 10.8 and 11.0 months, respectively; and median TTD, 11.2 and 14.7 months, respectively. Overall, 31.1% of patients experienced ≥1 adverse event (AE), leading to dose modification (12.0%), discontinuation (5.2%) or death (2.8%). Serious AEs (24.9%) included pulmonary embolism (1.7%), pleural effusion (1.7%), and pneumonia (1.5%).Conclusion: In this real-world subgroup analysis of Korean patients in the ASTRIS study, osimertinib demonstrated comparable clinical efficacy to that attained in the global ASTRIS study and other clinical trials, with no new safety concerns. [ABSTRACT FROM AUTHOR]

Background: Data concerning the rate of pulmonary embolism (PE) in Asian patients with chronic obstructive pulmonary disease (COPD) exacerbation are sparse, and no study has shown predictors of PE in these patients. Objectives: The purpose of the present study was to investigate the prevalence and predictors of PE in Korean patients with COPD exacerbation. Methods: Hospitalized patients with COPD exacerbations were prospectively enrolled into this study and underwent computed tomography (CT) pulmonary angiography and indirect CT venography. Results: The most common cause of COPD exacerbation was lower respiratory tract infection (82%; n = 84), followed by PE (5%; n = 5). Eight patients (8%) had venous thromboembolism, and deep vein thrombosis (DVT) was seen in 6%, with proximal DVT in 4%. On multivariate analysis, the absence of symptoms of respiratory infection and plasma D-dimer elevation (≥500 μg/l) were significant factors predicting PE in patients with COPD exacerbations (odds ratio 31, 95% confidence interval 2-563, p = 0.02, and odds ratio 25, 95% confidence interval 1-464, p = 0.03, respectively). Conclusions: PE comprises approximately 5% of the etiologies of COPD exacerbations in Koreans. The absence of symptoms suggestive of respiratory infection and elevated plasma D-dimer levels were significant predictors of PE in this population. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]