Treatment Decision Drivers in Stage III Non-Small-Cell Lung Cancer: Outcomes of a Web-Based Survey of Oncologists in the United States.

PURPOSE: We conducted a cross-sectional survey of practicing medical oncologists in the United States to obtain insight into physician and patient treatment decision making in stage III non-small-cell lung cancer (NSCLC). METHODS: A convenience sample of 150 oncologists completed a 38-question Web-based survey in January 2019. RESULTS: Surveyed oncologists (82% community based) had an average of 15 years of clinical experience and had treated an average of 20 patients newly diagnosed with stage III NSCLC in the previous 6 months. Oncologists reported presenting 55% of their patients with stage III NSCLC to tumor boards. For patients with new unresectable stage III NSCLC seen in the previous 6 months, concurrent chemoradiation therapy (cCRT) was reported as the initial treatment in an average of 48% of patients. The most frequent reason for delays in starting the initial chosen treatment was insurance preauthorization processes (reported by 65% of oncologists). A total of 55% of all patients with unresectable stage III NSCLC who received cCRT went on to receive consolidation immunotherapy; for patients who received consolidation chemotherapy after cCRT, the rate of immunotherapy was lower (42%). Biomarker test results were given as the reason for oncologists not recommending immunotherapy after cCRT in approximately a quarter of cases. The 112 oncologists with eligible patients who declined immunotherapy reported previous treatment fatigue as the reason in 34% of patients and insurance challenges in 19% of patients. CONCLUSION: Oncologists reported notable deviations from treatment guidelines for stage III NSCLC. Our findings highlight important opportunities to improve decision making and the coordination of care in stage III NSCLC.

Expression-based discovery of variation in the human glutathione S-transferase M3 promoter and functional analysis in a glioma cell line using allele-specific chromatin immunoprecipitation.

Discovery and functional evaluation of biologically significant regulatory single nucleotide polymorphisms (SNP) in carcinogen metabolism genes is a difficult challenge because the phenotypic consequences may be both transient and subtle. We have used a gene expression screening approach to identify a functional regulatory SNP in glutathione S-transferase M3 (GSTM3). Anttila et al. proposed that variation in GSTM3 expression was affected by exposure to cigarette smoke and inheritance of the GSTM1-null genotype. To investigate the mechanism of GSTM3 expression was affected by exposure to cigarette smoke and inheritance of the GSTM1-null genotype. To investigate the mechanism of GSTM3 expression variation, we measured GSTM3 expression in lymphoblast cells from a human Centre d'Etude du Polymorphisme Humain family and observed a low expression phenotype. Promoter sequencing revealed two novel GSTM3 promoter SNPs: A/C and A/G SNPs, 63 and 783 bp upstream of the codon 1 start site, respectively. In this pedigree, the two children homozygous for the -63C/C genotype had 8-fold lower GSTM3 expression relative to the two children with the -63A/A genotype, with no association between A-783G SNP and GSTM3 expression. Further evaluation using genotyped glioma cell lines and with luciferase reporter constructs showed that the -63C allele was associated with lower GSTM3 expression (P < 0.0001 and P < 0.003). RNA pol II chromatin immunoprecipitation was combined with quantitative probed-based allelic discrimination genotyping to provide direct evidence of a 9-fold reduced RNA pol II binding capacity for the -63C allele. These results show that the GSTM3 -63C allele strongly affects gene expression in human cell lines and suggests that individuals who carry the low expression allele may be deficient in glutathione transferase catalyzed biological functions.