Impact of neuroimaging in the pretreatment evaluation of early stage non-small cell lung cancer.

BACKGROUND: There are limited data and conflicting guideline recommendations regarding the role of neuroimaging in the pretreatment evaluation of non-small cell lung cancer (NSCLC). METHODS: We performed a retrospective, pragmatic cohort study of patients with NSCLC diagnosed between January 1 and December 31, 2015. Eligible patients were identified from an institutional tumor registry. We collected all records of pretreatment neuroimaging within 12 weeks of diagnosis, including CT head (CT) and MRI brain (MRI). We abstracted the indication for neuroimaging, presence of central neurologic symptoms and cancer stage (with and without neuroimaging findings) from the tumor registry and the electronic health record. RESULTS: We identified 216 evaluable patients with newly diagnosed NSCLC. 157 of 216 patients (72.7%) underwent neuroimaging as part of initial staging, and 41 (26%) were found to have brain metastases. Of 43 patients with central neurologic symptoms at the time of neuroimaging, 28 (67%) had brain metastasis. In patients without central neurologic symptoms, brain metastases were discovered in 0 of 33 patients with clinical stage I or II, 4 of 36 (11%) with clinical stage III and 9 of 45 (20%) with clinical stage IV disease. CONCLUSIONS: In patients with early stage NSCLC (i.e. clinical stage I and II) without central neurologic symptoms, brain metastases are unlikely. The continued use of neuroimaging in the pretreatment evaluation of clinical stage I patients without central neurologic symptoms is not needed.

Functional and metabolic impairment in cigarette smoke-exposed macrophages is tied to oxidative stress.

Cigarette smoke inhalation exposes the respiratory system to thousands of potentially toxic substances and causes chronic obstructive pulmonary disease (COPD). COPD is characterized by cycles of inflammation and infection with a dysregulated immune response contributing to disease progression. While smoking cessation can slow the damage in COPD, lung immunity remains impaired. Alveolar macrophages (AMΦ) are innate immune cells strategically poised at the interface between lungs, respiratory pathogens, and environmental toxins including cigarette smoke. We studied the effects of cigarette smoke on model THP-1 and peripheral blood monocyte derived macrophages, and discovered a marked inhibition of bacterial phagocytosis which was replicated in primary human AMΦ. Cigarette smoke decreased AMΦ cystic fibrosis transmembrane conductance regulator (CFTR) expression, previously shown to be integral to phagocytosis. In contrast to cystic fibrosis macrophages, smoke-exposed THP-1 and AMΦ failed to augment phagocytosis in the presence of CFTR modulators. Cigarette smoke also inhibited THP-1 and AMΦ mitochondrial respiration while inducing glycolysis and reactive oxygen species. These effects were mitigated by the free radical scavenger N-acetylcysteine, which also reverted phagocytosis to baseline levels. Collectively these results implicate metabolic dysfunction as a key factor in the toxicity of cigarette smoke to AMΦ, and illuminate avenues of potential intervention.

Residence in Rural Areas of the United States and Lung Cancer Mortality. Disease Incidence, Treatment Disparities, and Stage-Specific Survival.

RATIONALE: There is increased lung cancer mortality in rural areas of the United States. However, it remains unclear to what extent rural-urban differences in disease incidence, stage at diagnosis, or treatment explain this finding. OBJECTIVES: To explore the relationship between smoking rates, lung cancer incidence, and lung cancer mortality in populations across the rural-urban continuum and to determine whether survival is decreased in rural patients diagnosed with lung cancer and whether this is associated with rural-urban differences in stage at diagnosis or the treatment received. METHODS: We conducted a retrospective cohort study of 348,002 patients diagnosed with lung cancer between 2000 and 2006. Data from metropolitan, urban, suburban, and rural areas in the United States were obtained from the Surveillance, Epidemiology, and End Results program database. County-level population estimates for 2003 were obtained from the U.S. Census Bureau, and corresponding estimates of smoking prevalence were obtained from published literature. The exposure was rurality, defined by the rural-urban continuum code area linked to each cohort participant by county of residence. Outcomes included lung cancer incidence, mortality, diagnostic stage, and treatment received. MEASUREMENTS AND MAIN RESULTS: Lung cancer mortality increased with rurality in a dose-dependent fashion across the rural-urban continuum. The most rural areas had almost twice the smoking prevalence and lung cancer incidence of the largest metropolitan areas. Rural patients diagnosed with stage I non-small cell lung cancer underwent fewer surgeries (69% vs. 75%; P < 0.001) and had significantly reduced median survival (40 vs. 52 mo; P = 0.0006) compared with the most urban patients. Stage at diagnosis was similar across the rural-urban continuum, as was median survival for patients with stages II-IV lung cancer. CONCLUSIONS: Higher rural smoking rates drive increased disease incidence and per capita lung cancer mortality in rural areas of the United States. There were no rural-urban discrepancies in diagnostic stage, suggesting similar access to diagnostic services. Rural patients diagnosed with stage I non-small cell lung cancer had shorter survival, which may reflect disparities in access to surgical care. No survival difference for patients with advanced-stage lung cancer is attributed to lack of effective treatment during the time period of this study.