The National Lung Screening Trial (NLST) of 53,454 current and former healthy smokers demonstrated that low dose computed tomography (LDCT) was effective in detecting lung tumors at an earlier stage and increasing survival from lung cancer. Lung cancer is by far the leading cause of cancer mortality, with a 5-year survival rate of about 17%. 5-year survival rate is about 54% for localized tumors, indicating that LDCT could substantially reduce mortality rates among the estimated annual 224,000 newly diagnosed cases. In December 2013, the United States Preventive Services Task Force (USTSPF) recommended annual screening with LDCT to adult smokers between the ages of 55 and 80. The risks associated with LDCT include false positives, radiation exposure, and the costs of screening. To improve the benefit/cost ratio, the USPSTF and the National Cancer Institute acknowledge that there is a need to identify additional lung cancer risk factors to better characterize the high risk target populations that would benefit from LDCT screening. The current study proposes to study the effects of a nicotine dependence behavior, the time to first cigarette (TFFC) after waking, on the early detection of lung cancer and overall survival time in the NLST. Recently, an early TTFC (within 15 minutes) has been shown to double the risk of all major histological types of lung cancer compared to smokers who waited an hour or more for their first cigarette. The association is dose-dependent, with a trend toward increasing risk with an earlier TTFC. The findings were independently replicated in several large-scale studies. The doubling of risk is observed among smokers, after careful adjustment for smoking history using a variety of models of cigarette exposure history. The mechanism underlying the association between TTFC and lung cancer appears to reflect the intensity of smoking, a critical determinant of tobacco carcinogen exposure that is not accounted for by standard smoking exposure measures such as duration and frequency. The TTFC is an equal if not better predictor of nicotine and carcinogen uptake in smokers than cigarettes per day, which explains its association with lung cancer risk, as well as with the risk of other tobacco-related cancers. A 30-pack year history of smoking was the inclusion criteria for the NLST, and is currently recommended for annual screening for lung cancer with low-dose CT. The NLST has collected information on TTFC in a subset of its participants, but the effect of TTFC on early detection has not yet been evaluated.
The goal of this project is to determine if a specific smoking nicotine dependence behavior, the time of day of the first cigarette, is associated with an earlier detection of lung cancer in a clinical trial of smokers screened for lung cancer by low-dose computed tomography. The results will help identify smokers at high risk of lung cancer who can benefit from early detection and improved survival time.
