Time to first cigarette and early detection in the National Lung Screening Trial

 描述（由申请人提供）：对53，454名当前和以前的健康吸烟者进行的国家肺部筛查试验（NLST）表明，低剂量计算机断层扫描（LDCT）可有效检测早期肺部肿瘤并提高肺癌生存率。肺癌是目前癌症死亡率的主要原因，5年生存率为 约17%。5-局部肿瘤的年存活率约为54%，这表明LDCT可以大大降低估计每年224，000例新诊断病例的死亡率。2013年12月，美国预防服务工作组（USTSPF）建议每年对55至80岁的成年吸烟者进行LDCT筛查。与LDCT相关的风险包括假阳性、辐射暴露和筛查费用。为了提高效益/成本比，USPSTF和美国国家癌症研究所承认，有必要确定其他肺癌风险因素，以更好地表征将受益于LDCT筛查的高风险目标人群。本研究拟研究尼古丁依赖行为、清醒后第一支烟时间（TFFC）对NLST肺癌早期发现和总生存时间的影响。最近，早期TTFC（15分钟内）已被证明与等待第一支烟一小时或更长时间的吸烟者相比，所有主要组织学类型的肺癌风险增加一倍。这种关联是剂量依赖性的，具有早期TTFC风险增加的趋势。这些发现在几项大规模研究中得到了独立重复。在使用各种香烟暴露史模型仔细调整吸烟史后，在吸烟者中观察到风险加倍。TTFC和肺癌之间的相关性的机制似乎反映了吸烟的强度，这是烟草致癌物暴露的一个关键决定因素，不能通过标准的吸烟暴露措施（如持续时间和频率）来解释。TTFC是吸烟者每天尼古丁和致癌物摄入的同等预测因子，如果不是更好的话，这解释了它与肺癌风险以及其他烟草相关癌症风险的相关性。30包年的吸烟史是NLST的入选标准，目前建议每年用低剂量CT筛查肺癌。NLST已经在其参与者的一个子集中收集了关于TTFC的信息，但尚未评估TTFC对早期发现的影响。

 DESCRIPTION (provided by applicant): 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.