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

 描述(申请人提供)：对53,454名现在和以前的健康吸烟者进行的国家肺筛查试验(NLST)表明，低剂量计算机断层扫描(LDCT)在早期发现肺癌和提高肺癌生存率方面是有效的。到目前为止，肺癌是癌症死亡的主要原因，5年存活率为 大约17%。局部肿瘤的5年生存率约为54%，这表明LDCT可以显著降低估计每年22.4万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55岁至80岁的成年吸烟者每年进行LDCT筛查。与LDCT相关的风险包括假阳性、辐射暴露和筛查成本。为了提高效益/成本比，USPSTF和国家癌症研究所承认，有必要确定更多的肺癌风险因素，以更好地表征将受益于LDCT筛查的高危目标人群。目前的研究建议研究尼古丁依赖行为，即醒来后第一支烟的时间(TFFC)对NLST中肺癌的早期检测和总体生存时间的影响。最近，与等待一个小时或更长时间才抽第一支烟的吸烟者相比，早期TTFC(15分钟内)患所有主要组织学类型肺癌的风险增加了一倍。这种关联是剂量依赖的，早期TTFC的风险有增加的趋势。这些发现在几项大规模研究中得到了独立的重复。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增加了一倍。TTFC与肺癌之间联系的潜在机制似乎反映了吸烟的强度，吸烟是烟草致癌物暴露的关键决定因素，标准的吸烟暴露衡量标准，如持续时间和频率，没有考虑到这一点。对于吸烟者中尼古丁和致癌物摄入量的预测，TTFC即使不是更好，也是等同于每天吸烟，这解释了它与肺癌风险以及其他与烟草相关的癌症风险的关联。有30年的吸烟史是NLST的纳入标准，目前推荐用于低剂量CT的肺癌年度筛查。NLST收集了一部分参与者关于TTFC的信息，但TTFC对早期发现的影响尚未得到评估。

 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.