National Lung Screening Trial

2002年9月启动的国家肺筛查试验（NLST）仍然是NCI消除肺癌死亡和痛苦目标的一个至关重要的组成部分。不幸的是，肺癌仍然是癌症死亡的主要原因。到目前为止，随机对照试验的筛查方式，如胸部X线和痰细胞学尚未证明任何影响肺癌死亡率。因此，如果没有有效的筛查或有效疗法的实质性改进，在降低肺癌死亡率方面几乎没有取得进展。令人鼓舞的是，技术进步，特别是低剂量技术的出现，快速，计算机螺旋计算机断层扫描，允许检测较小的肺结节。其他潜在的早期检测策略，如血清、血浆和痰液生物标志物，目前还处于初步阶段，在进行肺癌筛查的随机对照试验之前，需要进行大量的改进和验证。NLST将确定目前最有希望的早期检测策略，低剂量螺旋CT（LDCT）是否降低肺癌死亡率。 NLST旨在检测使用LDCT与胸部X线（CXR）相比肺癌死亡率降低20%或更高，如果存在这种益处。该试验建立在PLCO癌症筛查试验的基础上，该试验正在研究CXR筛查与社区护理相比的有用性。马约诊所CT队列研究的已发表结果为螺旋CT筛查提供了警示。研究人员将历史性的马约肺项目（密集CXR筛查）的结果与他们的CT参与者的一个子集的结果进行了比较，这些CT参与者在肺癌风险因素方面与前一项研究的参与者相当，并且在肺癌死亡率方面没有差异。 NLST是一项具有充分统计把握度的随机对照临床试验，能够评估肺癌死亡率。NLST于2002年9月开始，将53，000多名重度和/或长期吸烟者随机分配到低剂量螺旋计算机断层扫描（CT）或胸部X线检查（CXR）。参与者接受了初始和两次后续筛选检查。收到阳性或可疑筛查结果的参与者将被通知并转介给他们的初级保健医生，以确定适当的后续程序。 筛查在放射科的先进设备上进行，并配备经过NLST程序专门培训和认证的高素质工作人员。螺旋CT设备反映了目前在美国学术实践中使用的设备。GE、西门子、飞利浦和东芝是CT制造商的代表。他们代表了世界上所有这种专用设备的制造商。重要的是，最低限度需要四个面板探测器，随着机构进行资本投资，设备将升级到8、16和64个面板探测器。已制定了一项密集的质量保证计划，以确保遵守统一的图像采集参数、图像质量和剂量最小化参数。 低剂量螺旋CT的概念是以尽可能低的剂量优化图像采集，并利用肺通气提供的对比度。所有场所的所有设备的辐射剂量均受到仔细监测和控制。美国国家科学院最近公布的证据表明，应谨慎地尽量减少辐射照射，因为10至100 mSv范围内的剂量与原子弹幸存者患癌症死亡的风险增加有关。低剂量筛查与NLST中55至74岁吸烟者的低辐射风险一致。 将每年联系参与者，以确定其当前的健康状况。随访包括确定不良医疗结局、癌症发病率、死亡原因和死亡率影响。

The National Lung Screening Trial (NLST), launched in September 2002, continues to be a critically important component of the NCI goal to eliminate death and suffering from lung cancer. Unfortunately, lung cancer remains the leading cause of cancer death. To date, randomized controlled trials of screening modalities such as chest x-ray and sputum cytology have not demonstrated any impact on lung cancer mortality. Therefore, without effective screening or substantive improvements in effective therapies little progress has been made in lowering lung cancer mortality. Promisingly, technological advances, specifically, the advent of low-dose techniques with rapid, computerized helical computed tomography, have allowed detection of smaller lung nodules. Other potential early detection strategies such as serum, plasma and sputum biomarkers are currently preliminary, and require substantial refinement and validation before examination in a randomized, controlled trial for lung cancer screening. The NLST will determine whether the most promising current strategy for early detection, low-dose helical CT (LDCT) lowers lung cancer mortality. The NLST was designed to detect a 20% or greater reduction in lung cancer mortality with the use of LDCT over chest X-ray (CXR), should such a benefit exist. The trial built upon the PLCO Cancer Screening Trial, which is studying the usefulness of CXR screening compared with community care. Published findings from the Mayo Clinic CT cohort study provide a cautionary note about screening with spiral CT. The researchers compared findings from the historic Mayo Lung Project (intense CXR screening) with findings from a subset of their CT participants who were comparable to the former study's participants in terms of lung cancer risk factors and showed ¿no difference in ¿ lung cancer mortality rates¿. NLST is a well-powered, randomized controlled clinical trial able to assess lung cancer mortality with ample statistical power. NLST began in September 2002 and randomized over 53,000 heavy and/or long-term smokers to low-dose, helical computed tomography (CT) or chest X-ray (CXR). Participants received an initial and two subsequent screening exams. Participants who receive a positive or suspicious screening result are notified and referred to their primary care practitioner to determine appropriate follow up procedures. Screening occurs on sophisticated state-of-the-art equipment in radiology departments with highly qualified staff specifically trained and certified in NLST procedures. The helical CT equipment reflects that currently in use in academic practices across the United States. GE, Siemens, Philips and Toshiba are the CT manufacturers represented. They represent all the manufacturers of this specialty equipment in the world. Importantly, a minimum four-panel detector is required and equipment upgrades to 8, 16 and 64 panel detectors occur as the institutions make capital investments. An intensive quality assurance program has been developed to ensure adherence to harmonized, image acquisition parameters, image quality and dose-minimization parameters. The concept of low-dose helical CT is to optimize image acquisition with the lowest dose possible and take advantage of the contrast provided by lung aeration. Radiation dose is carefully monitored and controlled for all equipment at all sites. Recent evidence announced by the National Academy of Sciences indicates the prudence of minimizing radiation exposure, as doses in the 10 ¿ 100 mSv range have been associated with an elevated risk of cancer death in atomic bomb survivors. The low dose screen administered is consonant with a low radiation risk in the 55 ¿ 74 year old smokers in the NLST. Participants will be contacted annually to determine current health status. Follow up includes ascertainment of adverse medical outcomes, cancer incidence, cause of death, and mortality impact.