编译：南南和北北
来源：桓兴医讯
背景（Background）
现在美国指南推荐对高危人员进行小剂量CT肺癌筛查。初次筛查后出现新结节的报告少见、且由于采用的定义不同而经常前后矛盾。在“比利时-荷兰随机化肺癌筛查试验（NELSON）”中，我们旨在确定后续筛查时新实性结节发生情况及其发生肺癌的概率。
US guidelines now recommend lung cancer screening with low-dose CT for high-risk individuals. Reports of new nodules after baseline screening have been scarce and are inconsistent because of differences in definitions used. We aimed to identify the occurrence of new solid nodules and their probability of being lung cancerat incidence screening rounds in the Dutch-Belgian Randomized Lung Cancer Screening Trial (NELSON).
方法（Method）
在这项正在进行的多中心随机对照NELSON试验中，2003年12月23日至2006年7月6日之间，入组了15822名参试者，并随机分组为接受小剂量CT筛查（n=7915）组、非筛查组（n=7907），参试者入组条件为吸烟25年、至少15支/天，或吸烟30年、10支/天，且仍在吸烟、或戒烟不足10年。从2004年6月28日至2006年12月18日，7557名人员进行了小剂量CT的首轮筛查，7295名进行了第二轮、第三轮筛查。我们纳入所有有实性非钙化结节的参试者进行分析，这些结节由NELSON试验的放射科医生判定登记为新发结节、或既往筛查时小于15mm3（本研究检出极限），通过软件半自动计算出结节体积。我们通过估测结节≥25%的体积变化来计算结节体积倍增最长时间，这代表前一次筛查以来最低增长率的时间。根据组织学结果做出肺癌诊断，良性诊断则基于组织学结果或结节大小稳定至少2年。NELSON试验在trialregister.nl网站注册，注册号ISRCTN63545820。
In the ongoing, multicentre, randomised controlled NELSON trial, between Dec 23, 2003, and July6, 2006, 15 822 participants who had smoked at least 15 cigarettes a day for more than 25 years or ten cigarettes a day for more than 30 years and were current smokers, or had quit smoking less than 10 years ago, were enrolled and randomly assigned to receive either screening with low-dose CT (n=7915) or noscreening (n=7907). From Jan 28, 2004, to Dec 18, 2006, 7557 individuals underwent baseline screening with low-dose CT; 7295 participants underwent second and third screening rounds. We included all participants with solid non-calcified nodules, registered by the NELSON radiologists as new or smaller than 15 mm3 (study detection limit) at previous screens. Nodule volume was generated semiautomatically by software. We calculated the maximum volume doubling time for nodules with an estimated percentage volume change of 25% or more, representing the minimum growth rate for the time since the previous scan. Lung cancer diagnosis was based on histology, and benignity was based on histologyor stable size for at least 2 years. The NELSON trial is registered at trialregister.nl, number ISRCTN63545820.
发现（Findings）
我们对第二轮或第三轮筛查时至少有一个实性非钙化结节的参试者资料进行了分析。在这两轮的筛查中，NELSON试验的放射科医生登记了787名参试者有1222个新发实性结节。49名（6%）新发实性结节的参试者有1个新实性结节为肺癌，发现50名肺癌，代表了所有新实性结节的4%。34名（68%）诊断为I期肺癌。结节体积区分良恶性效能高（接收者运行曲线下面积[AUC]为0.795[95%CI为0.728-0.862]，p<0.0001），体积小于27mm3的结节发生肺癌概率低（417个结节中有2个结节为肺癌[0.5%]，肺癌概率为0.5%[95%CI为0.0-1.9]），体积27mm3-206mm3的结节发生肺癌概率中等（542个结节中有17个[3.1%]，肺癌概率为3.1%[1.9-5.0]），206mm3或以上的结节肺癌概率高（172个结节中有29个[16.9%]，肺癌概率为16.9%[12.0-23.2]）。体积阈值27mm3或以上，肺癌敏感度超过95%。
We analysed data for participants with at least one solid non-calcified nodule at the second or third screening round. In the two incidence screening rounds, the NELSON radiologists registered 1222 new solid nodules in 787 (11%) participants. A new solid nodule was lung cancer in 49 (6%) participants with new solid nodules and, in total, 50 lung cancers were found, representing 4% of all new solid nodules. 34 (68%) lung cancers were diagnosed at stage I. Nodule volume had a high discriminatory power (area under the receiver operating curve 0·795 [95%CI 0·728–0·862]; p<0·0001). Nodules smaller than 27 mm3 had a low probability of lung cancer (two [0·5%] of 417 nodules; lung cancer probability0·5% [95% CI 0·0–1·9]), nodules with a volume of 27 mm3 up to 206 mm3 had anintermediate probability (17 [3·1%] of 542 nodules; lung cancer probability3·1% [1·9–5·0]), and nodules of 206 mm3 or greater had ahigh probability (29 [16·9%] of 172 nodules; lung cancer probability 16·9% [12·0–23·2]). A volume cutoff value of 27 mm3 or greater had more than 95% sensitivity for lung cancer.
解释（Interpretation）
我们的研究表明，在5-7%的进行小剂量CT肺癌筛查人员中，每一轮次的筛查可检测出新实性结节。这些新实性结节即使体积小，是恶性的概率也高。应当考虑将这些结果进入未来的筛查指南中，新实性结节应当比首轮筛查出的结节进行更严密的随诊。
Our study shows that new solid nodules are detected at each screening round in 5–7% of individuals who undergo screening for lung cancer with low-dose CT. These new nodules have a high probability of malignancy even at a small size. These findings should be considered in future screening guidelines, and new solid nodules should be followed up more aggressively than nodules detected at baseline screening.
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