A large randomized national trial has provided the first evidence of a significant reduction in lung cancer deaths with a screening test.

The National Lung Screening Trial (NLST) reported a 20.3% reduction in lung cancer mortality among heavy smokers screened with low-dose helical computed tomography (CT), as compared with those given standard chest x-rays. The trial enrolled more than 53,000 older, high-risk individuals.

In addition, deaths from any cause, including lung cancer, were 7% lower among participants screened with low-dose helical CT, also known as spiral CT.

The initial results were released today by the study sponsor, the U.S. National Cancer Institute, after the study’s independent data and safety monitoring board recommended halting the trial.

“The fact that low-dose helical CT provides a decided benefit is a result that will have implications for screening and management of lung cancer for many years to come,” Dr. Christine Berg, project officer for the lung screening study at the NCI, said in a statement.

Beginning in 2002, the NLST recruited about 53,500 American men and women, aged 55-74 years, who were current or former smokers with a smoking history of at least 30 pack-years. It randomly assigned them to receive three annual screens with low-dose helical CT or chest x-ray. Helical CT uses x-rays to obtain a multiple-image scan of the entire chest during a 7- to 15-second breath-hold, whereas a standard chest x-ray produces only a single image of the chest from a sub-second breath-hold.

At the time of the Oct. 20, 2010 analysis, 354 deaths from lung cancer had occurred in the CT arm vs. 442 in the chest x-ray group. Approximately 25% of deaths in the NLST were due to lung cancer.

NCI director Dr. Harold E. Varmus said the well-designed study used rigorous scientific methods and that its findings could spare countless lives.

“Lung cancer is the leading cause of cancer mortality in the U.S. and throughout the world, so a validated approach that can reduce lung cancer mortality by even 20% has the potential to spare very significant numbers of people from the ravages of this disease,” he said. “But these findings should in no way distract us from continued effort to curtail the use of tobacco, which will remain the major causative factor for lung cancer and several other diseases.”

Like other screening strategies, the use of low-dose helical CT has disadvantages including the cumulative effects of radiation from multiple CT scans, complications among patients who need additional testing to make a definitive lung cancer diagnosis, and the anxiety and added cost associated with investigating incidental findings picked up on CT.

In 2009, investigators reported that low-dose CT screening was associated with twice the rate of false positives and more unneeded interventions, compared with chest x-ray, in a randomized feasibility trial that preceded the NLST. But low-dose CT also detected twice as many lung cancers as did chest x-ray screens in that study.

Although the NLST trial cohort was ethnically representative of the high-risk U.S. population, the researchers noted that participants were highly motivated and screened at major medical centers. Thus, the results may not accurately predict the effect of CT screening for other populations.

“What has happened here is that the technology shows you can cut down on lung cancer deaths, the leading cause of cancer mortality, and save nearly as many lives as the number of people who die from breast cancer per year. We as a medical community now need to figure out how to do this in a way that the cost is acceptable to the public,” Dr. Bruce E. Johnson, an official with the American Society of Clinical Oncology and director of the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute in Boston, said in a statement.

A more detailed analysis of the NLST results is expected to be published in the coming months, although a paper describing its design and protocol was published Nov. 3 by the journal Radiology.

The trial was conducted at 33 sites across the country by the American College of Radiology Imaging Network and the Lung Screening Study group.

The study was sponsored by the National Cancer Institute.

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

一项大规模随机化试验首次证明，用低剂量螺旋CT进行筛查可以显著降低受试者肺癌死亡率。

美国国家肺筛查试验(NLST)始于2002年，试验由美国放射学会影像网络和肺筛查研究组织在全美33处不同地点进行，共纳入53,500例高肺癌风险的美国老年男性和女性。受试者年龄在55~74岁间且均为重度吸烟者(吸烟史≥30包·年)。受试者被安排随机接受3次/年的低剂量螺旋计算机断层扫描(CT)或胸部X线摄影。

截至2010年10月20日，CT组共有354例患者死于肺癌，而X线胸片组有442例。在NLST全部死亡患者中有25%死于肺癌。与通过标准胸部X线筛检相比，应用低剂量螺旋CT对重度吸烟者进行筛查可使这类患者的肺癌死亡率降低20.3%；应用低剂量螺旋CT筛查的受试者的全死因死亡率(包括肺癌)较未接受此筛检者低7%。

在2009年曾有一项随机化试验对低剂量CT筛查的可行性进行了研究，结果表明，CT筛查的假阳性率是X线胸片筛查的2倍，还使患者所接受的不必要的干预措施增多，但低剂量CT筛查出肺癌患者的人数较胸部X线多出1倍。

NLST所纳入的受试者在种族构成上对研究总体(美国高危人群)具备代表性，但这些受试者接受筛检的积极性很高，且其接受筛检的地点均局限于大型医学中心。所以，本研究的相关结论或许无法准确预测对其他人群进行CT筛查的结果。低剂量螺旋CT同样存在一些缺点：首先，多重CT扫描会加重患者的辐射累积；某些肺癌诊断未明需要额外检查的患者可能出现放射相关并发症；再者，通过CT影像发现一些偶然病变可能会使患者出现焦虑或增加他们经济上的负担。

本研究表明，利用低剂量螺旋CT筛检可使肺癌死亡率降低20%，这一益处一旦得以确人，将为肺癌的筛查和治疗带来重大变革，将有无数肺癌患者因为此项技术而免于死亡(相当于每年死于乳腺癌的人数总和)。

本研究由美国国立癌症研究所赞助。

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