Scientists have found a 20% percent reduction in deaths from lung cancer among current or former heavy smokers who were screened with low-dose helical computed tomography (CT) versus those screened by chest X-ray. The primary research results from the National Lung Screening Trial (NLST) were published online today in the New England Journal of Medicine.

This article provides a more extensive analysis of the data originally reported in November 2010 while providing additional data to the public and research community without barriers to access. Sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, the NLST is a nearly decade-long study that establishes low-dose helical CT as the first validated screening test which can reduce mortality due to lung cancer.

A validated screening test
?Today?s publication gives researchers, policy makers, and the public full access to primary findings from the NLST to guide the use of low-dose helical CT scanning by current and former smokers,? said Harold Varmus, M.D., NCI director. ?The NCI marshaled the scientific and financial resources required for this expansive study, because only trials such as this allow us to say which methods of screening are effective, and how effective, in defined populations. Having a validated screening test that provides significant, but partial, protection against death from lung cancer complements ? but should not be seen as replacing ? ongoing efforts to control use of tobacco and to find other ways to prevent and treat lung cancer.?

30 pack-years
The NLST was a randomized national trial involving 53,454 current and former heavy smokers ages 55 to 74. Participants were required to have a smoking history of at least 30 pack-years and were either current or former smokers without signs, symptoms, or history of lung cancer. Pack-years are calculated by multiplying the average number of packs of cigarettes smoked per day by the number of years a person has smoked.


Multiple-image scan
Participants in the NLST were randomly assigned to receive three annual screens with either low-dose helical CT (often referred to as spiral CT) or standard chest X-ray. Helical CT uses X-rays to obtain a multiple-image scan of the entire chest, while a standard chest X-ray produces a single image of the whole chest in which anatomic structures overlie one another.

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Additional tests required
The paper published today provides important details about the number of screens that identified abnormalities potentially related to lung cancer (positive screens) and how many of those positive screens turned out to be false positives, meaning that the positive finding did not prove to be lung cancer upon follow-up. On average over the three rounds of screening exams, 24.2% of the low-dose helical CT screens were positive and 6.9% of the chest X-rays were positive. In both arms of the trial, the majority of positive screens led to additional tests.

Across all three rounds, when a positive screening result was found, 96.4% of the low-dose helical CT tests and 94.5% of the chest X-ray exams were false positive. The vast majority of false positive results was probably due to the detection of normal lymph nodes or inflamed tissues. False positive results not due to lung cancer were typically confirmed by follow-up CT scans that showed no change in the finding over time.

Low-dose helical CT vs, standard Chest X-ray
The published results also provide insight into the type of lung cancers found by screening and the stages at which they were diagnosed. Adenocarcinomas, which begin in cells that line the lungs, and squamous cell carcinomas, which arise from the thin, flat fish-scale-like cells that line passages of the respiratory tract, were detected in the early stages of disease in both arms of the trial. Both types of lung cancer were detected more frequently at the earliest stage by low-dose helical CT compared to chest X-ray. Small-cell lung cancers, which are very aggressive tumors and grow in the tissues of the lung, were infrequently detected at early stages by low-dose helical CT or chest X-ray. Knowing what types of lung cancers are detectable and at what stage they are most detectable by different screening modalities should help researchers refine the use of these tools for future patients.

Optimal frequency and duration of screening
Additional studies based on the complete NLST data set are ongoing and will include reports on cost-effectiveness of low-dose helical CT as well as the ability to use the data to develop models that may help indicate whether other groups of smokers, such as light smokers or younger smokers, would benefit from screening with low-dose helical CT. Other modeling studies are expected to examine the optimal frequency and duration of screening.

Few and relatively minor adverse events
Adverse events, which are harms from the actual screening examinations, were few and relatively minor in the NLST. The rate of complications among people who underwent a diagnostic evaluation prompted by a positive screen was under 2% for either type of screening. Among those who did have complications, 16 people screened with low-dose helical CT (10 of whom had lung cancer) and 10 chest X-ray participants (all with lung cancer) died within 60 days of a follow-up invasive diagnostic procedure.

Invasive diagnostic procedures include bronchoscopy, where an instrument is inserted through the nose or mouth into the airways, and percutaneous lung needle biopsy, where a needle is inserted into the lung through the chest to remove a small piece of tissue for examination. While it is not known whether the diagnostic procedures caused these deaths, the low frequency of death within 60 days of an invasive procedure in the NLST suggests that death following evaluation of positive screens occurs rarely.

Low radiation exposure
Radiation exposure associated with low-dose helical CT in the NLST is much lower than that associated with a regular diagnostic chest CT. The authors note any harm from exposure to radiation during the screenings could not be measured directly. Because the effect of such exposure is a long-term outcome, potential harms will need to be modeled in future studies.

It should also be noted that the population enrolled in this study, while ethnically representative of the U.S. population of smokers at high risk for lung cancer, was a highly motivated and primarily urban group that was screened at major medical centers. Thus, these results alone may not accurately predict the effects of recommending low-dose helical CT scanning for other populations.

?These primary findings from the NLST provide a valuable insight into how to potentially decrease death due to lung cancer. But the most important method of decreasing lung cancer rates remains for smokers to quit smoking and for those who don?t smoke to continue with their healthy behaviors,? said NLST co-investigator, Christine Berg, M.D., of the NCI.

The NLST was conducted by the American College of Radiology Imaging Network, a medical imaging research network focused on the conduct of multi-center imaging clinical trials, and the Lung Screening Study group, which was initially established by the NCI to examine the feasibility of the NLST.

For more information:
– National Lung Screening Trial Research Team. Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. N Engl J Med. Online June 29, 2011. In print, August 4, 2011.
– Sox HC. Better Evidence about Screening for Lung C
ancer. N Engl J Med 2011; 365:455-457 August 4, 2011
– NCI: Lung cancer and screening
– NCI: Q&A on the NLST
Video discussion of the design and outcomes of the NLST.


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