Risk‐based selection from the general population in a screening trial: Selection criteria, recruitment and power for the Dutch‐Belgian randomised lung cancer multi‐slice CT screening trial (NELSON)

Abstract

A method to obtain the optimal selection criteria, taking into account available resources and capacity and the impact on power, is presented for the Dutch-Belgian randomised lung cancer screening trial (NELSON). NELSON investigates whether 16-detector multi-slice computed tomography screening will decrease lung cancer mortality compared to no screening. A questionnaire was sent to 335,441 (mainly) men, aged 50-75. Smoking exposure (years smoked, cigarettes/day, years quit) was determined, and expected lung cancer mortality was estimated for different selection scenarios for the 106,931 respondents, using lung cancer mortality data by level of smoking exposure (US Cancer Prevention Study I and II). Selection criteria were chosen so that the required response among eligible subjects to reach sufficient sample size was minimised and the required sample size was within our capacity. Inviting current and former smokers (quit 10 years ago) who smoked >15 cigarettes/day during >25 years or >10 cigarettes/day during >30 years was most optimal. With a power of 80%, 17,300-27,900 participants are needed to show a 20-25% lung cancer mortality reduction 10 years after randomisation. Until October 18, 2005 11,103 (first recruitment round) and 4,325 (second recruitment round) (total 5 15,428) participants have been randomised. Selecting participants for lung cancer screening trials based on risk estimates is feasible and helpful to minimize sample size and costs. When pooling with Danish trial data (n 5 64,000) NELSON is the only trial without screening in controls that is expected to have 80% power to show a lung cancer mortality reduction of at least 25% 10 years after randomisation. ' 2006 Wiley-Liss, Inc.Key words: lung cancer; screening; computed tomography; power; risk estimation Lung cancer is the most common cause of cancer-related death in men and the second most common cause of cancer-related death in women in Europe. 1 Because lung cancer is often in an advanced stage at the time of diagnosis, 5-year-survival is only 15% or less. 2 Japanese studies and the US Early Lung Cancer Action Project (ELCAP) showed that in a high-risk population more lung cancers can be detected by spiral computed tomography (CT) screening than by chest X-ray screening. 3,4 These and other observational studies with spiral CT screening showed that 55-85% of CTdetected lung cancers at baseline screening in a high-risk population of current and former smokers are at a surgically removable stage (stage I). 5 Although these results seem promising, observational studies are prone to lead-time, length-time and overdiagnosis bias. Only in a randomised design, disease-specific mortality between the screened and the unscreened population, instead of survival, can be compared. Lead-time, length-time and overdiagnosis do not bias the analysis in such comparisons. 6 Therefore, in the United States the National Lung Screening Trial (NLST) was launched in 2002 7 and in the Netherlands and Belgium, the NEL-SON trial, a Dutch acronym for ÔDutch-Belgian lu...

Lung Cancer Screening with CT

“…Preliminary data from four randomized controlled trials (RCTs) using CT screening in the intervention arm have been published (16)(17)(18)(19)(20)(21). Three of these trials were conducted in advance of large multi-center national trials to determine the feasibility of enrollment into a randomized trial by generalists (16)(17)(18).…”

“…In 2003, the NELSON trial was launched, a Dutch-Belgian trial that randomized roughly 16,000 high risk participants to receive either annual CT screening (at years 1, 2 and 4) versus a control arm receiving no screening (19,20). The NELSON is the only trial in which the control arm receives no screening intervention, and has 80% power to show a lung cancer mortality reduction of at least 25% by 10 years after randomization.…”

The impact of radiologists’ expertise on screen results decisions in a CT lung cancer screening trial

“…Participants were current and former heavy smokers, aged 50-75 years. Recruitment procedures and selection criteria in the NELSON trial have been published [13]. In total, 15,822 individuals were randomised to no screening (N=7,907) or screening (N= 7,915) by low-dose chest CT at baseline (1st round), 1 year later (2nd round), 3 years later (3rd round) and 5.5 years later (4th round), and extra low-dose follow-up CT examinations in case of an indeterminate screening result [14] (Fig.…”

The tumor immune microenvironment in octogenarians with stage I non-small cell lung cancer

“…2,3 In a published study analyzing Surveillance, Epidemiology, and End Results (SEER) data, of all 316,882 patients with lung cancer, 45,912 patients (14%) were 80 years of age, 33% were 70-79 years of age, and 53% were <70 years of age. 2 In addition, with the anticipated increase in detection of lung cancer via computed tomography (CT) screenings, [4][5][6] an even greater number of elderly patients may be diagnosed with early-stage lung cancer.…”