Lung cancer risk test trial: study design, participant baseline characteristics, bronchoscopy safety, and establishment of a biospecimen repository

Our plain-English summary of Lung cancer risk test trial: study design, participant baseline characteristics, bronchoscopy safety, and establishment of a biospecimen repository, by E.L. Crawford, A. Levin, F. Safi, et al (BMC Pulmonary Medicine, 2016).

The study

• Authors: E.L. Crawford, A. Levin, F. Safi, M. Lu, A. Baugh, X. Zhang, J. Yeo, S.A. Khuder, A.M. Boulos, P. Nana-Sinkam, P.P. Massion, D.A. Arenberg, D. Midthun, P.J. Mazzone, S.D. Nathan, R. Wainz, G. Silvestri, J. Tita, J.C. Willey
• Journal: BMC Pulmonary Medicine
• Published: 2016;16:16
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The Lung Cancer Risk Test (LCRT) trial is a prospective cohort study comparing lung cancer incidence among persons with a positive or negative value for the LCRT, a 15 gene test measured in normal bronchial epithelial cells (NBEC). The purpose of this article is to describe the study design, primary endpoint, and safety; baseline characteristics of enrolled individuals; and establishment of a bio-specimen repository.

Methods/design: Eligible participants were aged 50-90 years, current or former smokers with 20 pack-years or more cigarette smoking history, free of lung cancer, and willing to undergo bronchoscopic brush biopsy for NBEC sample collection. NBEC, peripheral blood samples, baseline CT, and medical and demographic data were collected from each subject.

Discussion: Over a two-year span (2010-2012), 403 subjects were enrolled at 12 sites. At baseline 384 subjects remained in study and mean age and smoking history were 62.9 years and 50.4 pack-years respectively, with 34% current smokers. Obstructive lung disease (FEV1/FVC <0.7) was present in 157 (54%). No severe adverse events were associated with bronchoscopic brushing. An NBEC and matched peripheral blood bio-specimen repository was established. The demographic composition of the enrolled group is representative of the population for which the LCRT is intended. Specifically, based on baseline population characteristics we expect lung cancer incidence in this cohort to be representative of the population eligible for low-dose Computed Tomography (LDCT) lung cancer screening. Collection of NBEC by bronchial brush biopsy/bronchoscopy was safe and well-tolerated in this population. These findings support the feasibility of testing LCRT clinical utility in this prospective study. If validated, the LCRT has the potential to significantly narrow the population of individuals requiring annual low-dose helical CT screening for early detection of lung cancer and delay the onset of screening for individuals with results indicating low lung cancer risk. For these individuals, the small risk incurred by undergoing once in a lifetime bronchoscopic sample collection for LCRT may be offset by a reduction in their CT-related risks. The LCRT biospecimen repository will enable additional studies of genetic basis for COPD and/or lung cancer risk.

Trial Registration: The LCRT Study, NCT 01130285, was registered with Clinicaltrials.gov on May 24, 2010.

In plain English

This article described the design and early findings of the Lung Cancer Risk Test (LCRT) trial. It is a prospective cohort study at 12 medical institutions testing whether a 15-gene test, measured in normal cells brushed from the airway during bronchoscopy, can predict who will develop lung cancer. From 2010 to 2012, 403 current or former smokers aged 50 to 90 with at least 20 pack-years of smoking were enrolled. Eighteen were removed because lung cancer was diagnosed at the enrolling bronchoscopy or on later tests, and one withdrew, leaving 384. Their mean age was 62.9 years and their mean smoking history was 50.4 pack-years. Of the 384, 54 (14%) reported work-related asbestos exposure. The article did not analyze asbestos further. Of 290 people with lung function tests, 157 (54%) had COPD. No serious adverse events were attributed to the study procedures. Some people had bronchoscopy for research rather than for their medical care. Among them, 9 people had 11 mild events possibly or probably related to the study procedures. Two years after the study began, 5 subjects (1.3%) had developed lung cancer, and the gene test results remained blinded. The authors concluded that the brushing was safe and well-tolerated and that the trial is feasible.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Multi-site prospective cohort study (originally planned as a nested case-control study). This article reports the study design, baseline characteristics and early secondary endpoints, not the test's predictive accuracy.
• Who was studied: 403 current or former smokers aged 50 to 90 years with at least 20 pack-years of cigarette smoking and no known lung cancer, enrolled at 12 medical institutions, with enrollment completed in March 2012. 384 remained in the cohort after 18 were removed for prevalent lung cancer and 1 withdrew.
• Exposure: Cigarette smoking (mean 50.4 pack-years) was the entry criterion. The test studied was a 15-gene test in normal bronchial epithelial cells. Self-reported work-related exposures included asbestos in 54 subjects (14%), farming in 41 (11%), and chemicals or plastics, welding, foundry or steel milling, and painting.
• Main results:
  • Of the 403 enrolled, 18 were removed because prevalent lung cancer was diagnosed at the enrolling bronchoscopy or in later tests, and 1 withdrew, leaving 384 subjects.
  • Among the 384 subjects, mean age was 62.9 years (standard deviation 8.2) and mean smoking history was 50.4 pack-years.
  • At enrollment, 253 of the 384 subjects (65.9%) met the US Preventive Services Task Force age and pack-year criteria for annual lung cancer screening.
  • Lung function test data were available for 290 subjects. Of these, 157 (54%) had COPD by test criteria.
  • Self-reported COPD status matched the diagnosis by lung function testing in 67% of subjects.
  • No serious adverse events were attributable to the study, and there were no study-related adverse events in the standard-of-care bronchoscopy group.
  • The study-driven bronchoscopy group included bronchoscopies done for this study or for another research study. In this group, 9 subjects had 11 adverse events possibly (9) or probably (2) related to the study procedures. All adverse events were classified as mild.
  • Matched blood and airway cell samples were collected and banked for 361 of the 384 subjects (94%).
  • Two years after the study began, 5 subjects (1.3%) without lung cancer at enrollment had developed bronchogenic carcinoma.
• The authors' conclusion: The authors concluded that collecting airway cells by bronchial brushing was safe and well-tolerated in this population, and that the findings support the feasibility of testing the LCRT's clinical usefulness in this prospective study.
• Limitations the authors state:
  • Because the study was blinded, the authors could give no further details about the subjects who developed lung cancer, and the test's predictive results were not yet reported.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Bellwether Trial, Bronchoscopy, Cohort Study, Biopsy, Obstructive Lung Disease, FEV1/FVC Ratio, Low-Dose CT Screening.

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