title: Lung cancer risk test trial: study design, participant baseline characteristics, bronchoscopy safety, and establishment of a biospecimen repository.
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
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  The LCRT Study, NCT 01130285, was registered with Clinicaltrials.gov on May 24, 2010.
authors.affiliation: Department of Pulmonary and Critical Care, The University of Toledo Medical Center, Toledo, OH, USA.
authors.forename: E L
authors.initials: EL
authors.lastname: Crawford
authors.affiliation: Department of Biostatistics, Henry Ford Hospital System, Detroit, MI, USA.
authors.forename: A
authors.initials: A
authors.lastname: Levin
authors.affiliation: Department of Pulmonary and Critical Care, The University of Toledo Medical Center, Toledo, OH, USA.
authors.forename: F
authors.initials: F
authors.lastname: Safi
authors.affiliation: Department of Biostatistics, Henry Ford Hospital System, Detroit, MI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Pulmonary and Critical Care, The University of Toledo Medical Center, Toledo, OH, USA.
authors.forename: A
authors.initials: A
authors.lastname: Baugh
authors.affiliation: Department of Pulmonary and Critical Care, The University of Toledo Medical Center, Toledo, OH, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pulmonary and Critical Care, The University of Toledo Medical Center, Toledo, OH, USA.
authors.forename: J
authors.initials: J
authors.lastname: Yeo
authors.affiliation: Department of Pulmonary and Critical Care, The University of Toledo Medical Center, Toledo, OH, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Khuder
authors.affiliation: Department of Pulmonary and Critical Care, The University of Toledo Medical Center, Toledo, OH, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Boulos
authors.affiliation: Ohio State University James Comprehensive Cancer Center and Solove Research Institute, Columbus, OH, USA.
authors.forename: P
authors.initials: P
authors.lastname: Nana-Sinkam
authors.affiliation: Thoracic Program, Vanderbilt Ingram Cancer Center, Nashville, TN, USA.
authors.forename: P P
authors.initials: PP
authors.lastname: Massion
authors.affiliation: University of Michigan, Ann Arbor, MI, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Arenberg
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: D
authors.initials: D
authors.lastname: Midthun
authors.affiliation: Cleveland Clinic, Cleveland, OH, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Mazzone
authors.affiliation: Inova Fairfax Hospital, Falls Church, VA, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Nathan
authors.affiliation: The Toledo Hospital, Toledo, OH, USA.
authors.forename: R
authors.initials: R
authors.lastname: Wainz
authors.affiliation: Medical University of South Carolina, Charleston, SC, USA.
authors.forename: G
authors.initials: G
authors.lastname: Silvestri
authors.affiliation: Mercy/St. Vincent's Hospital, Toledo, OH, USA.
authors.forename: J
authors.initials: J
authors.lastname: Tita
authors.affiliation: Department of Pulmonary and Critical Care, The University of Toledo Medical Center, Toledo, OH, USA. james.willey2@utoledo.edu.
authors.forename: J C
authors.initials: JC
authors.lastname: Willey
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000383:Agriculture; D001194:Asbestos; D018070:Biological Specimen Banks; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D001999:Bronchoscopy; D015331:Cohort Studies; D055088:Early Detection of Cancer; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D005541:Forced Expiratory Volume; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008173:Lung Diseases, Obstructive / Q000453:epidemiology* / Q000503:physiopathology; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000706:statistics & numerical data*; D011446:Prospective Studies; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D018570:Risk Assessment / Q000379:methods; D012907:Smoking / Q000453:epidemiology*; D036542:Tomography, Spiral Computed; D014797:Vital Capacity
chemical_list: D001194:Asbestos