title: Clinical Utility of a Bronchial Genomic Classifier in Patients With Suspected Lung Cancer.
abstract: BACKGROUND
  Bronchoscopy is often the initial diagnostic procedure performed in patients with pulmonary lesions suggestive of lung cancer. A bronchial genomic classifier was previously validated to identify patients at low risk for lung cancer after an inconclusive bronchoscopy. In this study, we evaluated the potential of the classifier to reduce invasive procedure utilization in patients with suspected lung cancer.
  
  
  METHODS
  In two multicenter trials of patients undergoing bronchoscopy for suspected lung cancer, the classifier was measured in normal-appearing bronchial epithelial cells from a mainstem bronchus. Among patients with low and intermediate pretest probability of cancer (n = 222), subsequent invasive procedures after an inconclusive bronchoscopy were identified. Estimates of the ability of the classifier to reduce unnecessary procedures were calculated.
  
  
  RESULTS
  Of the 222 patients, 188 (85%) had an inconclusive bronchoscopy and follow-up procedure data available for analysis. Seventy-seven (41%) patients underwent an additional 99 invasive procedures, which included surgical lung biopsy in 40 (52%) patients. Benign and malignant diseases were ultimately diagnosed in 62 (81%) and 15 (19%) patients, respectively. Among those undergoing surgical biopsy, 20 (50%) were performed in patients with benign disease. If the classifier had been used to guide decision making, procedures could have been avoided in 50% (21 of 42) of patients undergoing further invasive testing. Further, among 35 patients with an inconclusive index bronchoscopy who were diagnosed with lung cancer, the sensitivity of the classifier was 89%, with 4 (11%) patients having a false-negative classifier result.
  
  
  CONCLUSIONS
  Invasive procedures after an inconclusive bronchoscopy occur frequently, and most are performed in patients ultimately diagnosed with benign disease. Using the genomic classifier as an adjunct to bronchoscopy may reduce the frequency and associated morbidity of these invasive procedures.
  
  
  BACKGROUND
  ClinicalTrials.gov; Nos. NCT01309087 and NCT00746759; URL: www.clinicaltrials.gov.
authors.affiliation: Pulmonary, Allergy, and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. Electronic address: avachani@mail.med.upenn.edu.
authors.forename: Anil
authors.initials: A
authors.lastname: Vachani
authors.affiliation: Veracyte Inc, South San Francisco, CA.
authors.forename: Duncan H
authors.initials: DH
authors.lastname: Whitney
authors.affiliation: Allegro Diagnostics, Boston, MA.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Parsons
authors.affiliation: Division of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA.
authors.forename: Marc
authors.initials: M
authors.lastname: Lenburg
authors.affiliation: Allergy, Pulmonary, and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: J Scott
authors.initials: JS
authors.lastname: Ferguson
authors.affiliation: Division of Pulmonary and Critical Care, Department of Medicine, Medical University of South Carolina, Charleston, SC.
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Silvestri
authors.affiliation: Division of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA.
authors.forename: Avrum
authors.initials: A
authors.lastname: Spira
mesh_terms: D000368:Aged; D001706:Biopsy / Q000379:methods; D001980:Bronchi / Q000473:pathology*; D001999:Bronchoscopy / Q000009:adverse effects* / Q000379:methods; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D023281:Genomics / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
keywords: bronchoscopy; clinical utility; gene expression; lung cancer