title: Impact of a bronchial genomic classifier on clinical decision making in patients undergoing diagnostic evaluation for lung cancer.
abstract: BACKGROUND
  Bronchoscopy is frequently used for the evaluation of suspicious pulmonary lesions found on computed tomography, but its sensitivity for detecting lung cancer is limited. Recently, a bronchial genomic classifier was validated to improve the sensitivity of bronchoscopy for lung cancer detection, demonstrating a high sensitivity and negative predictive value among patients at intermediate risk (10-60 %) for lung cancer with an inconclusive bronchoscopy. Our objective for this study was to determine if a negative genomic classifier result that down-classifies a patient from intermediate risk to low risk (<10 %) for lung cancer would reduce the rate that physicians recommend more invasive testing among patients with an inconclusive bronchoscopy.
  
  
  METHODS
  We conducted a randomized, prospective, decision impact survey study assessing pulmonologist recommendations in patients undergoing workup for lung cancer who had an inconclusive bronchoscopy. Cases with an intermediate pretest risk for lung cancer were selected from the AEGIS trials and presented in a randomized fashion to pulmonologists either with or without the patient's bronchial genomic classifier result to determine how the classifier results impacted physician decisions.
  
  
  RESULTS
  Two hundred two physicians provided 1523 case evaluations on 36 patients. Invasive procedure recommendations were reduced from 57 % without the classifier result to 18 % with a negative (low risk) classifier result (p < 0.001). Invasive procedure recommendations increased from 50 to 65 % with a positive (intermediate risk) classifier result (p < 0.001). When stratifying by ultimate disease diagnosis, there was an overall reduction in invasive procedure recommendations in patients with benign disease when classifier results were reported (54 to 41 %, p < 0.001). For patients ultimately diagnosed with malignant disease, there was an overall increase in invasive procedure recommendations when the classifier results were reported (50 to 64 %, p = 0.003).
  
  
  CONCLUSIONS
  Our findings suggest that a negative (low risk) bronchial genomic classifier result reduces invasive procedure recommendations following an inconclusive bronchoscopy and that the classifier overall reduces invasive procedure recommendations among patients ultimately diagnosed with benign disease. These results support the potential clinical utility of the classifier to improve management of patients undergoing bronchoscopy for suspect lung cancer by reducing additional invasive procedures in the setting of benign disease.
authors.affiliation: Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Suite 5233, 1685 Highland Avenue, Madison, WI, 53705, USA. jsferguson@medicine.wisc.edu.
authors.forename: J Scott
authors.initials: JS
authors.lastname: Ferguson
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, 300 Pasteur Dr, H3143 MC 5236, Stanford, CA, 94305, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Van Wert
authors.affiliation: Veracyte, Inc, 6000 Shoreline Ct, #300, South San Francisco, CA, 94080, USA.
authors.forename: Yoonha
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Veracyte, Inc, 6000 Shoreline Ct, #300, South San Francisco, CA, 94080, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rosenbluth
authors.affiliation: Veracyte, Inc, 6000 Shoreline Ct, #300, South San Francisco, CA, 94080, USA.
authors.forename: Kate Porta
authors.initials: KP
authors.lastname: Smith
authors.affiliation: Veracyte, Inc, 6000 Shoreline Ct, #300, South San Francisco, CA, 94080, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Division of Computational Biomedicine, Department of Medicine, Boston University Medical Center, 715 Albany St, Boston, MA, 02118, USA.
authors.forename: Avrum
authors.initials: A
authors.lastname: Spira
mesh_terms: D001999:Bronchoscopy / Q000379:methods*; D000066491:Clinical Decision-Making; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D023281:Genomics / Q000379:methods*; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging*; D008175:Lung Neoplasms / Q000145:classification* / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015203:Reproducibility of Results; D014057:Tomography, X-Ray Computed / Q000379:methods*
keywords: Biomarkers; Bronchoscopy; Clinical utility; Decision making; Gene expression; Lung cancer; Solitary pulmonary nodule