A Bronchial Genomic Classifier for the Diagnostic Evaluation of XXXX .

@entity1 @entity358 @entity5 @entity2
BACKGROUND: Bronchoscopy is frequently nondiagnostic in @entity1 with @entity358 suspected to be @entity2 . This often results in additional invasive testing, although many lesions are benign. We sought to validate a bronchial-airway gene-expression classifier that could improve the diagnostic performance of bronchoscopy. METHODS: Current or former smokers undergoing bronchoscopy for suspected @entity2 were enrolled at 28 centers in two multicenter prospective studies (AEGIS-1 and AEGIS-2). A gene-expression classifier was measured in epithelial cells collected from the normal-appearing mainstem bronchus to assess the probability of @entity2 . RESULTS: A total of 639 @entity1 in AEGIS-1 (298 @entity1 ) and AEGIS-2 (341 @entity1 ) met the criteria for inclusion. A total of 43% of bronchoscopic examinations were nondiagnostic for @entity2 , and invasive procedures were performed after bronchoscopy in 35% of @entity1 with benign lesions. In AEGIS-1, the classifier had an area under the receiver-operating-characteristic curve (AUC) of 0.78 (95% confidence interval [CI], 0.73 to 0.83), a sensitivity of 88% (95% CI, 83 to 92), and a specificity of 47% (95% CI, 37 to 58). In AEGIS-2, the classifier had an AUC of 0.74 (95% CI, 0.68 to 0.80), a sensitivity of 89% (95% CI, 84 to 92), and a specificity of 47% (95% CI, 36 to 59). The combination of the classifier plus bronchoscopy had a sensitivity of 96% (95% CI, 93 to 98) in AEGIS-1 and 98% (95% CI, 96 to 99) in AEGIS-2, independent of lesion size and location. In 101 @entity1 with an intermediate pretest probability of @entity5 , the negative predictive value of the classifier was 91% (95% CI, 75 to 98) among @entity1 with a nondiagnostic bronchoscopic examination. CONCLUSIONS: The gene-expression classifier improved the diagnostic performance of bronchoscopy for the detection of @entity2 . In intermediate-risk @entity1 with a nondiagnostic bronchoscopic examination, a negative classifier score provides support for a more conservative diagnostic approach. (Funded by Allegro Diagnostics and others; AEGIS-1 and AEGIS-2 ClinicalTrials.gov numbers, NCT01309087 and NCT00746759.).
