title: Diagnostic characteristics of a serum biomarker in patients with positron emission tomography scans.
abstract: BACKGROUND
  Surgery for pulmonary nodules results in a benign diagnosis in 10% to 30% of cases. Computed tomography and fluorodeoxyglucose-positron emission tomography (FDG-PET) are highly sensitive but less specific. High-risk patients (age > 55 years and smoke > 15 pack-years) for lung cancer with negative FDG-PET scans, or low-risk patients (age < 55 years or smoke < 15 pack-years) with FDG-PET-avid lesions may have higher rates of benign nodules. We hypothesized that our serum biomarker improves diagnostic accuracy by providing greater specificity.
  
  
  METHODS
  Fifty-eight patients with pulmonary nodules (< or = 3 cm) were prospectively enrolled. We tested the accuracy of our proteomic biomarker in the serum by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Malignancy rates, contingency tables, sensitivity, and specificity analyses were calculated for the entire group and in a subset of patients at high risk for benign disease.
  
  
  RESULTS
  We identified 46 (79%) lung cancers and 12 (21%) benign lesions. Forty-five nodules were FDG-PET-avid. In 36 high-risk patients with FDG-PET-avid lesions, 32 (89%) had cancer. Of the remaining 22 lower-risk patients, 14 (64%) had cancer (p = 0.02). The serum biomarker sensitivity was 26.1%, specificity was 91.7%, positive predictive value was 92%, negative predictive value was 24%, and overall accuracy was 40%. The serum signature accurately predicted all eight benign nodules in this 22-patient subset.
  
  
  CONCLUSIONS
  The serum protein biomarker has a high specificity. This biomarker has a high positive predictive value but low negative predictive value and may improve noninvasive evaluation of lung nodules. Validation in a larger population is warranted.
authors.affiliation: Department of Thoracic Surgery, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232, USA. eric.grogan@vanderbilt.edu
authors.forename: Eric L
authors.initials: EL
authors.lastname: Grogan
authors.forename: Stephen
authors.initials: S
authors.lastname: Deppen
authors.forename: Chad V
authors.initials: CV
authors.lastname: Pecot
authors.forename: Joe B
authors.initials: JB
authors.lastname: Putnam
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Nesbitt
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.forename: Rama
authors.initials: R
authors.lastname: Rajanbabu
authors.forename: Bridget
authors.initials: B
authors.lastname: Ory
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lambright
authors.forename: Pierre P
authors.initials: PP
authors.lastname: Massion
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D055613:Multiple Pulmonary Nodules / Q000097:blood* / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D001798:Blood Proteins