title: EarlyCDT®-Lung test: improved clinical utility through additional autoantibody assays.
abstract: Tumor-associated autoantibodies (AAbs) have been described in patients with lung cancer, and the EarlyCDT®-Lung test that measures such AAbs is available as an aid for the early detection of lung cancer in high-risk populations. Improvements in specificity would improve its cost-effectiveness, as well as reduce anxiety associated with false positive tests. Samples from 235 patients with newly diagnosed lung cancer and matched controls were measured for the presence of AAbs to a panel of six (p53, NY-ESO-1, CAGE, GBU4-5, Annexin I, and SOX2) or seven (p53, NY-ESO-1, CAGE, GBU4-5, SOX2, HuD, and MAGE A4) antigens. Data were assessed in relation to cancer type and stage. The sensitivity and specificity of these two panels were also compared in two prospective consecutive series of 776 and 836 individuals at an increased risk of developing lung cancer. The six-AAb panel gave a sensitivity of 39% with a specificity of 89 %, while the seven-AAb panel gave a sensitivity of 41 % with a specificity of 91 % which, once adjusted for occult cancers in the population, resulted in a specificity of 93 %. Analysis of these AAb assays in the at-risk population confirmed that the seven-AAb panel resulted in a significant increase in the specificity of the test from 82 to 90 %, with no significant change in sensitivity. The change from a six- to a seven-AAb assay can improve the specificity of the test and would result in a PPV of 1 in 8 and an overall accuracy of 92 %.
authors.affiliation: Centre of Excellence for Autoimmunity in Cancer, The University of Nottingham, Nottingham, UK. Caroline.Chapman@nottingham.ac.uk
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Chapman
authors.forename: Graham F
authors.initials: GF
authors.lastname: Healey
authors.forename: Andrea
authors.initials: A
authors.lastname: Murray
authors.forename: Peter
authors.initials: P
authors.lastname: Boyle
authors.forename: Chris
authors.initials: C
authors.lastname: Robertson
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Peek
authors.forename: Jared
authors.initials: J
authors.lastname: Allen
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Thorpe
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Hamilton-Fairley
authors.forename: Celine B
authors.initials: CB
authors.lastname: Parsy-Kowalska
authors.forename: Isabel K
authors.initials: IK
authors.lastname: MacDonald
authors.forename: William
authors.initials: W
authors.lastname: Jewell
authors.forename: Paul
authors.initials: P
authors.lastname: Maddison
authors.forename: John F R
authors.initials: JF
authors.lastname: Robertson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D055088:Early Detection of Cancer / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011933:Reagent Kits, Diagnostic; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D001323:Autoantibodies; D011933:Reagent Kits, Diagnostic