Autoantibody profiling for lung cancer screening longitudinal retrospective analysis of CT screening cohorts.
Recommendations for lung cancer screening present a tangible opportunity to integrate predictive blood-based assays with radiographic imaging. This study compares performance of autoantibody markers from prior discovery in sample cohorts from two CT screening trials. One-hundred eighty non-cancer and 6 prevalence and 44 incidence cancer cases detected in the Mayo Lung Screening Trial were tested using a panel of six autoantibody markers to define a normal range and assign cutoff values for class prediction. A cutoff for minimal specificity and best achievable sensitivity were applied to 256 samples drawn annually for three years from 95 participants in the Kentucky Lung Screening Trial. Data revealed a discrepancy in quantile distribution between the two apparently comparable sample sets, which skewed the assay's dynamic range towards specificity. This cutoff offered 43% specificity (102/237) in the control group and accurately classified 11/19 lung cancer samples (58%), which included 4/5 cancers at time of radiographic detection (80%), and 50% of occult cancers up to five years prior to diagnosis. An apparent ceiling in assay sensitivity is likely to limit the utility of this assay in a conventional screening paradigm. Pre-analytical bias introduced by sample age, handling or storage remains a practical concern during development, validation and implementation of autoantibody assays. This report does not draw conclusions about other logical applications for autoantibody profiling in lung cancer diagnosis and management, nor its potential when combined with other biomarkers that might improve overall predictive accuracy.
Division of Pulmonary and Critical Care Medicine, University of Kentucky, Lexington, Kentucky, United States of America.
Kourtney
K
Trudgen
Division of Pulmonary and Critical Care Medicine, University of Kentucky, Lexington, Kentucky, United States of America.
Nada H
NH
Khattar
Division of Pulmonary and Critical Care Medicine, University of Kentucky, Lexington, Kentucky, United States of America.
Eric
E
Bensadoun
Division of Medical Oncology, University of Kentucky, Lexington, Kentucky, United States of America.
Susanne
S
Arnold
Department of Statistics, University of Kentucky, Lexington, Kentucky, United States of America.
Arnold J
AJ
Stromberg
Division of Pulmonary and Critical Care Medicine, University of Kentucky, Lexington, Kentucky, United States of America ; Lexington Veteran's Administration Medical Center, Lexington, Kentucky, United States of America.
Edward A
EA
Hirschowitz
D000368:Aged; D000912:Antibodies, Neoplasm / Q000097:blood / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000097:blood* / Q000276:immunology; D016022:Case-Control Studies; D055088:Early Detection of Cancer; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D040081:Protein Array Analysis; D014057:Tomography, X-Ray Computed / Q000379:methods*
D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor