View Abstract

A7360 - Performance Characteristics of CYFRA 21.1 Measurements by Compensated Backscattering Interferometry for the Early Detection of Lung Cancer
Author Block: M. Kammer1, A. K. Kussrow2, M. Hoeksema3, D. J. Bornhop2, P. P. Massion3; 1Biomedical Engineering, Vanderbilt University, Nashville, TN, United States, 2Chemistry and Vanderbilt Institute for Chemical Biology, Vanderbilt University, Nashville, TN, United States, 3Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States.
Introduction: Although the large majority of indeterminate pulmonary nodules (IPNs) are benign, there are currently no effective predictive tools to discriminate benign from malignant nodules, leading to a large number of follow-up computed tomography CTs, unnecessary invasive biopsies, anxiety, and wasted healthcare spending. Here we postulated that our novel diagnostic methodology, compensated backscattering interferometry (CBSI), will dramatically lower the limits of quantitation of one of the best candidate biomarkers for lung cancer in the population, i.e. CYFRA 21.1, and will increase the discriminatory power of the biomarker, changing its clinical utility. Methods: Measurement of CYFRA 21.1 by CBSI was obtained in quintuplicates across individuals with indeterminate lung nodules (controls n=75), Stages 1, 2 lung squamous (SCCs, n=44), Adenocarcimonas (ADCs, n=44) and all stages small cell carcinomas (SCLCs, n=61). An independent analysis was performed on aliquots of the same serum samples by commercial ELISA. Results: The limits of quantitation for CYFRA 21.1 by CBSI are 40 pg/mL by CBSI as compared to 3 ng/mL by ELISA. The concentrations of the biomarker candidate CYFRA 21.1 measured by CBSI dramatically redefines the concentration of the biomarker in the control population due to the improved limits of quantitation. CBSI measurements are reproducible against technical replicates over days and 3 cycles of freezing and thawing. The biomarker shows performance characteristics suitable for early detection of lung cancer (including stage 1 disease) with positive diagnostic likelihood ratios (DLRs) between 17.5 and 56.6 and negative DLRs between 0.02-0.25 for tree histological subtypes. CBSI method outperforms a commercial assay which is otherwise considered a standard in diagnostic testing, primarily for its ability to redefine the concentrations in the control population. Conclusion: CYFRA 21.1 measurements by CBSI offer diagnostic performances for the distinction between benign lung nodules from lung cancers with unprecedented accuracy. Should our approach withstand clinical validation from external and independent datasets, the result will be improved non-invasive testing and may be paradigm-shifting in the clinical management of patients with lung cancer.