Tumor-Associated Autoantibodies: Re-Optimization of EarlyCDT-Lung Diagnostic Performance and Its Application to Indeterminate Pulmonary Nodules
Open Access
- 1 January 2017
- journal article
- research article
- Published by Scientific Research Publishing, Inc. in Journal of Cancer Therapy
- Vol. 08 (05), 506-517
- https://doi.org/10.4236/jct.2017.85043
Abstract
Background: Low-dose computed tomography (CT) screening reduces lung cancer mortality but costs are prohibitive for most healthcare budgets due to high false positive rates. An adjunctive test able to distinguish malignant from benign pulmonary nodules would be hugely beneficial. EarlyCDT-Lung measures serum autoantibodies to tumor-associated antigens and has found clinical acceptance to aid early detection of lung cancer for high risk patients. However performance was optimized for screening. The construction of a receiver-operating characteristic (ROC) curve would enable optimization of performance for alternative settings, including nodule malignancy. Methods: A Monte-Carlo search method was used to construct a ROC curve using a case-control cohort, enabling high and low specificity versions of EarlyCDT-Lung to be determined. These were used for a theoretical evaluation of a nodule cohort, and positive predictive value (PPV) was calculated under the assumption of independence of risk source. Patients or their nodules are typically classified into three risk groups: low (0% - 10%), intermediate (10% - 65%) and high (>65%) risk of malignancy. The predicted shift in risk group by application of the high and low specificity versions, along with the current commercial EarlyCDT-Lung, was then estimated. Results: The ROC curve, with an area under the curve of 0.743, was constructed. The high specificity (98%), low specificity (49%) and current commercial (91% specificity) versions of EarlyCDT-Lung re-classified 27%, 23% and 26% of intermediate nodules, respectively, to either a higher (10%, 8% and 10%) or lower (17%, 15% and 16%) risk group. Conclusion: A ROC curve was constructed to allow performance prediction of EarlyCDT-Lung at different specificities in the indeterminate nodule setting. This enabled risk re-classification of intermediate risk nodules, and could therefore facilitate alternative more appropriate intervention. We have shown how a multivariate biomarker test can add to the interpretation of pulmonary nodules and therefore aid patient management.Keywords
This publication has 19 references indexed in Scilit:
- EarlyCDT®-Lung test: improved clinical utility through additional autoantibody assaysTumor Biology, 2012
- Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic ScreeningThe New England Journal of Medicine, 2011
- EarlyCDT-Lung: An Immunobiomarker Test as an Aid to Early Detection of Lung CancerCancer Prevention Research, 2011
- Clinical validation of an autoantibody test for lung cancerAnnals of Oncology, 2010
- Technical validation of an autoantibody test for lung cancerAnnals of Oncology, 2010
- Projected Cancer Risks From Computed Tomographic Scans Performed in the United States in 2007Archives of Internal Medicine, 2009
- Validation of two models to estimate the probability of malignancy in patients with solitary pulmonary nodulesThorax, 2008
- Limitations of Screening for Lung Cancer with Low-Dose Spiral Computed TomographyClinical Cancer Research, 2005
- The Sentinel Within: Exploiting the Immune System for Cancer BiomarkersJournal of Proteome Research, 2005
- Lung Cancer Screening with CT: Mayo Clinic ExperienceRadiology, 2003