Edwin J Ostrin1, Leonidas E Bantis2, David O Wilson3, Nikul Patel4, Renwei Wang5, Deepali Kundnani4, Jennifer Adams-Haduch5, Jennifer B Dennison4, Johannes F Fahrmann4, Hsienchang Thomas Chiu6, Adi Gazdar7, Ziding Feng8, Jian-Min Yuan9, Samir M Hanash4. 1. Department of General Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: ejostrin@mdanderson.org. 2. Department of Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, Kansas. 3. Division of Pulmonary, Allergy and Critical Care Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania. 4. McCombs Institute for the Early Detection and Treatment of Cancer, University of Texas MD Anderson Cancer Center, Houston, Texas. 5. UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania. 6. Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, Texas. 7. Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas. 8. Department of Biostatistics, Fred Hutchinson Cancer Center, Seattle, Washington. 9. Division of Pulmonary, Allergy and Critical Care Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
Abstract
RATIONALE: The workup and longitudinal monitoring for subjects presenting with pulmonary nodules is a pressing clinical problem. A blood-based biomarker panel potentially has utility for identifying subjects at higher risk for harboring a malignant nodule for whom additional workup would be indicated or subjects at reduced risk for whom imaging-based follow-up would be indicated. OBJECTIVES: To assess whether a previously described four-protein biomarker panel, reported to improve assessment of lung cancer risk compared with a smoking-based lung cancer risk model, can provide discrimination between benign and malignant indeterminate pulmonary nodules. METHODS: A previously validated multiplex enzyme-linked immunoassay was performed on matched case and control samples from each cohort. MEASUREMENTS: The biomarker panel was tested in two case-control cohorts of patients presenting with indeterminate pulmonary nodules at the University of Pittsburgh Medical Center and the University of Texas Southwestern. MAIN RESULTS: In both cohorts, the biomarker panel resulted in improved prediction of lung cancer risk over a model on the basis of nodule size alone. Of particular note, the addition of the marker panel to nodule size greatly improved sensitivity at a high specificity in both cohorts. CONCLUSIONS: A four-marker biomarker panel, previously validated to improve lung cancer risk prediction, was found to also have utility in distinguishing benign from malignant indeterminate pulmonary nodules. Its performance in improving sensitivity at a high specificity indicates potential utility of the marker panel in assessing likelihood of malignancy in otherwise indeterminate nodules.
RATIONALE: The workup and longitudinal monitoring for subjects presenting with pulmonary nodules is a pressing clinical problem. A blood-based biomarker panel potentially has utility for identifying subjects at higher risk for harboring a malignant nodule for whom additional workup would be indicated or subjects at reduced risk for whom imaging-based follow-up would be indicated. OBJECTIVES: To assess whether a previously described four-protein biomarker panel, reported to improve assessment of lung cancer risk compared with a smoking-based lung cancer risk model, can provide discrimination between benign and malignant indeterminate pulmonary nodules. METHODS: A previously validated multiplex enzyme-linked immunoassay was performed on matched case and control samples from each cohort. MEASUREMENTS: The biomarker panel was tested in two case-control cohorts of patients presenting with indeterminate pulmonary nodules at the University of Pittsburgh Medical Center and the University of Texas Southwestern. MAIN RESULTS: In both cohorts, the biomarker panel resulted in improved prediction of lung cancer risk over a model on the basis of nodule size alone. Of particular note, the addition of the marker panel to nodule size greatly improved sensitivity at a high specificity in both cohorts. CONCLUSIONS: A four-marker biomarker panel, previously validated to improve lung cancer risk prediction, was found to also have utility in distinguishing benign from malignant indeterminate pulmonary nodules. Its performance in improving sensitivity at a high specificity indicates potential utility of the marker panel in assessing likelihood of malignancy in otherwise indeterminate nodules.
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