Development and Validation of a Plasma Biomarker Panel for Discerning Clinical Significance of Indeterminate Pulmonary Nodules

• Published in: Journal of thoracic oncology Vol. 8; no. 1; pp. 31 - 36
• Main Authors: Daly, Shaun, Rinewalt, Daniel, Fhied, Cristina, Basu, Sanjib, Mahon, Brett, Liptay, Michael J., Hong, Edward, Chmielewski, Gary, Yoder, Mark A., Shah, Palmi N., Edell, Eric S., Maldonado, Fabien, Bungum, Aaron O., Borgia, Jeffrey A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2013; International Association for the Study of Lung Cancer
• Subjects: Adult; Aged; Aged, 80 and over; Area Under Curve; Biomarkers, Tumor - blood; Chemokine CCL3 - blood; Chemokine CXCL12 - blood; Cytokines - blood; Female; Granuloma - blood; Humans; Interleukin 1 Receptor Antagonist Protein - blood; Interleukin-10 - blood; Interleukin-2 Receptor alpha Subunit - blood; Interleukin-6 - blood; Low-dose computed tomography screening; Lung cancer; Lung Neoplasms - blood; Lung Neoplasms - diagnosis; Male; Middle Aged; Multiple Pulmonary Nodules - blood; Multiple Pulmonary Nodules - diagnostic imaging; Multiple Pulmonary Nodules - pathology; Nodules; Plasma biomarkers; Pneumonia - blood; Predictive Value of Tests; Radiography; Respiratory Tract Infections - blood; ROC Curve; Solitary Pulmonary Nodule - blood; Solitary Pulmonary Nodule - diagnostic imaging; Solitary Pulmonary Nodule - pathology; Tumor Necrosis Factor-alpha - blood; Validation; Young Adult; Validation; Low-dose computed tomography screening; Plasma biomarkers; Lung cancer; Nodules
• ISSN: 1556-0864; 1556-1380; 1556-1380
• DOI: 10.1097/JTO.0b013e31827627f8

The recent findings of the National Lung Screening Trial showed 24.2% of individuals at high risk for lung cancer having one or more indeterminate nodules detected by low-dose computed tomography–based screening, 96.4% of which were eventually confirmed as false positives. These positive scans necessitate additional diagnostic procedures to establish a definitive diagnosis that adds cost and risk to the paradigm. A plasma test able to assign benign versus malignant pathology in high-risk patients would be an invaluable tool to complement low-dose computed tomography–based screening and promote its rapid implementation. We evaluated 17 biomarkers, previously shown to have value in detecting lung cancer, against a discovery cohort, comprising benign (n = 67) cases and lung cancer (n = 69) cases. A Random Forest method based analysis was used to identify the optimal biomarker panel for assigning disease status, which was then validated against a cohort from the Mayo Clinic, comprising patients with benign (n = 61) or malignant (n = 20) indeterminate lung nodules. Our discovery efforts produced a seven-analyte plasma biomarker panel consisting of interleukin 6 (IL-6), IL-10, IL-1ra, sIL-2Rα, stromal cell-derived factor-1α+β, tumor necrosis factor α, and macrophage inflammatory protein 1 α. The sensitivity and specificity of our panel in our validation cohort is 95.0% and 23.3%, respectively. The validated negative predictive value of our panel was 93.8%. We developed a seven-analyte plasma biomarker panel able to identify benign nodules, otherwise deemed indeterminate, with a high degree of accuracy. This panel may have clinical utility in risk-stratifying screen-detected lung nodules, decrease unnecessary follow-up imaging or invasive procedures, and potentially avoid unnecessary morbidity, mortality, and health care costs.