TY - JOUR
T1 - Development and validation of a plasma biomarker panel for discerning clinical significance of indeterminate pulmonary nodules
AU - Daly, Shaun
AU - Rinewalt, Daniel
AU - Fhied, Cristina
AU - Basu, Sanjib
AU - Mahon, Brett
AU - Liptay, Michael J.
AU - Hong, Edward
AU - Chmielewski, Gary
AU - Yoder, Mark A.
AU - Shah, Palmi N.
AU - Edell, Eric S.
AU - Maldonado, Fabien
AU - Bungum, Aaron O.
AU - Borgia, Jeffrey A.
N1 - Funding Information:
This work was supported by the Illinois Chapter of the American Cancer Society (JB), the LUNGevity Foundation (JB), The Respiratory Health Association of Metropolitan Chicago (JB), the Mary Denny Weaver Chair of Cancer Research (ML), and generous philanthropic gifts made by the Sapiente Family.
PY - 2013/1
Y1 - 2013/1
N2 - INTRODUCTION: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.
AB - INTRODUCTION: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.
KW - Low-dose computed tomography screening
KW - Lung cancer
KW - Nodules
KW - Plasma biomarkers
KW - Validation
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U2 - 10.1097/JTO.0b013e31827627f8
DO - 10.1097/JTO.0b013e31827627f8
M3 - Article
C2 - 23201823
AN - SCOPUS:84871940924
SN - 1556-0864
VL - 8
SP - 31
EP - 36
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 1
ER -