Risk assessment for indeterminate pulmonary nodules using a novel, plasma-protein based biomarker assay.
Neil N Trivedi, Mehrdad Arjomandi, James K Brown, Tess Rubenstein, Abigail D Rostykus, Stephanie Esposito, Eden Axler, Mike Beggs, Heng Yu, Luis Carbonell, Alice Juang, Sandy Kamer, Bhavin Patel, Shan Wang, Amanda L Fish, Zaid Haddad, Alan Hb Wu
Author Information
Neil N Trivedi: San Francisco Veterans Affairs Medical Center, 4150 Clement St, San Francisco, CA, USA.
Mehrdad Arjomandi: San Francisco Veterans Affairs Medical Center, 4150 Clement St, San Francisco, CA, USA.
James K Brown: San Francisco Veterans Affairs Medical Center, 4150 Clement St, San Francisco, CA, USA.
Tess Rubenstein: San Francisco Veterans Affairs Medical Center, 4150 Clement St, San Francisco, CA, USA.
Abigail D Rostykus: San Francisco Veterans Affairs Medical Center, 4150 Clement St, San Francisco, CA, USA.
Stephanie Esposito: The University of Pennsylvania, Philadelphia, USA.
Eden Axler: The University of Michigan, 500 S State St, Ann Arbor, MI, USA.
Mike Beggs: MagArray Inc, Milpitas, CA, USA.
Heng Yu: MagArray Inc, Milpitas, CA, USA.
Luis Carbonell: MagArray Inc, Milpitas, CA, USA.
Alice Juang: MagArray Inc, Milpitas, CA, USA.
Sandy Kamer: MagArray Inc, Milpitas, CA, USA.
Bhavin Patel: MagArray Inc, Milpitas, CA, USA.
Shan Wang: MagArray Inc, Milpitas, CA, USA.
Amanda L Fish: MagArray Inc, Milpitas, CA, USA.
Zaid Haddad: Vancouver, BC, Canada.
Alan Hb Wu: University of California, San Francisco, USA.
BACKGROUND: The increase in lung cancer screening is intensifying the need for a noninvasive test to characterize the many indeterminate pulmonary nodules (IPN) discovered. Correctly identifying non-cancerous nodules is needed to reduce overdiagnosis and overtreatment. Alternatively, early identification of malignant nodules may represent a potentially curable form of lung cancer. OBJECTIVE: To develop and validate a plasma-based multiplexed protein assay for classifying IPN by discriminating between those with a lung cancer diagnosis established pathologically and those found to be clinically and radiographically stable for at least one year. METHODS: Using a novel technology, we developed assays for plasma proteins associated with lung cancer into a panel for characterizing the risk that an IPN found on chest imaging is malignant. The assay panel was evaluated with a cohort of 277 samples, all from current smokers with an IPN 4-30 mm. Subjects were divided into training and test sets to identify a Support Vector Machine (SVM) model for risk classification containing those proteins and clinical factors that added discriminatory information to the Veteran's Affairs (VA) Clinical Factors Model. The algorithm was then evaluated in an independent validation cohort. RESULTS: Among the 97 validation study subjects, 68 were grouped as having intermediate risk by the VA model of which the SVM model correctly identified 44 (65%) of these intermediate-risk samples as low (n=16) or high risk (n=28). The SVM model negative predictive value (NPV) was 94% and its sensitivity was 94%. CONCLUSION: The performance of the novel plasma protein biomarker assay supports its use as a noninvasive risk assessment aid for characterizing IPN. The high NPV of the SVM model suggests its application as a rule-out test to increase the confidence of providers to avoid aggressive interventions for their patients for whom the VA model result is an inconclusive, intermediate risk.
