Risk assessment for indeterminate pulmonary nodules using a novel, plasma-protein based biomarker assay
| Autor: | James K. Brown, Alan H.B. Wu, Neil N. Trivedi, Tess Rubenstein, Mehrdad Arjomandi, Heng Yu, Abigail D. Rostykus, Zaid Haddad, Amanda L Fish, Alice Juang, Shan X. Wang, Luis Carbonell, Michael Beggs, Eden Axler, Stephanie Esposito, Sandy Kamer, Bhavin Patel |
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| Rok vydání: | 2018 |
| Předmět: |
Oncology
medicine.medical_specialty diagnosis Article Clinical Research Internal medicine Medicine pulmonary nodules Overdiagnosis Lung cancer Lung Cancer business.industry Prevention biomarkers risk models General Medicine medicine.disease Blood proteins 4.1 Discovery and preclinical testing of markers and technologies lung cancer Biomarker (medicine) business Indeterminate Risk assessment Risk classification Lung cancer screening 4.2 Evaluation of markers and technologies |
| Zdroj: | Biomedical research and clinical practice, vol 3, iss 4 Biomedical research and clinical practice |
| Popis: | Author(s): Trivedi, Neil N; Arjomandi, Mehrdad; Brown, James K; Rubenstein, Tess; Rostykus, Abigail D; Esposito, Stephanie; Axler, Eden; Beggs, Mike; Yu, Heng; Carbonell, Luis; Juang, Alice; Kamer, Sandy; Patel, Bhavin; Wang, Shan; Fish, Amanda L; Haddad, Zaid; Wu, Alan Hb | Abstract: BackgroundThe 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.ObjectiveTo 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.MethodsUsing 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.ResultsAmong 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%.ConclusionThe 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. |
| Databáze: | OpenAIRE |
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