Kathryn J. Long MD , Gerard A. Silvestri MD , Michael N. Kammer PhD , Sarah Gibbs MD , Wei Wu MD, PhD , Monica Johal MPH , Sudhakar Pipavath MD , Trevor Pitcher PhD , James Jett MD , Viswam S. Nair MD
{"title":"Validation of a High-Specificity Blood Autoantibody Test to Detect Lung Cancer in Pulmonary Nodules","authors":"Kathryn J. Long MD , Gerard A. Silvestri MD , Michael N. Kammer PhD , Sarah Gibbs MD , Wei Wu MD, PhD , Monica Johal MPH , Sudhakar Pipavath MD , Trevor Pitcher PhD , James Jett MD , Viswam S. Nair MD","doi":"10.1016/j.chpulm.2024.100130","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Pulmonary nodules (PNs) are frequently detected by chest CT scan, which is increasingly used in clinical practice. Accurately identifying malignant nodules can pose a diagnostic challenge; therefore, a high-specificity biomarker could help clinicians identify malignant nodules and ideally lead to the earlier diagnosis of lung cancer.</div></div><div><h3>Research Question</h3><div>What are the performance characteristics of a blood-based biomarker for identifying malignancy in patients with a CT-detected PN?</div></div><div><h3>Study Design and Methods</h3><div>Banked plasma samples from 2 independent prospective observational cohorts of patients presenting with benign or malignant PNs 8 to 30 mm in size were tested using a 7-autoantibody panel. Sensitivity, specificity, and positive predictive value of the autoantibody test (AAT) to identify cancer were calculated for the individual and combined cohorts.</div></div><div><h3>Results</h3><div>Overall, 447 patients (263 and 184 from each cohort) were included in the analysis with a prevalence of malignancy of 55%. The performance of the AAT between the 2 cohorts was similar. The AAT demonstrated a specificity of 90% (95% CI, 85%-93%), a positive predictive value of 66% (95% CI, 52%-77%), sensitivity of 16% (95% CI, 12%-22%), and false-positive rate of 10% in the combined cohort. Using a pretest probability of cancer cutoff of 20% improved the positive predictive value to 76% (95% CI, 61%-88%) and resulted in a 52% decrease in the number of false-positive test results. In the subset of patients who had 18F-fluorodeoxyglucose PET imaging performed for clinical purposes (n = 222), specificity of the AAT was higher (93% vs 58%, <em>P</em> < .001), but the sensitivity was lower than 18F-fluorodeoxyglucose PET scan (17% vs 75%, <em>P</em> < .001).</div></div><div><h3>Interpretation</h3><div>This study validates the specificity of a blood-based autoantibody biomarker for identifying malignancy in patients with indeterminate PNs. This rule-in biomarker may help to expedite workup of malignant nodules.</div></div><div><h3>Clinical Trial Registration</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>; No.: NCT01752114; URL: <span><span>www.clinicaltrials.gov</span><svg><path></path></svg></span></div></div>","PeriodicalId":94286,"journal":{"name":"CHEST pulmonary","volume":"3 1","pages":"Article 100130"},"PeriodicalIF":0.0000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CHEST pulmonary","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2949789224000965","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Pulmonary nodules (PNs) are frequently detected by chest CT scan, which is increasingly used in clinical practice. Accurately identifying malignant nodules can pose a diagnostic challenge; therefore, a high-specificity biomarker could help clinicians identify malignant nodules and ideally lead to the earlier diagnosis of lung cancer.
Research Question
What are the performance characteristics of a blood-based biomarker for identifying malignancy in patients with a CT-detected PN?
Study Design and Methods
Banked plasma samples from 2 independent prospective observational cohorts of patients presenting with benign or malignant PNs 8 to 30 mm in size were tested using a 7-autoantibody panel. Sensitivity, specificity, and positive predictive value of the autoantibody test (AAT) to identify cancer were calculated for the individual and combined cohorts.
Results
Overall, 447 patients (263 and 184 from each cohort) were included in the analysis with a prevalence of malignancy of 55%. The performance of the AAT between the 2 cohorts was similar. The AAT demonstrated a specificity of 90% (95% CI, 85%-93%), a positive predictive value of 66% (95% CI, 52%-77%), sensitivity of 16% (95% CI, 12%-22%), and false-positive rate of 10% in the combined cohort. Using a pretest probability of cancer cutoff of 20% improved the positive predictive value to 76% (95% CI, 61%-88%) and resulted in a 52% decrease in the number of false-positive test results. In the subset of patients who had 18F-fluorodeoxyglucose PET imaging performed for clinical purposes (n = 222), specificity of the AAT was higher (93% vs 58%, P < .001), but the sensitivity was lower than 18F-fluorodeoxyglucose PET scan (17% vs 75%, P < .001).
Interpretation
This study validates the specificity of a blood-based autoantibody biomarker for identifying malignancy in patients with indeterminate PNs. This rule-in biomarker may help to expedite workup of malignant nodules.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
