Clinical validation of a blood-based classifier for diagnostic evaluation of asymptomatic individuals with pulmonary nodules

Abstract

BackgroundThe number of pulmonary nodules detected in the US is expected to increase substantially following recent recommendations for nationwide CT-based lung cancer screening. Given the low specificity of CT screening, non-invasive adjuvant methods are needed to differentiate cancerous lesions from benign nodules to help avoid unnecessary invasive procedures in the asymptomatic population. We have constructed a serum-based multi-biomarker panel and assessed its clinical accuracy in a retrospective analysis of samples collected from participants with suspicious radiographic findings in the Prostate, Lung, Chest and Ovarian (PLCO) cancer screening trial.MethodsStarting with a set of 9 candidate biomarkers, we identified 8 that exhibited limited pre-analytical variability with increasing clotting time, a key pre-analytical variable associated with the collection of serum. These 8 biomarkers were evaluated in a training study consisting of 95 stage I NSCLC patients and 186 smoker controls where a 5-biomarker pulmonary nodule classifier (PNC) was selected. The clinical accuracy of the PNC was determined in a blinded study of asymptomatic individuals comprising 119 confirmed malignant nodule cases and 119 benign nodule controls selected from the PLCO screening trial.ResultsA PNC comprising 5 biomarkers: CEA, CYFRA 21-1, OPN, SCC, and TFPI, was selected in the training study. In an independent validation study, the PNC resolved lung cancer cases from benign nodule controls with an AUC of 0.653 (p < 0.0001). CEA and CYFRA 21-1, two of the markers included in the PNC, also accurately distinguished malignant lesions from benign controls.ConclusionsA 5-biomarker blood test has been developed for the diagnostic evaluation of asymptomatic individuals with solitary pulmonary nodules.Electronic supplementary materialThe online version of this article (doi:10.1186/s12014-017-9158-9) contains supplementary material, which is available to authorized users.

Clinical Validation of a Protein Biomarker Panel for Non-Small Cell Lung Cancer

“…Although LDCT screening for lung cancer is associated with the low specificity (73.4%)4 and the resulting high rate of false-positives (96.4%),3 annual LDCT-screening for lung cancer was recently recommended for high-risk individuals 5. However, in this recommendation, the need for more research into the use of biomarkers to complement LDCT screening was also stressed 56…”

“…The main concern raised by clinicians performing lung cancer CT screening is the high prevalence of one or more lung nodules, with many being undiagnosed as either malignant or benign 36. In Korea, LDCT screening showed that 35% of subjects had at least one or more non-calcified lung nodule, and lung cancer detection rates were 0.36% 14.…”