Clinical Utility of a Plasma Protein Classifier for Indeterminate Lung Nodules

Abstract

Evaluation of indeterminate pulmonary nodules is a complex challenge. Most are benign but frequently undergo invasive and costly procedures to rule out malignancy. A plasma protein classifier was developed that identifies likely benign nodules that can be triaged to CT surveillance to avoid unnecessary invasive procedures. The clinical utility of this classifier was assessed in a prospective-retrospective analysis of a study enrolling 475 patients with nodules 8-30 mm in diameter who had an invasive procedure to confirm diagnosis at 12 sites. Using this classifier, 32.0 % (CI 19.5-46.7) of surgeries and 31.8 % (CI 20.9-44.4) of invasive procedures (biopsy and/or surgery) on benign nodules could have been avoided. Patients with malignancy triaged to CT surveillance by the classifier would have been 24.0 % (CI 19.2-29.4). This rate is similar to that described in clinical practices (24.5 % CI 16.2-34.4). This study demonstrates the clinical utility of a non-invasive blood test for pulmonary nodules.

Trial registration: ClinicalTrials.gov NCT01752101.

Keywords: Biomarker; Clinical utility; Lung cancer; Lung nodule; Prospective; Xpresys lung.

Fig. 1

Flowchart of subjects included in clinical utility analyses along with categorization of subjects by procedure, outcome and classifier report. ‘LB’ and ‘IND’ represent a classifier ‘Likely Benign’ and ‘Indeterminate’ report, respectively. Dx indicates diagnostic, Non-Dx is a non-diagnostic procedure, and Dx Biopsy includes patients with a biopsy only and those that had a diagnostic biopsy followed by surgery

Fig. 2

The incorporation of the classifier into the ACCP guidelines for lung nodule management. Newly identified lung nodules between 8 and 30 mm in diameter are assessed using the plasma protein classifier. The classifier results are integrated into the physician’s assessment of cancer risk