Clinical Utility of a Plasma Protein Classifier for Indeterminate Lung Nodules.

Anil Vachani,Dao Nguyen,Alexander Porter,Scott Law,Zane Hammoud,Stephen Hunsucker,Paul Kearney,Sandra Starnes,Xiao-Jun Li,Christina Williamson,Steven Springmeyer,Neri Cohen

doi:10.1007/s00408-015-9800-0

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00408-015-9800-0) contains supplementary material, which is available to authorized users.

Highlights

A large number of pulmonary nodules are identified annually in the U.S presenting a difficult clinical challenge, as the majority prove to be of benign origin [1]
353 patients were eligible for the clinical utility analysis; 287 (81.3 %, Confidence intervals (CIs) 76.8–85.2 %) were diagnosed with non-small cell lung cancer (NSCLC), and 66 (18.7 %, CI 14.8–23.2 %) diagnosed with a benign lung nodule (Fig. 1)
This study presents the clinical utility of a protein classifier for the management of indeterminate pulmonary nodules

Summary

Introduction

A large number of pulmonary nodules are identified annually in the U.S presenting a difficult clinical challenge, as the majority prove to be of benign origin [1]. Physicians are faced with developing a diagnostic strategy that identifies nodules that are malignant and yet minimizes the risks of invasive procedures on benign nodules. The classifier was further validated in patients with indeterminate pulmonary nodules to identify likely benign nodules with high accuracy (negative predictive value 90 %, sensitivity 92 % and specificity 20 %). The intent of the present study is to evaluate the clinical utility of this classifier in a multicenter study of patients with indeterminate nodules undergoing invasive diagnostic procedures. The classifier reports ‘‘likely benign’’ when the probability of the lung nodule having benign etiology is high (NPV at least 84 %) and the remainder are reported as ‘‘indeterminate.’’ In accordance with best practices, the classifier was adjusted for evaluation of archival specimens included in this study (see Supplementary). Physicians and patients were blinded to the protein classifier results and laboratory personnel blinded to clinical outcomes

Study Design and Population

Results

Discussion