A Nasal Swab Classifier to Evaluate the Probability of Lung Cancer in Patients with Pulmonary Nodules

Background Accurate assessment of the probability of lung cancer (pCA) is critical in patients with pulmonary nodules (PN) to help guide decision-making. We sought to validate a clinical-genomic classifier developed using whole-transcriptome sequencing of nasal epithelial cells from patients with a PN ≤ 30 mm who smoke or have previously smoked. Research Question Can the probability of lung cancer in individuals with a PN and a history of smoking be predicted by a classifier that utilizes clinical factors and genomic data from nasal epithelial cells obtained by cytologic brushing? Study Design and Methods Machine learning was used to train a classifier using genomic and clinical features on 1,120 patients with PN labeled as benign or malignant established by a final diagnosis or a minimum of 12 months of radiographic surveillance. The classifier was designed to yield low, intermediate, and high-risk categories. The classifier was validated in an independent set of 312 patients, including 63 patients with a prior history of cancer (other than lung cancer), comparing the classifier prediction with the known clinical outcome. Results In the primary validation set, sensitivity and specificity for low-risk classification are 96% and 42% while sensitivity and specificity for high-risk classification is 58% and 90%. Sensitivity is similar across stages of non-small cell lung cancer, independent of subtype. Performance compared favorably to clinical-only risk models. Analysis of 63 patients with prior cancer shows similar performance as did subanalyses of patients with light vs. heavy smoking burden and those eligible for lung cancer screening vs. those who were not. Interpretation The nasal classifier provides an accurate assessment of pCA in individuals with a PN ≤ 30mm who smoke or have previously smoked. Classifier-guided decision-making could lead to fewer diagnostic procedures in patients without cancer and more timely treatment in patients with lung cancer.