• Carla R Lamb, Kimberly M Rieger-Christ, Chakravarthy Reddy, Jing Huang, Jie Ding, Marla Johnson, P Sean Walsh, William A Bulman, Lori R Lofaro, Momen M Wahidi, David J Feller-Kopman, Avrum Spira, Giulia C Kennedy, and Peter J Mazzone.
• Department of Pulmonary and Critical Care Medicine, Lahey Hospital and Medical Center, Burlington, MA. Electronic address: carla.r.lamb@lahey.org.
• Chest. 2024 Apr 1; 165 (4): 100910191009-1019.

BackgroundAccurate assessment of the probability of lung cancer (pCA) is critical in patients with pulmonary nodules (PNs) 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 QuestionCan the pCA in individuals with a PN and a history of smoking be predicted by a classifier that uses clinical factors and genomic data from nasal epithelial cells obtained by cytologic brushing?Study Design And MethodsMachine learning was used to train a classifier using genomic and clinical features on 1,120 patients with PNs 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.ResultsIn the primary validation set, sensitivity and specificity for low-risk classification were 96% and 42%, whereas sensitivity and specificity for high-risk classification was 58% and 90%, respectively. Sensitivity was similar across stages of non-small cell lung cancer, independent of subtype. Performance compared favorably with clinical-only risk models. Analysis of 63 patients with prior cancer showed 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.InterpretationThe nasal classifier provides an accurate assessment of pCA in individuals with a PN ≤ 30 mm 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.Copyright © 2024. Published by Elsevier Inc.

16 keywords...

hide…