Circulating Tumor-Macrophage Fusion Cells and Circulating Tumor Cells Complement Non-Small-Cell Lung Cancer Screening in Patients with Suspicious Lung-RADS 4 Nodules

Yariswamy Manjunath, Kanve Nagaraj Suvilesh, Jonathan B. Mitchem, Diego M. Avella Patino, Eric T. Kimchi, Kevin F. Staveley-O'Carroll, Klaus Pantel, Huang Yi, Guangfu Li, Peter K. Harris, Aadel A. Chaudhuri, Jussuf T. Kaifi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSELow-dose computed tomography (LDCT) screening of high-risk patients decreases lung cancer-related mortality. However, high false-positive rates associated with LDCT result in unnecessary interventions. To distinguish non-small-cell lung cancer (NSCLC) from benign nodules, in the present study, we integrated cellular liquid biomarkers in patients with suspicious lung nodules (lung cancer screening reporting and data system [Lung-RADS] 4).METHODSProspectively, 7.5 mL of blood was collected from 221 individuals (training set: 90 nonscreened NSCLC patients, 74 high-risk screening patients with no/benign nodules [Lung-RADS 1-3], and 20 never smokers; validation set: 37 patients with suspicious nodules [Lung-RADS 4]). Circulating tumor cells (CTCs), CTC clusters, and tumor-macrophage fusion (TMF) cells were identified by blinded analyses. Screening patients underwent a median of two LDCTs (range, 1-4) with a median surveillance time of 30 (range, 11-50) months.RESULTSIn the validation set of 37 Lung-RADS 4 patients, all circulating cellular biomarker counts (P <.005; Wilcoxon test) and positivity rates were significantly higher in 23 biopsy-proven NSCLC patients (CTCs: 23 of 23 [100%], CTC clusters: 6 of 23 [26.1%], and TMF cells: 15 of 23 [65.2%]) than in 14 patients with biopsy-proven benign nodules (6 of 14 [42.9%], 0 of 14 [0%], and 2 of 14 [14.3%]). On the basis of cutoff values from the training set, logistic regression with receiver operating characteristic and area under the curve analyses demonstrated that CTCs (sensitivity: 0.870, specificity: 1.0, and area under the curve: 0.989) and TMF cells (0.652; 0.880; 0.790) complement LDCT in diagnosing NSCLC in Lung-RADS 4 patients.CONCLUSIONCellular liquid biomarkers have a potential to complement LDCT interpretation of suspicious Lung-RADS 4 nodules to distinguish NSCLC from benign lung nodules. A future prospective, large-scale, multicenter clinical trial should validate the role of cellular liquid biomarkers in improving diagnostic accuracy in high-risk patients with Lung-RADS 4 nodules.

Original languageEnglish (US)
Article numbere2100378
JournalJCO Precision Oncology
Volume6
Issue number1
DOIs
StatePublished - Apr 1 2022
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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