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David S. Ettinger, MD, FACP, FCCP


Can a Liquid Biomarker Augment Early Screening for Lung Cancer?

By: Victoria Kuhr, BA
Posted: Thursday, September 29, 2022

Cellular liquid biomarkers appear to complement low-dose computed tomography (CT) interpretations of suspicious nodules, which may help to distinguish non–small-cell lung cancer (NSCLC) from benign lung nodules without an invasive biopsy. Additionally, Jussuf T. Kaifi, MD, PhD, of the University of Missouri, Columbia, and colleagues proposed that circulating tumor cells (CTCs) and circulating large tumor-macrophage fusion (TMF) cells may improve the sensitivity and specificity of NSCLC diagnosis in patients with suspicious nodules. These findings were published in JCO Precision Oncology.

“This study demonstrated that integrating cellular liquid biomarkers, CTCs, and TMF cells into standardized low-dose CT screening protocols can improve accuracy of NSCLC detection in high-risk patients who have nodules detected by low-dose CT,” explained Dr. Kaifi in a University of Missouri press release.

The study investigators collected 7.5 mL of blood from 221 patients in the training and validation sets. The training set included 90 nonscreened patients with NSCLC, 74 high-risk screening patients with no or benign-appearing nodules (Lung-RADS 1–3), and 20 nonsmokers in the control group. The validation set included 37 patients with suspicious nodules (Lung-RADS 4). The study identified CTCs, CTC clusters, and TMF cells.

The 221 patients had a median of two low-dose CT scans, with a median surveillance time of 30 months. In the validation set of 37 patients with suspicious nodules, all circulating cellular biomarker counts and positivity rates were significantly higher in 23 patients with biopsy-proven NSCLC than in 14 patients with biopsy-proven benign nodules. CTC clusters were detected in all 90 patients with NSCLC and in 30 patients with no or benign-appearing nodules. However, CTC clusters were not found in high-risk patients with no or benign-appearing lung nodules. Overall, 48% of patients with NSCLC tested positive for giant TMF cells, suggesting that TMF cells alone may not be a reliable biomarker for early cancer detection.

Disclosures: For full disclosures of the study authors, visit

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