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Article | Open Access

Prognostic Value of Circulating Tumor Cells and Cancer Associated Macrophage-Like Cells in Metastatic Non-Small Cell Lung Cancer Patients: A Retrospective Exploratory Analysis

Marco Siringo#,1,2( )Michela De Meo#,1Alain Jonathan Gelibter3Chiara Nicolazzo§,4,5Paola Gazzaniga§,5
Department of Molecular Medicine, Sapienza University of Rome, Rome, 00161, Italy
Medical Oncology, Sant’Andrea University Hospital, Sapienza University of Rome, Via di Grottarossa 1035–1039, Rome, 00189, Italy
Medical Oncology, Department of Radiological, Oncological and Pathological Science, Policlinico Umberto I, Sapienza University of Rome, Viale Regina Elena 324, Rome, 00161, Italy
Department of Life Science, Health and Health Professions, Link Campus University, Via del Casale di San Pio V, Rome, 00165, Italy
Department of Experimental Medicine, Sapienza University, Rome, 00161, Italy

#These authors contributed equally to this work

§These authors share senior authorship

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Abstract

Objectives

Although immune checkpoint inhibitors (ICIs) and targeted therapies have reshaped treatment non-small cell lung cancer (NSCLC) paradigms, prognosis remains poor for many patients due to delayed diagnosis and resistance mechanisms. Liquid biopsy offers a minimally invasive approach to monitoring tumor evolution. Among circulating biomarkers, circulating tumor cells (CTCs) and cancer-associated macrophage-like cells (CAM-Ls) may provide complementary prognostic insights. The study aimed to evaluate the prognostic role of CTC and CAM-Ls dynamic in metastatic NSCLC patients.

Methods

We retrospectively analyzed 77 patients with metastatic NSCLC who underwent CTC and CAM-L evaluation via the CellSearch® system at baseline (T0) and after three months of first-line treatment (T1) including chemotherapy, targeted therapy, or ICIs. Survival outcomes were analyzed using Kaplan-Meier and Cox regression analyses.

Results

Conversion to CTC-negative status at T1 was associated with improved outcomes, with median overall survival (OS) and progression-free survival (PFS) of 33 and 18 months, respectively, vs. 10 and 6 months in persistently positive patients (both p < 0.001). CTC negativity at T1 remained an independent prognostic factor for OS (HR: 6.68) and PFS (HR: 5.91, both p < 0.0001). CAM-L positivity at T1 also correlated with longer OS (30 vs. 12 months) and PFS (13 vs. 6 months, both p < 0.0001), particularly among ICI-treated patients. Combined CTC and CAM-L assessment further refined risk stratification.

Conclusions

Dynamic monitoring of CTCs and CAM-Ls provides actionable prognostic information in metastatic NSCLC. CTC-negative status predicted longer OS and PFS, while CAM-L positivity at T1 was associated with improved outcomes, particularly in ICI-treated patients. Combined assessment of both biomarkers may directly inform therapeutic decision-making, through early detection of outcomes.

References

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Oncology Research
Article number: 11

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Cite this article:
Siringo M, Meo MD, Gelibter AJ, et al. Prognostic Value of Circulating Tumor Cells and Cancer Associated Macrophage-Like Cells in Metastatic Non-Small Cell Lung Cancer Patients: A Retrospective Exploratory Analysis. Oncology Research, 2026, 34(2): 11. https://doi.org/10.32604/or.2025.069832

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Received: 01 July 2025
Accepted: 26 November 2025
Published: 19 January 2026
© The Author 2026.

This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.