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ARTICLE

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 Siringo1,2,#,*, Michela De Meo1,#, Alain Jonathan Gelibter3, Chiara Nicolazzo4,5,§, Paola Gazzaniga5,§
1 Department of Molecular Medicine, Sapienza University of Rome, Rome, 00161, Italy
2 Medical Oncology, Sant’Andrea University Hospital, Sapienza University of Rome, Via di Grottarossa 1035–1039, Rome, 00189, Italy
3 Medical Oncology, Department of Radiological, Oncological and Pathological Science, Policlinico Umberto I, Sapienza University of Rome, Viale Regina Elena 324, Rome, 00161, Italy
4 Department of Life Science, Health and Health Professions, Link Campus University, Via del Casale di San Pio V, Rome, 00165, Italy
5 Department of Experimental Medicine, Sapienza University, Rome, 00161, Italy
* Corresponding Author: Marco Siringo. Email: email
# These authors contributed equally to this work
§ These authors share senior authorship
(This article belongs to the Special Issue: Liquid Biopsy: A Powerful Tool for Exploring Tumor Biology)

Oncology Research https://doi.org/10.32604/or.2025.069832

Received 01 July 2025; Accepted 26 November 2025; Published online 22 December 2025

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.

Keywords

CellSearch®; circulating cancer-associated macrophage-like cells; circulating tumor cells; immunotherapy; non-small-cell lung cancer

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