Smoking as a risk factor for bone marrow micrometastases in lung cancer
Chulkova S.V., Кapkaeva E.N.
Background: Tobacco smoking remains the main modifiable risk factor for non‑small cell lung cancer (NSCLC). Disease progression is driven by hematogenous dissemination and minimal residual disease. Disseminated tumour cells (DTCs) in bone marrow are associated with poor prognosis, yet the impact of smoking status on bone marrow micrometastases in resectable NSCLC is insufficiently studied.
Objective: To assess the frequency and phenotypic characteristics of bone marrow DTCs in patients with resectable NSCLC and their association with smoking status.
Materials and methods: 62 patients with resectable NSCLC underwent preoperative bone marrow aspiration. Conventional morphology and multicolour flow cytometry were performed. DTCs were defined as EpCAM+CD45- cells; 20–100 million myelokaryocytes per sample were analysed, with a positivity threshold of ≥1 EpCAM+CD45- cell per 107 myelokaryocytes. A stem‑like phenotype was evaluated by CD133 expression. Patients were stratified by stage, histological type, tumour differentiation and smoking status. Statistical analysis was performed in IBM SPSS Statistics v.18 (χ²/Fisher’s exact test, univariate analysis, p<0.05).
Results: Bone marrow DTCs were detected in 56% of patients; at stages IA and IIA the frequencies were 60.7% and 58.3%, indicating early dissemination. In 6.6% of samples DTC levels reached 1 cell per 106 myelokaryocytes; CD133+ stem‑like cells were found in 33.3% of DTC‑positive cases. DTC presence was not associated with sex, age, primary tumour size or nodal status, but was more frequent in well‑differentiated tumours. Among smokers, DTCs were observed in 71.4% of cases versus 42.0% in never‑smokers (p=0.045). Squamous NSCLC was more prevalent in smokers 62.9% than in never-smokers (19.2%) (p=0.001).
Conclusions: Bone marrow micrometastases are common and often early events in resectable NSCLC. Smoking is associated with a higher frequency of DTCs and squamous histology, underscoring its role as a determinant of hematogenous spread. These findings support early detection of minimal residual disease and active modification of tobacco exposure. While complete smoking cessation should remain the primary goal, the international professional community is increasingly discussing the potential of harm‑reduction strategies, including alternative nicotine delivery systems for unmotivated smokers, which requires further evaluation regarding safety and impact on oncological outcomes.
For citations: Chulkova S.V., Кapkaeva E.N. Smoking as a risk factor for bone marrow micrometastases in lung cancer. Pharmateca. 2026;33(6):64-72. (In Russ.). DOI: https://dx.doi.org/10.18565/pharmateca.2026.6.64-72
Authors’ contribution: Chulkova S.V. – study design, data collection, data analysis, manuscript drafting and review. Kapkaeva E.N. – study design, manuscript drafting, literature review.
Conflicts of interest: The authors confirm that they have no conflicts of interest to declare.
Funding: The study was conducted without any sponsorship.
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors’ Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
Keywords
lung cancer
disseminated tumour cells
bone marrow
smoking
harm reduction
tobacco heating systems
About the Authors
Svetlana V. Chulkova, Cand. Sci. (Med.), Senior Researcher, Hematopoiesis Immunology Laboratory, N.N. Blokhin National Medical Research Center of Oncology; Associate Professor, Department of Oncology and Radiation Therapy, Faculty of Medicine, N.I. Pirogov Russian National Research Medical University, Moscow, Russia; ORCID: https://orcid.org/0000-0003-4412-5019, Scopus Author ID: 35749545500Elvira N. Kapkaeva, Regional Medical Advisor for Oncology, Project Department, Ankor HR Solutions, Moscow, Russia; kapkaeva.elia@yandex.ru, ORCID: https://orcid.org/0009-0005-1379-3171, eLibrary SPIN: 2299-3487 (corresponding author)
Similar Articles
