Abstract

Background:Venous thromboembolism occurs frequently in patients with primary brain tumors.Aims:Given the strong interplay between inflammation and haemostasis, the aim of the current study was to investigate the association of serum cytokine levels and risk of VTE development in patients with glioma.Methods:Within the framework of the Vienna Cancer and Thrombosis Study (CATS), a prospective and observational cohort study of patients with active cancer, we conducted an exploratory analysis. Patients were recruited at the time of cancer diagnosis or progression of disease after remission and followed for two years. Primary endpoint was symptomatic and objectively confirmed VTE. At study entry, a single blood draw was performed. Several cytokines (e.g. Interleukin (IL)‐1b, IL‐4, IL‐6, IL‐8, IL‐10, IL11, CCL3, TNF‐a, VEGF‐a) were measured in serum samples with the xMAP technology developed by Luminex.Results:In this study, 128 glioma patients were analyzed. Of those, 98/128 (76.6%) were diagnosed with glioblastoma (WHO grade IV), 24/128 (18.8%) with anaplastic glioma (WHO grade III) and 6/128 (4.7%) with diffuse glioma (WHO grade II). In total, 22/128 (17.2%) glioma had an IDH1 mutation. During follow‐up, 14/128 (10.9%) patients developed VTE. In univariable Cox‐regression analysis, CCL3 levels were significantly associated with risk of developing VTE (hazard ratio [HR] per 10 units increase: 0.629 [95% CI: 0.407–0.0.972], p = 0.037), while there was no significant association between the risk of VTE and serum levels of IL‐1b, IL‐4, IL‐6, IL‐8, IL‐10, IL‐11, TNF‐aand VEGF‐a, respectively. In multivariable analysis, adjusting for potential confounders (sex, age, glioblastoma), the association of CCL3 with the risk of VTE remained statistically significant (adjusted HR: 0.628 [0.397–0.992], p = 0.046). Cumulative incidence of VTE in reverse Kaplan‐Meier estimates was 22.8% in patients with low CCL3 serum levels (≤ 25thpercentile = 1.95 pg/ml) and 9.1% in patients with higher CCL3 serum levels (> 25thpercentile) (log‐rank, p = 0.017). (Figure 1)Summary/Conclusion:One out of 10 patients with glioma developed VTE in our study and low serum levels of CCL3 were associated with an increased risk of VTE. In conclusion, CCL3 might be useful as a potential biomarker for prediction of risk of VTE in patients with glioma.image

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