Abstract
Venous thromboembolism (VTE) is a common complication of cancer that severely increases morbidity and mortality. Patients with intracranial tumors are more likely to develop VTE than patients with cancers at other sites. Conversely, limited tools exist to identify patients with high thrombotic risk. Upon activation, neutrophils release their content through different mechanisms triggering thrombosis. We explored the ability of microRNAs (miRNAs) and plasma markers of neutrophil activation measured before surgery to predict the risk of early post-surgical pulmonary embolism (PE) in glioma and meningioma patients. We recruited and prospectively followed 50 patients with glioma and 50 with meningioma, 34% of whom in each group developed an early objectively-diagnosed post-surgical PE. We measured miRNA expression and neutrophil markers (cell-free DNA, nucleosomes, calprotectin and myeloperoxidase) before surgery. In glioma patients, we adjusted and validated a predictive model for post-surgical PE with 6 miRNAs: miR-363-3p, miR-93-3p, miR-22-5p, miR-451a, miR-222-3p and miR-140-3p (AUC = 0.78; 95% Confidence Interval (CI) [0.63, 0.94]) and another with cfDNA and myeloperoxidase as predictors (AUC = 0.71; 95% CI [0.52, 0.90]). Furthermore, we combined both types of markers and obtained a model with myeloperoxidase and miR-140-3p as predictors (AUC = 0.79; 95% CI [0.64, 0.94]). In meningioma patients we fitted and validated a predictive model with 6 miRNAs: miR-29a-3p, miR-660-5p, miR-331-3p, miR-126-5p, miR-23a-3p and miR-23b-3p (AUC = 0.69; 95% CI [0.52, 0.87]). All our models outperformed the Khorana score. This is the first study that analyzes the capability of plasma miRNAs and neutrophil activation markers to predict early post-surgical PE in glioma and meningioma patients. The estimation of the thrombotic risk before surgery may promote a tailored thromboprophylaxis in a selected group of high-risk patients, in order to minimize the incidence of PE and avoid bleedings.
Highlights
Cancer patients have a higher risk of venous thromboembolism (VTE) than non-cancer patients.As a consequence, the prognosis of cancer patients is worsened, with an increase in morbidity and mortality that exacerbates health costs [1]
The frequency of Venous thromboembolism (VTE) after brain surgery is further increased [3]. It is different in malignant brain tumors such as glioma than in benign tumors such as meningioma, where operated patients have a risk of VTE up to
These patients were all the available glioma patients with follow-up completed at the time of the validation stage commencement, and a random selection of meningioma patients with an incidence of pulmonary embolism (PE) similar to that of the whole original cohort
Summary
Cancer patients have a higher risk of venous thromboembolism (VTE) than non-cancer patients. The prognosis of cancer patients is worsened, with an increase in morbidity and mortality that exacerbates health costs [1]. VTE than patients who have cancers at other sites [2]. High-grade brain tumors correlate with a higher rate of VTE, including both deep vein thrombosis and pulmonary embolism (PE), being glioma one of the most thrombogenic among intracranial tumors [2]. The frequency of VTE after brain surgery is further increased [3]. It is different in malignant brain tumors such as glioma than in benign tumors such as meningioma, where operated patients have a risk of VTE up to
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