Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Moik, F; Prager, G; Thaler, J; Posch, F; Wiedemann, S; Schramm, T; Englisch, C; Mackman, N; Pabinger, I; Ay, C.
Hemostatic Biomarkers and Venous Thromboembolism Are Associated With Mortality and Response to Chemotherapy in Patients With Pancreatic Cancer.
Arterioscler Thromb Vasc Biol. 2021; 41(11): 2837-2847.
Doi: 10.1161/ATVBAHA.121.316463
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Moik Florian
- Co-Autor*innen der Med Uni Graz
- Posch Florian
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- Abstract:
- Objective: Pancreatic cancer activates coagulation and increases risk of venous thromboembolism (VTE). We aimed at characterizing the association of hemostatic biomarkers and VTE with mortality and chemotherapy response. Approach and Results: Pancreatic cancer patients (N=145) were included in a prospective, observational cohort study (CATS [Vienna Cancer and Thrombosis Study]). Hemostatic biomarkers (D-dimer, extracellular vesicle-tissue factor activity, prothrombin fragment 1+2, fibrinogen, factor VIII, PAI-1 [plasminogen activator inhibitor 1], sP-selectin [soluble P-selectin], thrombin generation assay) were measured at inclusion. The impact of VTE on overall survival/progression-free survival (OS/PFS) was evaluated by multistate modeling. The association of biomarkers with OS was analyzed by Cox-regression and with PFS and disease control rate in patients initiating palliative chemotherapy (n=95) by Cox-regression and logistic regression. Multivariable analysis included stage, grade, sex, age, performance status, VTE (time-dependent), vascular infiltration/compression, and tumor marker levels (carbohydrate-antigen 19-9, carcinoembryonic antigen). VTE occurrence was associated with shorter OS (transition hazard ratio, 3.40 [95% CI, 2.05-5.64]) and shorter PFS (transition hazard ratio, 2.10 [1.16-3.79]). Median post-VTE OS/PFS in months was 5.5 [2.2-6.5] and 3.0 [1.5-3.9], compared with 13.4 [9.7-16.6] and 7.5 [5.9-9.8] in patients without VTE (both P<0.001). D-dimer, extracellular vesicle-tissue factor activity, PAI-1, and sP-selectin were associated with increased mortality (hazard ratio per doubling, 1.27 [1.00-1.61]; 1.63 [1.14-2.36]; 1.25 [1.06-1.47]; 1.52 [1.05-2.20]). In patients initiating palliative chemotherapy, higher D-dimer predicted shorter PFS (hazard ratio per doubling, 1.27 [1.01-1.60]) and lower disease control rate (odds ratio per doubling, 0.59 [0.36-0.98]). Conclusions: VTE diagnosis is associated with shorter OS and PFS. Higher baseline levels of D-dimer, extracellular vesicle-tissue factor activity, PAI-1, and sP-selectin were independently prognostic for increased mortality, and D-dimer predicted response to palliative chemotherapy.
- Find related publications in this database (using NLM MeSH Indexing)
- Aged - administration & dosage
- Anticoagulants - therapeutic use
- Antineoplastic Agents - adverse effects, therapeutic use
- Biomarkers - blood
- Disease Progression - administration & dosage
- Extracellular Vesicles - metabolism
- Female - administration & dosage
- Fibrin Fibrinogen Degradation Products - metabolism
- Hemostasis - administration & dosage
- Humans - administration & dosage
- Incidence - administration & dosage
- Male - administration & dosage
- Middle Aged - administration & dosage
- P-Selectin - blood
- Pancreatic Neoplasms - blood, diagnosis, drug therapy, mortality
- Plasminogen Activator Inhibitor 1 - blood
- Progression-Free Survival - administration & dosage
- Prospective Studies - administration & dosage
- Risk Assessment - administration & dosage
- Risk Factors - administration & dosage
- Thromboplastin - metabolism
- Time Factors - administration & dosage
- Treatment Outcome - administration & dosage
- Venous Thromboembolism - blood, diagnosis, drug therapy, mortality
- Find related publications in this database (Keywords)
- biomarkers
- hemostasis
- mortality
- neoplasms
- venous thromboembolism