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Prognostic value of plasma d-dimer levels in patients with glioblastoma multiforme – Results from a pilot study

Die Prognostische Bedeutung des Plasma D-Dimer Spiegels bei Patienten mit Glioblastoma Multiforme – Ergebnisse einer Pilot Studie

Zusammenfassung

Das Glioblastoma multiforme (GBM) ist der häufigste maligne Primärtumor des Zentralnervensystems und geht mit einer Aktivierung des Gerinnungssystems einher. Unklar in diesem Zusammenhang ist, ob D-Dimer, ein Fibrin-Spaltprodukt, mit der Tumoraktivität assoziiert ist und prognostische Bedeutung in Bezug auf das Gesamtüberleben hat. Wir untersuchten den Zusammenhang von Plasma D-Dimer Spiegeln und klinischen Endpunkten bei 23 Patienten mit histologisch verifiziertem GBM. Der Studieneinschluss erfolgte zwei bis drei Wochen nach neurochirurgischer Intervention und vor dem Beginn der adjuvanten Therapie (Radio-Chemotherapie). Innerhalb eines medianen Beobachtungszeitraums von 7,3 Monaten (Interquartilbereich, 3,5–22 Monate), starben 21 Patienten (91,3%). Erhöhte D-Dimer Plasmas Spiegel waren signifikant mit Gesamtüberleben assoziiert (log rank p = 0,002). Die Hazard Ratio für Patienten mit erhöhten D-Dimer Spiegeln lag bei 10.8 (95% Konfidenzintervall, 1,3–93,1; p = 0,03), verglichen mit Patienten mit niedrigeren Werten. Ähnliche, signifikante Ergebnisse fanden sich auch im Bezug auf das tumorprogressionsfreie Überleben (log rank p = 0.002). Erhöhte D-Dimer Spiegel war zusätzlich auch mit dem auftreten venöser Thromboembolien assoziiert (log rank p = 0,025). Bei Patienten mit GBM fanden sich Hinweise das D-Dimer Plasma Spiegel dem Überleben und der Tumorprogression assoziiert ist. Die Resultate vorliegender Pilot-Studie müssen anhand einer großen, prospektiven Studie bestätigt werden.

Summary

Glioblastoma multiforme (GBM), the most common primary tumor of the central nervous system, is associated with a state of hypercoagulability. We hypothesized that tumor activity is displayed by elevated d-dimer plasma levels and that d-dimer might be used as a predictor of survival in patients with glioblastoma multiforme. We studied effects on clinical outcomes of d-dimer levels obtained two to three weeks following histologic confirmation of the diagnosis of GBM at surgery or needle biopsy, but prior to chemotherapy or radiation therapy, in 23 patients. During a median follow-up of 7.3 months (interquartile range 3.5 to 22 months), we observed a total of 21 deaths (91.3%). Elevated d-dimer levels were significantly associated with mortality compared to normal values (log rank p = 0.002). The adjusted hazard ratio for death in patients with elevated d-dimer levels was 10.8 (95% confidence interval, 1.3 to 93.1; p = 0.03), compared to controls. Similar effect sizes were revealed when analyzing the association between progression-free survival and d-dimer levels (log rank p = 0.002). Additionally, patients with elevated d-dimer levels were more likely to suffer from venous thromboembolism compared to patients with normal values (log rank p = 0.025). Our data support the assumption that d-dimer levels are related to adverse outcome in patients with GBM. However, our results need to be confirmed by a large, prospective cohort study.

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Correspondence to Matthias Hoke.

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Hoke, M., Dieckmann, K., Koppensteiner, R. et al. Prognostic value of plasma d-dimer levels in patients with glioblastoma multiforme – Results from a pilot study. Wien Klin Wochenschr 123, 199–203 (2011). https://doi.org/10.1007/s00508-011-1556-9

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  • DOI: https://doi.org/10.1007/s00508-011-1556-9

Keywords

  • Glioblastoma multiforme
  • D-dimer
  • Survival
  • Progression-free survival
  • Venous thromboembolism