Venous thromboembolism and survival in patients with high-grade glioma

Ralph Simanek, Rainer Vormittag, Marco Hassler, Karl Roessler, Martin Schwarz, Christoph Zielinski, Ingrid Pabinger, Christine Marosi, Ralph Simanek, Rainer Vormittag, Marco Hassler, Karl Roessler, Martin Schwarz, Christoph Zielinski, Ingrid Pabinger, Christine Marosi

Abstract

Patients with malignancy, particularly patients with high-grade glioma (HGG; WHO grade III/IV), have an increased risk of venous thromboembolism (VTE). It has been suggested that VTE predicts survival in cancer patients. The aim of our study was to investigate the occurrence of symptomatic VTE and its impact on survival in patients with HGG. Consecutive patients (n = 63; 36 female, 27 male; median age, 58 years) who had neurosurgical intervention between October 2003 and December 2004 were followed after surgery until October 2005. Objectively confirmed VTE was recorded as an event. All patients had received thrombosis prophylaxis with low-molecular-weight heparin (LMWH) during the immediate postoperative period. Subsequently, 56 patients received radiochemotherapy, 6 radiotherapy, and 1 chemotherapy only. Patients were followed over a median time period of 348 days. Fifteen patients (24%) developed VTE. Pulmonary embolism was diagnosed in nine patients (60%) and was fatal twice. The cumulative probability of VTE was 21% after three months and 26% after 12 months. The highest frequency of VTE was observed in patients with biopsy and subtotal tumor resection (n = 37; multivariate hazard ratio, 3.58; 95% CI = 0.98-13.13; P = 0.054) compared with patients with total resection. Survival did not significantly differ among patients with and without VTE and was 53% after 12 months in both groups. Patients with HGG, particularly those with biopsy and subtotal resection, are at high risk to develop VTE postoperatively. Thrombosis was not associated with a significant reduction of survival.

Figures

Fig. 1
Fig. 1
Cumulative probability of VTE.
Fig. 2
Fig. 2
Cumulative probability of VTE, according to type of surgery.
Fig. 3
Fig. 3
Cumulative probability of survival, according to VTE.
Fig. 4
Fig. 4
Cumulative probability of survival according to type of surgery.

References

    1. Alcalay A, Wun T, Khatri V, Chew HK, Harvey D, Zhou H, White RH. Venous thromboembolism in patients with colorectal cancer: Incidence and effect on survival. J Clin Oncol. 2006;24:1112–1118.
    1. Altinbas M, Coskun HS, Er O, Ozkan M, Eser B, Unal A, Cetin M, Soyuer S. A randomized clinical trial of combination chemotherapy with and without low-molecular-weight-heparin in small cell lung cancer. J Thromb Haemost. 2004;2:1266–1271.
    1. Bergqvist D, Agnelli G, Cohen AT, Eldor A, Nilsson PE, Le Moigne-Amrani A, Dietrich-Neto F. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med. 2002;346:975–980.
    1. Blackwell K, Hurwitz H, Lieberman G, Novotny W, Snyder S, Dewhirst M, Greenberg C. Circulating D-dimer levels are better predictors of overall survival and disease progression than carcinoembryonic antigen levels in patients with metastatic colorectal carcinoma. Cancer. 2004;101:77–82.
    1. Brandes AA, Scelzi E, Salmistraro G, Ermani M, Carollo C, Berti F, Zampieri P, Baiocchi C, Fiorentino MV. Incidence of risk of thromboembolism during treatment high-grade gliomas: A prospective study. Eur J Cancer. 1997;33:1592–1596.
    1. Browd SR, Ragel BT, Davis GE, Scott AM, Skalabrin EJ, Couldwell WT. Prophylaxis for deep venous thrombosis in neurosurgery: A review of the literature. Neurosurg Focus. 2004;17:E1.
    1. Danish SF, Burnett MG, Stein SC. Prophylaxis for deep venous thrombosis in patients with craniotomies: A review. Neurosurg Focus. 2004;17:E2.
    1. De Cicco M. The prothrombotic state in cancer: Pathogenic mechanisms. Crit Rev Oncol Hematol. 2004;50:187–196.
    1. Fine HA, Wen PY, Maher EA, Viscosi E, Batchelor T, Lakhani N, Figg WD, Purow BW, Borkowf CB. Phase II trial of thalidomide and carmustine for patients with recurrent high-grade gliomas. J Clin Oncol. 2003;21:2299–2304.
    1. Geerts WH, Pineo GF, Heit JA, Bergqvist D, Lassen MR, Colwell CW, Ray JG. Prevention of venous thromboembolism: The Seventh ACCP Conference on on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126:338S–400S.
    1. Gerber DE, Grossman SA, Streiff MB. Management of venous thromboembolism in patients with primary and metastatic brain tumors. J Clin Oncol. 2006;24:1310–1318.
    1. Goldhaber SZ, Dunn K, Gerhard-Herman M, Park JK, Black PM. Low rate of venous thromboembolism after craniotomy for brain tumor using multimodality prophylaxis. Chest. 2002;122:1933–1937.
    1. Hamada K, Kuratsu J, Saitoh Y, Takeshima H, Nishi T, Ushio Y. Expression of tissue factor correlates with grade of malignancy in human glioma. Cancer. 1996;77:1877–1883.
    1. Iorio A, Agnelli G. Low-molecular-weight and unfractionated heparin for prevention of venous thromboembolism in neurosurgery: A meta-analysis. Arch Intern Med. 2000;160:2327–2332.
    1. Kakkar AK, Levine MN, Kadziola Z, Lemoine NR, Low V, Patel HK, Rustin G, Thomas M, Quigley M, Williamson RC. Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: The Fragmin Advanced Malignancy Outcome Study (FAMOUS) J Clin Oncol. 2004;22:1944–1948.
    1. Kayser-Gatchalian MC, Kayser K. Thrombosis and intracranial tumors. J Neurol. 1975;209:217–224.
    1. Klerk CP, Smorenburg SM, Otten HM, Lensing AW, Prins MH, Piovella F, Prandoni P, Bos MM, Richel DJ, van Tienhoven G, Buller HR. The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Oncol. 2005;23:2130–2135.
    1. Laws ER, Parney IF, Huang W, Anderson F, Morris AM, Asher A, Lillehei KO, Bernstein M, Brem H, Sloan A, Berger MS, Chang S. Survival following surgery and prognostic factors for recently diagnosed malignant glioma: Data from the Glioma Outcomes Project. J Neurosurg. 2003;99:467–473.
    1. Lee AY, Rickles FR, Julian JA, Gent M, Baker RI, Bowden C, Kakkar AK, Prins M, Levine MN. Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. J Clin Oncol. 2005;23:2123–2129.
    1. Levine M, Hirsh J, Gent M, Arnold A, Warr D, Falanga A, Samosh M, Bramwell V, Pritchard KI, Stewart D, Goodwin P. Double-blind randomised trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer. Lancet. 1994;343:886–889.
    1. Marras LC, Geerts WH, Perry JR. The risk of venous thromboembolism is increased throughout the course of malignant glioma: An evidence-based review. Cancer. 2000;89:640–646.
    1. Prandoni P, Lensing AW, Cogo A, Cuppini S, Villalta S, Carta M, Cattelan AM, Polistena P, Bernardi E, Prins MH. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med. 1996;125:1–7.
    1. Prandoni P, Falanga A, Piccioli A. Cancer and venous thromboembolism. Lancet Oncol. 2005;6:401–410.
    1. Rasmussen MS. Preventing thromboembolic complications in cancer patients after surgery: A role for prolonged thromboprophylaxis. Cancer Treat Rev. 2002;28:141–144.
    1. Rickles FR, Edwards RL. Activation of blood coagulation in cancer: Trousseau’s syndrome revisited. Blood. 1983;62:14–31.
    1. Sorensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med. 2000;343:1846–1850.
    1. Streiff MB, Segal J, Grossman SA, Kickler TS, Weir EG. ABO blood group is a potent risk factor for venous thromboembolism in patients with malignant gliomas. Cancer. 2004;100:1717–1723.
    1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–996.

Source: PubMed

3
Se inscrever