Management of vasogenic edema in patients with primary and metastatic brain tumors
- Jan Drappatz, MD
Jan Drappatz, MD
- Associate Director
- Adult Neuro-Oncology Program
- Associate Professor
- Departments of Neurology and Medicine
- University of Pittsburgh
The vasogenic edema that surrounds many brain tumors contributes significantly to morbidity. This edema results from disruption of the blood brain barrier, allowing protein-rich fluid to accumulate in the extracellular space .
The pathogenesis of peritumoral vasogenic edema and the use of glucocorticoids are reviewed here. The acute treatment of elevated intracranial pressure (ICP) is discussed elsewhere. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'General management' and "Evaluation and management of elevated intracranial pressure in adults", section on 'Specific therapies'.)
Tumor-related disruption in the blood brain barrier is caused by two major mechanisms:
●The absence of tight endothelial cell junctions in tumor blood vessels. These vessels develop in response to angiogenic factors such as vascular endothelial growth factor (VEGF)  and basic fibroblast growth factor (bFGF, FGF - 2) .
- Peritumoral edema. In: The Gliomas, WB Saunders, Philadelphia 1999. p.107.
- Senger DR, Van de Water L, Brown LF, et al. Vascular permeability factor (VPF, VEGF) in tumor biology. Cancer Metastasis Rev 1993; 12:303.
- Baethmann A, Maier-Hauff K, Schürer L, et al. Release of glutamate and of free fatty acids in vasogenic brain edema. J Neurosurg 1989; 70:578.
- Black KL, Hoff JT, McGillicuddy JE, Gebarski SS. Increased leukotriene C4 and vasogenic edema surrounding brain tumors in humans. Ann Neurol 1986; 19:592.
- Takahashi JA, Fukumoto M, Igarashi K, et al. Correlation of basic fibroblast growth factor expression levels with the degree of malignancy and vascularity in human gliomas. J Neurosurg 1992; 76:792.
- Carlson MR, Pope WB, Horvath S, et al. Relationship between survival and edema in malignant gliomas: role of vascular endothelial growth factor and neuronal pentraxin 2. Clin Cancer Res 2007; 13:2592.
- Provias J, Claffey K, delAguila L, et al. Meningiomas: role of vascular endothelial growth factor/vascular permeability factor in angiogenesis and peritumoral edema. Neurosurgery 1997; 40:1016.
- Strugar JG, Criscuolo GR, Rothbart D, Harrington WN. Vascular endothelial growth/permeability factor expression in human glioma specimens: correlation with vasogenic brain edema and tumor-associated cysts. J Neurosurg 1995; 83:682.
- Yano S, Shinohara H, Herbst RS, et al. Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis. Cancer Res 2000; 60:4959.
- Dobrogowska DH, Lossinsky AS, Tarnawski M, Vorbrodt AW. Increased blood-brain barrier permeability and endothelial abnormalities induced by vascular endothelial growth factor. J Neurocytol 1998; 27:163.
- Machein MR, Kullmer J, Fiebich BL, et al. Vascular endothelial growth factor expression, vascular volume, and, capillary permeability in human brain tumors. Neurosurgery 1999; 44:732.
- Intensive and postoperative care of intracranial tumors. In: Neurological and Neurosurgical Intensive Care, 3rd, Raven Press, New York 1993. p.309.
- Alberti E, Hartmann A, Schütz HJ, Schreckenberger F. The effect of large doses of dexamethasone on the cerebrospinal fluid pressure in patients with supratentorial tumors. J Neurol 1978; 217:173.
- Jarden JO, Dhawan V, Moeller JR, et al. The time course of steroid action on blood-to-brain and blood-to-tumor transport of 82Rb: a positron emission tomographic study. Ann Neurol 1989; 25:239.
- Sinha S, Bastin ME, Wardlaw JM, et al. Effects of dexamethasone on peritumoural oedematous brain: a DT-MRI study. J Neurol Neurosurg Psychiatry 2004; 75:1632.
- Koehler PJ. Use of corticosteroids in neuro-oncology. Anticancer Drugs 1995; 6:19.
- GALICICH JH, FRENCH LA, MELBY JC. Use of dexamethasone in treatment of cerebral edema associated with brain tumors. J Lancet 1961; 81:46.
- Batchelor T, DeAngelis LM. Medical management of cerebral metastases. Neurosurg Clin N Am 1996; 7:435.
- Kim H, Lee JM, Park JS, et al. Dexamethasone coordinately regulates angiopoietin-1 and VEGF: a mechanism of glucocorticoid-induced stabilization of blood-brain barrier. Biochem Biophys Res Commun 2008; 372:243.
- Neurological effects of steroid treatment. In: Neurological Complications of Cancer Treatment, Butterworth-Heinemann, Boston p.173.
- Vecht CJ, Hovestadt A, Verbiest HB, et al. Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain tumors: a randomized study of doses of 4, 8, and 16 mg per day. Neurology 1994; 44:675.
- Use of glucocorticoids in neuro-oncology. In: Neurological complications of cancer, Marcel Dekker, New York 1995. p.199.
- Kehlet H, Binder C, Blichert-Toft M. Glucocorticoid maintenance therapy following adrenalectomy: assessment of dosage and preparation. Clin Endocrinol (Oxf) 1976; 5:37.
- Vick NA, Wilson CB. Total care of the patient with a brain tumor with consideration of some ethical issues. Neurol Clin 1985; 3:705.
- Kaal EC, Vecht CJ. The management of brain edema in brain tumors. Curr Opin Oncol 2004; 16:593.
- Ryken TC, McDermott M, Robinson PD, et al. The role of steroids in the management of brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol 2010; 96:103.
- Pitter KL, Tamagno I, Alikhanyan K, et al. Corticosteroids compromise survival in glioblastoma. Brain 2016; 139:1458.
- Kanda F, Okuda S, Matsushita T, et al. Steroid myopathy: pathogenesis and effects of growth hormone and insulin-like growth factor-I administration. Horm Res 2001; 56 Suppl 1:24.
- Paddon-Jones D, Wolfe RR, Ferrando AA. Amino acid supplementation for reversing bed rest and steroid myopathies. J Nutr 2005; 135:1809S.
- Schiff D. Pneumocystis pneumonia in brain tumor patients: risk factors and clinical features. J Neurooncol 1996; 27:235.
- Henson JW, Jalaj JK, Walker RW, et al. Pneumocystis carinii pneumonia in patients with primary brain tumors. Arch Neurol 1991; 48:406.
- Rice WR, Singleton FM, Linke MJ, Walzer PD. Regulation of surfactant phosphatidylcholine secretion from alveolar type II cells during Pneumocystis carinii pneumonia in the rat. J Clin Invest 1993; 92:2778.
- Watling CJ, Cairncross JG. Acetazolamide therapy for symptomatic plateau waves in patients with brain tumors. Report of three cases. J Neurosurg 2002; 97:224.
- Gerstner ER, Duda DG, di Tomaso E, et al. VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer. Nat Rev Clin Oncol 2009; 6:229.
- Batchelor TT, Sorensen AG, di Tomaso E, et al. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 2007; 11:83.
- Vredenburgh JJ, Cloughesy T, Samant M, et al. Corticosteroid use in patients with glioblastoma at first or second relapse treated with bevacizumab in the BRAIN study. Oncologist 2010; 15:1329.
- Tjuvajev J, Uehara H, Desai R, et al. Corticotropin-releasing factor decreases vasogenic brain edema. Cancer Res 1996; 56:1352.
- Villalona-Calero MA, Eckardt J, Burris H, et al. A phase I trial of human corticotropin-releasing factor (hCRF) in patients with peritumoral brain edema. Ann Oncol 1998; 9:71.
- Hariharan, S, Shapiro, W, Chang, S, et al. Phase II randomized dose-ranging trial of human corticotrophin releasing factor in symptomatic brain tumor patients. Neurology 2000; 54:A12.
- Recht L, Mechtler LL, Wong ET, et al. Steroid-sparing effect of corticorelin acetate in peritumoral cerebral edema is associated with improvement in steroid-induced myopathy. J Clin Oncol 2013; 31:1182.
- Portnow J, Suleman S, Grossman SA, et al. A cyclooxygenase-2 (COX-2) inhibitor compared with dexamethasone in a survival study of rats with intracerebral 9L gliosarcomas. Neuro Oncol 2002; 4:22.