Recurrent Meningioma: Systemic Therapy
Illustrative Case Series
Recurrent Meningioma: Systemic Therapy
By William B. Ershler, MD
The patient is a 56-year-old woman with known meningioma first resected in 1999 followed by external beam irradiation. In 2005, she developed progressive right leg weakness and had a second operation and course of radiation. The surgical pathology on that occasion revealed a grade II meningioma with significant vascular component. Recurrent disease was diagnosed in 2008 and she was treated with radiosurgery.
She has been recently admitted for progressive weakness and increase in seizure activity. An MRI demonstrated growth predominantly of a lesion located in the left parasagittal area. There was also parasagittal disease on the right that was essentially unchanged (compared to 2008), but other lesions inferior and lateral along the dura on the left showed evidence for growth.
On this occasion she has been seen by both her neurosurgeon and radiotherapist and next-step treatment approaches are under consideration. Accordingly, the role for systemic therapy has been raised and medical oncology opinion was requested.
Commentary
Meningiomas are the most common primary brain tumors of the central nervous system with an annual incidence of approximately 6 cases/100,000 person-years.1 The great majority are benign, but approximately 20% are atypical, or anaplastic, and demonstrate more rapid growth and a tendency to recur after initial therapy.2 Initial therapy for symptomatic or growing benign meningiomas is maximum safe resection, whereas radiation therapy is usually added for atypical and anaplastic lesions or for inoperable, progressive grade I lesions.3,4 Additional radiation or repeat surgery is often considered for recurrent disease, but these options are often limited by the accumulated dose of radiation or the extent of surgery required. Thus, there has been interest in examining the role for systemic therapy under these circumstances.
Unfortunately, most efforts at systemic therapy, including chemotherapy, hormonal, and immunomodulators, have met with unsatisfactory results including both lack of efficacy and toxicity.4
Chemotherapeutic approaches have included temozolomide5 and hydroxyurea6 but with little objective benefit. However, enthusiasm for treatment with hormonal agents was based on the demonstration of estrogen, progesterone, and androgen receptors in tumor samples from as many as two-thirds of cases.4 Yet, such treatments did not result in improvement in meaningful outcomes. For example, the Southwest Oncology Group (SWOG) conducted a trial of tamoxifen in 21 patients and observed only one partial response.7
With the demonstration that the great majority (approximately 90%) of meningiomas express somatostatin receptors, treatment with the somatostatin analogue octreotide has been undertaken. Indeed, in a pilot study, 5 of 16 (31%) patients who had recurrent meningiomas known to have somatostatin receptors on the basis of radiolabeled octreotide scan experienced partial response to octreotide therapy.8 The use of agents in this class remains under clinical investigation.
In addition to hormone receptors, meningioma cells, particularly those from high-grade tumors, are also known to express vascular endothelial growth factor receptor,9,10 thus providing rationale for targeted angiogenesis inhibitors. Indeed, two recent reports have provided retrospective analyses of patients with aggressive meningiomas treated with the VEGF inhibitor bevacizumab.11,12 These reports both indicate promise for drugs in this class, as toxicity was both minimal and manageable, and evidence for tumor regression or stable disease was observed in some patients. Clearly, it would seem that such targeted approaches provide the best chance for reaching a level of disease control, and hopefully this will be clearly demonstrated in the ongoing Phase 2 trials.
Thus, with regard to the management of the patient presented, if surgical and radiation options have been exhausted, I would recommend obtaining an octreotide scan. If positive, I would treat with the long-acting formulation of octreotide. If somatostatin receptor is not apparent by scan, or if octreotide proves ineffective, my next step would be a trial of bevacizumab.
References
1. CTRBUS. Central Brain Tumor Registry of the United States: 2010 Statistical Report: Primary brain and central nervous system tumors diagnosed in the United States in 2004-2006; 2010.
2. Mawrin C, Perry A. Pathological classification and molecular genetics of meningiomas. J Neurooncol 2010;99:379-391.
3. Alexiou GA, et al. Management of meningiomas. Clin Neurol Neurosurg 2010;112:177-182.
4. Wen PY, et al. Medical therapies for meningiomas. J Neurooncol 2010;99:365-378.
5. Chamberlain MC, et al. Temozolomide for treatment-resistant recurrent meningioma. Neurol 2004;62:1210-1212.
6. Weston GJ, et al. Hydroxyurea treatment of meningiomas: A pilot study. Skull Base 2006;16:157-160.
7. Goodwin JW, et al. A phase II evaluation of tamoxifen in unresectable or refractory meningiomas: A Southwest Oncology Group study. J Neurooncol 1993;15:75-77.
8. Chamberlain MC, et al. Recurrent meningioma: Salvage therapy with long-acting somatostatin analogue. Neurol 2007;69:969-973.
9. Pistolesi S, et al. Angiogenesis in intracranial meningiomas: Immunohistochemical and molecular study. Neuropathol Appl Neurobiol 2004;30:118-125.
10. Rogers L, et al. Intracranial meningiomas of atypical (WHO grade II) histology. J Neurooncol 2010;99:393-405.
11. Lou E, et al. Bevacizumab therapy for adults with recurrent/progressive meningioma: A retrospective series. J Neurooncol 2012.
12. Nayak L, et al. Atypical and anaplastic meningiomas treated with bevacizumab. J Neurooncol 2012; Apr 29 [Epub ahead of print].
The patient is a 56-year-old woman with known meningioma first resected in 1999 followed by external beam irradiation. In 2005, she developed progressive right leg weakness and had a second operation and course of radiation.Subscribe Now for Access
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