Background: Complete surgical resection is the first-line therapy for meningiomas. However, tumor location and biological aggressiveness can make surgical cure impossible. Treatment options for these refractory meningiomas include further surgery, conventional external beam irradiation, stereotactic radiosurgery, and systemic therapies. In this paper, we discuss new and emerging systemic therapies when these "local" treatment options are not successful. Methods: We reviewed predictors of refractory meningiomas and novel systemic therapies in the treatment of refractory meningiomas. Results: Tumor location, atypical or malignant histologic subtypes, and staining for the Ki-67 protein (MIB-1 antibody) with a high labeling index are the best predictors of tumor recurrence. Novel systemic treatment options include angiogenesis inhibition, meningioma cell growth inhibition, blockade of growth factor effects, inhibition of intracellular secondary pathways, and gene therapies. Conclusions: MIB-1 labeling index staining is a good predictor for refractory meningiomas. Currently, the best-studied systemic treatment for patients with refractory meningiomas is hydroxyurea. Blockade of the growth hormone receptor by pegvisomant is promising because in vivo and in vitro studies have shown good results and the drug has a known side effect profile.
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