Peritumoral brain edema in intracranial meningiomas: the emergence of vascular endothelial growth factor-directed therapy

Meningioma is the second most common type of adult intracranial neoplasm. A substantial subset of patients present with peritumoral brain edema (PTBE), which can cause significant morbidity via mass effect, complicate surgical management, and impact the safety of stereotactic radiosurgery. Recent studies suggest a close relationship between vascular endothelial growth factor-A (VEGF-A) expression and PTBE development in meningiomas. The authors performed a systematic review of the literature on the pathogenesis of PTBE in meningiomas, the effectiveness of steroid therapy, the role played by VEGF-A, and the current clinical evidence for antiangiogenic therapy to treat peritumoral brain edema. Mounting evidence suggests VEGF-A is secreted directly by meningioma cells to induce angiogenesis and edemagenesis of tumoral as well as peritumoral brain tissue. The VEGF-A cascade results in recruitment of cerebral-pial vessels and disruption of the tumor-brain barrier, which appear to be requisite for VEGF-A to have an edemagenic effect. Results of preliminary clinical studies suggest VEGF-directed therapy has modest activity against recurrent and progressive meningioma growth but can alleviate PTBE in some patients. A comprehensive understanding of the VEGF-A pathway and its modulators may hold the key to an effective therapeutic approach to treating PTBE associated with meningiomas. Further clinical trials with larger patient cohorts and longer follow-up periods are warranted to confirm the efficacy of VEGF-directed therapy.