No abstract

Evolving interest in meningioma, the most common primary brain tumor, has refined contemporary management of these tumors. Problematic, however, is the paucity of prospective clinical trials that provide an evidence-based algorithm for managing meningioma. The current review summarizes the published literature regarding the treatment of newly diagnosed and recurrent meningioma, with an emphasis on outcomes stratified by World Health Organization (WHO) tumor grade. In particular this review focuses on patient outcomes following treatment (either adjuvant or at recurrence) with surgery or radiation therapy inclusive of radiosurgery and fractionated irradiation. Phase II trials for patients with meningioma have recently completed accrual within the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) consortia, and phase III studies are being developed. However, at present, there are no completed prospective, randomized trials assessing the role of either surgery or radiotherapy. Successful completion of future studies will require a multidisciplinary effort, dissemination of the current knowledge base, improved implementation of WHO grading criteria, standardization of response criteria and other outcome endpoints, and concerted efforts to address weaknesses in present treatment paradigms, particularly for patients with progressive or recurrent low grade meningioma, or with high-grade meningioma. In parallel efforts, Response Assessment in Neuro-Oncology (RANO) subcommittees are developing a manuscript on systemic therapies for meningioma, and a separate article proposing standardized endpoint and response criteria for meningioma.

Background. The outcomes of patients with surgery-and radiation-refractory meningiomas treated with medical therapies are poorly defined. Published reports are limited by small patient numbers, selection bias, inclusion of mixed histologic grades and stages of illness, and World Health Organization (WHO) criteria changes. This analysis seeks to define outcome benchmarks for future clinical trial design.Methods. A PubMed literature search was performed for all English language publications on medical therapy for meningioma. Reports were tabulated and analyzed for number of patients, histologic grade, prior therapy, overall survival, progression-free survival (PFS), and radiographic response.Results. Forty-seven publications were identified and divided by histology and prior therapies, including only those that treated patients who were surgery and radiation refractory for further analysis. This included a variety of agents (hydroxyurea, temozolomide, irinotecan, interferon-a, mifepristone, octreotide analogues, megestrol acetate, bevacizumab, imatinib, erlotinib, and gefitinib) from retrospective, pilot, and phase II studies, exploratory arms of other studies, and a single phase III study. The only outcome extractable from all studies was the PFS 6-month rate, and a weighted average was calculated separately for WHO grade I meningioma and combined WHO grade II/III meningioma. For WHO I meningioma, the weighted average PFS-6 was 29% (95% confidence interval [CI]: 20.3% -37.7%). For WHO II/III meningioma, the weighted average PFS-6 was 26% (95% CI: 19.3% -32.7%).Conclusions. This comprehensive review confirms the poor outcomes of medical therapy for surgery-and radiation-refractory meningioma. We recommend the above PFS-6 benchmarks for future trial design.