Thomas Kaley1, Igor Barani1, Marc Chamberlain1, Michael McDermott1, Katherine Panageas1, Jeffrey Raizer1, Leland Rogers1, David Schiff1, Michael Vogelbaum1, Damien Weber1, Patrick Wen1. 1. Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York (T.K.); Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (I.B.); Department of Neurology, University of Washington, Seattle, Washington (M.C.); Department of Neurosurgery, University of California, San Francisco, San Francisco, California (M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (K.P.); Department of Neurology, Northwestern University, Chicago, Illinois (J.R.); Department of Radiation Oncology, Gamma West Cancer Services, Salt Lake City, Utah (L.R.); Department of Neurology, University of Virginia, Charlottesville, Virginia (D.S.); Department of Neuro-Oncology, Cleveland Clinic, Cleveland, Ohio (M.V.); Division of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland (D.W.); Center for Neuro-Oncology, Dana-Farber Cancer Institute/Brigham and Women's Center, Boston, Massachsetts (P.W.).
Abstract
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-α, 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.
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-α, 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.
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