High Grade Meningiomas: Current Therapy Based on Tumor Biology

Abstract

Atypical (WHO grade II) and malignant meningiomas (WHO Grade III) are a rare subset of primary intracranial tumors. Due to the high recurrence rate after surgical resection and radiotherapy, there has been a recent interest in exploring other systemic treatment options for these refractory tumors. Recent advances in molecular sequencing of tumors have elucidated new pathways and drug targets currently being studied. This article provides a thorough overview of novel investigational therapeutics, including targeted therapy, immunotherapy, and new technological modalities for atypical and malignant meningiomas. There is encouraging preclinical evidence regarding the efficacy of the emerging treatments discussed in this chapter. Several clinical trials are currently recruiting patients to translate targeted molecular therapy for recurrent and high-grade meningiomas.

Management of High-Grade Meningioma: Present, Past and Promising Future

“…Loss of chromosome 22 [18] More frequently (87%) Less frequently (58%) are malignant, making up the bulk of meningiomas (WHO grade III) [8,10]. After age 65, the chance of high grade meningiomas dramatically increases with age.…”

“…It is thought that individuals with the genetic condition Neurofibromatosis type 2 (NF2) have an increased chance of developing meningioma. Additionally, meningiomas that are malignant or numerous may be more common in NF2 patients [10]. While postmenopausal women without these traits are more likely to have Grade I meningiomas, meningioma patients with past CVA and those with grade 4/4 vascularity are more likely to develop WHO Grade II-III tumors [11] (Table 1).…”

Related mechanisms, current treatments, and new perspectives in meningioma

“…Eccentric nuclei, open chromatin, macronucleoli, and eosinophilic perinuclear inclusions, which might be whorled fibrils or compact, waxy spheres 32,33 …”

“…It is possible that is why the EGFR inhibitors called erlotinib and gefitinib did not have significant survival at phase II studies in meningioma 79 . The 12‐month follow‐up demonstrated that for benign tumors, the 12‐month survival rate without any progression was 13%, and the 12‐month rate of overall survival was 50% 33 . The 6‐month survival rate for atypical meningioma and malignant meningioma tumors was 29%; the 12‐month survival rate was only 18%; and the 6‐month rate of overall survival was 71%; however, the 12‐month rate of overall survival was 65% 79 .…”

“…When the HH ligand binds to PTCH1, it suppresses SMO; therefore, the suppressed SMO then interacts with fused homologous suppressor protein (SUFU), activating the glioma‐associated oncogene homolog (GL1) protein to activate target genes 112,113 . SMO mutations are seen in around 5.5% of grade 1 meningiomas without changes in NF2, TRAF7, KLF4, and AKT1 mutations 33,56 . Two specific hotspot mutations are discovered in the SMO gene, and the presence of GRB2‐Associated Binding Protein 1 (GAB1) in some meningiomas suggests HH pathway activity 56 .…”