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International audience; PURPOSE: Meningiomas represent the most frequent tumor of the central nervous system in adults. While most meningiomas are efficiently treated by surgery and radiotherapy/radiosurgery, there is a small portion of radiation- and surgery-refractory tumors for which there is no clear recommendation for optimal management. The French National Tumor Board Meeting on Meningiomas (NTBM) offers a glimpse on the current management of such patients. METHODS: We retrospectively reviewed the charts of patients presented to the multidisciplinary Meeting between 2016 and 2019. We selected patients with a progressive disease after at least two treatments, including surgery and radiotherapy. RESULTS: In this multicentric cohort of 86 cases, patients harbored 17 (19.8%) WHO Grade I, 48 (55.8%) WHO Grade II and 21 (24.4%) WHO Grade III tumors. The median number of treatments received before inclusion was 3 (range: 2 - 11). Following the Board Meeting, 32 patients (37.2%) received chemotherapy, 11 (12.8%) surgery, 17 (19.8%) radiotherapy, 14 (16.3%) watchful observation and 12 (13.9%) palliative care. After a mean follow-up of 13 months post-inclusion, 32 patients (37.2%) had died from their disease. The mean progression free survival was 27 months after radiotherapy, 10 months after surgery, 8.5 months after chemotherapy (Bevacizumab: 9 months - Octreotide/Everolimus: 8 months). CONCLUSIONS: Surgery- and radiation-refractory meningiomas represent a heterogeneous group of tumors with a majority of WHO Grade II cases. If re-irradiation and redo-surgery are not possible, bevacizumab and octreotide-everolimus appear as a valuable option in heavily pre-treated patients considering the current EANO guidelines.

Skull base meningiomas may present as clinically aggressive tumors despite being histologically benign. Here we describe a clinico-radiological entity of diffuse midline skull base meningiomas responsible for several neurological morbidities, including hearing and vision loss, intracranial hypertension, secondary hydrocephalus and tonsillar herniation with spinal cord compression. Surgery and radiotherapy were ineffective in stopping the clinical course of those tumors. After targeted sequencing of known mutated genes in meningiomas, we discovered TRAF7 mutations in two out of four tumors, stressing the importance of focusing the research efforts of the meningioma community in understanding the mechanisms underlying TRAF7 related meningioma tumorigenesis.

International audience; Patients with surgery- and radiation-refractory meningiomas have a poor outcome. Due to our lack of knowledge concerning multi-recurrent meningioma natural history, their clinical course is poorly defined. This retrospective study aims at defining patterns of relapse in order to help in the definition of response criteria in future clinical trials. We performed a retrospective review of surgery- and radiotherapy-refractory meningioma cases with interpretable radiological follow-up treated in our department. Tumor volumes were measured on 3D T1 Gadolinium volumetric sequences using a semi-automated algorithm for tumor segmentation. Twenty nine patients with multi-treated meningioma (11 WHO Grade II, 5 de novo WHO Grade III and 13 transformed WHO Grade III), were evaluated. Median PFS was 16 months for patients with Grade II meningiomas. In patients with Grade III meningiomas, the de novo subgroup had a median PFS of 4 months compared with 7 months in patients with malignant transformation. Volumetric analysis of tumor growth concerned 95 tumor nodules in 50 relapses. The mean growth rate of tumor nodules was 10.4 cm3/year (95 % CI 7.3–14.8 cm3/year). Three patterns of tumor growth were described: “classical” for 9 (31 %) patients, “local multi-nodular” for 6 (21 %) patients and “multi-nodular metastatic” for the last 14 (48 %) patients. Considering all tumor nodules, median time to tumor progression (TTP) was 3.7 months. Progressing tumors represent the most frequent histological subgroup of surgery and radiation-refractory meningiomas while tumors with multi-nodular metastatic dissemination are the prominent radiological pattern of progression.

Meningiomas, although mostly benign, may sometimes present aggressive features and raise issues concerning alternative treatment options besides surgery. In order to gain new insights in meningioma biology and develop alternative treatments, several meningioma mouse models have been engineered during the past two decades. As rodents very rarely develop spontaneous meningiomas, animal models have been first developed by implanting human meningioma cells derived from a primary tumor and meningioma cell lines subcutaneously into athymic mice. Induction of de novo meningiomas in rodents with mutagens, such as nitrosourea, has also been reported. Advances in our understanding of molecular genetics of meningioma have pinpointed the central role of NF2 tumor suppressor gene in the pathogenesis of those tumors. These discoveries have led to the creation of a genetically engineered model utilizing conditional mutagenesis to specifically inactivate the mouse Nf2 gene in arachnoidal cells, resulting in the formation of intracranial meningothelial hyperplasia and meningiomas and thus reproducing the main mechanism of human meningeal tumorigenesis. This powerful new technology significantly improves on prior models and may open avenues of investigation never before possible in meningioma research. We present here a review of current meningioma mouse models used in translational therapeutics with associated imaging and pre-clinical studies.