Kinetics of tumor size and peritumoral brain edema before, during, and after systemic therapy in recurrent WHO grade II or III meningioma

Furtner, Julia; Schöpf, Veronika; Seystahl, Katharina; Rhun, Émilie Le; Rudà, Roberta; Roelcke, Ulrich; Koeppen, Susanne; Berghoff, Anna Sophie; Marosi, Christine; Clément, Paul M.; Faedi, Marina; Watts, Colin; Wick, Wolfgang; Soffietti, Riccardo; Weller, Michael

doi:10.1093/neuonc/nov183

Cited by 60 publications

(51 citation statements)

References 26 publications

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“…The anti-VEGF monoclonal antibody bevacizumab has shown efficacy against recurrent meningioma in a Phase II clinical trial with PFS-6 of 87, 77 and 46% in grade I, II and III tumors, respectively [75]. There is also a role for bevacizumab for control of peritumoral edema or for decreasing the need for corticosteroids in meningiomas in a recent retrospective series [76]. A Phase II prospective trial of bevacizumab is ongoing (NCT01125046).…”

Section: Systemic Treatmentsmentioning

confidence: 99%

An Overview of Meningiomas

et al. 2018

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Meningiomas are the most common primary intracranial tumor. Important advances are occurring in meningioma research. These are expected to accelerate, potentially leading to impactful changes on the management of meningiomas in the near and medium term. This review will cover the histo- and molecular pathology of meningiomas, including recent 2016 updates to the WHO classification of CNS tumors. We will discuss clinical and radiographic presentation and therapeutic management. Surgery and radiotherapy, the two longstanding primary therapeutic modalities, will be discussed at length. In addition, data from prior and ongoing investigations of other treatment modalities, including systemic and targeted therapies, will be covered. This review will quickly update the reader on the contemporary management and future directions in meningiomas. [Formula: see text].

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Section: Systemic Treatmentsmentioning

confidence: 99%

An Overview of Meningiomas

et al. 2018

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“…Furtner et al recently published a retrospective analysis of serial cranial MRI in patients with WHO II and III recurrent meningioma treated with systemic therapy [15]. They conducted a detailed analysis of the MRI images obtained before, during and after treatment and measured the tumor volume, maximum tumor diameter and volume of peritumoral edema.…”

Section: Treatment and Dose Modificationmentioning

confidence: 99%

A phase II trial of bevacizumab and everolimus as treatment for patients with refractory, progressive intracranial meningioma

et al. 2016

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Meningiomas that progress after standard therapies are challenging with limited effective chemotherapy options. This phase II trial evaluated the efficacy of everolimus plus bevacizumab in patients with recurrent, progressive meningioma after treatment with surgical resection and local radiotherapy when appropriate. Patients with recurrent meningioma (WHO grade I, II, or III) following standard treatments with surgical resection and radiotherapy received bevacizumab (10 mg/kg IV days 1 and 15) and everolimus (10 mg PO daily) each 28 day cycle. Evaluation of response occurred every 2 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, overall survival and safety. Seventeen patients with a median age of 59 years (29-84) received study treatment. WHO grades at study entry included: I, 5 (29 %); II, 7 (41 %); III, 4 (24 %); unknown, 1 (6 %). Patients received a median of 8 cycles (1-37); all patients are off study treatment. A best response of SD was observed in 15 patients (88 %), and 6 patients had SD for >12 months. Overall median PFS was 22 months (95 % CI 4.5-26.8) and was greater for patients with WHO grade II and III compared to grade I tumors (22.0 months vs 17.5 months). Four patients discontinued treatment due to toxicity (proteinuria, 2; colitis, 1, thrombocytopenia, 1). However, other grade 3 toxicity was uncommon, and no patient had grade 4 toxicity. The combination of everolimus and bevacizumab was well-tolerated, and produced stable disease in 88 % of patients; the median duration of disease stabilization of 10 months (2-29). The median PFS from this prospective trial was similar to previous retrospective reports of bevacizumab in the treatment of recurrent meningioma.

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“…Some clinical studies have analyzed octreotide efficacy in patients with meningioma, yet their conclusions remain disputed and are sometimes undefined. 10,17,18,21,23,38,40,42,45 Moreover, the results of octreotide treatment in meningioma cells in vitro have been contradictory. 4,26 Therefore, should we reject octreotide for meningioma therapy?…”

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Octreotide therapy in meningiomas: in vitro study, clinical correlation, and literature review

Graillon

Reverter

Defilles

et al. 2017

Journal of Neurosurgery

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OBJECTIVE Meningiomas express somatostatin receptor subtype 2 (SST2), which is targeted by the somatostatin analog octreotide. However, to date, using somatostatin analog therapy for the treatment of these tumors in clinical practice has been debated. This study aims to clarify the in vitro effects of octreotide on meningiomas for precise clinical applications. METHODS The effects of octreotide were analyzed in a large series of 80 meningiomas, including 31 World Health Organization (WHO) Grade II and 4 WHO Grade III tumors, using fresh primary cell cultures to study the impact on cell viability, apoptosis, and signal transduction pathways. RESULTS SST2 mRNA was detected in 100% of the tested meningiomas at levels similar to those observed in other SST2-expressing tumors, neuroendocrine tumors, or pituitary adenomas. Octreotide significantly decreased cell proliferation in 88% of meningiomas but did not induce cell death. On average, cell proliferation was more inhibited in the meningioma group expressing a high level of SST2 than in the low-SST2 group. Moreover, octreotide response was positively correlated to the level of merlin protein and inversely correlated to the level of phosphorylated p70-S6 kinase, a downstream effector of the PI3K/Akt/mammalian target of rapamycin (mTOR) pathway. Octreotide inhibited Akt phosphorylation and activated tyrosine phosphatase without impacting the extracellular regulated kinase (ERK) pathway. CONCLUSIONS Octreotide acts exclusively as an antiproliferative agent and does not promote apoptosis in meningioma in vitro. Therefore, in vivo, octreotide is likely to limit tumor growth rather than induce tumor shrinkage. A meta-analysis of the literature reveals an interest in octreotide for the treatment of WHO Grade I tumors, particularly those in the skull base for which the 6-month progression-free survival level reached 92%. Moreover, somatostatin analogs, which are well-tolerated drugs, could be of interest for use as co-targeting therapies for aggressive meningiomas.

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Kinetics of tumor size and peritumoral brain edema before, during, and after systemic therapy in recurrent WHO grade II or III meningioma

Abstract: Background. The efficacy of systemic antineoplastic therapy on recurrent World Health Organization (WHO) grades II and III meningiomas is unclear.

Cited by 60 publications

References 26 publications

An Overview of Meningiomas

An Overview of Meningiomas

A phase II trial of bevacizumab and everolimus as treatment for patients with refractory, progressive intracranial meningioma

Octreotide therapy in meningiomas: in vitro study, clinical correlation, and literature review

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