Systemic therapy for relapsed/refractory meningioma: Is there potential for antiangiogenic agents?

Dasanu, Constantin A; Samara, Yazeed; Codreanu, Ion; Limonadi, Farhad M; Hamid, Omid; Alvarez-Argote, Juliana

doi:10.1177/1078155218799850

Cited by 13 publications

(14 citation statements)

References 57 publications

(95 reference statements)

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“…As such, if moderate dose escalation is pursued, using the physical advantage of the proton beam's properties to conform the dose deposition at a specific depth, the administration of PT in nonbenign meningioma should be considered ( Table 3). This has been the dose-strategy of all groups delivering PT for non-benign meningioma with doses up to 72 GyRBE (median/mean, [62][63][64][65][66][67][68] administered to these patients with no demonstrable increase the reported toxicity ( Table 2). The reported outcome after PT is good, with a median 5-year LC of 52% for WHO grade II-III tumors ( Table 2) but caution should be exercised not to overestimate these results due to the small number (16-35; median 23) of patients and short follow-up intervals of those series ( Table 2).…”

Section: Discussionmentioning

confidence: 99%

“…The therapeutic strategy is often limited but salvage options may include additional surgery and/or re-treatment with a radiation-modality such as brachytherapy (65,66), photon radiotherapy including but not limited to normo-or hypo-fractionated radiotherapy/ radiosurgery, and PT (32). Systemic therapy, including the administration of check-point inhibitors (67), is usually ineffective and rarely translates into radiological objective responses, although WHO grades II-III meningioma patients appear to benefit more from chemotherapy than whose with grade I disease (5,68). Rechallenging these patients with radiation therapy again could potentially cause serious radiation-induced adverse events, as the organs at risk, including but not limited to the optic apparatus, brainstem and cochlea, have received a substantial dose of radiation already.…”

Section: Discussionmentioning

confidence: 99%

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Proton Therapy for Intracranial Meningioma for the Treatment of Primary/Recurrent Disease Including Re-Irradiation

et al. 2020

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Meningeal tumors represent approximately 10–25% of primary brain tumors and occur usually in elderly female patients. Most meningiomas are benign (80–85%) and for symptomatic and/or large tumors, surgery, with or without radiation therapy (RT), has been long established as an effective means of local tumor control. RT can be delivered to inoperable lesions or to those with non-benign histology and for Simpson I–III and IV–V resection. RT can be delivered with photons or particles (protons or carbon ions) in stereotactic or non-stereotactic conditions. Particle therapy delivered for these tumors uses the physical properties of charged carbon ions or protons to spare normal brain tissue (i.e. Bragg peak), with or without or a dose-escalation paradigm for non-benign lesions. PT can substantially decrease the dose delivered to the non-target brain tissues, including but not limited to the hippocampi, optic apparatus or cochlea. Only a limited number of meningioma patients have been treated with PT in the adjuvant or recurrent setting, as well as for inoperable lesions with pencil beam scanning and with protons only. Approximately 500 patients with image-defined or WHO grade I meningioma have been treated with protons. The reported outcome, usually 5-year local tumor control, ranges from 85 to 99% (median, 96%). For WHO grade II or III patients, the outcome of only 97 patients has been published, reporting a median tumor local control rate of 52% (range, 38–71.1). Only 24 recurring patients treated previously with photon radiotherapy and re-treated with PT were reported. The clinical outcome of these challenging patients seems interesting, provided that they presented initially with benign tumors, are not in the elderly category and have been treated previously with conventional radiation dose of photons. Overall, the number of meningioma patients treated or-re-irradiated with this treatment modality is small and the clinical evidence level is somewhat low (i.e. 3b–5). In this review, we detail the results of upfront PT delivered to patients with meningioma in the adjuvant setting and for inoperable tumors. The outcome of meningioma patients treated with this radiation modality for recurrent tumors, with or without previous RT, will also be reviewed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Proton Therapy for Intracranial Meningioma for the Treatment of Primary/Recurrent Disease Including Re-Irradiation

et al. 2020

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“…One study found in primary, non-NF2 mutated meningiomas, the pro-tumor inflammatory mediator IL-1β induced methylation of the NF2 promotor through various mediators that could act as novel targets ( 26 ). Other mutations like TRAF7, AKT1, KLF4, SMO, and PIK3CA were more recently described ( 27 , 28 ) and may represent therapeutic targets ( 29 – 31 ). In one particular study, grade I meningiomas harboring AKT1 mutations had predominantly M2-subtype infiltrating macrophages, indicating a locally immunosuppressed tumor microenvironment ( 32 ).…”

Section: Genetic Alterations Of Meningiomasmentioning

confidence: 99%

Basis for Immunotherapy for Treatment of Meningiomas

et al. 2020

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Meningiomas are common tumors that account for approximately one third of CNS tumors diagnosed every year. They are classified by the World Health Organization in grades I-III. Higher grades have an increased rate of growth, invasiveness, rate of recurrence, and worse outcomes than lower grades. Most meningiomas are grade I, while ~18% of meningiomas are grade II and III in hospital-based series. Meningiomas are typically “benign” tumors that are treated with surgery and radiation. However, when they recur or are unresectable, treatment options are very limited, especially since they are chemotherapy-resistant. Recent advances in the treatment of cancers with immunotherapy have focused on checkpoint blockade as well as other types of immunotherapy. There is emerging evidence supporting the use of immunotherapy as a potentially effective treatment strategy for meningioma patients. The immune microenvironment of meningiomas is a complex interplay of genetic alterations, immunomodulatory protein expression, and tumor-immune cell interactions. Meningiomas are known to be infiltrated by immune cells including microglia, macrophages, B-cells, and T-cells. Several mechanisms contribute to decreased an ti-tumor immune response, allowing tumor growth and evasion of the immune system. We discuss the most current knowledge on the immune micro-environment of meningiomas, preclinical findings of immunotherapy in meningiomas, meningioma immunotherapy clinical trials, and also offer insight into future prospects for immunotherapies in meningiomas.

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“…Several retrospective studies reported improved local tumor control following treatment with anti-angiogenic agents, such as bevacizumab, vatalanib, or sunitinib in recurrent, radioresistant, high-grade meningiomas [ 5 , 10 , 11 , 12 ]. The antiangiogenic effects of these agents are mainly based on blocking the vascular endothelial growth factor (VEGF) signaling pathway, one of the key mechanisms of tumorigenesis in general [ 13 ] and in the development of meningiomas in particular [ 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Occurrence of Fibrotic Tumor Vessels in Grade I Meningiomas Is Strongly Associated with Vessel Density, Expression of VEGF, PlGF, IGFBP-3 and Tumor Recurrence

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et al. 2020

Cancers

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Angiogenesis is a key feature during oncogenesis and remains a potential target of antiangiogenic therapy. While commonly described in high-grade lesions, vascularization and its correlation with prognosis in grade I meningiomas is largely unexplored. In the histological classification, not only the number but also the composition of blood vessels seems to be important. Therefore, tumor vessel density and fibrosis were correlated with clinical and imaging variables and prognosis in 295 patients with intracranial grade I meningioma. Expression of pro-angiogenic proteins within the meningiomas was investigated by proteome analyses and further validated by immunohistochemical staining. Fibrotic tumor vessels (FTV) were detected in 48% of all tumors and strongly correlated with vessel density, but not with the histopathological tumor subtype. Occurrence of FTV was correlated with a 2-fold increased risk of recurrence in both univariate and multivariate analyses. Explorative proteome analyses revealed upregulation of VEGF (vascular endothelial growth factor), PlGF (placental growth factor), and IGFBP-3 (insulin-like growth factor-binding protein-3) in tumors displaying FTV. Immunohistochemical analyses confirmed strong correlations between tumor vessel fibrosis and expression of VEGF, PlGF, and IGFBP-3. Presence of FTV was strongly associated with disruption of the arachnoid layer on preoperative MRI in univariate and multivariate analyses. In summary, the occurrence of fibrotic tumor vessels in grade I meningiomas is strongly associated with vessel density, disruption of the arachnoid layer, expression of VEGF, PlGF, IGFBP-3 and tumor recurrence.

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Systemic therapy for relapsed/refractory meningioma: Is there potential for antiangiogenic agents?

Cited by 13 publications

References 57 publications

Proton Therapy for Intracranial Meningioma for the Treatment of Primary/Recurrent Disease Including Re-Irradiation

Proton Therapy for Intracranial Meningioma for the Treatment of Primary/Recurrent Disease Including Re-Irradiation

Basis for Immunotherapy for Treatment of Meningiomas

Occurrence of Fibrotic Tumor Vessels in Grade I Meningiomas Is Strongly Associated with Vessel Density, Expression of VEGF, PlGF, IGFBP-3 and Tumor Recurrence

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