Förderung der integrinbasierten Meningeomzellmigration durch Bestrahlung mit Photonen, nicht jedoch durch Bestrahlung mit Kohlenstoffionen

Simon, Florian; Dittmar, Jan-Oliver; Brons, Stephan; Orschiedt, Lena; Urbschat, Steffi; Weber, Klaus-Josef; Debus, Jürgen; Combs, Stephanie E.; Rieken, Stefan

doi:10.1007/s00066-014-0778-y

Cited by 5 publications

(4 citation statements)

References 35 publications

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“…Madani et al describe that dose-painting intensity-modulated proton therapy (IMPT) using a SIB is a feasible therapy option with excellent dose coverage with minimal or no dose to brain, brainstem or optical system [ 38 ]. A study by Simon concludes that carbon-ion RT could be the preferred therapy option [ 39 ]. Similarly, Harrabi et al describe that proton beam RT shows dosimetric advantages over conventional radiotherapy that might be essential for neurologic function [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Recurrence pattern analysis after [68Ga]-DOTATATE-PET/CT -planned radiotherapy of high-grade meningiomas

et al. 2018

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BackgroundThe aim of the present study was to evaluate the influence of the applied safety margins of modern intensity-modulated radiotherapy (IMRT) in patients with high-grade meningiomas on local control and recurrence patterns.MethodsTwenty patients with a neuropathological diagnosis of a high-grade meningioma (WHO°II or °III) treated with adjuvant or definitive radiotherapy between 2010 and 2015 were included in the present retrospective analysis. All patients were planned PET-based. Recurrence patterns were assessed by means of MRI and/or DOTATATE-PET/computertomography (CT).ResultsThe median follow-up was 31.0 months [95% confidence interval (CI): 20.1–42.0] and the progression-free survival (PFS) after 24 months was 87.5%. Overall, four patients had a local recurrence of their meningioma. Of these, three were located in field according to the prior radiotherapy treatment region, while only one patient had a distant relapse. There were no independent factors influencing progression-free or overall survival (OS).ConclusionAfter radiotherapy (RT), patients with atypical or anaplastic meningiomas still have a defined risk of tumor recurrence. The aim of the present study was to examine mono-institutional data concerning target volume definition and recurrence patterns after radiotherapy of high-grade meningiomas as there are limited data available. Our data suggest that extended safety margins are necessary to achieve a favorable local control for high-grade meningiomas.

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Section: Discussionmentioning

confidence: 99%

Recurrence pattern analysis after [68Ga]-DOTATATE-PET/CT -planned radiotherapy of high-grade meningiomas

et al. 2018

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“…There are two recent reports confirming our observation on charged particle effects on cell migration and related signaling pathways. Simon et al ( 44 ) were able to show that migration of meningioma cells was promoted by photon but not by carbon ion irradiation. Our results on an increased cell migration associated with an elevated phosphorylation status of the EGFR and AKT–ERK1/2 pathway following X-ray but not carbon irradiation was partially confirmed by corresponding findings of Jin and colleagues ( 45 ).…”

Section: Discussion and Resumementioning

confidence: 99%

Differential Superiority of Heavy Charged-Particle Irradiation to X-Rays: Studies on Biological Effectiveness and Side Effect Mechanisms in Multicellular Tumor and Normal Tissue Models

Walenta

Mueller‐Klieser

2016

Front. Oncol.

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This review is focused on the radiobiology of carbon ions compared to X-rays using multicellular models of tumors and normal mucosa. The first part summarizes basic radiobiological effects, as observed in cancer cells. The second, more clinically oriented part of the review, deals with radiation-induced cell migration and mucositis. Multicellular spheroids from V79 hamster cells were irradiated with X-rays or carbon ions under ambient or restricted oxygen supply conditions. Reliable oxygen enhancement ratios could be derived to be 2.9, 2.8, and 1.4 for irradiation with photons, 12C+6 in the plateau region, and 12C+6 in the Bragg peak, respectively. Similarly, a relative biological effectiveness of 4.3 and 2.1 for ambient pO2 and hypoxia was obtained, respectively. The high effectiveness of carbon ions was reflected by an enhanced accumulation of cells in G2/M and a dose-dependent massive induction of apoptosis. These data clearly show that heavy charged particles are more efficient in sterilizing tumor cells than conventional irradiation even under hypoxic conditions. Clinically relevant doses (3 Gy) of X-rays induced an increase in migratory activity of U87 but not of LN229 or HCT116 tumor cells. Such an increase in cell motility following irradiation in situ could be the source of recurrence. In contrast, carbon ion treatment was associated with a dose-dependent decrease in migration with all cell lines and under all conditions investigated. The radiation-induced loss of cell motility was correlated, in most cases, with corresponding changes in β1 integrin expression. The photon-induced increase in cell migration was paralleled by an elevated phosphorylation status of the epidermal growth factor receptor and AKT-ERK1/2 pathway. Such a hyperphosphorylation did not occur during 12C+6 irradiation under all conditions registered. Comparing the gene toxicity of X-rays with that of particles using the γH2AX technique in organotypic cultures of the oral mucosa, the superior effectiveness of heavy ions was confirmed by a twofold higher number of foci per nucleus. However, proinflammatory signs were similar for both treatment modalities, e.g., the activation of NFκB and the release of IL6 and IL8. The presence of peripheral blood mononuclear cell increased the radiation-induced release of the proinflammatory cytokines by factors of 2–3. Carbon ions are part of the cosmic radiation. Long-term exposure to such particles during extended space flights, as planned by international space agencies, may thus impose a medical and safety risk on the astronauts by a potential induction of mucositis. In summary, particle irradiation is superior to gamma-rays due to a higher radiobiological effectiveness, a reduced hypoxia-induced radioresistance, a multicellular radiosensitization, and the absence of a radiation-induced cell motility. However, the potential of inducing mucositis is similar for both radiation types.

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“…In meningioma, it has been demonstrated that integrins are widely expressed in a subtype and grading-dependent manner [46]. The integrins αvβ1, αvβ3, αvβ5 have been directly implicated in invasion [47][48][49][50]. Integrins seem to provide a reasonable target for specific anti-invasive therapy in meningioma, with two studies reporting promising results using preclinical orthotopic mouse meningioma models [50,51].…”

Section: Cell-cell and Cell-extracellular Matrix Interactionsmentioning

confidence: 99%

Molecular neuropathology of brain‐invasive meningiomas

et al. 2022

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Invasion of brain tissue by meningiomas has been identified as one key factor for meningioma recurrence. The identification of meningioma tumor tissue surrounded by brain tissue in neurosurgical samples has been touted as a criterion for atypical meningioma (CNS WHO grade 2), but is only rarely seen in the absence of other high‐grade features, with brain‐invasive otherwise benign (BIOB) meningiomas remaining controversial. While post‐surgery irradiation therapy might be initiated in brain‐invasive meningiomas to prevent recurrences, specific treatment approaches targeting key molecules involved in the invasive process are not established. Here we have compiled the current knowledge about mechanisms supporting brain tissue invasion by meningiomas and summarize preclinical models studying targeted therapies with potential inhibitory effects.

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Förderung der integrinbasierten Meningeomzellmigration durch Bestrahlung mit Photonen, nicht jedoch durch Bestrahlung mit Kohlenstoffionen

Abstract: Photon but not carbon-ion IR promotes serum-based meningioma cell migration. Fibronectin receptor integrin ανβ1 signaling can be identified as an important mechanism for serum- and photon-induced migration of WHO class I meningioma cells.

Cited by 5 publications

References 35 publications

Recurrence pattern analysis after [68Ga]-DOTATATE-PET/CT -planned radiotherapy of high-grade meningiomas

Recurrence pattern analysis after [68Ga]-DOTATATE-PET/CT -planned radiotherapy of high-grade meningiomas

Differential Superiority of Heavy Charged-Particle Irradiation to X-Rays: Studies on Biological Effectiveness and Side Effect Mechanisms in Multicellular Tumor and Normal Tissue Models

Molecular neuropathology of brain‐invasive meningiomas

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