Independent prognostic impact of DNA methylation class and chromosome 1p loss in WHO grade 2 and 3 meningioma undergoing adjuvant high-dose radiotherapy: comprehensive molecular analysis of EORTC 22042–26042

Maas, Sybren L. N.; Sievers, Philipp; Weber, Damien C.; Weller, Michael; van den Bent, Martin J.; Mair, Maximilian J.; Kros, Johan M.; Carparrotti, Fransesca; von Deimling, Andreas; Salvador, Villà Freixa; Peerdeman, Saskia Marguerite; Casas-Martin, Jose; Gorlia, Thierry; Sahm, Felix; Preusser, Matthias

doi:10.1007/s00401-023-02642-5

Cited by 7 publications

(2 citation statements)

References 11 publications

(17 reference statements)

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“…S2). This is in accordance with recent analyses, including a retrospective evaluation of patients enrolled in the EORTC 22042–26042 trial [ 10 , 27 – 29 ]. This growing evidence should be considered and validated in future research, particularly in prospective clinical trials.…”

Section: Discussionsupporting

confidence: 92%

Clinical implications of DNA methylation-based integrated classification of histologically defined grade 2 meningiomas

Ehret,

Perez,

Teichmann

et al. 2024

acta neuropathol commun

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The combination of DNA methylation analysis with histopathological and genetic features allows for a more accurate risk stratification and classification of meningiomas. Nevertheless, the implications of this classification for patients with grade 2 meningiomas, a particularly heterogeneous tumor entity, are only partially understood. We correlate the outcomes of histopathologically confirmed grade 2 meningioma with an integrated molecular-morphologic risk stratification and determine its clinical implications. Grade 2 meningioma patients treated at our institution were re-classified using an integrated risk stratification involving DNA methylation array-based data, copy number assessment and TERT promoter mutation analyses. Grade 2 meningioma cases according to the WHO 2021 criteria treated between 2007 and 2021 (n = 100) were retrospectively analyzed. The median clinical and radiographic follow-up periods were 59.8 and 54.4 months. A total of 38 recurrences and 17 deaths were observed. The local control rates of the entire cohort after 2-, 4-, and 6-years were 84.3%, 68.5%, and 50.8%, with a median local control time of 77.2 months. The distribution of the integrated risk groups were as follows: 31 low, 54 intermediate, and 15 high risk cases. In the multivariable Cox regression analysis, integrated risk groups were significantly associated with the risk of local recurrence (hazard ratio (HR) intermediate: 9.91, HR high-risk: 7.29, p < 0.01). Gross total resections decreased the risk of local tumor progression (HR gross total resection: 0.19, p < 0.01). The comparison of 1p status and integrated risk groups (low vs. intermediate/high) revealed nearly identical local control rates within their respective subgroups. In summary, only around 50% of WHO 2021 grade 2 meningiomas have an intermediate risk profile. Integrated molecular risk stratification is crucial to guide the management of patients with grade 2 tumors and should be routinely applied to avoid over- and undertreatment, especially concerning the use of adjuvant radiotherapy.

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Section: Discussionsupporting

confidence: 92%

Clinical implications of DNA methylation-based integrated classification of histologically defined grade 2 meningiomas

Ehret,

Perez,

Teichmann

et al. 2024

acta neuropathol commun

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“…However, due to the limited number of WHO G3 cases and cases with residual disease with adequate molecular information available, further analysis on these subgroups could not be performed and larger prospective cohorts are advocated. 49 …”

Section: Discussionmentioning

confidence: 99%

Radiotherapy intensification for atypical and malignant meningiomas: A systematic review

Gaito,

Goyal,

Rieu

et al. 2023

Neuro-Oncology Practice

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Background The outcomes of non-benign (WHO Grade 2 and 3) meningiomas are suboptimal and radiotherapy (RT) dose intensification strategies have been investigated. The purpose of this review is to report on clinical practice and outcomes with particular attention to RT doses and techniques. Methods The PICO criteria (Population, Intervention, Comparison and Outcomes) were used to frame the research question, directed at outlining the clinical outcomes in patients with G2-3 meningiomas treated with radiotherapy (RT). The same search strategy was run in Embase and MEDLINE and, after deduplication, returned 1807 records. These were manually screened for relevance and 25 were included. Results Tumour outcomes and toxicities are not uniformly reported in the selected studies since different endpoints and time points have been used by different authors. Many risk factors for worse outcomes are described, the most common being suboptimal RT. This includes no or delayed RT, low doses, older techniques. A positive association between RT dose and progression-free survival (PFS) has been highlighted by analysing the studies in this review (10/25) that report the same endpoint (5y-PFS). Conclusion This literature review has shown that standard practice RT leads to suboptimal tumour control rates in G2-3 meningiomas, with a significant proportion of disease recurring after a relatively short follow-up. Randomised controlled trials are needed in this setting to define the optimal RT approach. Given the increasing data to suggest a benefit of higher RT doses for high-risk meningiomas, novel RT technologies with highly conformal dose distributions are preferential to achieve optimal target coverage and organs at risk (OARs) sparing.

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Ein 34-Genexpressionsbiomarker zur Prädiktion des onkologischen Outcomes und des Therapieansprechens nach Bestrahlung bei Meningeomen

Deng,

Sahm,

Debus

et al. 2024

Strahlenther Onkol

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Independent prognostic impact of DNA methylation class and chromosome 1p loss in WHO grade 2 and 3 meningioma undergoing adjuvant high-dose radiotherapy: comprehensive molecular analysis of EORTC 22042–26042

Cited by 7 publications

References 11 publications

Clinical implications of DNA methylation-based integrated classification of histologically defined grade 2 meningiomas

Clinical implications of DNA methylation-based integrated classification of histologically defined grade 2 meningiomas

Radiotherapy intensification for atypical and malignant meningiomas: A systematic review

Ein 34-Genexpressionsbiomarker zur Prädiktion des onkologischen Outcomes und des Therapieansprechens nach Bestrahlung bei Meningeomen

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