{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:33:27Z","timestamp":1792172007651,"version":"4.4.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012353","name":"DKTK","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012353","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002839","name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002839","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["acta neuropathol commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2009=\u2009100) were retrospectively analyzed. The median clinical and radiographic follow-up periods were 59.8 and 54.4\u00a0months. 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\u00a0months. 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, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). Gross total resections decreased the risk of local tumor progression (HR gross total resection: 0.19, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). 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.<\/jats:p>","DOI":"10.1186\/s40478-024-01739-6","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T14:02:28Z","timestamp":1715176948000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Clinical implications of DNA methylation-based integrated classification of histologically defined grade 2 meningiomas"],"prefix":"10.1186","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6177-1755","authenticated-orcid":false,"given":"Felix","family":"Ehret","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eil\u00eds","family":"Perez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Teichmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Meier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Geiler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosmas","family":"Zeus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Franke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8232-4994","authenticated-orcid":false,"given":"Siyer","family":"Roohani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Wasilewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Onken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Vajkoczy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonille","family":"Schweizer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7906-5629","authenticated-orcid":false,"given":"David","family":"Kaul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Capper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"issue":"Supplement_5","key":"1739_CR1","doi-asserted-by":"publisher","first-page":"v1","DOI":"10.1093\/neuonc\/noac202","volume":"24","author":"QT Ostrom","year":"2022","unstructured":"Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C, Barnholtz-Sloan JS (2022) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2015\u20132019. 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The other authors declare no conflicts of interest or competing interests pertinent to this work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"74"}}