Morshed Ramin A, Nguyen Minh P, Choudhury Abrar, Al-Adli Nadeem N, Magill Stephen T, Haddad Alexander F, Mirchia Kanish, Lucas Calixto-Hope G, Theodosopoulos Philip V, McDermott Michael W, Chen William C, Raleigh David R
Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Department of Radiation Oncology, University of California, San Francisco, San Francisco, California, USA.
Neurosurgery. 2025 Jan 7. doi: 10.1227/neu.0000000000003324.
Extent of resection (EOR) is prognostic for meningioma outcomes. DNA methylation profiling can shed light on biological drivers and therapeutic vulnerabilities. The goal of this study was to re-evaluate the impact of EOR on clinical outcomes across meningioma DNA methylation groups.
Patients with sporadic meningiomas who underwent resection from a multicenter, international cohort were retrospectively reviewed. Gross vs subtotal resection (GTR vs STR, respectively) was determined based on postoperative MRI. The Kaplan-Meier method, log-rank statistics, and multivariable Cox proportional hazard analyses were performed to evaluate the impact of EOR on local freedom from recurrence (LFFR) and overall survival (OS).
In total, 587 patients (Male: 195, Female: 392) underwent 644 surgeries for intracranial meningioma (GTR: 438, STR: 206), with 124 surgeries (19.3%) for recurrent intracranial meningiomas. The cohort included 375 (58.2%) World Health Organization (WHO) Grade 1, 202 (31.4%) WHO Grade 2, and 67 (10.4%) WHO Grade 3 meningiomas based on histological criteria. DNA methylation profiling was used to categorize meningiomas as Merlin-intact (N = 214, 33.2%), Immune-enriched (N = 236, 36.6%), or Hypermitotic (N = 194, 30.1%). GTR was associated with longer LFFR across all meningioma DNA methylation groups (Merlin-intact P < .0001; Immune-enriched P = .013; Hypermitotic P = .001) and was associated with longer OS for Hypermitotic meningiomas (P = .0022). In multivariable Cox proportional hazard analyses, EOR was significantly associated with LFFR across all DNA methylation groups and WHO grades but was significantly associated with OS only for Hypermitotic meningiomas (hazard ratio [GTR vs STR] 0.64, 95% CI 0.43-0.97, P = .034).
MRI-defined GTR is associated with improved LFFR across all meningioma DNA methylation groups and improved OS for patients with Hypermitotic meningiomas. These data continue to support maximal safe resection when feasible and demonstrate how molecular classification systems complement rather than supersede the prognostic impact of surgery.
切除范围（EOR）对脑膜瘤的预后具有预测价值。DNA甲基化谱分析有助于揭示生物学驱动因素和治疗弱点。本研究的目的是重新评估EOR对不同脑膜瘤DNA甲基化组临床结局的影响。
对来自多中心国际队列的接受手术切除的散发性脑膜瘤患者进行回顾性分析。根据术后MRI确定大体切除与次全切除（分别为GTR和STR）。采用Kaplan-Meier法、对数秩统计和多变量Cox比例风险分析来评估EOR对局部无复发生存率（LFFR）和总生存期（OS）的影响。
共有587例患者（男性195例，女性392例）接受了644次颅内脑膜瘤手术（GTR：438例，STR：206例），其中124次手术（19.3%）为复发性颅内脑膜瘤。根据组织学标准，该队列包括375例（58.2%）世界卫生组织（WHO）1级、202例（31.4%）WHO 2级和67例（10.4%）WHO 3级脑膜瘤。DNA甲基化谱分析用于将脑膜瘤分类为Merlin完整型（N = 214，33.2%）、免疫富集型（N = 236，36.6%）或有丝分裂活跃型（N = 194，30.1%）。在所有脑膜瘤DNA甲基化组中，GTR均与更长的LFFR相关（Merlin完整型P <.0001；免疫富集型P =.013；有丝分裂活跃型P =.001），并且在有丝分裂活跃型脑膜瘤中与更长的OS相关（P =.0022）。在多变量Cox比例风险分析中，EOR在所有DNA甲基化组和WHO分级中均与LFFR显著相关，但仅在有丝分裂活跃型脑膜瘤中与OS显著相关（风险比[GTR与STR] 0.64，95% CI 0.43 - 0.97，P =.034）。
MRI定义的GTR与所有脑膜瘤DNA甲基化组中改善的LFFR相关，并且在有丝分裂活跃型脑膜瘤患者中与改善的OS相关。这些数据继续支持在可行时进行最大安全切除，并证明了分子分类系统如何补充而非取代手术的预后影响。
