IDH 野生型 (-wt) 状态是诊断胶质母细胞瘤 (GBM) 的先决条件；然而，具有低级别或间变形态的 IDH-wt 神经胶质瘤历来被排除在 GBM 试验之外，并且可能代表一个独特的预后实体。虽然烷化剂化疗可改善 IDH-wt GBM 和 IDH 突变胶质瘤的总生存期 (OS) 和无进展生存期 (PFS)，无论级别如何，但对于 IDH-wt 弥漫性组织学低级别胶质瘤的益处尚不清楚。对世界卫生组织 (WHO) 2-3 级神经胶质瘤（2009 年至今）的随机临床试验进行荟萃分析，使用具有逆方差的随机效应模型确定烷基化化疗对 IDH-wt 和 IDH-mutant 神经胶质瘤的影响我们确定了 6 项试验，涉及 1,204 名患者（430 名 IDH 野生型，774 名 IDH 突变型），这些试验评估了烷基化放化疗与单独放疗的比较，使我们能够进行重点分析在放疗中添加烷基化化疗的价值。对于 IDH-wt 肿瘤患者，烷化化疗联合放疗与改善 PFS 相关（HR：0.77 [95% CI 0.62-0.97]，P=.03），但与 OS 无关（HR：0.87 [95% CI 0.64-1.18] ]，P=.17)。对于 IDH 突变肿瘤患者，烷化化疗联合放疗改善了 OS（HR：0.52 [95%CI 0.42-0.64]，P<.001）和 PFS（HR=0.47 [95%CI 0.39-0.57]，P） <.001) 与单独放疗相比。对于有或没有 1p19q 编码缺失的 IDH 突变神经胶质瘤，获益程度相似。对于 IDH 突变神经胶质瘤患者，烷基化化疗可降低 48% 的死亡率和 53% 的进展率。 IDH-wt 弥漫性组织学低级别胶质瘤的最佳治疗仍有待确定，因为几乎没有证据支持烷基化化疗对 OS 有益。© 作者 2024。由牛津大学出版社代表神经学会出版肿瘤学。版权所有。如需商业重复使用，请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限均可通过我们网站文章页面上的“权限”链接通过我们的 RightsLink 服务获得 - 欲了解更多信息，请联系journals.permissions@oup.com。

IDH-wildtype (-wt) status is a pre-requisite for the diagnosis of glioblastoma (GBM); however, IDH-wt gliomas with low grade or anaplastic morphology have historically been excluded from GBM trials and may represent a distinct prognostic entity. While alkylating agent chemotherapy improves overall survival (OS) and progression-free survival (PFS) for IDH-wt GBM and also IDH-mutant gliomas, irrespective of grade, the benefit for IDH-wt diffuse histologic lower grade gliomas is unclear.We performed a meta-analysis of randomized clinical trials for World Health Organization (WHO) grade 2-3 gliomas (2009 to present) to determine the effect of alkylating chemotherapy on IDH-wt and -mutant gliomas using a random-effects model with inverse-variance pooling.We identified six trials with 1,204 patients (430 IDH-wt, 774 IDH-mutant) that evaluated alkylating chemoradiotherapy versus radiotherapy alone, allowing us to perform an analysis focused on the value of adding alkylating chemotherapy to radiotherapy. For patients with IDH-wt tumors, alkylating chemotherapy added to radiotherapy was associated with improved PFS (HR:0.77 [95%CI 0.62-0.97], P=.03) but not OS (HR:0.87 [95%CI 0.64-1.18], P=.17). For patients with IDH-mutant tumors, alkylating chemotherapy added to radiotherapy improved both OS (HR:0.52 [95%CI 0.42-0.64], P<.001) and PFS (HR=0.47 [95%CI 0.39-0.57], P<.001) compared to radiotherapy alone. The magnitude of benefit was similar for IDH-mutant gliomas with or without 1p19q-codeletion.Alkylating chemotherapy reduces mortality by 48% and progression by 53% for patients with IDH-mutant gliomas. Optimal management of IDH-wt diffuse histologic lower grade gliomas remains to be determined, as there is little evidence supporting an OS benefit from alkylating chemotherapy.© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.