Neth Bryan J, Kraft Robert M, Eschbacher Kathryn L, Johnson Derek R, Decker Paul A, Sener Ugur T, Uhm Joon H, Ruff Michael W, Schwartz Jonathan D, Breen William G, Maqbool Muhammad Asad, Daniels David J, Burns Terry C, Parney Ian F, Raghunathan Aditya, Kizilbash Sani H
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Department of Medical Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
J Neurooncol. 2025 Jun;173(2):369-381. doi: 10.1007/s11060-025-04994-2. Epub 2025 Mar 6.
Primary gliomas arising within midline structures of the central nervous system are associated with a worse prognosis compared with hemispheric gliomas. In adults, compared to their pediatric counterparts, adult midline gliomas are not as clearly characterized on the clinical behavior, prognostic factors, and treatment approaches for these diseases.
This retrospective cohort assessed all adult (≥ 18 years) patients from our institution with diffuse gliomas arising from midline structures at time of diagnosis (2014-2020). Molecular features characterized using immunohistochemistry, targeted next-generation sequencing, and chromosomal microarray analysis were collected. Patient characteristics were compared across groups using analysis of variance, Kruskal-Wallis, and the chi-square test as appropriate. Cumulative progression-free survival (PFS) and overall survival (OS) probabilities were estimated using the Kaplan-Meier method. Comparisons across groups were made using the log rank test.
79 patients were included in analysis, with a median follow-up of 22.5 months (range, 0.6-123). The mean age at diagnosis was 44.5 years (range, 19.4-76.4), and 51% (n = 40) were female. Thalamus/basal ganglia was the most common primary tumor location (47%), followed by the brainstem (30%), and cerebellum (23%). For the entire cohort, median PFS was 11.5 months (95% CI 9.4-20.1), and median OS was 25.5 months (95% CI 22.0-38.2). We grouped primary tumor types into four distinct diagnostic entities based on integrated histological and molecular features, which had survival differences (log-rank p = 0.007)-diffuse midline glioma, H3 K27-altered (17% with median OS 19.4 months); astrocytoma, IDH-wild type, not otherwise specified (42% with median OS 25.5 months); glioblastoma, IDH-wild type (24% with median OS 11.0 months); and astrocytoma, IDH-mutant (18% with OS 63.3 months). There were no cases of IDH-mutant tumors in the thalamus/basal ganglia. IDH-mutant tumors had better prognosis (OS: IDH-mutant 63.3 months, IDH-wild type 22.5 months, log-rank p = 0.003). Tumor enhancement and diffusion restriction at initial diagnosis was associated with worse prognosis (OS: enhancing 22.0 months, non-enhancing 64.5 months, log-rank p < 0.001; OS: restriction 20.3 months, no restriction 30.6 months, log-rank p = 0.028).
There is significant molecular heterogeneity between midline gliomas which has prognostic implications. These findings emphasize the need to molecularly characterize these tumors to facilitate personalized treatment approaches.
与半球胶质瘤相比，起源于中枢神经系统中线结构的原发性胶质瘤预后更差。在成人中，与儿童中线胶质瘤相比，成人中线胶质瘤在这些疾病的临床行为、预后因素和治疗方法方面的特征并不那么明确。
这项回顾性队列研究评估了我院所有诊断时（2014 - 2020年）起源于中线结构的弥漫性胶质瘤的成年（≥18岁）患者。收集了使用免疫组织化学、靶向二代测序和染色体微阵列分析所表征的分子特征。根据情况，使用方差分析、Kruskal - Wallis检验和卡方检验对各组患者特征进行比较。使用Kaplan - Meier方法估计累积无进展生存期（PFS）和总生存期（OS）概率。使用对数秩检验进行组间比较。
79例患者纳入分析，中位随访时间为22.5个月（范围0.6 - 123个月）。诊断时的平均年龄为44.5岁（范围19.4 - 76.4岁），51%（n = 40）为女性。丘脑/基底节是最常见的原发肿瘤部位（47%），其次是脑干（30%）和小脑（23%）。对于整个队列，中位PFS为11.5个月（95%CI 9.4 - 20.1），中位OS为25.5个月（95%CI 22.0 - 38.2）。根据综合组织学和分子特征，我们将原发性肿瘤类型分为四个不同的诊断实体，它们的生存期存在差异（对数秩p = 0.007）——弥漫性中线胶质瘤，H3 K27改变（17%，中位OS 19.4个月）；星形细胞瘤，IDH野生型，未另作说明（42%，中位OS 25.5个月）；胶质母细胞瘤，IDH野生型（24%，中位OS 11.0个月）；以及星形细胞瘤，IDH突变型（18%，OS 63.3个月）。丘脑/基底节未发现IDH突变型肿瘤病例。IDH突变型肿瘤预后较好（OS：IDH突变型63.3个月，IDH野生型22.5个月，对数秩p = 0.003）。初始诊断时肿瘤强化和弥散受限与预后较差相关（OS：强化型22.0个月，非强化型64.5个月，对数秩p < 0.001；OS：受限型20.3个月，无受限型30.6个月，对数秩p = 0.028）。
中线胶质瘤之间存在显著的分子异质性，具有预后意义。这些发现强调了对这些肿瘤进行分子特征分析以促进个性化治疗方法的必要性。
