Chehade Georges, Lawson Tévi Morel, Lelotte Julie, Daoud Lina, Di Perri Dario, Whenham Nicolas, Duprez Thierry, Tajeddine Nicolas, Tissir Fadel, Raftopoulos Christian
Department of Neurosurgery, Saint-Luc University Hospital, Université Catholique de Louvain, 10 Hippocrate Av, 1St Floor, Woluwe-Saint-Lambert, 1200, Brussels, Belgium.
Developmental Neurobiology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium.
Acta Neurochir (Wien). 2023 Apr;165(4):1075-1085. doi: 10.1007/s00701-023-05544-3. Epub 2023 Mar 15.
Glioblastoma is an aggressive tumor that has a dismal prognosis even with multimodal treatment. However, some patients survive longer than expected. The objective of this study was to revisit patients diagnosed with glioblastoma according to the 2021 WHO classification and analyze clinical and molecular characteristics associated with long-term survival (LTS).
We retrospectively analyzed 120 IDH-wildtype glioblastomas operated on at our institution between 2013 and 2018. We divided them into LTS patients, surviving more than 3 years, and non-LTS patients, and then compared their features. Additionally, we performed DNA methylation-based brain tumor classification in LTS patients.
Sixteen patients were long-term survivors. Age < 70 years, MGMT promoter methylation, extent of resection ≥ 95%, and administration of radiochemotherapy were associated with LTS (P = 0.005, P < 0.001, P = 0.048, and P = 0.008, respectively). In addition, when these factors were combined, the probability of LTS was 74% (95% CI: 62--84). The methylome analysis confirmed the diagnosis of glioblastoma in the majority of the tested LTS patients. Regarding subtypes, 29% of cases were mesenchymal (MES), 43% were RTK1, and 29% were RTK2. Interestingly, RTK1 and RTK2 cases tended to have longer overall survival than MES cases (P = 0.057). Moreover, the only tested LTS patient with an unmethylated MGMT promoter had an "adult-type diffuse high-grade glioma, IDH-wildtype, subtype E" rather than a glioblastoma. This tumor was characterized by multinucleated giant cells and a somatic mutation in POLE.
We suggest that glioblastoma patients with a combination of favorable prognostic factors can achieve LTS in 74% of cases. In addition, methylome analysis is important to ascertain the type of glioma in LTS patients, especially when the MGMT promoter is unmethylated.
胶质母细胞瘤是一种侵袭性肿瘤，即使采用多模式治疗，预后也很差。然而，一些患者存活时间比预期长。本研究的目的是重新评估根据2021年世界卫生组织分类诊断为胶质母细胞瘤的患者，并分析与长期生存（LTS）相关的临床和分子特征。
我们回顾性分析了2013年至2018年在我院接受手术的120例异柠檬酸脱氢酶（IDH）野生型胶质母细胞瘤患者。我们将他们分为存活超过3年的LTS患者和非LTS患者，然后比较他们的特征。此外，我们对LTS患者进行了基于DNA甲基化的脑肿瘤分类。
16例患者为长期存活者。年龄<70岁、O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化、切除范围≥95%以及放化疗的应用与LTS相关（P分别为0.005、<0.001、0.048和0.008）。此外，当这些因素综合起来时，LTS的概率为74%（95%置信区间：62-84）。甲基化组分析在大多数测试的LTS患者中证实了胶质母细胞瘤的诊断。关于亚型，29%的病例为间充质型（MES），43%为受体酪氨酸激酶1型（RTK1），29%为受体酪氨酸激酶2型（RTK2）。有趣的是，RTK1和RTK2病例的总生存期往往比MES病例长（P=0.057）。此外，唯一检测的MGMT启动子未甲基化的LTS患者患有“成人型弥漫性高级别胶质瘤，IDH野生型，E亚型”而非胶质母细胞瘤。该肿瘤的特征是多核巨细胞和POLE基因的体细胞突变。
我们认为，具有有利预后因素组合的胶质母细胞瘤患者在74%的病例中可实现LTS。此外，甲基化组分析对于确定LTS患者的胶质瘤类型很重要，尤其是当MGMT启动子未甲基化时。
