School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK.
Department of Neurosurgery, King's College Hospital, London, UK.
Acta Neurochir (Wien). 2024 Oct 5;166(1):394. doi: 10.1007/s00701-024-06300-x.
The methylation of the O6-Methylguanine-DNA Methyltransferase (MGMT) promoter is a valid biomarker for predicting response to therapy with alkylating agents and, independently, prognosis in IDH-wildtype(IDH-w) glioblastoma. We aim to study the impact of its methylation in overall survival of the unresectable IDH-w glioblastoma undergoing biopsy and systemic treatment.
We collected six-year retrospective (2017-2023) data at a quaternary neurosurgery center for patients undergoing biopsy as the only surgical procedure for an unresectable IDH wildtype glioblastoma. Data was collected from patient records including neuro-oncology multidisciplinary team meeting (MDT) documentation. Patients were grouped into categories according to different types of treatment received after biopsy (no treatment, chemotherapy (CT), radiotherapy (RT), chemoradiotherapy (CRT), chemoradiotherapy with adjuvant temozolomide (CRT with adjuvant TMZ), EORTC-NCIC protocol followed by second line treatment) and according to methylation status (unmethylated (< 5%), borderline methylated (5-15%) and strongly methylated (> 15%)). Survival analysis was performed.
166 glioblastoma IDH wildtype patients were included in the study with mean age of 62.5 years (M: F = 1.5: 1). 70 (49.3%) patients had unmethylated MGMT status (< 5%), 29 (20.4%) patients had borderline methylated MGMT status (5-15%) and 43 (30.2%) patients had methylated MGMT status (> 15%). 36 (25.3%) patients did not receive any treatment post biopsy, 13 (9.1%) received CT only, 27 (19%) RT only, 12 (8.4%) CRT, 33 (23.2%) CRT with adjuvant TMZ, whereas 21 (14.7%) received EORTC-NCIC protocol along with second line treatment. In biopsy only group, there was no notable difference in survival outcomes among the different methylation statuses. For biopsy and any-other-form-of-treatment methylated groups showed a distinct trend of better survival compared to the borderline or unmethylated groups. Overall, methylated patients had better survival as compared to unmethylated or borderline groups.
Methylated MGMT status are predictors for better overall survival in unresectable IDH wildtype glioblastoma patients undergoing biopsy and treatment regardless of the treatment modality.
O6-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）启动子的甲基化是预测烷基化剂治疗反应和 IDH 野生型（IDH-w）胶质母细胞瘤预后的有效生物标志物。我们旨在研究在接受活检和全身治疗的不可切除的 IDH-w 胶质母细胞瘤中，其甲基化对总生存期的影响。
我们在一家四级神经外科中心收集了六年的回顾性（2017-2023 年）数据，这些数据来自于为不可切除的 IDH 野生型胶质母细胞瘤患者进行活检的患者。数据来自于患者记录，包括神经肿瘤多学科团队会议（MDT）记录。根据活检后接受的不同治疗类型（无治疗、化疗（CT）、放疗（RT）、放化疗（CRT）、放化疗联合辅助替莫唑胺（CRT 联合辅助 TMZ）、EORTC-NCIC 方案后二线治疗）和甲基化状态（未甲基化（<5%）、边界甲基化（5-15%）和强甲基化（>15%））将患者分为不同类别。进行生存分析。
本研究共纳入 166 例 IDH 野生型胶质母细胞瘤患者，平均年龄为 62.5 岁（M：F=1.5:1）。70 例（49.3%）患者的 MGMT 状态为未甲基化（<5%），29 例（20.4%）患者的 MGMT 状态为边界甲基化（5-15%），43 例（30.2%）患者的 MGMT 状态为强甲基化（>15%）。36 例（25.3%）患者活检后未接受任何治疗，13 例（9.1%）仅接受 CT，27 例（19%）仅接受 RT，12 例（8.4%）接受 CRT，33 例（23.2%）接受 CRT 联合辅助 TMZ，21 例（14.7%）接受 EORTC-NCIC 方案联合二线治疗。在仅活检组中，不同甲基化状态之间的生存结果无显著差异。在活检和其他任何形式的治疗甲基化组中，与边界或未甲基化组相比，生存趋势明显更好。总体而言，甲基化患者的总生存期优于未甲基化或边界甲基化患者。
在接受活检和治疗的不可切除的 IDH 野生型胶质母细胞瘤患者中，MGMT 甲基化状态是预测总生存期的指标，与治疗方式无关。
