The role of extent of resection, chemoradiation, and MGMT promoter methylation in overall survival in a large cohort of IDH-wildtype glioblastoma.

IF 3 2区医学 Q2 CLINICAL NEUROLOGY

Neurosurgical focus Pub Date : 2025-08-01 DOI:10.3171/2025.5.FOCUS25350

Megan Parker, Austin Carmichael, Antolin Serrano-Farias, Melanie Alfonzo Horowitz, Kristin J Redmond, Calixto-Hope G Lucas, Debraj Mukherjee, Youssef Comair, Chetan Bettegowda, Jordina Rincon-Torroella

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Abstract

Objective: Although MGMT promoter methylation, gross-total resection (GTR), and adjuvant chemoradiation therapy are known to independently improve clinical outcomes for patients with glioblastoma (GBM), their combined influence remains unclear. In the present study, the authors investigated the complementary role of these factors in GBM prognosis.

Methods: The 2022 National Cancer Database was queried for individuals with histologically confirmed IDH-wildtype GBM WHO grade 4 and available MGMT promoter methylation status data. Demographic, clinical, and treatment-related variables were analyzed. Kaplan-Meier survival and multivariate Cox proportional hazards analyses were conducted, stratified by MGMT promoter methylation and chemoradiation therapy status.

Results: A total of 27,858 patients were included in the analysis. Chemotherapy, radiation therapy, and MGMT promoter methylation status were independently associated with improved survival in the overall cohort (p < 0.001). In Kaplan-Meier analysis, MGMT promoter methylation was associated with improved overall survival for individuals who received standard chemoradiation therapy (p < 0.001) but not for individuals who did not receive chemoradiation therapy (p = 0.649). In the overall cohort, GTR was associated with a 40% improvement in overall survival relative to excisional biopsy (HR 0.633 [95% CI 0.52-0.77], p < 0.001) in multivariate analysis. In patients with MGMT promoter-methylated tumors, GTR was associated with a 70% (HR 0.30 [95% CI 0.12-0.71], p = 0.007) improvement in overall survival compared with excisional biopsy in those who did not receive chemoradiation therapy, but GTR did not significantly improve survival in those who received chemoradiation therapy (HR 0.97 [95% CI 0.54-1.73], p = 0.912). For patients with MGMT promoter-unmethylated tumors, GTR was associated with improved overall survival for both those who received chemoradiation therapy (HR 0.48 [95% CI 0.33-0.70], p < 0.001) and those who did not (HR 0.50 [95% CI 0.28-0.89], p = 0.018).

Conclusions: In this large registry study, the authors demonstrated that maximizing the extent of resection improves overall survival, especially for individuals with MGMT unmethylated GBM or those not receiving chemoradiation therapy. However, the impact of gross-total resection requires further investigation in patients with MGMT promoter-methylated GBM who receive adjuvant therapy. These findings support future studies exploring new diagnostic techniques for preoperative evaluation of MGMT methylation to aid surgical planning.

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在一大批idh野生型胶质母细胞瘤患者中，切除程度、放化疗和MGMT启动子甲基化在总生存率中的作用

目的：虽然已知MGMT启动子甲基化、总全切除（GTR）和辅助放化疗可以单独改善胶质母细胞瘤（GBM）患者的临床预后，但它们的综合影响尚不清楚。在本研究中，作者探讨了这些因素在GBM预后中的互补作用。方法：查询2022年国家癌症数据库中组织学证实的idh -野生型GBM （WHO 4级）患者和可用的MGMT启动子甲基化状态数据。分析人口统计学、临床和治疗相关变量。根据MGMT启动子甲基化和放化疗状态进行分层，进行Kaplan-Meier生存和多变量Cox比例风险分析。结果：共纳入27,858例患者。在整个队列中，化疗、放疗和MGMT启动子甲基化状态与生存率的提高独立相关（p < 0.001）。Kaplan-Meier分析显示，接受标准放化疗的患者MGMT启动子甲基化与总体生存率的提高相关（p < 0.001），而未接受放化疗的患者则无相关（p = 0.649）。在整个队列中，在多变量分析中，与切除活检相比，GTR与总生存率提高40%相关（HR 0.633 [95% CI 0.52-0.77], p < 0.001）。在MGMT启动子甲基化肿瘤患者中，与未接受放化疗的切除活检患者相比，GTR与70%的总生存率改善相关（HR 0.30 [95% CI 0.12-0.71], p = 0.007），但GTR未显着改善接受放化疗的患者的生存率（HR 0.97 [95% CI 0.54-1.73], p = 0.912）。对于MGMT启动子未甲基化的肿瘤患者，无论是接受放化疗的患者（HR 0.48 [95% CI 0.33-0.70], p < 0.001）还是未接受放化疗的患者（HR 0.50 [95% CI 0.28-0.89], p = 0.018）， GTR都与总生存率的提高相关。结论：在这项大型注册研究中，作者证明了最大程度的切除可提高总体生存率，特别是对于MGMT未甲基化的GBM患者或未接受放化疗的患者。然而，对于接受辅助治疗的MGMT启动子甲基化GBM患者，总切除的影响需要进一步研究。这些发现支持未来研究探索新的诊断技术，用于术前评估MGMT甲基化，以帮助手术计划。

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