新诊断的异柠檬酸脱氢酶野生型脑胶质瘤分子亚群的切除阈值。

Extent of Resection Thresholds in Molecular Subgroups of Newly Diagnosed Isocitrate Dehydrogenase-Wildtype Glioblastoma.

机构信息

Vivian L. Smith Department of Neurosurgery, McGovern Medical School, the University of Texas Health Science Center at Houston, Houston , Texas , USA.

Ohisama Neurosurgical and Dental Clinic, Hiroshima , Japan.

出版信息

Neurosurgery. 2024 Oct 1;95(4):932-940. doi: 10.1227/neu.0000000000002964. Epub 2024 Apr 30.

Abstract

BACKGROUND AND OBJECTIVES

Maximizing the extent of resection (EOR) improves outcomes in glioblastoma (GBM). However, previous GBM studies have not addressed the EOR impact in molecular subgroups beyond IDH1/IDH2 status. In the current article, we evaluate whether EOR confers a benefit in all GBM subtypes or only in particular molecular subgroups.

METHODS

A retrospective cohort of newly diagnosed GBM isocitrate dehydrogenase (IDH)-wildtype undergoing resection were prospectively included in a database (n = 138). EOR and residual tumor volume (RTV) were quantified with semiautomated software. Formalin-fixed paraffin-embedded tumor tissues were analyzed by targeted next-generation sequencing. The association between recurrent genomic alterations and EOR/RTV was evaluated using a recursive partitioning analysis to identify thresholds of EOR or RTV that may predict survival. The Kaplan-Meier methods and multivariable Cox proportional hazards regression methods were applied for survival analysis.

RESULTS

Patients with EOR ≥88% experienced 44% prolonged overall survival (OS) in multivariable analysis (hazard ratio: 0.56, P = .030). Patients with alterations in the TP53 pathway and EOR <89% showed reduced OS compared to TP53 pathway altered patients with EOR>89% (10.5 vs 18.8 months; HR: 2.78, P = .013); however, EOR/RTV was not associated with OS in patients without alterations in the TP53 pathway. Meanwhile, in all patients with EOR <88%, PTEN -altered had significantly worse OS than PTEN -wildtype (9.5 vs 15.4 months; HR: 4.53, P < .001).

CONCLUSION

Our results suggest that a subset of molecularly defined GBM IDH-wildtype may benefit more from aggressive resections. Re-resections to optimize EOR might be beneficial in a subset of molecularly defined GBMs. Molecular alterations should be taken into consideration for surgical treatment decisions in GBM IDH-wildtype.

摘要

背景与目的

最大限度地切除肿瘤(EOR)可改善胶质母细胞瘤(GBM)的预后。然而,以前的 GBM 研究并未针对 IDH1/IDH2 状态以外的分子亚组探讨 EOR 的影响。在本研究中,我们评估 EOR 是否对所有 GBM 亚型都有益,还是仅对特定的分子亚组有益。

方法

我们前瞻性地纳入了一个数据库中接受切除手术的新诊断为异柠檬酸脱氢酶(IDH)野生型 GBM 的回顾性队列(n=138)。使用半自动软件来量化 EOR 和残留肿瘤体积(RTV)。对福尔马林固定石蜡包埋的肿瘤组织进行靶向二代测序分析。采用递归分区分析评估复发性基因组改变与 EOR/RTV 之间的关系,以确定可能预测生存的 EOR 或 RTV 阈值。采用 Kaplan-Meier 方法和多变量 Cox 比例风险回归方法进行生存分析。

结果

在多变量分析中,EOR≥88%的患者总生存(OS)延长 44%(风险比:0.56,P=.030)。与 EOR>89%的 TP53 通路改变患者相比,EOR<89%且 TP53 通路改变的患者 OS 降低(10.5 与 18.8 个月;HR:2.78,P=.013);然而,EOR/RTV 与 TP53 通路未改变的患者的 OS 无关。同时,在所有 EOR<88%的患者中,PTEN 改变的患者 OS 明显差于 PTEN 野生型患者(9.5 与 15.4 个月;HR:4.53,P<.001)。

结论

我们的结果表明,一组特定的分子定义的 IDH 野生型 GBM 可能从积极的切除中获益更多。为了优化 EOR 进行再次切除可能对一组特定的分子定义的 GBM 有益。在 IDH 野生型 GBM 中,应考虑分子改变来制定手术治疗决策。

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