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初诊进展期胶质母细胞瘤患者的生存与异柠檬酸脱氢酶 1 基因(IDH1)突变状态无关。

Survival in patients with glioblastoma at a first progression does not correlate with isocitrate dehydrogenase (IDH)1 gene mutation status.

机构信息

Department of Neurosurgery, Kyorin University Faculty of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo.

Department of Neurosurgery, The Japanese Red Cross Medical Center, 4-1-20 Hiroo, Shibuya, Tokyo.

出版信息

Jpn J Clin Oncol. 2021 Jan 1;51(1):45-53. doi: 10.1093/jjco/hyaa162.

Abstract

BACKGROUNDS

Mutations in the isocitrate dehydrogenase (IDH)1 gene are favourable prognostic factors in newly diagnosed diffuse gliomas, whereas it remains controversial in the recurrent glioblastoma setting.

METHODS

A total of 171 patients with newly diagnosed glioblastoma, either 'primary' glioblastoma or 'secondary' glioblastoma, treated at Kyorin University Hospital or Japanese Red Cross Medical Center from 2000 to 2015 were included. Patients with confirmed IDH1 status and O6-methylguanine-DNA methyltransferase promoter methylation status were retrospectively analysed for overall survival from the initial diagnosis (n = 147) and after the first progression (n = 122).

RESULTS

IDH1 mutation but not IDH2 was noted in 19 of 147 patients with glioblastoma (12.9%). In patients with 'primary' glioblastoma (n = 136), median overall survival after the first progression was 13.5 and 10.5 months for mutant IDH1 and wild-type IDH1 glioblastoma, respectively (P = 0.747). Multivariate analysis revealed O6-methylguanine-DNA methyltransferase promoter methylation, and Karnofsky Performance status 60 or higher, were independent prognostic factors for better overall survival after the first progression. When 'primary' glioblastoma and 'secondary' glioblastoma were combined, median overall survival from the first progression was not significantly different between the mutant IDH1 group (10.1 months) and wild-type IDH1 group (10.5 months) (P = 0.559), whereas median overall survival from the initial diagnosis was significantly different (47.5 months vs.18.3 months, respectively; P = 0.035).

CONCLUSIONS

These results suggest that IDH1 mutation may not be a prognostic factor for survival at the first progression of patients with 'primary' glioblastoma and pretreated 'secondary' glioblastoma, and further warrant investigation in prospective studies.

摘要

背景

异柠檬酸脱氢酶(IDH)1 基因突变是新诊断弥漫性神经胶质瘤的有利预后因素,而在复发性胶质母细胞瘤中仍存在争议。

方法

共纳入 171 例 2000 年至 2015 年在庆应义塾大学医院或日本红十字医疗中心治疗的新诊断为胶质母细胞瘤的患者,包括“原发性”胶质母细胞瘤或“继发性”胶质母细胞瘤。对有明确 IDH1 状态和 O6-甲基鸟嘌呤-DNA 甲基转移酶启动子甲基化状态的患者进行回顾性分析,以评估从初始诊断(n=147)和第一次进展后(n=122)的总生存期。

结果

147 例胶质母细胞瘤患者中有 19 例(12.9%)存在 IDH1 突变,但不存在 IDH2 突变。在“原发性”胶质母细胞瘤患者(n=136)中,突变型 IDH1 和野生型 IDH1 胶质母细胞瘤患者在第一次进展后的中位总生存期分别为 13.5 个月和 10.5 个月(P=0.747)。多变量分析显示 O6-甲基鸟嘌呤-DNA 甲基转移酶启动子甲基化和 Karnofsky 表现状态 60 或更高是第一次进展后总生存期更好的独立预后因素。当“原发性”胶质母细胞瘤和“继发性”胶质母细胞瘤合并时,突变型 IDH1 组(10.1 个月)和野生型 IDH1 组(10.5 个月)从第一次进展后的中位总生存期无显著差异(P=0.559),而从初始诊断后的中位总生存期有显著差异(分别为 47.5 个月和 18.3 个月;P=0.035)。

结论

这些结果表明,IDH1 突变可能不是“原发性”胶质母细胞瘤和预处理“继发性”胶质母细胞瘤患者第一次进展时生存的预后因素,需要在前瞻性研究中进一步证实。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba50/7767982/3476072c3535/hyaa162f1.jpg

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