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异柠檬酸脱氢酶 1 突变型恶性星形细胞瘤更适合手术切除,且与最大程度手术切除相关的生存获益更大。

IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection.

机构信息

Corresponding author: Daniel P. Cahill, MD, PhD, Department of Neurosurgery, 32 Fruit Street - Yawkey 9E, Massachusetts General Hospital, Brain Tumor Center/Neuro-Oncology, Boston, MA 02114.

出版信息

Neuro Oncol. 2014 Jan;16(1):81-91. doi: 10.1093/neuonc/not159. Epub 2013 Dec 4.

Abstract

BACKGROUND

IDH1 gene mutations identify gliomas with a distinct molecular evolutionary origin. We sought to determine the impact of surgical resection on survival after controlling for IDH1 status in malignant astrocytomas-World Health Organization grade III anaplastic astrocytomas and grade IV glioblastoma.

METHODS

Clinical parameters including volumetric assessment of preoperative and postoperative MRI were recorded prospectively on 335 malignant astrocytoma patients: n = 128 anaplastic astrocytomas and n = 207 glioblastoma. IDH1 status was assessed by sequencing and immunohistochemistry.

RESULTS

IDH1 mutation was independently associated with complete resection of enhancing disease (93% complete resections among mutants vs 67% among wild-type, P < .001), indicating IDH1 mutant gliomas were more amenable to resection. The impact of residual tumor on survival differed between IDH1 wild-type and mutant tumors. Complete resection of enhancing disease among IDH1 wild-type tumors was associated with a median survival of 19.6 months versus 10.7 months for incomplete resection; however, no survival benefit was observed in association with further resection of nonenhancing disease (minimization of total tumor volume). In contrast, IDH1 mutants displayed an additional survival benefit associated with maximal resection of total tumor volume (median survival 9.75 y for >5 cc residual vs not reached for <5 cc, P = .025).

CONCLUSIONS

The survival benefit associated with surgical resection differs based on IDH1 genotype in malignant astrocytic gliomas. Therapeutic benefit from maximal surgical resection, including both enhancing and nonenhancing tumor, may contribute to the better prognosis observed in the IDH1 mutant subgroup. Thus, individualized surgical strategies for malignant astrocytoma may be considered based on IDH1 status.

摘要

背景

IDH1 基因突变可鉴定出具有独特分子进化起源的神经胶质瘤。我们试图在控制恶性星形细胞瘤-WHO 三级间变性星形细胞瘤和四级胶质母细胞瘤的 IDH1 状态后,确定手术切除对生存的影响。

方法

前瞻性地记录了 335 例恶性星形细胞瘤患者的临床参数,包括术前和术后 MRI 的体积评估:n = 128 例间变性星形细胞瘤和 n = 207 例胶质母细胞瘤。通过测序和免疫组织化学评估 IDH1 状态。

结果

IDH1 突变与增强病变的完全切除独立相关(突变体中 93%的完全切除率与野生型相比为 67%,P <.001),表明 IDH1 突变型神经胶质瘤更适合切除。残留肿瘤对生存的影响在 IDH1 野生型和突变型肿瘤之间存在差异。IDH1 野生型肿瘤中增强病变的完全切除与不完全切除的中位生存期相比为 19.6 个月与 10.7 个月;然而,在非增强病变(总肿瘤体积最小化)进一步切除方面并未观察到生存获益。相比之下,IDH1 突变体表现出与总肿瘤体积最大切除相关的额外生存获益(残余>5cc 时的中位生存期为 9.75 年,而残余<5cc 时未达到,P =.025)。

结论

在恶性星形胶质细胞瘤中,手术切除与 IDH1 基因型相关的生存获益不同。最大程度的手术切除,包括增强和非增强肿瘤,可能有助于改善 IDH1 突变亚组的预后。因此,可能需要根据 IDH1 状态考虑对恶性星形细胞瘤的个体化手术策略。

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