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手术切除复发性胶质母细胞瘤中存活肿瘤与治疗效果的组织病理学定量。

Histopathologic quantification of viable tumor versus treatment effect in surgically resected recurrent glioblastoma.

机构信息

Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

出版信息

J Neurooncol. 2019 Jan;141(2):421-429. doi: 10.1007/s11060-018-03050-6. Epub 2018 Nov 16.

DOI:10.1007/s11060-018-03050-6
PMID:30446903
Abstract

PURPOSE

The prognostic impact of the histopathologic features of recurrent glioblastoma surgical specimens is unknown. We sought to determine whether key histopathologic characteristics in glioblastoma tumors resected after chemoradiotherapy are associated with overall survival (OS).

METHODS

The following characteristics were quantified in recurrent glioblastoma specimens at our institution: extent of viable tumor (accounting for % of specimen comprised of tumor and tumor cellularity), mitoses per 10 high-power fields (0, 1-10, > 10), Ki-67 proliferative index (0-100%), hyalinization (0-6; none to extensive), rarefaction (0-6), hemosiderin (0-6), and % of specimen comprised of geographic necrosis (0-100%; converted to 0-6 scale). Variables associated with OS in univariate analysis, as well as age, eastern cooperative oncology group performance status (ECOG PS), extent of repeat resection, time from initial diagnosis to repeat surgery, and O-methylguanine-DNA methyltransferase promoter methylation, were included in a multivariable Cox proportional hazards model.

RESULTS

37 specimens were assessed. In a multivariate model, high Ki-67 proliferative index was the only histopathologic characteristic associated with worse OS following repeat surgery for glioblastoma (hazard ratio (HR) 1.3, 95% CI 1.1-1.5, p = 0.003). Shorter time interval from initial diagnosis to repeat surgery (HR 1.11, 95% CI 1.02-1.21, p = 0.016) and ECOG PS ≥ 2 (HR 4.19, 95% CI 1.72-10.21, p = 0.002) were also independently associated with inferior OS.

CONCLUSION

In patients with glioblastoma undergoing repeat resection following chemoradiotherapy, high Ki-67 index in the recurrent specimen, short time to recurrence, and poor PS are independently associated with worse OS. Histopathologic quantification of viable tumor versus therapy-related changes has limited prognostic influence.

摘要

目的

复发性胶质母细胞瘤手术标本的组织病理学特征对预后的影响尚不清楚。我们旨在确定在放化疗后切除的胶质母细胞瘤肿瘤中关键的组织病理学特征是否与总生存(OS)相关。

方法

在我们机构的复发性胶质母细胞瘤标本中定量评估了以下特征:存活肿瘤的程度(占标本中肿瘤和肿瘤细胞密度的百分比)、每 10 高倍视野的有丝分裂数(0、1-10、>10)、Ki-67 增殖指数(0-100%)、玻璃样变性(0-6;无至广泛)、稀疏(0-6)、含铁血黄素(0-6)以及标本中包含的地理性坏死的比例(0-100%;转换为 0-6 标度)。单变量分析中与 OS 相关的变量,以及年龄、东部合作肿瘤学组表现状态(ECOG PS)、重复切除的程度、从初始诊断到重复手术的时间以及 O-甲基鸟嘌呤-DNA 甲基转移酶启动子甲基化,均纳入多变量 Cox 比例风险模型。

结果

共评估了 37 个标本。在多变量模型中,高 Ki-67 增殖指数是复发性胶质母细胞瘤手术后 OS 较差的唯一组织病理学特征(风险比(HR)1.3,95%置信区间(CI)1.1-1.5,p=0.003)。从初始诊断到重复手术的时间间隔较短(HR 1.11,95%CI 1.02-1.21,p=0.016)和 ECOG PS≥2(HR 4.19,95%CI 1.72-10.21,p=0.002)也与较差的 OS 独立相关。

结论

在接受放化疗后行重复切除的胶质母细胞瘤患者中,复发性标本中 Ki-67 指数高、复发时间短和 PS 差与 OS 较差独立相关。存活肿瘤与治疗相关变化的组织病理学定量分析对预后的影响有限。

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