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分子定义的低级别胶质瘤手术的影响:综合临床、影像学和分子分析。

The impact of surgery in molecularly defined low-grade glioma: an integrated clinical, radiological, and molecular analysis.

机构信息

Department of Neurology, Erasmus University Medical Center (Erasmus MC) Cancer Institute, Rotterdam, the Netherlands.

Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.

出版信息

Neuro Oncol. 2018 Jan 10;20(1):103-112. doi: 10.1093/neuonc/nox176.

Abstract

BACKGROUND

Extensive resections in low-grade glioma (LGG) are associated with improved overall survival (OS). However, World Health Organization (WHO) classification of gliomas has been completely revised and is now predominantly based on molecular criteria. This requires reevaluation of the impact of surgery in molecularly defined LGG subtypes.

METHODS

We included 228 adults who underwent surgery since 2003 for a supratentorial LGG. Pre- and postoperative tumor volumes were assessed with semiautomatic software on T2-weighted images. Targeted next-generation sequencing was used to classify samples according to current WHO classification. Impact of postoperative volume on OS, corrected for molecular profile, was assessed using a Cox proportional hazards model.

RESULTS

Median follow-up was 5.79 years. In 39 (17.1%) histopathologically classified gliomas, the subtype was revised after molecular analysis. Complete resection was achieved in 35 patients (15.4%), and in 54 patients (23.7%) only small residue (0.1-5.0 cm3) remained. In multivariable analysis, postoperative volume was associated with OS, with a hazard ratio of 1.01 (95% CI: 1.002-1.02; P = 0.016) per cm3 increase in volume. The impact of postoperative volume was particularly strong in isocitrate dehydrogenase (IDH) mutated astrocytoma patients, where even very small postoperative volumes (0.1-5.0 cm) already negatively affected OS.

CONCLUSION

Our data provide the necessary reevaluation of the impact of surgery in molecularly defined LGG and support maximal resection as first-line treatment for molecularly defined LGG. Importantly, in IDH mutated astrocytoma, even small postoperative volumes have negative impact on OS, which argues for a second-look operation in this subtype to remove minor residues if safely possible.

摘要

背景

低级别胶质瘤(LGG)的广泛切除与总生存期(OS)的改善相关。然而,世界卫生组织(WHO)的胶质瘤分类已完全修订,现在主要基于分子标准。这需要重新评估手术在分子定义的 LGG 亚型中的作用。

方法

我们纳入了 228 名自 2003 年以来因幕上 LGG 接受手术的成年人。术前和术后肿瘤体积通过 T2 加权图像上的半自动软件进行评估。靶向下一代测序用于根据当前的 WHO 分类对样本进行分类。使用 Cox 比例风险模型评估术后体积对 OS 的影响,校正了分子特征。

结果

中位随访时间为 5.79 年。在 39 例(17.1%)经组织病理学分类的胶质瘤中,在分子分析后对其亚型进行了修订。35 名患者(15.4%)实现了完全切除,54 名患者(23.7%)仅残留少量肿瘤(0.1-5.0cm3)。多变量分析显示,术后体积与 OS 相关,体积每增加 1cm3,风险比为 1.01(95%CI:1.002-1.02;P=0.016)。术后体积的影响在异柠檬酸脱氢酶(IDH)突变星形细胞瘤患者中尤为显著,即使术后体积非常小(0.1-5.0cm)也会对 OS 产生负面影响。

结论

我们的数据提供了对手术在分子定义的 LGG 中的作用进行重新评估的必要依据,并支持将最大程度的切除作为分子定义的 LGG 的一线治疗。重要的是,在 IDH 突变的星形细胞瘤中,即使是较小的术后体积也会对 OS 产生负面影响,这表明在这种亚型中,如果安全可行,应进行二次手术以切除较小的残留肿瘤。

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