Lu Victor M, Alvi Mohammed A, McDonald Kerrie L, Daniels David J
1Prince of Wales Clinical School, The University of New South Wales, Sydney, Australia; and.
2Department of Neurologic Surgery and.
J Neurosurg Pediatr. 2019 Mar 1;23(3):308-316. doi: 10.3171/2018.9.PEDS18419. Epub 2018 Nov 30.
OBJECTIVE Pediatric high-grade gliomas (pHGGs), including diffuse intrinsic pontine glioma, present a prognostic challenge given their lethality and rarity. A substitution mutation of lysine for methionine at position 27 in histone H3 (H3K27M) has been shown to be highly specific to these tumors. Data are accumulating regarding the poor outcomes of patients with these tumors; however, the quantification of pooled outcomes has yet to be done, which could assist in prioritizing management. The aim of this study was to quantitatively pool data in the current literature on the H3K27M mutation as an independent prognostic factor in pHGG. METHODS Searches of seven electronic databases from their inception to March 2018 were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted and pooled using a meta-analysis of proportions. Meta-regression was used to identify potential sources of heterogeneity. RESULTS Six observational studies satisfied the selection criteria for inclusion. They reported the survival outcomes of a pooled cohort of 474 pHGG patients, with 258 (54%) and 216 (46%) patients positive and negative, respectively, for the H3K27M mutation. Overall, the presence of the mutation was independently and significantly associated with a worse prognosis (HR 3.630, p < 0.001). Overall survival was significantly shorter (by 2.300 years; p = 0.008) when the H3K27M mutation was present in pHGG. Meta-regression did not identify any study covariates of heterogeneous concern. CONCLUSIONS According to the current literature, pHGG patients positive for the H3K27M mutation are more than 3 times more susceptible to succumbing to this disease by more than 2 years, compared to patients negative for the mutation. More robust outcome data are required to improve our quantitative understanding of this pathological entity in order to assist in prioritizing clinical management. Future larger prospective studies are required to overcome inherent biases in the current literature to validate the quantitative findings of this study. ABBREVIATIONS CI = confidence interval; GRADE = Grades of Recommendation Assessment, Development and Evaluation; HR = hazard ratio; MD = mean difference; NOS = Newcastle-Ottawa Scale; OS = overall survival; pHGG = pediatric high-grade glioma; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RE = random effects.
目的 小儿高级别胶质瘤（pHGGs），包括弥漫性脑桥内在型胶质瘤，因其致死性和罕见性而带来了预后方面的挑战。组蛋白H3第27位赖氨酸被甲硫氨酸替代的突变（H3K27M）已被证明对这些肿瘤具有高度特异性。关于这些肿瘤患者预后不良的数据正在不断积累；然而，尚未对汇总结果进行量化，而这有助于确定管理的优先顺序。本研究的目的是对当前文献中关于H3K27M突变作为pHGG独立预后因素的数据进行定量汇总。方法 根据系统评价和Meta分析的首选报告项目（PRISMA）指南，对7个电子数据库从建库至2018年3月进行检索。采用比例Meta分析提取并汇总数据。使用Meta回归识别潜在的异质性来源。结果 6项观察性研究符合纳入选择标准。它们报告了474例pHGG患者汇总队列的生存结果，其中H3K27M突变阳性患者258例（54%），阴性患者216例（46%）。总体而言，该突变的存在与较差的预后独立且显著相关（风险比3.630，p < 0.001）。当pHGG中存在H3K27M突变时，总生存期显著缩短（缩短2.300年；p = 0.008）。Meta回归未发现任何引起异质性关注的研究协变量。结论 根据当前文献，与突变阴性患者相比，H3K27M突变阳性的pHGG患者死于该病的可能性高出3倍多，且死亡时间提前超过2年。需要更可靠的预后数据来提高我们对这种病理实体的定量认识，以协助确定临床管理的优先顺序。未来需要开展更大规模的前瞻性研究，以克服当前文献中固有的偏倚，从而验证本研究的定量结果。缩写词 CI = 置信区间；GRADE = 推荐分级评估、制定和评价；HR = 风险比；MD = 平均差；NOS = 纽卡斯尔-渥太华量表；OS = 总生存期；pHGG = 小儿高级别胶质瘤；PRISMA = 系统评价和Meta分析的首选报告项目；RE = 随机效应
