DataSheet_1_Prognostic Implication of Patient Age in H3K27M-Mutant Midline Gliomas.docx

IntroductionPediatric and adult H3K27M-mutant midline gliomas have variable clinical presentations, prognoses, and molecular backgrounds. In this study, we integrated data from published studies to investigate the differences between these two groups.
MethodsPubMed and Web of Science were searched for potential data. Studies were included if they had available individual participant data on patients age of H3K27M-mutant midline gliomas. For time-to-event analyses, Kaplan-Meier analysis and Cox regression models were carried out; corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of age and clinical covariates on progression-free survival (PFS) and overall survival (OS).
ResultsWe included 43 studies comprising 272 adults and 657 pediatric midline gliomas with H3K27M mutation for analyses. In adults, there was a male predilection whereas females were slightly more common than males in the pediatric group. Spinal cord tumors were more frequent in adults. The prevalence of H3.1 K27M mutation was significantly higher in the pediatric cohort. Compared to adult patients, pediatric H3K27M-mutant midline gliomas exhibited more aggressive features including higher rates of pathologic features of high-grade tumors and Ki67 proliferation index, and had a shorter PFS and OS. Genetically, ACVR1 mutations were more common whereas MGMT methylation, FGFR1, and NF1 mutations were less prevalent in the pediatric cohort.
ConclusionPediatric H3K27M-mutant midline gliomas were demographically, clinically, and molecularly distinct from adult patients, highlighting an opportunity to refine the risk stratification for these neoplasms.

引言 携带H3K27M突变的中线胶质瘤（H3K27M-mutant midline gliomas）在儿童与成人群体中，临床表现、预后及分子背景均存在异质性。本研究整合已发表研究的数据，旨在探究这两个群体之间的差异。
方法 本研究通过检索PubMed与Web of Science数据库获取潜在研究数据。纳入标准为：研究需包含携带H3K27M突变的中线胶质瘤患者的个体参与者数据。针对生存时间分析，本研究采用Kaplan-Meier分析与Cox回归模型；计算相应的风险比（HR）与95%置信区间（CI），以分析年龄及临床协变量对无进展生存期（PFS）与总生存期（OS）的影响。
结果 本研究共纳入43项研究，涵盖272例成人及657例儿童携带H3K27M突变的中线胶质瘤患者用于分析。成人群体中男性占比更高，而儿童群体中女性略多于男性。成人患者中脊髓胶质瘤的发生率更高。儿童队列中H3.1 K27M突变的检出率显著更高。与成人患者相比，儿童携带H3K27M突变的中线胶质瘤具有更具侵袭性的表型：包括高级别肿瘤病理特征比例更高、Ki67增殖指数更高，且无进展生存期与总生存期更短。分子层面，儿童队列中ACVR1突变更为常见，而MGMT甲基化、FGFR1及NF1突变的检出率更低。
结论 儿童携带H3K27M突变的中线胶质瘤在人口统计学、临床及分子特征层面均与成人患者存在显著差异，这为优化此类肿瘤的风险分层策略提供了依据。