Lim-Fat Mary Jane, Cotter Jennifer A, Touat Mehdi, Vogelzang Jayne, Sousa Cecilia, Pisano Will, Geduldig Jack, Bhave Varun, Driver Joseph, Kao Pei-Chi, McGovern Alana, Ma Clement, Margol Ashley S, Cole Kristina, Smith Amy, Goldman Stewart, Kaneva Kristiyana, Truong AiLien, Nazemi Kellie J, Wood Matthew D, Wright Karen D, London Wendy B, Warren Katherine E, Wen Patrick Y, Bi Wenya Linda, Alexandrescu Sanda, Reardon David A, Ligon Keith L, Yeo Kee Kiat
Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada (M.J.L.-F.).
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Neuro Oncol. 2024 Dec 5;26(12):2364-2376. doi: 10.1093/neuonc/noae142.
The frequency and significance of IDH mutations in glioma across age groups are incompletely understood. We performed a multi-center retrospective age-stratified comparison of patients with IDH-mutant gliomas to identify age-specific differences in clinico-genomic features, treatments, and outcomes.
Clinical, histologic, and sequencing data from patients with IDH-mutant, grades 2-4 gliomas, were collected from collaborating institutions between 2013 and 2019. Patients were categorized as pediatric (<19 years), young adult (YA; 19-39 years), or older adult (≥40 years). Clinical presentation, treatment, histologic, and molecular features were compared across age categories using Fisher's exact test or analysis-of-variance. Cox proportional-hazards regression was used to determine the association of age and other covariates with overall (OS) and progression-free survival (PFS).
We identified a cohort of 379 patients (204 YA) with IDH-mutant glioma with clinical data. There were 155 (41%) oligodendrogliomas and 224 (59%) astrocytomas. YA showed significantly shorter PFS and shorter median time-to-malignant transformation (MT) compared to pediatric and adult groups, but no significant OS difference. Adjusting for pathology type, extent of resection, and upfront therapy in multivariable analysis, the YA group was independently prognostic of shorter PFS than pediatric and adult groups. Among astrocytomas, CDK4/6 copy number amplifications were associated with both shorter PFS and shorter OS. Among oligodendrogliomas, PIK3CA and CDKN2A/2B alterations were associated with shorter OS.
IDH-mutant glioma YA patients had significantly shorter PFS and time to MT but did not differ in OS compared to pediatric and adult groups. Treatment approaches varied significantly by patient age and warrant further study as addressable age-associated outcome drivers.
不同年龄组胶质瘤中异柠檬酸脱氢酶（IDH）突变的频率及意义尚未完全明确。我们对IDH突变型胶质瘤患者进行了多中心回顾性年龄分层比较，以确定临床基因组特征、治疗方法及预后方面的年龄特异性差异。
收集2013年至2019年间合作机构中IDH突变的2-4级胶质瘤患者的临床、组织学和测序数据。患者分为儿童组（<19岁）、青年成人组（YA；19-39岁）或老年成人组（≥40岁）。使用Fisher精确检验或方差分析比较各年龄组的临床表现、治疗、组织学和分子特征。采用Cox比例风险回归确定年龄及其他协变量与总生存期（OS）和无进展生存期（PFS）的关联。
我们确定了一组379例有临床数据的IDH突变型胶质瘤患者（204例为青年成人组）。其中有155例（41%）少突胶质细胞瘤和224例（59%）星形细胞瘤。与儿童组和成人组相比，青年成人组的无进展生存期显著缩短，恶性转化（MT）的中位时间也更短，但总生存期无显著差异。在多变量分析中，校正病理类型、切除范围和初始治疗后，青年成人组的无进展生存期比儿童组和成人组独立预后更差。在星形细胞瘤中，细胞周期蛋白依赖性激酶4/6（CDK4/6）拷贝数扩增与较短的无进展生存期和总生存期均相关。在少突胶质细胞瘤中，磷脂酰肌醇-3激酶催化亚基α（PIK3CA）和细胞周期蛋白依赖性激酶抑制剂2A/2B（CDKN2A/2B）改变与较短的总生存期相关。
IDH突变型胶质瘤青年成人患者的无进展生存期和至恶性转化时间显著缩短，但与儿童组和成人组相比，总生存期无差异。治疗方法因患者年龄而异，作为可解决的年龄相关预后驱动因素值得进一步研究。
