Lam Keng, Ozkizilkaya Hanim I, Milton Denái R, Dono Antonio, Liu Yajie, Kundu Suprateek, Kumar Vinodh A, Johnson Jason M, Esquenazi Yoshua, Patel Chirag B, Ballester Leomar Y
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Pathology, University of Southern California.
Neurooncol Adv. 2025 Apr 28;7(1):vdaf088. doi: 10.1093/noajnl/vdaf088. eCollection 2025 Jan-Dec.
Several molecular alterations have been identified to provide prognosis for patients with isocitrate dehydrogenase (IDH)-mutant astrocytoma. However, contemporary baseline survival data with respect to their molecular alterations are lacking. The prognostic value of histologic grading remains controversial.
This was a retrospective multi-site study of adult IDH-mutant diffuse astrocytoma patients. Overall survival (OS) was estimated using the Kaplan-Meier method. Associations between OS and measures of interest were evaluated using Cox proportional hazards regression models.
We identified 241 eligible patients. The most frequent mutations were IDH1 (98%), TP53 (91%), ATRX (70%), ARID1A (8%), BRCA2 (6%), TSC2 (6%), CDKN2A (6%), and CREBBP (6%). IDH2 mutations were identified in 2%. By univariate analysis, age > 40 (hazard ratio [HR], 2.03; 95% CI, 1.20-3.45; = .009) was associated with worse OS. Wildtype BRCA2 compared with mutated BRCA2 (HR, 0.42; 95% CI, 0.20-0.90; = .024) and Central Nervous System World Health Organization (CNS WHO) grade 2 astrocytoma compared with grade 3 disease (HR, 0.40; 95% CI, 0.21-0.78; = .007) were associated with better OS. In multivariable analysis, age > 40 (HR, 2.06; 95% CI, 1.18-3.59; = .011) was associated with worse OS and CNS WHO grade 2 (HR, 0.42; 95% CI, 0.21-0.83; = .012) remained associated with improved OS. We identified an association between increased tumor mutation burden (TMB) and worse OS.
Age and CNS WHO grade remain essentials for risk stratification among -mutant astrocytoma patients. Further studies are warranted to determine the prognostic implications of mutations and TMB.
已确定几种分子改变可为异柠檬酸脱氢酶（IDH）突变型星形细胞瘤患者提供预后信息。然而，目前缺乏关于其分子改变的当代基线生存数据。组织学分级的预后价值仍存在争议。
这是一项对成年IDH突变型弥漫性星形细胞瘤患者的回顾性多中心研究。采用Kaplan-Meier方法估计总生存期（OS）。使用Cox比例风险回归模型评估OS与感兴趣指标之间的关联。
我们确定了241例符合条件的患者。最常见的突变是IDH1（98%）、TP53（91%）、ATRX（70%）、ARID1A（8%）、BRCA2（6%）、TSC2（6%）、CDKN2A（6%）和CREBBP（6%）。IDH2突变在2%的患者中被发现。单因素分析显示，年龄>40岁（风险比[HR]，2.03；95%置信区间，1.20 - 3.45；P = 0.009）与较差的OS相关。野生型BRCA2与突变型BRCA2相比（HR，0.42；95%置信区间，0.20 - 0.90；P = 0.024），以及中枢神经系统世界卫生组织（CNS WHO）2级星形细胞瘤与3级疾病相比（HR，0.40；95%置信区间，0.21 - 0.78；P = 0.007）与较好的OS相关。多因素分析中，年龄>40岁（HR，2.06；95%置信区间，1.18 - 3.59；P = 0.011）与较差的OS相关，而CNS WHO 2级（HR，0.42；95%置信区间，0.21 - 0.83；P = 0.012）仍与改善的OS相关。我们发现肿瘤突变负担（TMB）增加与较差的OS之间存在关联。
年龄和CNS WHO分级仍然是IDH突变型星形细胞瘤患者风险分层的关键因素。有必要进一步研究以确定IDH突变和TMB的预后意义。
