异柠檬酸脱氢酶 (IDH) 基因 IDH1 或 IDH2 的突变定义了一组成人弥漫性胶质瘤，与 IDH 野生型胶质母细胞瘤相比，诊断年龄更小，预后更好。在 IDH 突变神经胶质瘤中，一小部分星形细胞肿瘤呈现 4 级组织学特征和不良预后。在分子研究中，CDKN2A/B 纯合缺失可独立预测不良预后和短生存期。因此，2021 年 WHO 分类现在也承认这种分子特征（CDKN2A/B 缺失）足以将星形细胞瘤分类为 IDH 突变型、WHO 4 级，无论组织学分级如何。在这里，我们调查了具有和不具有 CDKN2A/B 缺失的 WHO 4 级 IDH 突变型星形细胞瘤患者的结局，以比较这些组并评估有助于生存的临床和放射学因素。我们回顾性地鉴定了 79 名 IDH 突变型星形细胞瘤患者，其中五个国际机构以及由 51 名 IDH 突变星形细胞瘤患者组成的对照组（组织学 4 级，未检测到 CDKN2A/B 缺失）在初次诊断时检测到 CDKN2A/B 缺失。我们汇总了所有患者的临床和影像学特征。我们发现 CDKN2A/B 缺失与显着较差的总生存期 (OS; p = 0.0004) 和无进展生存期 (PFS; p = 0.0026) 相关，中位 OS 为 5.0 年且 PFS 为 3.0 年，而仅根据组织学标准指定为 4 级的肿瘤的 PFS 为 10.1 和 5.0 年。多变量分析证实 CDKN2A/B 缺失对于 OS (HR = 3.51，p < 0.0001) 和 PFS (HR = 2.35，p = 0.00095) 都是强阴性预测因素。此外，在CDKN2A/B缺失的肿瘤中，术前对比增强是较差OS（HR 2.19，95% CI 1.22-3.93，p = 0.0090）和PFS（HR = 1.74，95% CI= 1.02-2.97）的显着预测因子，p = 0.0420）。这些发现强调了 IDH 突变型星形细胞瘤中 CDKN2A/B 缺失的严重预后影响，并强调需要进一步细化肿瘤预后分类。我们的结果为治疗试验提供了基线患者结果的关键基准，强调了除了组织学分级之外，CDKN2A/B 状态评估在 IDH 突变星形细胞瘤患者的临床试验设计和治疗决策中的重要性。© 2024。作者。

Mutations in the Isocitrate Dehydrogenase (IDH) genes, IDH1 or IDH2, define a group of adult diffuse gliomas associated with a younger age at diagnosis and better prognosis than IDH wild-type glioblastoma. Within IDH mutant gliomas, a small fraction of astrocytic tumors present with grade 4 histologic features and poor prognosis. In molecular studies, homozygous deletion of CDKN2A/B is independently predictive of poor prognosis and short survival. As a consequence, 2021 WHO classification now also recognizes this molecular feature, CDKN2A/B deletion, as sufficient for classifying an astrocytoma as IDH-mutant, WHO Grade 4, regardless of histological grading. Here, we investigate outcomes of patients with WHO Grade 4 IDH-mutant astrocytoma both with and without CDKN2A/B deletion, to compare these groups and evaluate clinical and radiographic factors that contribute to survival.We retrospectively identified 79 patients with IDH-mutant astrocytoma with CDKN2A/B deletion detected at initial diagnosis across five international institutions as well as a comparison group of 51 patients with IDH-mutant, astrocytoma, histologically Grade 4 without detectable CDKN2A/B deletion. We assembled clinical and radiographic features for all patients.We find that CDKN2A/B deletion was associated with significantly worse overall survival (OS; p = 0.0004) and progression-free survival (PFS; p = 0.0026), with median OS of 5.0 years and PFS of 3.0 years, compared to 10.1 and 5.0 years for tumors with a grade 4 designation based only on histologic criteria. Multivariate analysis confirmed CDKN2A/B deletion as a strong negative prognosticator for both OS (HR = 3.51, p < 0.0001) and PFS (HR = 2.35, p = 0.00095). In addition, in tumors with CDKN2A/B deletion, preoperative contrast enhancement is a significant predictor of worse OS (HR 2.19, 95% CI 1.22-3.93, p = 0.0090) and PFS (HR = 1.74, 95% CI = 1.02-2.97, p = 0.0420).These findings underscore the severe prognostic impact of CDKN2A/B deletion in IDH-mutant astrocytomas and highlight the need for further refinement of tumor prognostic categorization. Our results provide a key benchmark of baseline patient outcomes for therapeutic trials, underscoring the importance of CDKN2A/B status assessment, in addition to histologic grading, in clinical trial design and therapeutic decision-making for IDH-mutant astrocytoma patients.© 2024. The Author(s).