Blobner Jens, Ruf Viktoria, Weller Jonathan, Teske Nico, Forbrig Robert, Thon Niklas, Albert Nathalie L, von Baumgarten Louisa, Schoenecker Stephan, Tonn Joerg-Christian, Ringel Florian, Harter Patrick N, Karschnia Philipp
Department of Neurosurgery, LMU University Hospital of the Ludwig-Maximilians-University Munich, Marchioninistr. 15, Munich, 81377, Germany.
Center for Neuropathology and Prion Research, Medical Faculty, Ludwig-Maximilians-University Munich, Munich, Germany.
J Neurooncol. 2025 Jul 23. doi: 10.1007/s11060-025-05173-z.
The 2021 WHO classification of CNS tumors allows flexibility in the grading of IDH-mutant astrocytic gliomas, leading to some ambiguity. Following the approval of vorasidenib for WHO grade 2 astrocytomas and oligodendrogliomas based on the positive Phase III INDIGO trial, identifying prognostic criteria to differentiate between grade 2 and grade 3 tumors has become increasingly important.
We retrospectively searched our institutional database for patients meeting the diagnostic criteria for IDH-mutant astrocytomas (grade 2 and 3) according to the WHO 2021 classification. Clinical, radiological and molecular data were collected; outcome was compared using log-rank analysis and prognostic markers were subsequently forwarded in a multivariate model.
We identified 91 patients with IDH-mutant astrocytomas with available neuropathological and clinical data, including 61 WHO grade 2 (67.0%) and 30 WHO grade 3 (33.0%) tumors. At a median follow-up of 89 months, median progression-free survival was 67 months for WHO grade 2 and 53 months for WHO grade 3 tumors. Median overall survival was 216 months for WHO grade 3 tumors, while it was not reached for WHO grade 2 tumors. Univariate analysis showed that higher WHO grade, increased mitotic count, elevated Ki67 indices and preoperative contrast enhancement were associated with poorer outcomes; however, only contrast enhancement retained prognostic significance on multivariate analysis (p = 0.03 for overall survival, p = 0.02 for progression-free survival).
While our findings await confirmation in larger prospective cohorts, neuropathological grading criteria might need to be accompanied by clinical information including contrast enhancement to prognostically distinguish grade 2 from grade 3 tumors.
2021年世界卫生组织（WHO）中枢神经系统肿瘤分类在异柠檬酸脱氢酶（IDH）突变型星形细胞瘤分级方面具有灵活性，导致了一些模糊性。基于III期INDIGO试验的阳性结果，伏立西尼被批准用于WHO 2级星形细胞瘤和少突胶质细胞瘤，因此确定区分2级和3级肿瘤的预后标准变得越来越重要。
我们回顾性检索了机构数据库中符合WHO 2021分类标准的IDH突变型星形细胞瘤（2级和3级）患者。收集了临床、放射学和分子数据；使用对数秩分析比较结果，并随后在多变量模型中分析预后标志物。
我们确定了91例有可用神经病理学和临床数据的IDH突变型星形细胞瘤患者，其中包括61例WHO 2级（67.0%）和30例WHO 3级（33.0%）肿瘤。中位随访89个月时，WHO 2级肿瘤的中位无进展生存期为67个月，WHO 3级肿瘤为53个月。WHO 3级肿瘤的中位总生存期为216个月，而WHO 2级肿瘤未达到。单变量分析显示，WHO分级较高、有丝分裂计数增加、Ki67指数升高和术前增强扫描与较差的预后相关；然而，多变量分析中只有增强扫描保留了预后意义（总生存期p = 0.03，无进展生存期p = 0.02）。
虽然我们的研究结果有待在更大的前瞻性队列中得到证实，但神经病理学分级标准可能需要结合包括增强扫描在内的临床信息，以在预后方面区分2级和3级肿瘤。
