Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital Universitaire Pitié-Salpêtrière, DMU Neurosciences, Department of Neuropathology, Paris, France.
Department of Radiation Oncology, Institut de Cancérologie Strasbourg Europe (ICANS), Strasbourg, France.
Neuropathol Appl Neurobiol. 2023 Aug;49(4):e12928. doi: 10.1111/nan.12928.
The distinction between CNS WHO grade 2 and grade 3 is instrumental in choosing between observational follow-up and adjuvant treatment for resected astrocytomas IDH-mutant. However, the criteria of CNS WHO grade 2 vs 3 have not been updated since the pre-IDH era.
Maximal mitotic activity in consecutive high-power fields corresponding to 3 mm was examined for 118 lower-grade astrocytomas IDH-mutant. The prognostic value for time-to-treatment (TTT) and overall survival (OS) of mitotic activity and other putative prognostic factors (including age, performance status, pre-surgical tumour volume, multilobar involvement, post-surgical residual tumour volume and midline involvement) was assessed for tumours with ATRX loss and the absence of CDKN2A homozygous deletion or CDK4 amplification, contrast enhancement, histological necrosis and microvascular proliferation.
Seventy-one per cent of the samples had <6 mitoses per 3 mm . Mitotic activity, residual volume and multilobar involvement were independent prognostic factors of TTT. The threshold of ≥6 mitoses per 3 mm identified patients with a shorter TTT (median 18.5 months). A residual volume ≥1 cm also identified patients with a shorter TTT (median 24.5 months). The group defined by <6 mitoses per 3 mm and a residual volume <1 cm had the longest TTT (median 73 months) and OS (100% survival at 7 years). These findings were confirmed in a validation cohort of 52 tumours.
Mitotic activity and post-surgical residual volume can be combined to evaluate the prognosis for patients with resected astrocytomas IDH-mutant. Patients with <6 mitoses per 3 mm and a residual volume <1 cm were the best candidates for observational follow-up.
在选择对 IDH 突变型切除星形细胞瘤进行观察性随访或辅助治疗时，中枢神经系统（CNS）世界卫生组织（WHO）2 级和 3 级之间的区别至关重要。然而，自 IDH 时代之前以来，CNS WHO 2 级与 3 级的标准尚未更新。
对 118 例 IDH 突变的低级别星形细胞瘤连续高倍视野中的最大有丝分裂活性进行检查，以 3mm 为标准。对 ATRX 缺失且无 CDKN2A 纯合缺失或 CDK4 扩增、对比增强、组织学坏死和微血管增生的肿瘤，评估有丝分裂活性和其他潜在预后因素（包括年龄、表现状态、术前肿瘤体积、多叶受累、术后残留肿瘤体积和中线受累）对治疗时间（TTT）和总生存（OS）的预后价值。
71%的样本有<6 个有丝分裂/3mm。有丝分裂活性、残留体积和多叶受累是 TTT 的独立预后因素。≥6 个有丝分裂/3mm 的阈值可识别 TTT 较短的患者（中位数 18.5 个月）。残留体积≥1cm 也可识别 TTT 较短的患者（中位数 24.5 个月）。<6 个有丝分裂/3mm 和残留体积<1cm 的组 TTT 最长（中位数 73 个月），OS （7 年时 100%生存）最长。在 52 例肿瘤的验证队列中证实了这些发现。
有丝分裂活性和术后残留体积可结合起来评估 IDH 突变型切除星形细胞瘤患者的预后。<6 个有丝分裂/3mm 和残留体积<1cm 的患者是观察性随访的最佳候选者。
