Department of Neurooncology, Neurology Clinic and National Centre for Tumour Disease, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
J Neurol. 2013 Mar;260(3):847-55. doi: 10.1007/s00415-012-6718-9. Epub 2012 Oct 27.
Ischemic strokes, intracranial hemorrhages (ICH) and deep venous thromboembolism (DVT) are clinically important events in patients with gliomas. In this multicentre, noninterventional observational study, current data pertaining to frequency, contributing factors and outcomes of vascular events during times of anti-angiogenic therapy with the antibody against vascular endothelial growth factor, bevacizumab (BEV) was collected from the German Glioma Network. Among 3,889 glioma patients, 70 ischemic strokes (1.8 %) and 123 ICH (3.2 %) were recorded. 143 DVT (5.0 %) were recorded in 2,855 patients. Rates of DVT and ICH, but not of ischemic strokes, increased with the World Health Organization (WHO) grade of glioma. In 81 BEV-treated patients, five ischemic strokes (6.2 %), one ICH (1.2 %) and six DVT (7.4 %) were documented. Compared to patients that were not treated with BEV, ischemic stroke rate was significantly higher during treatment with BEV (p < 0.001). The rates of DVT (p = 0.123) or ICH (p = 0.571) in BEV-treated patients did not differ. On cerebral magnetic resonance imaging (MRI), BEV-related ischemic strokes appeared as diffusion-restricted sites next to contrast-enhancing tumor. 67 % of ICH, 61 % of ischemic strokes and 18 % of DVT occurred postoperatively (within 30 days after tumor resection). Outcome after postoperative ICH was significantly worse than after spontaneous ICH (p = 0.008). Ischemic stroke outcomes did not differ between postoperative and spontaneous occurrence (p = 0.401). Rate of pulmonary embolism did not differ significantly between postoperative and spontaneous DVT (p = 0.133). Relatively low rates of ICH and DVT might be partially due to a high proportion of low-grade gliomas in this patient cohort. The finding of a relevant number of symptomatic, therapy-associated intracerebral diffusion restrictions should be controlled in ongoing phase III studies.
缺血性中风、颅内出血 (ICH) 和深部静脉血栓形成 (DVT) 是胶质瘤患者的重要临床事件。在这项多中心、非干预性观察研究中，从德国神经胶质瘤网络中收集了当前与抗血管内皮生长因子抗体贝伐单抗 (BEV) 抗血管生成治疗期间血管事件的频率、促成因素和结果相关的数据。在 3889 名胶质瘤患者中，记录了 70 例缺血性中风 (1.8%) 和 123 例 ICH (3.2%)。在 2855 名患者中记录了 143 例 DVT (5.0%)。DVT 和 ICH 的发生率随着世界卫生组织 (WHO) 胶质瘤分级的增加而增加，但缺血性中风的发生率则不然。在 81 名接受 BEV 治疗的患者中，记录了 5 例缺血性中风 (6.2%)、1 例 ICH (1.2%)和 6 例 DVT (7.4%)。与未接受 BEV 治疗的患者相比，BEV 治疗期间缺血性中风的发生率显著更高 (p<0.001)。接受 BEV 治疗的患者 DVT 发生率 (p=0.123) 或 ICH 发生率 (p=0.571) 无差异。在脑磁共振成像 (MRI) 上，BEV 相关的缺血性中风表现为紧邻增强肿瘤的弥散受限部位。67%的 ICH、61%的缺血性中风和 18%的 DVT 发生在术后 (肿瘤切除后 30 天内)。术后 ICH 的预后明显差于自发性 ICH (p=0.008)。术后和自发性发生的缺血性中风的结果没有差异 (p=0.401)。术后和自发性 DVT 的肺栓塞发生率无显著差异 (p=0.133)。ICH 和 DVT 的相对较低发生率可能部分归因于该患者队列中低级别胶质瘤的比例较高。在正在进行的 III 期研究中，应控制与治疗相关的颅内弥散受限的症状数量。
