文章：

抗VEGF治疗在胶质母细胞瘤中的出血和缺血风险

Hemorrhagic and ischemic risks of anti-VEGF therapies in glioblastoma 

原文发布日期：2025-05-21 

英文摘要：

Glioblastoma (GBM) is one of the most aggressive primary brain tumors, characterized by extensive neovascularization and a highly infiltrative phenotype. Anti-vascular endothelial growth factor (VEGF) therapies, such as bevacizumab, have emerged as significant adjunct treatments for recurrent and high-grade GBM by targeting abnormal tumor vasculature. Despite demonstrated benefits in slowing tumor progression and alleviating peritumoral edema, these agents are associated with notable vascular complications, including hemorrhagic and ischemic events. Hemorrhagic complications range from minor intracranial microbleeds to life-threatening intracranial hemorrhages (ICH). Mechanistically, VEGF inhibition disrupts endothelial function and decreases vascular integrity, making already fragile tumor vessels prone to rupture. Glioma-associated vascular abnormalities, including disorganized vessel networks and compromised blood-brain barrier, further exacerbate bleeding risks. Concurrent use of anticoagulants, hypertension, and genetic predispositions also significantly elevate hemorrhagic risk. In addition to bleeding complications, ischemic events are increasingly recognized in patients receiving anti-VEGF therapy. Reduced vascular endothelial cells (ECs) survival and diminished microvascular density can lead to regional hypoperfusion and potentially precipitate cerebrovascular ischemia. Impaired vasoreactivity and increased vascular resistance, often accompanied by endothelial dysfunction and microvascular rarefaction, contribute to elevated stroke and arterial thrombotic risk. This review synthesizes current evidence on hemorrhagic and ischemic complications arising from anti-VEGF therapy in GBM. We discuss underlying pathophysiological mechanisms, risk factors, and clinically relevant biomarkers, as well as prevention strategies—such as rigorous blood pressure (BP) control and close monitoring of coagulation parameters. We further highlight emerging avenues in precision medicine, including pharmacogenomic profiling and targeted adjunct agents that protect vascular integrity, aimed at mitigating adverse vascular events while preserving therapeutic efficacy. The goal is to optimize outcomes for GBM patients by balancing the benefits of anti-VEGF therapy with vigilant management of its inherent vascular risks. In addition, this study analyzes existing clinical trials of the use of anti-VEGF drugs in the treatment of gliomas using data from the clinicaltirals.gov website. 

摘要翻译：

胶质母细胞瘤（GBM）是最具侵袭性的原发性脑肿瘤之一，以异常新生血管生成和高浸润性表型为特征。抗血管内皮生长因子（VEGF）疗法（如贝伐珠单抗）通过靶向肿瘤异常血管系统，已成为复发性及高级别GBM的重要辅助治疗手段。尽管该疗法在延缓肿瘤进展和减轻瘤周水肿方面具有明确获益，但也会引发显著的血管并发症，包括出血性和缺血性事件。出血并发症可从轻微颅内微出血到危及生命的颅内出血（ICH）。从机制上看，VEGF抑制会破坏内皮细胞功能、降低血管完整性，使本就脆弱的肿瘤血管更易破裂。胶质瘤相关的血管异常（包括血管网络结构紊乱和血脑屏障受损）进一步加剧出血风险。抗凝药物的使用、高血压及遗传易感性也会显著增加出血风险。

除出血并发症外，抗VEGF治疗患者中缺血事件也日益受到关注。血管内皮细胞存活率下降和微血管密度减少可能导致局部低灌注，进而引发脑血管缺血。血管反应性受损和血管阻力增加（常伴随内皮功能障碍和微血管稀疏）共同推高中风及动脉血栓风险。本综述整合了当前关于抗VEGF治疗在GBM中引发出血与缺血并发症的证据，探讨了潜在病理生理机制、风险因素和临床相关生物标志物，以及预防策略（如严格血压控制和凝血参数监测），并重点介绍了精准医学新方向——包括药物基因组学分析和保护血管完整性的靶向辅助药物，旨在降低血管不良事件风险的同时维持治疗效果。最终目标是通过平衡抗VEGF治疗的获益与对其固有血管风险的 vigilant 管理，优化GBM患者的临床结局。此外，本研究利用ClinicalTrials.gov网站数据，对现有抗VEGF药物治疗胶质瘤的临床试验进行了分析。

原文链接：

Hemorrhagic and ischemic risks of anti-VEGF therapies in glioblastoma