研究动态
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贝伐单抗-IRDye800CW 用于荧光引导脑膜瘤手术中的肿瘤检测(LUMINA 试验):一项单中心 I 期研究。

Bevacizumab-IRDye800CW for tumor detection in fluorescence-guided meningioma surgery (LUMINA trial): a single-center phase I study.

发表日期:2024 Jul 05
作者: Bianca M Dijkstra, Quirine C F Cordia, Julie Nonnekens, Gert Jan Meersma, Venkata Sasank Donthu, Wouter B Nagengast, Schelto Kruijff, Wilfred F A den Dunnen, Frank A E Kruyt, Rob J M Groen
来源: Brain Structure & Function

摘要:

脑膜瘤是最常见的脑肿瘤之一,可以通过全切除术进行治愈。次全切除会增加复发的机会。通过使用针对上调生物标志物的荧光示踪剂在术中识别不可见的肿瘤残留物可能有助于优化脑膜瘤切除。这称为分子荧光引导手术(MFGS)。血管内皮生长因子 α (VEGFα) 已被确定为合适的脑膜瘤生物标志物,并且可以用贝伐单抗-IRDye800CW 靶向。这项前瞻性 I 期试验的目的是确定贝伐单抗-IRDye800CW 用于颅内脑膜瘤 MFGS 的安全性和可行性。手术前 2-4 天施用 4.5、10 或 25 毫克示踪剂。术中使用标准神经外科显微镜验证荧光,术后使用荧光成像系统(Pearl 和 Odyssey CLx)和光谱分析组织标本以确定最佳剂量。比较了几种组织类型的摄取量并与 VEGFα 表达相关。没有发生与使用贝伐单抗-IRDye800CW 相关的不良事件。经过两次中期分析,根据离体肿瘤与背景的比率,10 mg 是最佳剂量。尽管标准的术中成像显示没有荧光,但使用定制成像系统进行的术后分析显示,与未受影响的硬脑膜和大脑相比,肿瘤中的荧光摄取较高。此外,可以使用荧光成像区分肿瘤对硬脑膜(硬脑膜尾)的侵袭和对骨的侵袭。荧光强度与VEGFα表达有良好的相关性。Bevacizumab-IRDye800CW可安全用于脑膜瘤患者; 10 mg 贝伐单抗-IRDye800CW 提供了足够的肿瘤与背景比。需要对当前可用的神经外科显微镜进行调整,以实现术中目标 IRDye800CW 的可视化。需要进行 II/III 期试验来系统地研究 MFGS 联合贝伐珠单抗-IRDye800CW 对更大范围患者进行脑膜瘤手术的益处。
Meningiomas are one of the most frequently occurring brain tumors and can be curatively treated with gross-total resection. A subtotal resection increases the chances of recurrence. The intraoperative identification of invisible tumor remnants by using a fluorescent tracer targeting an upregulated biomarker could help to optimize meningioma resection. This is called molecular fluorescence-guided surgery (MFGS). Vascular endothelial growth factor α (VEGFα) has been identified as a suitable meningioma biomarker and can be targeted with bevacizumab-IRDye800CW.The aim of this prospective phase I trial was to determine the safety and feasibility of bevacizumab-IRDye800CW for MFGS for intracranial meningiomas by administering 4.5, 10, or 25 mg of the tracer 2-4 days prior to surgery. Fluorescence was verified during the operation with the standard neurosurgical microscope, and tissue specimens were postoperatively analyzed with fluorescence imaging systems (Pearl and Odyssey CLx) and spectroscopy to determine the optimal dose. Uptake was compared in several tissue types and correlated with VEGFα expression.No adverse events related to the use of bevacizumab-IRDye800CW occurred. After two interim analyses, 10 mg was the optimal dose based on ex vivo tumor-to-background ratio. Although the standard intraoperative imaging revealed no fluorescence, postoperative analyses with tailored imaging systems showed high fluorescence uptake in tumor compared with unaffected dura mater and brain. Additionally, tumor invasion of the dura mater (dural tail) and invasion of bone could be distinguished using fluorescence imaging. Fluorescence intensity showed a good correlation with VEGFα expression.Bevacizumab-IRDye800CW can be safely used in patients with meningioma; 10 mg bevacizumab-IRDye800CW provided an adequate tumor-to-background ratio. Adjustments of the currently available neurosurgical microscopes are needed to achieve visualization of targeted IRDye800CW intraoperatively. A phase II/III trial is needed to methodically investigate the benefit of MFGS with bevacizumab-IRDye800CW for meningioma surgery in a larger cohort of patients.