使用贝伐单抗-800CW在内镜经蝶窦手术中对垂体神经内分泌肿瘤进行荧光检测：一项非随机、非盲法、单中心可行性和剂量探索试验[DEPARTURE试验]
Fluorescence detection of pituitary neuroendocrine tumour during endoscopic transsphenoidal surgery using bevacizumab-800CW: a non-randomised, non-blinded, single centre feasibility and dose finding trial [DEPARTURE trial].
作者信息
Schmidt I, Vergeer R A, Postma M R, van den Berg G, Sterkenburg A J, Korsten-Meijer A G W, Feijen R A, Kruijff S, van Beek A P, den Dunnen W F A, Robinson D J, van Dijk J M C, Nagengast W B, Kuijlen J M A
机构信息
Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Neurosurgery, University of Groningen, University Medical Center Groningen, P.O. Box 30.001 (AB-71), Groningen, 9700 RB, The Netherlands.
出版信息
Eur J Nucl Med Mol Imaging. 2025 Jan;52(2):660-668. doi: 10.1007/s00259-024-06947-9. Epub 2024 Oct 11.
PURPOSE
Achieving endocrine remission by gross total resection is challenging in pituitary neuroendocrine tumours (PitNETs) with cavernous sinus invasion. This study aims to assess the safety, feasibility, and optimal dose for intraoperative fluorescence imaging as an added instrument to discriminate PitNET from surrounding tissue using bevacizumab-800CW, targeting vascular endothelial growth factor A (VEGF-A).
METHODS
In part I, dose-escalation (0-4∙5-10-25 mg) was performed in 4 groups of 3 patients with PitNETs Knosp grade 3-4. In part II, after interim analysis, the 10 mg and 25 mg groups were expanded to a total of 6 patients. Quantitative fluoroscence molecular endoscopy consisted of wide field fluorescence molecular endoscopy and multi-diameter single fiber reflectance / single fiber fluorescence spectroscopy. Mean fluorescence intensity (MFI) of the fresh surgical specimen was calculated and VEGF-staining was performed.
RESULTS
Eighteen patients were included. All doses were well tolerated. Three serious adverse events were registered, but none were tracer-related. Part I showed an adequate in-vivo tumour-to-background ratio for both 10 mg (TBR 2∙00 [1∙86, 2∙19]) and 25 mg (TBR 2∙10, [1∙86, 2∙58]). Part II revealed a substantially higher MFI in the 25 mg group. With both 10 mg and 25 mg a statistically significant difference between tumour and surrounding tissue was detected (p < 0∙0001). All surgical specimens had VEGF-A expression.
CONCLUSION
This study demonstrates the safety and feasibility of quantitative fluorescence molecular endoscopy during PitNET surgery. Both 10 mg and 25 mg bevacizumab-800CW result in clear differentiation in-vivo, with improved contrast ex-vivo (MFI) in the 25 mg group.
TRIAL REGISTRATION
NCT04212793 / Study Details| Detection of PitNET Tissue During TSS Using Bevacizumab800CW| ClinicalTrials.gov.
目的
对于侵犯海绵窦的垂体神经内分泌肿瘤（PitNETs），通过全切除实现内分泌缓解具有挑战性。本研究旨在评估术中荧光成像作为一种附加手段的安全性、可行性及最佳剂量，该成像使用靶向血管内皮生长因子A（VEGF-A）的贝伐单抗-800CW来区分PitNET与周围组织。
方法
在第一部分，对4组（每组3例）Knosp 3-4级PitNET患者进行剂量递增（0-4.5-10-25 mg）。在第二部分，经过中期分析后，将10 mg和25 mg组扩展至共6例患者。定量荧光分子内镜检查包括宽视野荧光分子内镜检查和多直径单纤维反射率/单纤维荧光光谱检查。计算新鲜手术标本的平均荧光强度（MFI）并进行VEGF染色。
结果
纳入18例患者。所有剂量耐受性良好。记录到3例严重不良事件，但均与示踪剂无关。第一部分显示10 mg（肿瘤与背景比值[TBR] 2.00 [1.86, 2.19]）和25 mg（TBR 2.10 [1.86, 2.58]）的体内肿瘤与背景比值均足够。第二部分显示25 mg组的MFI显著更高。10 mg和25 mg剂量时，肿瘤与周围组织之间均检测到统计学显著差异（p < 0.0001）。所有手术标本均有VEGF-A表达。
结论
本研究证明了PitNET手术期间定量荧光分子内镜检查的安全性和可行性。10 mg和25 mg贝伐单抗-800CW均可在体内实现清晰区分，25 mg组的体外对比度（MFI）有所改善。
试验注册
NCT04212793 / 研究详情| 使用贝伐单抗800CW在经蝶窦手术期间检测PitNET组织| ClinicalTrials.gov。
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