Stummer Walter, Holling Markus, Bendok Bernard R, Vogelbaum Michael A, Cox Ashley, Renfrow Sara L, Widhalm Georg, Ezrin Alan, DeSena Salvatore, Sackman Murray L, Wyse Joseph W
Department of Neurosurgery, University Hospital Münster, 48161 Münster, Germany.
Department of Neurosurgery, Mayo Clinic, Phoenix, AZ 85054, USA.
Brain Sci. 2022 Aug 6;12(8):1044. doi: 10.3390/brainsci12081044.
5-aminolevulinic acid (5-ALA; Gleolan, NX Development Corps., Lexington, USA) is approved for fluorescence-guided resections of suspected malignant gliomas. Experience has demonstrated that meningiomas also show fluorescence, which may be a useful surgical adjunct. We present an innovative design for a multi-center, prospective study to determine the clinical safety and potential benefit of fluorescence-guided resection of meningiomas with utmost bias reduction.
All patients with suspected meningioma (all grades) receive Gleolan 20 mg/kg 2-4 h prior to surgery supported by fluorescence excitation from a blue light source (Blue400, Zeiss Meditech, Oberkochen, Germany; FL400, Leica Microsystems, Heerbrugg, Switzerland). Surgeons are asked whether a residual tumor can be observed to fluoresce under blue light (BL) after the tumor is no longer recognizable using conventional illumination at the end of surgery. In addition, when faced with tissues of uncertain tissue type (so-called "indeterminate" tissue), this study records how often surgeons make a correct decision based on fluorescence and how this influences surgical strategy. The primary endpoint is the percentage of patients in whom one of these two benefits are observed. Other endpoints include the diagnostic accuracy of fluorescence compared to white light (WL) versus correlative histology. For bias reduction, pertinent data are derived from surgical videos reviewed by independent reviewers blinded to surgeons' assessments of tissue type and fluorescence status. Data will be included from approximately 100 study participants completing the study at approximately 15 centers in the United States, Germany, and Austria.
As of May 2022, 88 patients have completed the study. No adverse safety signal has been detected.
Preliminary data confirm the feasibility of our study design. Accrual is targeted for completion in the third quarter of 2022.
5-氨基乙酰丙酸（5-ALA；Gleolan，美国列克星敦的NX开发公司）已被批准用于疑似恶性胶质瘤的荧光引导切除术。经验表明，脑膜瘤也会显示荧光，这可能是一种有用的手术辅助手段。我们提出了一种创新设计的多中心前瞻性研究，以最大程度减少偏倚，确定荧光引导下切除脑膜瘤的临床安全性和潜在益处。
所有疑似脑膜瘤（所有级别）患者在手术前2-4小时接受20mg/kg的Gleolan，由蓝光光源（德国奥伯科亨的蔡司医疗技术公司的Blue400；瑞士黑尔布鲁格的徕卡微系统公司的FL400）激发荧光提供支持。在手术结束时，当肿瘤在传统照明下无法辨认后，询问外科医生是否能观察到残留肿瘤在蓝光下发出荧光。此外，当面对组织类型不确定的组织（所谓的“不确定”组织）时，本研究记录外科医生基于荧光做出正确决策的频率以及这如何影响手术策略。主要终点是观察到这两种益处之一的患者百分比。其他终点包括荧光与白光（WL）相比相对于相关组织学的诊断准确性。为减少偏倚，相关数据来自独立 reviewers 审查的手术视频，这些 reviewers 对外科医生对组织类型和荧光状态的评估不知情。数据将纳入来自美国、德国和奥地利约15个中心完成研究的约100名研究参与者。
截至2022年5月，88名患者已完成研究。未检测到不良安全信号。
初步数据证实了我们研究设计的可行性。预计在2022年第三季度完成入组。
