Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial
Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial
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DOI：
10.1016/s1470-2045(06)70665-9
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发表时间：
2006-05-01
期刊：
影响因子：
51.1
通讯作者：
Hans-Jurgen, R
中科院分区：
文献类型：
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作者：
Stummer, W;Pichlmeier, U;Hans-Jurgen, R
背景：5-氨基乙酰丙酸是一种非荧光前体药物，可导致恶性胶质瘤细胞内的荧光卟啉蓄积，这一发现正在研究中，用于术中识别和切除这些肿瘤。方法322例23~73岁疑似恶性胶质瘤患者，随机分为5-氨基乙酰丙酸20 mg/kg组(n=161)和白光常规显微手术组(n=161)。主要终点是早期MRI上无对比增强肿瘤的患者数量(即术后72小时内获得的)和MRI评估的6个月无进展生存期。次要终点是术后MRI上残留肿瘤的体积、总存活率、神经功能缺失和毒性反应。我们报告了一项对完全分析人群中270名患者(139名被分配5-氨基乙酰丙酸，131名被分配白光)的中期分析的结果，其中排除了组织学和放射学结果不合格的患者，这些患者被掩盖了治疗分配；中期分析导致了按照方案定义的研究的终止。在完全分析的人群中，根据治疗意向分析主要和次要终点。这项研究在http://www.clinicaltrials.gov上注册为NCT00241670。发现的中位随访期为35.4个月(95%可信区间为1.0-56.7)。在接受5-氨基乙酰丙酸治疗的139名患者中，90名(65%)肿瘤完全切除，而在131名接受白光治疗的患者中，47名(36%)获得完全切除(两组之间的差异为29%[95%可信区间17-40]，p<；0.0001)。分配5-氨基乙酰丙酸的患者的6个月无进展生存率高于分配白光的患者(41.0%[32.849.2vs21.1%[14.0-28.2vs19.9%[9.1-30.7]，P=0.0003，Z检验)。两组在手术后7天内报告的严重不良事件或任何器官系统类别的不良事件的频率没有差异。来自5-氨基乙酰丙酸的解释肿瘤荧光使对比剂增强的肿瘤能够更彻底地切除，从而提高了恶性胶质瘤患者的无进展存活率。
Background 5-aminolevulinic acid is a non-fluorescent prodrug that leads to intracellular accumulation of fluorescent porphyrins in malignant gliomas-a finding that is under investigation for intraoperative identification and resection of these tumours. We aimed to assess the effect of fluorescence-guided resection with 5-aminolevulinic acid on surgical radicality, progression-free survival, overall survival, and morbidity.Methods 322 patients aged 23-73 years with suspected malignant glioma amenable to complete resection of contrast-enhancing tumour were randomly assigned to 20 mg/kg bodyweight 5-aminolevulinic acid for fluorescence-guided resection (n = 161) or to conventional microsurgery with white light (n = 161). The primary endpoints were the number of patients without contrast-enhancing tumour on early MRI (ie, that obtained within 72 h after surgery) and 6-month progression-free survival as assessed by MRI. Secondary endpoints were volume of residual tumour on postoperative MRI, overall survival, neurological deficit, and toxic effects. We report the results of an interim analysis with 270 patients in the full-analysis population (139 assigned 5-aminolevulinic acid, 131 assigned white light), which excluded patients with ineligible histological and radiological findings as assessed by central reviewers who were masked as to treatment allocation; the interim analysis resulted in termination of the study as defined by the protocol. Primary and secondary endpoints were analysed by intention to treat in the full-analysis population. The study is registered at http://www.clinicaltrials.gov as NCT00241670.Findings Median follow-up was 35.4 months (95% CI 1.0-56.7). Contrast-enhancing tumour was resected completely in 90 (65%) of 139 patients assigned 5-aminolevulinic acid compared with 47 (36%) of 131 assigned white light (difference between groups 29% [95% CI 17-40], p < 0.0001). Patients allocated 5-aminolevulinic acid had higher 6-month progression free survival than did those allocated white light (41.0% [32.8-49.2] vs 21.1% [14.0-28.2]; difference between groups 19.9% [9.1-30.7], p = 0.0003, Z test). Groups did not differ in the frequency of severe adverse events or adverse events in any organ system class reported within 7 days after surgery.Interpretation Tumour fluorescence derived from 5-aminolevulinic acid enables more complete resections of contrast-enhancing tumour, leading to improved progression-free survival in patients with malignant glioma.