Combination of ALA-induced fluorescence-guided resection and intraoperative open photodynamic therapy for recurrent glioblastoma: case series on a promising dual strategy for local tumor control
Combination of ALA-induced fluorescence-guided resection and intraoperative open photodynamic therapy for recurrent glioblastoma: case series on a promising dual strategy for local tumor control
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DOI：
10.3171/2019.11.jns192443
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发表时间：
2021-02-01
影响因子：
4.1
通讯作者：
Stummer, Walter
中科院分区：
文献类型：
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作者：
Schipmann, Stephanie;Muther, Michael;Stummer, Walter
目的高级别脑胶质瘤(HGG)预后较差，且不可避免，多为局部复发。因此，改善局部肿瘤控制的方案是必要的。光动力疗法(PDT)已经被研究过，但由于副作用和缺乏生存益处而被放弃。由5-氨基乙酰丙酸(5-ALA)诱导的细胞内卟啉被批准用于荧光引导切除(FGRS)，但也是光敏剂。在光的激活下，它们会产生活性氧物种，从而产生细胞毒性。作者提出了5-ALA-FGR和PDT的联合入路。方法复发性HGG在5-ALA-FGR后，激光扩散器被战略性地放置在切除腔内。PDT持续冲洗60min(635 nm，扩散器200 mW/cm，1h)，以保持光学清晰度和100%氧气通气量。分别于术后24小时、14天和每3个月行磁共振成像，包括弥散张量成像和表观弥散系数图。治疗后6个月观察到一个手术部位感染是唯一的不良事件。MRI显示20例中16例(80%)沿切除边缘可见细胞毒性水肿，多数为环状，与先前激光扩散器的位置(平均体积3.3 cm(3))相对应。肿胀对浸润性组织或未切除的强化肿瘤有选择性。在14天的随访中，以前的水肿区出现强化，有些病例在4-5个月后消失。中位无进展生存期(PFS)为6个月(95%可信区间4.8~7.2个月)。结论5-ALA-FGR联合PDT是一种安全、创新的局部肿瘤控制方法，具有良好的临床应用前景。有必要进行进一步的前瞻性研究，以评估长期疗效。
OBJECTIVE High-grade glioma (HGG) prognosis remains dismal, with inevitable, mostly local recurrence. Regimens for improving local tumor control are therefore needed. Photodynamic therapy (PDT) using porfimer sodium has been investigated but was abandoned due to side effects and lack of survival benefits. Intracellular porphyrins induced by 5-aminolevulinic acid (5-ALA) are approved for fluorescence-guided resections (FGRs), but are also photosensitizers. Activated by light, they generate reactive oxygen species with resultant cytotoxicity. The authors present a combined approach of 5-ALA FGR and PDT.METHODS After 5-ALA FGR in recurrent HGG, laser diffusors were strategically positioned inside the resection cavity. PDT was applied for 60 minutes (635 nm, 200 mW/cm diffusor, for 1 hour) under continuous irrigation for maintaining optical clarity and ventilation with 100% oxygen. MRI was performed at 24 hours, 14 days, and every 3 months after surgery, including diffusion tensor imaging and apparent diffusion coefficient maps.RESULTS Twenty patients were treated. One surgical site infection after treatment was noted at 6 months as the only adverse event. MRI revealed cytotoxic edema along resection margins in 16 (80%) of 20 cases, mostly annular around the cavity, corresponding to prior laser diffusor locations (mean volume 3.3 cm(3)). Edema appeared selective for infiltrated tissue or nonresected enhancing tumor. At the 14-day follow-up, enhancement developed in former regions of edema, in some cases vanishing after 4-5 months. Median progression-free survival (PFS) was 6 months (95% CI 4.8-7.2 months).CONCLUSIONS Combined 5-ALA FGR and PDT provides an innovative and safe method of local tumor control resulting in promising PFS. Further prospective studies are warranted to evaluate long-term therapeutic effects.