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使用5-氨基酮戊酸诱导的原卟啉IX对不可切除的恶性胶质瘤复发进行间质光动力治疗。

Interstitial photodynamic therapy of nonresectable malignant glioma recurrences using 5-aminolevulinic acid induced protoporphyrin IX.

作者信息

Beck Tobias J, Kreth Friedrich W, Beyer Wolfgang, Mehrkens Jan H, Obermeier Andreas, Stepp Herbert, Stummer Walter, Baumgartner Reinhold

机构信息

Laser Research Laboratory, Ludwig-Maximilians-University, Marchioninistr. 23, 81377 Munich, Germany.

出版信息

Lasers Surg Med. 2007 Jun;39(5):386-93. doi: 10.1002/lsm.20507.

Abstract

BACKGROUND AND OBJECTIVE

Limited knowledge of the light and temperature distribution within the target volume in combination with non-selective accumulation of the applied photosensitizers (PS) has hampered the clinical relevance of interstitial photodynamic therapy (iPDT) for treatment of malignant glioma patients. The current pilot study focused on the development and the clinical implementation of an accurate and reproducible irradiation scheme for iPDT using 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PPIX) as a selectively working PS.

STUDY DESIGN/MATERIALS AND METHODS: Monte Carlo simulations of fluence rate and heat transport simulations were performed using the optical properties of normal brain tissue infiltrated by tumor cells (absorption coefficient micro(a) = 0.2 cm(-1), reduced scattering coefficient: micro'(s) = 20 cm(-1)). A modified 3-D treatment-planning software was used to calculate both, the treatment-volume and the exact position of the light diffusers within the lesion. The feasibility and the risk of iPDT were tested in 10 patients with small and circumscribed recurrent malignant gliomas.

RESULTS

The optimum distance between the implanted light diffusers was determined to be 9 mm with regard to both fluence rate and temperature distribution. For this distance a temperature increase above 42 degrees C was not expected to occur. Up to six cylindrical light diffusers were stereotactically implanted to achieve a complete irradiation of the tumor volume, which was possible in every single patient (mean tumor volume: 5.9 cm3). The total applied light fluence was between 4,320 J and 11,520 J. Side effects of iPDT were not observed. Median survival was 15 months.

CONCLUSION

5-ALA iPDT in combination with a 3-D treatment-planning (which was based on optical and thermal simulations) is a safe and feasible treatment modality. The clinical impact of these findings deserves further prospective evaluation.

摘要

背景与目的

对靶区内光和温度分布的了解有限,再加上所应用的光敏剂(PS)的非选择性聚集,阻碍了间质光动力疗法(iPDT)在恶性胶质瘤患者治疗中的临床应用。当前的这项初步研究聚焦于开发并临床实施一种精确且可重复的iPDT照射方案,该方案使用5-氨基乙酰丙酸(5-ALA)诱导的原卟啉IX(PPIX)作为具有选择性作用的PS。

研究设计/材料与方法:利用肿瘤细胞浸润的正常脑组织的光学特性(吸收系数μ(a)=0.2 cm⁻¹,约化散射系数:μ'(s)=20 cm⁻¹)进行了注量率的蒙特卡罗模拟和热传输模拟。使用经过修改的三维治疗计划软件来计算治疗体积以及病变内光扩散器的确切位置。在10例患有小的、边界清楚的复发性恶性胶质瘤的患者中测试了iPDT的可行性和风险。

结果

就注量率和温度分布而言,植入的光扩散器之间的最佳距离确定为9毫米。对于这个距离,预计不会出现温度升高超过42℃的情况。通过立体定向植入多达六个圆柱形光扩散器,以实现对肿瘤体积的完全照射,每位患者均有可能做到(平均肿瘤体积:5.9 cm³)。总的施加光注量在4320 J至11520 J之间。未观察到iPDT的副作用。中位生存期为15个月。

结论

5-ALA iPDT联合基于光学和热模拟的三维治疗计划是一种安全可行的治疗方式。这些发现的临床影响值得进一步进行前瞻性评估。

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