School of Biomedical Engineering and Sciences, Virginia Tech - Wake Forest University, Blacksburg, VA, 24061, USA.
Laboratory for Energy and Microsystems Innovation, Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
Med Phys. 2017 Sep;44(9):4968-4980. doi: 10.1002/mp.12401. Epub 2017 Jul 25.
Irreversible electroporation (IRE) has been developed as a promising minimally invasive treatment to ablate spontaneous brain tumors with pulsed electric fields in canine patients. The purpose of the study is to determine the Peleg-Fermi parameters needed to incorporate pulse number and pulse duration into the therapeutic planning of IRE.
Seven canine patients were treated with IRE for spontaneous malignant glioma with MRI-based treatment planning. The treatment planning method consists of building patient-specific finite element models and using them to compute electric fields used in the IRE treatment. We evaluate the predictive power of tumor coverage with electric field alone vs. cell kill probability using radiographically confirmed clinical outcomes.
Results of post-treatment diagnostic imaging, tumor biopsies, and neurological examinations indicated successful tumor ablation without significant direct neurotoxicity in six of the seven dogs. Objective tumor responses were seen in four (80%) of five dogs with quantifiable target lesions according to RANO criteria. Two dogs experienced survivals in excess of 1 yr, including one dog that resulted in complete response to IRE treatment for 5+ years to date. Tumor fraction exposed to electric field over 600 V/cm was between 0.08 and 0.73, while tumor fraction exposed to electric field over 300 V/cm was between 0.17 and 0.95. Probability of cell kill of ≥ 90% was found in tumor volume fractions between 0.21 and 0.99.
We conclude that IRE is a safe and effective minimally invasive treatment for malignant glioma and can be predicted with the Peleg-Fermi cell kill probability function. A tumor coverage of ≥ 0.9 at a cell kill probability ≥ 90% can be used to guide IRE treatments of spontaneous malignant glioma based on the radiographically confirmed clinical outcomes achieved.
不可逆电穿孔（IRE）已被开发为一种有前途的微创治疗方法，通过在犬患者中施加脉冲电场来消融自发性脑肿瘤。本研究的目的是确定将脉冲数和脉冲持续时间纳入 IRE 治疗计划所需的 Peleg-Fermi 参数。
对 7 例自发性恶性神经胶质瘤患者进行 MRI 引导的 IRE 治疗。治疗计划方法包括建立患者特异性有限元模型，并使用这些模型计算 IRE 治疗中使用的电场。我们通过影像学证实的临床结果评估仅用电场覆盖肿瘤与细胞杀伤概率的预测能力。
治疗后诊断性影像学、肿瘤活检和神经学检查结果表明，在 7 例犬中，有 6 例成功消融肿瘤，且无明显的直接神经毒性。根据 RANO 标准，有 5 例可量化靶病灶的犬中有 4 例（80%）出现了客观肿瘤反应。2 只犬的存活时间超过 1 年，其中 1 只犬的 IRE 治疗完全缓解，至今已超过 5 年。暴露于 600 V/cm 以上电场的肿瘤部分在 0.08 到 0.73 之间，而暴露于 300 V/cm 以上电场的肿瘤部分在 0.17 到 0.95 之间。发现肿瘤体积分数在 0.21 到 0.99 之间时，细胞杀伤概率≥90%。
我们得出结论，IRE 是一种安全有效的恶性神经胶质瘤微创治疗方法，可以用 Peleg-Fermi 细胞杀伤概率函数来预测。根据影像学证实的临床结果，肿瘤覆盖率≥0.9 且细胞杀伤概率≥90%可用于指导自发性恶性神经胶质瘤的 IRE 治疗。
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