Predictive therapeutic planning for irreversible electroporation treatment of spontaneous malignant glioma.

Abstract

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.