Irreversible Electroporation for the Treatment of Brain Tumors: Pre-clinica! Results in a Canine Model of Spontaneous Glioma

摘要

Irreversible electroporation (IRE) is a nonthermal ablation technique that has been used for the treatment of numerous solid tumors. However, it has not been rigorously evaluated for use in brain tumors. Here we report the results of a pre-clinical study evaluating the safety of the NanoKnife IRE System for the treatment of spontaneous intracranial gliomas in a canine model. Client-owned dogs with biopsy-confirmed cerebral gliomas were eligible. Patient-specific treatment plans were generated using MRI-based tissue segmentation, volumetric meshing, and finite element modeling. IRE treatment was delivered using pulse parameters and electrode configurations derived from therapeutic plans using the NanoKnife System. The primary end point was an evaluation of safety over the 14 days immediately following treatment. Follow-up was continued for 1 year with serial neurological, laboratory, and brain MRI examinations. Seven dogs with gliomas were treated. The mean age of patients was 9.3 +/- 1.6 years, and the mean pre-treatment tumor volume was 1.9 +/- 1.4 cm3. The median preoperative Karnofsky Performance Score (KPS) was 70 (range, 30-75). Severe post-treatment toxicity was observed in 2/7 dogs, one of which developed fatal aspiration pneumonia and the other treatment associated cerebral edema, which resulted in transient neurological deterioration. Post-treatment diagnostic imaging, tumor biopsies, and neurological examinations indicated that tumor ablation was achieved without significant direct neurotoxicity in 6/7 dogs. The 14 day post-IRE KPS of the 6/7 dogs surviving to discharge was improved over pre-treatment values in all cases. Objective tumor responses were seen in 4/5 (80%) of dogs with quantifiable MRI target lesions. The median survival was 119 days (range, 1 to > 840 days). With the incorporation of additional therapeutic planning techniques, the NanoKnife System is a novel technology capable of rapid and controlled IRE ablation of cerebral gliomas.