Thomas L. Ellis, Paulo A. Garcia, John H. Rossmeisl Jr., Natalia Henao-Guerrero, John Robertson and Rafael V. Davalos
Nonthermal irreversible electroporation (NTIRE) is a novel, minimally invasive technique to treat cancer, which is unique because of its nonthermal mechanism of tumor ablation. This paper evaluates the safety of an NTIRE procedure to lesion normal canine brain tissue.
The NTIRE procedure involved placing electrodes into a targeted area of brain in 3 dogs and delivering a series of short and intense electric pulses. The voltages of the pulses applied were varied between dogs. Another dog was used as a sham control. One additional dog was treated at an extreme voltage to determine the upper safety limits of the procedure. Ultrasonography was used at the time of the procedure to determine if the lesions could be visualized intraoperatively. The volumes of ablated tissue were then estimated on postprocedure MR imaging. Histological brain sections were then analyzed to evaluate the lesions produced.
The animals tolerated the procedure with no apparent complications except for the animal that was treated at the upper voltage limit. The lesion volume appeared to decrease with decreasing voltage of applied pulses. Histological examination revealed cell death within the treated volume with a submillimeter transition zone between necrotic and normal brain.
The authors' results reveal that NTIRE at selected voltages can be safely administered in normal canine brain and that the volume of ablated tissue correlates with the voltage of the applied pulses. This preliminary study is the first step toward using NTIRE as a brain cancer treatment.
John H. Rossmeisl Jr., Paulo A. Garcia, Theresa E. Pancotto, John L. Robertson, Natalia Henao-Guerrero, Robert E. Neal II, Thomas L. Ellis and Rafael V. Davalos
Irreversible electroporation (IRE) is a novel nonthermal ablation technique that has been used for the treatment of solid cancers. However, it has not been evaluated for use in brain tumors. Here, the authors report on the safety and feasibility of using the NanoKnife IRE system for the treatment of spontaneous intracranial gliomas in dogs.
Client-owned dogs with a telencephalic glioma shown on MRI were eligible. Dog-specific treatment plans were generated by using MRI-based tissue segmentation, volumetric meshing, and finite element modeling. After biopsy confirmation of glioma, IRE treatment was delivered stereotactically with the NanoKnife system using pulse parameters and electrode configurations derived from therapeutic plans. The primary end point was an evaluation of safety over the 14 days immediately after treatment. Follow-up was continued for 12 months or until death with serial physical, neurological, laboratory, and MRI examinations.
Seven dogs with glioma were treated. The mean age of the dogs was 9.3 ± 1.6 years, and the mean pretreatment tumor volume was 1.9 ± 1.4 cm3. The median preoperative Karnofsky Performance Scale score was 70 (range 30–75). Severe posttreatment toxicity was observed in 2 of the 7 dogs; one developed fatal (Grade 5) aspiration pneumonia, and the other developed treatment-associated cerebral edema, which resulted in transient neurological deterioration. Results of posttreatment diagnostic imaging, tumor biopsies, and neurological examinations indicated that tumor ablation was achieved without significant direct neurotoxicity in 6 of the 7 dogs. The median 14-day post-IRE Karnofsky Performance Scale score of the 6 dogs that survived to discharge was 80 (range 60–90), and this score was improved over the pretreatment value in every case. Objective tumor responses were seen in 4 (80%) of 5 dogs with quantifiable target lesions. The median survival was 119 days (range 1 to > 940 days).
With the incorporation of additional therapeutic planning procedures, the NanoKnife system is a novel technology capable of controlled IRE ablation of telencephalic gliomas.