title: Safety and feasibility of the NanoKnife system for irreversible electroporation ablative treatment of canine spontaneous intracranial gliomas.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 cm(3). 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).
  
  
  CONCLUSIONS
  With the incorporation of additional therapeutic planning procedures, the NanoKnife system is a novel technology capable of controlled IRE ablation of telencephalic gliomas.
authors.affiliation: Department of Small Animal Clinical Sciences and.|Veterinary and Comparative Neurooncology Laboratory, Virginia-Maryland Regional College of Veterinary Medicine, and.|Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, Virginia; and.
authors.forename: John H
authors.initials: JH
authors.lastname: Rossmeisl
authors.affiliation: Veterinary and Comparative Neurooncology Laboratory, Virginia-Maryland Regional College of Veterinary Medicine, and.|Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, Virginia; and.
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Garcia
authors.affiliation: Department of Small Animal Clinical Sciences and.
authors.forename: Theresa E
authors.initials: TE
authors.lastname: Pancotto
authors.affiliation: Department of Small Animal Clinical Sciences and.|Veterinary and Comparative Neurooncology Laboratory, Virginia-Maryland Regional College of Veterinary Medicine, and.|Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, Virginia; and.
authors.forename: John L
authors.initials: JL
authors.lastname: Robertson
authors.affiliation: Department of Small Animal Clinical Sciences and.
authors.forename: Natalia
authors.initials: N
authors.lastname: Henao-Guerrero
authors.affiliation: Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, Virginia; and.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Neal
authors.affiliation: Department of Neurosurgery and Deep Brain Stimulation Program, School of Medicine, Wake Forest University, Winston-Salem, North Carolina.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Ellis
authors.affiliation: Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, Virginia; and.
authors.forename: Rafael V
authors.initials: RV
authors.lastname: Davalos
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy / Q000601:surgery / Q000662:veterinary*; D003131:Combined Modality Therapy; D004283:Dog Diseases / Q000188:drug therapy* / Q000601:surgery*; D004285:Dogs; D053672:Electrochemotherapy / Q000009:adverse effects / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D005910:Glioma / Q000188:drug therapy / Q000601:surgery / Q000662:veterinary*; D008297:Male; D019635:Neurosurgical Procedures / Q000295:instrumentation; D011446:Prospective Studies; D013687:Telencephalon
keywords: CTCAE = Common Terminology Criteria for Adverse Events; DICOM = Digital Imaging and Communications in Medicine; GBM = glioblastoma multiforme; IRE = irreversible electroporation; IV = intravenous; KPS = Karnofsky Performance Scale; PBS = phosphate-buffered saline; PD = progressive disease; PDMS = polydimethylsiloxane; PGP = probe guide pedestal; RANO = response assessment in neurooncology; SD = stable disease; brain tumor; dog; electroporation; glioma; neurosurgery; oncology