title: Hyperthermic Laser Ablation of Recurrent Glioblastoma Leads to Temporary Disruption of the Peritumoral Blood Brain Barrier.
abstract: BACKGROUND
  Poor central nervous system penetration of cytotoxic drugs due to the blood brain barrier (BBB) is a major limiting factor in the treatment of brain tumors. Most recurrent glioblastomas (GBM) occur within the peritumoral region. In this study, we describe a hyperthemic method to induce temporary disruption of the peritumoral BBB that can potentially be used to enhance drug delivery.
  
  
  METHODS
  Twenty patients with probable recurrent GBM were enrolled in this study. Fourteen patients were evaluable. MRI-guided laser interstitial thermal therapy was applied to achieve both tumor cytoreduction and disruption of the peritumoral BBB. To determine the degree and timing of peritumoral BBB disruption, dynamic contrast-enhancement brain MRI was used to calculate the vascular transfer constant (Ktrans) in the peritumoral region as direct measures of BBB permeability before and after laser ablation. Serum levels of brain-specific enolase, also known as neuron-specific enolase, were also measured and used as an independent quantification of BBB disruption.
  
  
  RESULTS
  In all 14 evaluable patients, Ktrans levels peaked immediately post laser ablation, followed by a gradual decline over the following 4 weeks. Serum BSE concentrations increased shortly after laser ablation and peaked in 1-3 weeks before decreasing to baseline by 6 weeks.
  
  
  CONCLUSIONS
  The data from our pilot research support that disruption of the peritumoral BBB was induced by hyperthemia with the peak of high permeability occurring within 1-2 weeks after laser ablation and resolving by 4-6 weeks. This provides a therapeutic window of opportunity during which delivery of BBB-impermeant therapeutic agents may be enhanced.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01851733.
authors.affiliation: Brain Laser Center, Department of Neurological Surgery, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, United States of America.|Department of Neurological Surgery, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, United States of America.|Center for Innovation in Neuroscience and Technology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, United States of America.|Department of Biomedical Engineering, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, United States of America.|Department of Mechanical Engineering and Material Sciences, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, United States of America.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Leuthardt
authors.affiliation: Department of Chemistry, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, United States of America.
authors.forename: Chong
authors.initials: C
authors.lastname: Duan
authors.affiliation: Neuro-Oncology Program, Division of Oncology, Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Brain Laser Center, Department of Neurological Surgery, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, United States of America.|Neuro-Oncology Program, Division of Oncology, Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, United States of America.
authors.forename: Jian L
authors.initials: JL
authors.lastname: Campian
authors.affiliation: Brain Laser Center, Department of Neurological Surgery, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, United States of America.|Department of Neurological Surgery, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, United States of America.
authors.forename: Albert H
authors.initials: AH
authors.lastname: Kim
authors.affiliation: Division of Neuroradiology, Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, United States of America.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Miller-Thomas
authors.affiliation: Division of Neuroradiology, Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, 63110, United States of America.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Shimony
authors.affiliation: Division of Neuro-Oncology, Lillian S. Wells Department of Neurological Surgery, McKnight Brain Institute, The University of Florida College of Medicine, Gainesville, Florida, 32610, United States of America.
authors.forename: David D
authors.initials: DD
authors.lastname: Tran
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000201:enzymology / Q000378:metabolism* / Q000601:surgery*; D003287:Contrast Media / Q000378:metabolism; D005909:Glioblastoma / Q000175:diagnosis / Q000201:enzymology / Q000378:metabolism* / Q000601:surgery*; D006801:Humans; D006979:Hyperthermia, Induced; D053685:Laser Therapy / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000097:blood; D025321:Surgery, Computer-Assisted
chemical_list: D003287:Contrast Media; D010751:Phosphopyruvate Hydratase