Journal Article

Hyperthermic Laser Ablation of Recurrent Glioblastoma Leads to Temporary Disruption of the Peritumoral Blood Brain Barrier

Kim, Michael J., Shimony, Joshua S., Leuthardt, Eric C., Miller-Thomas, Michelle M., Tran, David D., Duan, Chong, Campian, Jian L., Kim, Albert H.

2016

Overview

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. 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. 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. 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. ClinicalTrials.gov NCT01851733.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Ablation / Aged / Aged, 80 and over / Biology and Life Sciences / Blood / Blood-brain barrier / Blood-Brain Barrier - metabolism / Brain / Brain cancer / Brain damage / Brain Neoplasms - diagnosis / Brain Neoplasms - enzymology / Brain Neoplasms - metabolism / Brain Neoplasms - surgery / Brain tumors / Care and treatment / Catheters / Central nervous system / Chemical compounds / Chemotherapy / Contrast Media - metabolism / Cytotoxicity / Disruption / Drug delivery / Drug delivery systems / Drugs / Engineering and Technology / Fever / Glioblastoma / Glioblastoma - diagnosis / Glioblastoma - enzymology / Glioblastoma - metabolism / Glioblastoma - surgery / Glioblastomas / Glioma / Humans / Hyperthermia, Induced / Laser ablation / Laser Therapy - methods / Lasers / Magnetic Resonance Imaging / Medical imaging / Medicine / Medicine and Health Sciences / Membrane permeability / Middle Aged / Neurosurgery / NMR / Nuclear magnetic resonance / Oncology / Patient outcomes / Patients / Permeability / Pharmacology / Phosphopyruvate hydratase / Phosphopyruvate Hydratase - blood / Physical Sciences / Physiological aspects / Research and Analysis Methods / Serum levels / Surgery / Surgery, Computer-Assisted / Tumors