Therapeutic manipulation and bypass of the blood-brain barrier: powerful tools in glioma treatment.

Authors: Giantini-Larsen AM, Pandey A, Garton ALA, Rampichini M, Winston G, Goldberg JL, Magge R, Stieg PE, Souweidane MM, Ramakrishna R

The blood-brain barrier (BBB) remains an obstacle for delivery of chemotherapeutic agents to gliomas. High grade and recurrent gliomas continue to portend a poor prognosis. Multiple methods of bypassing or manipulating the BBB have been explored, including hyperosmolar therapy, convection-enhanced delivery (CED), laser-guided interstitial thermal therapy (LITT), and Magnetic Resonance Guided Focused Ultrasound (MRgFUS) to enhance delivery of chemotherapeutic agents to glial neoplasms. Here, we review these techniques, currently ongoing clinical trials to disrupt or bypass the BBB in gliomas, and the results of completed trials.

Introduction

Purpose Drug delivery with BBB opening (review)

Outcomes and Safety

Summary of Outcomes This review summarizes four techniques to manipulate or bypass the blood-brain barrier for glioma treatment: hyperosmolar therapy (mannitol with intra-arterial chemotherapy), convection-enhanced delivery (CED; catheter-based infusion of therapeutics), laser interstitial thermal therapy (LITT; hyperthermia-induced BBB disruption), and MR-guided focused ultrasound (MRgFUS; low-intensity sonication with microbubbles for transient BBB opening). Preclinical and clinical trial results demonstrate safety and feasibility, with increased drug concentrations in sonicated regions and modest improvements in progression-free and overall survival. Implantable ultrasound devices (SonoCloud) show promise for repeated BBB opening.

Brain Region

Targeted brain region(s) Not specified

Ultrasound Parameters

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