Focused ultrasound technology may overcome barrier to brain tumor treatments
New therapeutic and diagnostic clinical trials opening soon at UCSF Brain Tumor Center
The blood-brain barrier protects the brain from many viruses, bacteria, and other harmful small molecules that could be circulating throughout the body. However, this same barrier prevents many cancer therapies from reaching brain tumors.
This year, the UCSF Brain Tumor Center will be opening multiple clinical trials that use focused ultrasound to safely and temporarily disrupt the blood-brain barrier.
Focused ultrasound works by directing sound wave beams to a specific region in the brain using an implanted device or with the aid of real-time magnetic resonance imaging. At low frequencies, the combination of ultrasound waves and microbubbles injected into the blood can briefly open endothelial cells around the tumor.
This approach opens a transient gap that could allow for efficient delivery of drugs, antibodies and immune cells targeting brain tumors and creates an opportunity to improve treatment efficacy and patient outcomes, says John de Groot, MD, Division Chief of Neuro-Oncology within the Department of Neurological Surgery at UCSF.
In a new phase I/II clinical trial, recurrent glioblastoma patients will receive a prodrug that selectively accumulates in the tumor cells where it is metabolized into protoporphyrin IX. The energy produced by low intensity focused ultrasound then activates the drug, generating reactive oxygen species that kill tumor cells. This combination treatment is called sonodynamic therapy.
In collaboration with Northwestern University’s Robert H. Lurie Comprehensive Cancer Center, UCSF will open a trial using the Carthera implantable ultrasound device. The phase I/II clinical trial will enroll patients with recurrent glioblastoma with a planned surgery for tumor recurrence. At the time of surgery, a device with a fixed array of nine ultrasound transducers will be implanted in place of the skull. Once the patient has recovered from surgery, the device will be utilized to increase the delivery of carboplatin and paclitaxel to the tumor.
Disrupting the blood-brain barrier may also provide information about an individual patient’s tumor biology without the need for biopsy.
Liquid biopsies, which measure circulating tumor DNA (ctDNA) in the blood, have been successful in diagnosing many types of cancer, but the blood-brain barrier prevents measurable concentrations from entering the blood of brain tumor patients. Focused ultrasound can temporarily allow tumor ctDNA to enter the bloodstream.
In a new trial of glioblastoma patients, liquid biopsy will be collected before and after focused ultrasound treatment. Those biopsies will then be compared to a tissue sample taken after surgery to determine if biomarkers circulating in the blood correspond to those found in the tumor.
“If ctDNA is increased following focused ultrasound treatment, we may have a new tool to non-invasively assess tumor burden and understand how the disease changes over time,” de Groot said.
It may be especially helpful to identify whether changes on follow-up MRI scans are due to tumor progression or effects of treatment, such as radiation necrosis. Treatment-induced changes that mimic progression are referred to as pseudoprogression and can make it difficult to plan an appropriate treatment course.
As researchers continue to explore the use of focused ultrasound, de Groot believes that this technology may help guide new treatment strategies and enhance the efficacy of novel therapies.