Early Clinical Trial Results of Focused Ultrasound for Pediatric Brain Cancer

A Columbia University-led research team has reported encouraging early results from the first pediatric clinical trial using focused ultrasound (FUS) to temporarily open the blood–brain barrier (BBB) to support drug delivery, without the need for sedation. The team was led by Stergios Zacharoulis, MD, and Elisa Konofagou, PhD, with Cheng Chia Wu, MD, PhD (now at Virginia Tech and Children’s National Hospital).

Published in Science Translational Medicine, the study involved three children with diffuse midline glioma (DMG), previously classified as diffuse intrinsic pontine glioma (DIPG). These tumors form in critical midline brain structures and are difficult to remove surgically. DMG carries a poor prognosis, with a median overall survival of about one year, underscoring the urgent need for new approaches.

To perform BBB opening, the team developed a portable focused ultrasound platform called Delsona. The system uses a 250-kHz single-element transducer and includes real-time imaging, cavitation mapping guidance, neuronavigation guidance, and integrated tracking and sensor components. Delsona is currently being evaluated in clinical trials for Parkinson’s disease, Alzheimer’s disease, DMG, and peripheral neuropathy.

In the DMG trial, researchers delivered focused ultrasound with Definity® microbubbles immediately before administering panobinostat, a histone deacetylase (HDAC) inhibitor that showed survival benefit in preclinical DMG models when given after ultrasound-induced BBB opening. Treatments were delivered in an outpatient setting, as frequently as every two days, before panobinostat was later removed from the U.S. market.

Key outcomes from the first three participants:

·       BBB opening was successful in all three patients

·       Two patients had BBB opening at two separate tumor sites

·       In one case, it took one week to confirm BBB closure due to unclear contrast enhancement

·       Two participants showed clinical improvement, though some panobinostat-related toxicity was observed

·       One participant unexpectedly died during the trial period, but the death was unrelated to the study protocol

Overall, the results demonstrate that neuronavigation-guided focused ultrasound BBB opening is feasible, repeatable, and safe in children with DMG, supporting continued investigation.