A New Paradigm for Pediatric Brain Tumors

The brain is shielded from most toxins and pathogens by a highly complex network of blood vessels—the blood-brain barrier—that restricts the size and chemical composition of molecules that can cross through it and into brain tissue. This barrier is also one of the major challenges neuro-oncologists face in treating brain tumors: most chemotherapeutic agents are not able to penetrate the blood-brain barrier to reach brain and spinal cord tumors, or do so only in very low and ineffective amounts. For decades researchers have tested new agents in both pediatric and adult brain tumors with little success, “and there is tremendous room for improvement,” says Columbia pediatric oncologist Luca Szalontay, MD.

Dr. Szalontay co-leads Columbia’s Initiative for Drug Delivery Innovation (IDDI) along with radiation oncologist Cheng-Chia Wu, MD, PhD. Together with researchers from Columbia’s biomedical engineering department (Elisa Konofagou, PhD) and other colleagues at Columbia, the IDDI team has opened a trial testing a non-invasive method to circumvent the blood-brain barrier. The IDDI team hopes this new approach will improve the currently dismal outlook for the 700 children in the U.S. diagnosed each year with a special type of brain tumor, called diffuse midline glioma. 

Researchers at Columbia have long been at the leading edge of studies using focused ultrasound (FUS) with microbubbles in a variety of medical applications. Microbubbles, miniscule gas-filled spheres administered by infusion, respond to ultrasound, and can mechanically separate the cells that make up the blood-brain barrier, allowing higher concentrations of chemotherapeutic drugs to enter the brain. The Columbia study is among the first in the world to assess this new, non-invasive technique in children with brain tumors. “We hope to show that, using smaller doses of an active drug, we can achieve the same, or even better results, and avoid the systemic side effects for these children,” Dr. Szalontay says. 

The IDDI team worked with pediatric oncologist Jovana Pavisic, MD, who uses mathematical modeling to identify specific drugs that will be most effective against individual patient’s tumors and in cancers with poor outcomes. Using this drug prediction algorithm, Dr. Pavisic identified the targeted therapy etoposide as the potentially most effective agent in children with brain tumors called diffuse midline gliomas. The team is opening a study using focused ultrasound and etoposide for children with relapsed diffuse midline glioma. In addition, they are working with pediatric immuno-oncologist Robyn Gartrell, MD, to explore the use of FUS to deliver immunotherapy agents.

Since the late 2000s the number of pediatric brain and spinal tumors has been on a slight but steady uptick, and these often deadly diseases are on course to overtake leukemia as the most common cancers in children. Through research based on new technologies and new drugs the IDDI team is determined to provide children with these tumors a brighter future.