Brain Cancer, Childhood Cancer, Research and Clinical Trials

Pediatric brain tumor research: Enhancing treatment and quality of life

By Nicole Ferrara • May 24, 2023

Estimated reading time: 5 minutes

By Mayo Clinic staff

Pediatric brain tumors are rare, and their biology differs from adult brain tumors. This makes them more challenging to treat.

"It's critical that we develop new therapies and treatment methods, because right now the options are limited," says Jonathan Schwartz, D.O., a Mayo Clinic pediatric neuro-oncologist.

Researchers from Mayo Clinic's Pediatric Brain Tumor Clinic are developing targeted therapies and studying ways to improve the effectiveness of brain tumor treatments and reduce their side effects. Their goal is to improve the quality of life for children living with brain tumors.

Reducing radiation therapy's cognitive effects

Studies have shown that radiation therapy can cause declines in cognitive function in children who undergo that treatment for brain tumors. Mayo Clinic has led efforts to determine if a drug called memantine can reduce those toxic effects.

"Memantine might block receptors in the brain that are known to contribute to declines in attention, memory or thought processes," says Nadia Laack, M.D., chair of Radiation Oncology at Mayo Clinic in Rochester, Minnesota.

Dr. Laack led a pilot study that involved treating children with memantine before they started radiation therapy. The promising results led to a larger national investigation, which she is leading.

Split-course radiation for diffuse midline glioma

Reducing the toxic effects of radiation therapy is also the goal of a new Mayo Clinic study for children with brainstem diffuse midline glioma. A glioma is an abnormal growth of glial cells, which surround nerve cells and help them function. In young children, diffuse midline gliomas typically occur in the brainstem, which links the brain to the spinal cord and controls many functions vital to life such as heart rate, blood pressure and breathing. These gliomas can grow quickly, cause severe symptoms and have a two-year survival rate of only 10%.

Treatment for diffuse midline glioma most commonly includes six weeks of radiation therapy. Health care professionals consider a second course of radiation therapy if symptoms increase or if the tumor grows and other options are unavailable.

In the study, children have an initial two weeks of radiotherapy followed by close monitoring. "We delay a second two-week course until there is some evidence that the tumor is growing. If need be, we give a third two-week round later," says Anita Mahajan, M.D., a Mayo Clinic radiation oncologist. "We still monitor and treat the tumor, but this is an opportunity to use radiation more strategically."

Mayo Clinic researchers are assessing the time intervals between patients' first and second courses of radiation and any effects on treatment and survival that result from splitting the course.

Improving quality of life is the new study's primary goal. "Spending time at home participating in normal daily activities, instead of days in the hospital, is what makes a child and family's quality of life better," says Dr. Mahajan. "We're going to be with our patients through anything that presents. We want to have a positive impact on their lives."

Developing and delivering drugs

Other research seeks to develop medications to treat diffuse midline glioma. One approach targets a protein called STAT3 that helps control cell growth and division, cell movement and self-destruction of cells.. In a recent study, researchers in the Mayo Clinic Experimental Drug and Therapeutics for Pediatric Brain Tumor Laboratory demonstrated that a drug that inhibits STAT3’s function stopped tumor growth and prolonged survival in animal models.

Researchers in the laboratory have developed several drugs that inhibit STAT3 that could potentially go on to clinical testing.

Researchers are also looking for better ways to deliver existing therapies to brain tumors. "We have found that many drugs clear the brain too quickly to have the appropriate therapeutic effect," says David Daniels, M.D., Ph.D., a Mayo Clinic pediatric neurosurgeon and the laboratory's director.

The laboratory has developed a method of delivery that bypasses the blood-brain barrier to transport medication directly to a tumor over an extended period of five to seven days. Researchers have tested the system in laboratory specimens. Planning is underway for a phase 1 clinical trial.

CAR-NK cells, oncolytic therapies and AI

Mayo Clinic researchers also are designing chimeric antigen receptor (CAR)-engineered natural killer (NK) cells to treat pediatric brain cancer tumors.

"CAR-NK cells are genetically engineered soldiers," says Dr. Schwartz, the pediatric neuro-oncologist. "They can potentially be placed in the brain carrying antibodies directed against patients' specific tumors."

Using CAR-NK immunotherapy avoids the release of toxic cytokines into a patient's blood. "The incidence of graft-versus-host disease is much lower than CAR-T cell therapy," says Dr. Schwartz.

Mayo Clinic is also investigating improvements in oncolytic virus therapies. "We are genetically modifying viruses to target cancer cells and spare healthy cells. The goal is to lessen toxicity and to attract immune cells to improve efficacy," says Dr. Schwartz.

On another front, artificial intelligence (AI) projects involve extracting large quantities of data from medical imaging. Patterns from this data may help predict treatment response and cancer subtypes and determine if a tumor has progressed.

"These are truly unmet needs in pediatric neuro-oncology," says Dr. Schwartz.

Researchers at Mayo Clinic's Pediatric Brain Tumor Clinic are committed to finding new treatment options for children with this disease. "We are all on board with advancing the science," says Dr. Mahajan. "We are learning so much and hope to continue improving how we approach pediatric brain tumors."