UCSF Pediatric Focus

Zeroing In on Pediatric Brain Tumors

The UCSF-led Pacific Pediatric Neuro-Oncology Consortium (PNOC) clinical trials have begun to yield encouraging results for children with brain tumors.

Trials Range from Sequencing Through Enhanced Delivery

“The PNOC trials are beginning to demonstrate the value of personalized medicine for our patients,” says Nalin Gupta, MD, PhD, surgical director of the UCSF Pediatric Brain Center (PBC).

For example, a first-of-its-kind trial for diffuse intrinsic pontine glioma (DIPG), a universally fatal brain tumor, has demonstrated both the need for and the feasibility of gathering and analyzing samples quickly enough to use them for guidance in personalized treatments.

PNOC is a network of 15 leading children’s hospitals, started by neuro-oncologists from UCSF, that aims to accelerate the process of testing new therapies tailored to the cellular pathways or mutations of each child’s specific tumor. At UCSF, PNOC offers rapid enrollment in clinical trials, in conjunction with family-oriented care delivered by the Pediatric Brain Center's team of dedicated physicians, nurses, social workers and neuropsychologists.

The DIPG trial is the first in the United States to test the use of next-generation sequencing to inform an individualized treatment plan in children and young adults with newly diagnosed DIPG. Clinicians take advantage of advances in gene expression and sequencing technologies to devise a plan using Food and Drug Administration (FDA)-approved drugs, based on each child’s tumor characteristics.

“We have shown it’s feasible to collect and analyze samples in a timely fashion – and because not one single tumor looked like another, we’ve demonstrated the need for individualized, precision medicine approaches,” says Sabine Mueller, MD, PhD, MAS, the trial’s principal investigator.

The trial’s next phase tests whether the profiling can make a clinical difference, though Mueller believes the differences will truly emerge with the discovery of new and better therapies – including combination therapies – and ways to more effectively deliver drugs to the brain. Among the PNOC trials already in progress or due to start soon that address this need:

  • Using MRI-guided, convection-enhanced delivery of DIPG therapies to demonstrate whether delivering drugs directly to the tumor can yield improved clinical results.
  • Testing an immune-peptide vaccine for patients with DIPG and other midline gliomas. After standard radiation therapy, clinicians will deliver an immunotherapeutic vaccine designed to act against a characteristic genetic mutation for DIPG in children.
  • Testing the use of a modified oncolytic measles virus as a therapy to treat children with medulloblastoma and atypical teratoid/rhabdoid tumors. Clinicians will administer the therapy in one of two ways: during surgery when a recurrent tumor is localized, or directly into the cerebrospinal fluid via a lumbar puncture for a disseminated tumor.

Resources for Families

While the therapies offer hope for what have been incurable tumors, families undergoing these trials can take advantage of an interdisciplinary Pediatric Brain Center neuro-oncology clinic. Services and providers there include neurosurgery, endocrinology, ophthalmology, rehabilitation, dedicated nurse practitioners, social workers and a neuropsychologist to help with cognitive challenges.

“Children and families not only take advantage of the latest therapies, but also an integrated program of comprehensive support that helps them maintain a sense of normalcy,” says Heather Fullerton, MD, MAS, the PBC’s medical director.