Over the past 20+ years, work done by clinicians and scientists in the Morgan Adams Foundation Pediatric Brain Tumor Research Program has driven important discoveries and revolutionary new approaches to treating kids with cancer.
Here are some of the ways donor support has helped kids, teens, and young adults with brain tumors:
Low-grade glioma
Pediatric low-grade glioma (pLGG) is the most common brain tumor, comprising 35% of all diagnoses in kids. Pediatric LGG patients have satisfactory overall survival rates, but their quality of life can be very poor.
Mutations in BRAF are well known common genetic drivers of pLGG, and back in 2013, our researchers identified the v600e BRAF mutation. Based on that discovery, clinicians at Children’s Hospital Colorado were the first to use a specific treatment for pediatric low-grade glioma called RAF inhibition.
The groundbreaking work done in pediatrics also applied to adults as our team identified that epithelial glioblastoma is also driven by the v600e BRAF mutation.
Medulloblastoma
Medulloblastoma is one of the most common malignant brain tumors in kids, accounting for 15-20% of all pediatric brain tumors. There are four subgroups of medulloblastoma, and there is a wide variance in outcomes between the different subtypes. Overall survival is 60-80%, but the median survival for recurrent medulloblastoma is less than 12 months.
In the late 1990s, there was no standard treatment for infant medulloblastoma and the cancer was 100% fatal. Our neuro-oncologists were the first to use tandem high-dose chemotherapy with stem cell transplant. The first patient on the clinical trial was treated at Children’s Colorado and survived.
The combination of high-dose chemotherapy with stem cell rescue is still the standard treatment today, and that trial remains the foundation for all high-dose tandem clinical trials.
Ependymoma
Colorado is home to Dr. Nick Foreman, a world-leading expert in ependymoma. Dr. Foreman is the chair of the Children’s Oncology Group (COG) and International Society of Pediatric Oncology (SIOP) ependymoma working groups. The Morgan Adams Foundation has been funding complementary projects to improve outcomes in this disease since 2005.
Ependymoma is the third most common childhood brain tumor, usually affecting children under 5 years old. Posterior fossa group A (PFA) is the most common type of ependymoma, and it is curable only about 50% of the time when treated with the standard therapy of surgical resection and radiation. PFA ependymoma has a high recurrence rate with poor outcomes among patients whose cancer recurs.
Dr. Foreman’s research team identified that abnormalities in the chromosome drive most mortalities in PFA ependymoma. The team also identified that the standard treatment of surgery and radiation did not work for kids with that chromosome abnormality. Several clinical trials for PFA ependymoma have been proposed, all driven by the biological discoveries first made in Dr. Foreman’s lab.
Importantly, our team is able to identify the patients who have the chromosome abnormality at diagnosis, which determines their treatment. Additionally, the team have created a way to predict the patients who will develop the chromosome abnormality at relapse so they can be included in the high-risk category of treatment at diagnosis, with the hope that it will prevent recurrence.
High-grade glioma
Pediatric high-grade gliomas (pHGG) are the most aggressive of all childhood central nervous system (CNS) tumors and the most common cause of childhood cancer death. pHGG are highly invasive and often grow diffusely among normal cells, which means surgical removal may not be an option. Radiation therapy can provide some additional time, but the tumor almost always returns after radiation.
Researchers funded by The Morgan Adams Foundation were the first to identify that the DNA irregularity of MGMT methylation is an indicator of a patient’s prognosis and should be used to direct treatment. Our group was also the first to identify molecular subtypes of high-grade glioma which require different therapies.
Our research team is also driving discovery in specific subtypes of pHGG, including:
Diffuse intrinsic pontine glioma (DIPG) / Diffuse midline glioma (DMG)
Diffuse intrinsic pontine glioma (DIPG) is a type of high-grade glioma that forms in the brainstem. It is a deadly pediatric brain tumor that is effectively incurable.
The average survival for kids diagnosed with DIPG is less than 1 year. Fewer than 10% of DIPG patients are alive two years from diagnosis. Treatment options are extremely limited. Radiation is the only standard treatment, and even that shows minimal benefit: the tumor shrinks initially but resumes growing and becomes resistant to treatment.
For many decades, DIPG/DMG tumors were not biopsied because the brainstem is a difficult part of the brain to access surgically. Our doctors were the first in the United States to establish that biopsy of DIPG is safe. The availability of biopsy in DIPG made a huge difference because analysis of tumors at diagnosis has led to an explosion in the understanding of the biology of this deadly tumor.
Congenital glioblastoma multiforme (cGBM)
Neonatal or congenital GBM is a rare, malignant primary brain tumor that occurs in infants within the first few months of life. It has a poor overall prognosis with significant mortality and morbidity.
Researchers in the Morgan Adams Foundation Pediatric Brain Tumor Research Program were the first to prove that congenital GBM were not uniformly fatal and that low dose chemotherapy could cure these kids. This treatment is now the standard of care.
Further research by our group discovered that cGBM tumors are driven by specific mutations, making targeted therapy a good possibility for future treatments.
The Morgan Adams Foundation Pediatric Brain Tumor Research Program is made up of 8 principal investigators and more than 40 researchers, all working together to improve outcomes for kids and teens with brain tumors.
They are collaborative, open, and at the forefront of new research technologies and techniques. The team is creative and with so many bright minds, they approach a problem from dozens of perspectives and work together to determine the best way to find answers.
Ultimately, our doctors and researchers believe in the importance of coming up with new ideas. Without new ideas, it would be impossible to create safer and more effective treatments for cancer. They understand and appreciate that something that doesn’t work as expected may still result in new knowledge gained, and they’re not afraid to try something new in the lab.
The group is devoted to figuring out how to make novel techniques work so that new aspects of brain tumor biology will be revealed. Because that’s where new ideas come from.
Thanks to donor support, our group can focus entirely on their goal of helping kids with cancer. They are unique in their open-minded approach and willingness to collaborate with each other and with researchers at other institutions.
Great things are possible when we work together. We are grateful to everyone who has helped enable brilliant scientists to make discoveries that enable improvements in treating kids with cancer.
