The Largest High-Risk Medulloblastoma Trial Makes Monumental Strides Forward for Cancer Research, Increases Survival in Children by 19 Percent

Seattle Children’s is excited to announce results published today in JAMA Oncology. The study, “Randomized clinical trial of carboplatin 1 and isotretinoin in children with high-risk medulloblastoma: A report from the Children’s Oncology Group,” found that therapy intensification with carboplatin improved survival significantly for children with high-risk Group 3 medulloblastoma, the largest increase in survival in any high-risk medulloblastoma trial to date. The addition of carboplatin during radiation improved survival from 54 percent to 73 percent for children with high-risk Group 3 medulloblastoma, a 19 percent increase at five years.

The trial (ACNS0332) was sponsored by the Children’s Oncology Group (COG) with funding from the National Cancer Institute and was carried out at more than 200 COG member institutions from around the world. It’s the largest international trial involving children with high-risk medulloblastoma ever conducted.

“Since the advent of radiation and chemotherapy over a half century ago, we’ve never seen this big of an improvement in one clinical trial for kids with brain tumors, to my knowledge,” said Dr. James Olson, an oncologist at Seattle Children’s, professor at the Fred Hutchinson Cancer Research Center (FHCRC) and the University of Washington School of Medicine, who was the COG Study Chair for the trial and lead author. “From this point forward, for kids with the Group 3 subset of medulloblastoma, what this means is 20 more children out of every 100 will survive the disease than would have survived in the past. It’s a forever improvement, and it gives us a clear roadmap for the future.”

Dr. Sarah Leary, a co-investigator and medical director of the Pediatric Brain Tumor Program and clinical research in the Cancer and Blood Disorders Center at Seattle Children’s, says the results are monumental.

Brain tumors are the leading cause of disease-related death in children, and medulloblastoma is the most common malignant embryonal brain tumor. About 400 children are diagnosed each year with medulloblastoma in the U.S.

Although the ultimate goal is to replace the need for radiation and chemotherapy altogether, this study helps move research forward by pinpointing treatment approaches that are effective for specific subgroups of disease. Not all children with medulloblastoma will benefit from the addition of carboplatin, but for those who will, they will see a significant improvement in survival. According to Leary, genomic studies have identified at least four distinct molecular subgroups of medulloblastoma.

From this clinical trial, there are four key takeaways:

1. Molecular diagnosis is critical.
2. Aggressive treatment based on molecular diagnosis improves brain tumor survival for a group of high-risk children with medulloblastoma.
3. Clinical trials save lives.
4. Collaboration, both nationally and internationally, is imperative to help find better, more effective treatments for children with cancer.

Nearly 20 years ago, a pilot study was conducted by COG (99701). The study aimed to determine if carboplatin, a chemotherapy drug used to treat a variety of cancers, in conjunction with radiation and chemotherapy, could be given safely in children with high-risk medulloblastoma. During that initial study, it wasn’t clear whether the addition of carboplatin would help all children with medulloblastoma, or a subset of children with the disease. From that foundational research, this trial was initiated to better understand which specific subgroups may potentially benefit from the additional treatment approach.

The trial was conducted from 2007 to 2018 and included nearly 300 children and young adults ages 3 to 21. Although medulloblastoma is a broad term for the type of cancer, genetically, medulloblastoma is now considered four different diseases based on molecular grouping. The trial split participants into varying subtypes of medulloblastoma using molecular diagnosis and placed participants in groups based on the genetic analysis of their cancer.

“Genetic analysis is essential,” Olson said. “It not only helps us decide the right treatment, but it helps us make the right diagnosis from the beginning. It helps us decide the right treatment to give to the patients who will benefit the most and avoid toxic treatment to those who won’t benefit at all. Tumors may look the same under a microscope, but if they are genetically different, they will respond differently to various types of treatment approaches.”

Olson says the early pilot study provided incredible insights into the benefits of molecular diagnosis. He said they learned that for some types of pediatric brain tumors, the pathologic diagnosis was incorrect 70 percent of the time. That potentially means that 70 percent of the time, the best and most effective treatment approach may not have been utilized. It’s one of the reasons Seattle Children’s is spearheading integrated molecular diagnosis.

Seattle Children’s is internationally known for developing better ways to care for young people with cancers or blood disorders. Many Seattle Children’s oncologists are leaders in research to help transform treatment and improve outcomes.

“We have a long journey ahead, but we’ve made enormous progress,” Olson said. “We’ve improved survival for this group of kids to 73 percent. There is still too much toxicity, but we’re currently working on additional therapies that could replace radiation and chemotherapy. That’s our next step.”

Sammy Loch was diagnosed with medulloblastoma when she was a sophomore in high school. The diagnosis turned her world upside down. She underwent surgery, radiation, chemotherapy and spent countless months at Seattle Children’s. Leary was her oncologist at the time. When she was initially approached about enrolling in the study, Loch said the decision was put in her hands. After careful consideration, she decided to be a part of the trial.

“Participating in research was my way to give back and pay it forward,” said Loch. “It’s really exciting to know more people will survive because of the research I was involved in.”

Today, Loch is 27 years old and continues to pay it forward. She is a therapist for people with chronic health conditions, and she regularly participates in fundraising opportunities for pediatric cancer research. She has been cancer-free for more than 11 years.

To learn more about clinical trials offered at Seattle Children’s, visit Current Research Studies page or ClinicalTrials.gov. For brain tumors specifically, please visit our Brain Tumor page.

About The Children’s Oncology Group (COG)

COG (childrensoncologygroup.org), a member of the NCI National Clinical Trials Network (NCTN), is the world’s largest organization devoted exclusively to childhood and adolescent cancer research. COG unites over 10,000 experts in childhood cancer at more than 200 leading children’s hospitals, universities, and cancer centers across North America, Australia, and New Zealand in the fight against childhood cancer. Today, more than 90% of the 16,000 children and adolescents diagnosed with cancer each year in the United States are cared for at COG member institutions. Research performed by COG institutions over the past 50 years has transformed childhood cancer from a virtually incurable disease to one with a combined 5-year survival rate of 80%. COG’s mission is to improve the cure rate and outcomes for all children with cancer.