(MEMPHIS, Tenn. – November 05, 2025) By analyzing data from three clinical trials treating children with the brain tumor medulloblastoma, scientists at St. Jude Children's Research Hospital have designed an approach to safely reduce therapy, thereby lowering side effects. The analysis of almost 900 patients included genomic, molecular and survival information, which was used to create new treatment risk groups. Physicians and scientists can explore these findings in an easy-to-use web-based portal specifically designed for analyzing medulloblastoma data. The findings and portal platform were published recently in Neuro-Oncology and Cancer Research, respectively.
Medulloblastoma is a pediatric brain tumor treated with radiation and chemotherapy. In growing children, these therapies can have side effects or toxicities that impact their health later in life.
"We found data to support that 40% of patients with medulloblastoma can receive lower doses of craniospinal radiation therapy and almost all can receive less chemotherapy than they received in the clinical trials we analyzed and maintain the same or better survival," said Giles Robinson , MD, St. Jude Division of Neuro-oncology director, Department of Oncology , co-corresponding author on the Neuro-Oncology and Cancer Research studies.
Classifying patients for treatment
The researchers identified new groups of patients who could receive lower intensity treatment by studying clinical trial data. They looked at outcomes and compared them between the trials, taking into account the differences in treatment and each tumor's molecular features, such as DNA sequences and methylation profiles. This is the first time scientists have been able to harmonize treatment and molecular data across such a large cohort.
These findings led the researchers to identify new risk factors and predictors of therapy effectiveness. For example, patients whose tumor falls into one of the two most common molecular groups of the disease, G3 or G4, could be subdivided based on the loss and gain of certain chromosomes, the methylation subgroup and amplifications of the known oncogene MYC. The result is the ability to group patients into one of four actionable treatment recommendation groups from low to high intensity. This work provides a guide for classifying patients differently, which may ultimately lead to many patients receiving lower-intensity treatments and only a few requiring high-intensity treatments.
"Medulloblastoma is highly variable and can be divided into many different subcategories, so it has been unclear which factors are the most crucial for classifying patients into different treatment groups," Robinson said. "Our results provide a blueprint to better risk-stratify therapy so that not everyone receives such toxic treatment and only the most aggressive tumors receive the most aggressive therapy."
Robinson is launching a clinical trial to test these categorizations. That trial will be facilitated, in part, by a web-based medulloblastoma data portal.
Point-and-click to predict medulloblastoma outcomes
Molecular data used to classify patients for treatment can be obtuse and difficult to work with. The St. Jude scientists realized that the complexity of medulloblastoma would add to that challenge. So, they made the Medulloblastoma Meta-Analysis (MB-meta) Portal , which incorporates the data from the Neuro-Oncology analysis and its implications into an easy-to-use interface. Physicians, scientists and patients can choose the demographic, clinical and molecular features of interest, then see predicted survival for patients matching those features.
"We created the portal so anyone can perform a simple point-and-click, choosing variables to generate predicted survival curves for patients with medulloblastoma," said corresponding author of the Clinical Research study, Xin Zhou , PhD, St. Jude Department of Computational Biology , who was also a co-senior author on the Neuro-Oncology paper. "The survival curves tell the expected differences of survivors' outcome, based on the way the cohort is stratified."
The portal is a tool to help physicians assess different treatment strategies based on a patient's clinical and molecular data, as well as a resource to study medulloblastoma. "We've made this data available at anybody's fingertips," Zhou said. "We hope that it can lead to more insights, which we can one day use to fuel new clinical trials to better treat the disease."
As a proof of principle, the scientists used the portal to explore cancer-driving mutations in the gene KBTBD4. They identified two different novel subgroups of mutations in the gene, suggesting that there may be a better way to classify these patients. When they associated some KBTBD4 mutations with other molecular features, it also hinted at previously unknown disease biology, providing a new area of investigation into how these mutations drive disease, which may eventually lead to novel treatments.
Ultimately, the results from the two studies promise to work together to provide a brighter future for patients. "By making this data available through the portal," Robinson said, "We hope that others will explore and make findings, like ours, that may have a dramatic impact on quality of life, greatly improving it for future survivors of medulloblastoma."
Access the portal here: https://viz.stjude.cloud/st-jude-childrens-research-hospital/visualization/medulloblastoma-integrative-analysis-portal~2882
Authors and funding
Neuro-Oncology: The study's co-first authors are Kyle Smith, Sandeep Dhanda and Catherine Billups, St. Jude. The other senior authors are Arzu Onar-Thomas and Paul Northcott, St. Jude. The other authors are Edgar Sioson, Congyu Lu, Airen Zaldivar Peraza, Karishma Gangwani, Yimei Li, Qian Li Tong Lin and Amar Gajjar, St. Jude; Jeff Michalski, Washington University School of Medicine; Roger Packer, Children's National Hospital; James Olson and Sarah Leary, Seattle Children's Research Institute; and Maryam Fouladi, Nationwide Children's Hospital.
The study was supported by grants from the The Brain Tumor Charity, The Mark Foundation (Emerging Leader Award), St. Baldrick's Foundation (Robert J. Arceci Innovation Award), and the National Cancer
Institute (P30CA021765, CCSG 5P30CA021765-43 Developmental Funds, R01CA270785-01A1 and P01CA096832) and ALSAC, the fundraising and awareness organization of St. Jude.
Cancer Research: The study's co-first authors are Karishma Gangwani, Congyu Lu, Edgar Sioson and Sandeep Kumar Dhanda, St. Jude. The study's other authors are Airen Zaldívar Peraza, Gavriel Matt, Robin Paul, Jian Wang, Colleen Reilly, Aleksandar Acić, Kyle Smith, Tong Lin, Qian Li and Paul Northcott, St. Jude.
The study was supported by grants from the National Cancer Institute (P30CA021765) and ALSAC, the fundraising and awareness organization of St. Jude.
