Aditi Bagchi, MD, PhD

Medulloblastoma in infants

Utilizing this molecularly informed treatment strategy guides my approach as co-principal investigator of SJiMB21. SJiMB21 is a phase 2 clinical trial that uses molecular and clinical risk-based therapeutic approaches for newly diagnosed medulloblastoma in infants (0-3 years) and young children (3-5 years). This is the first clinical protocol to use DNA methylation-based classification to guide treatment for pediatric brain tumors.

Medulloblastoma can be classified into four molecular groups (WNT, SHH, G3 and G4) and 13 molecular subgroups (WNT, SHH-1, SHH-2, SHH-3, SHH4, G3/G4-1, G3/G4-2, G3/G4-3, G3/G4-4, G3/G4-5, G3/G4-6, G3/G4-7 and G3/G4-8) based on methylation profiles. Retrospective research has shown that the most common group and subgroup of medulloblastoma in infants are SHH-1 and SHH-2, which can be effectively treated without radiation. Meanwhile, the molecular group G3/G4 is much rarer and cannot be cured without radiation.

SJiMB21 uses methylation-based classification to profile medulloblastoma risk and stratify and assign treatment based on molecular group/subgroup. Using this approach, we design targeted treatment approaches that spare SHH patients of radiation. We treat SHH-2 patients with lower intensity systemic chemotherapy while SHH-1 patients receive a more intensified chemotherapy and G3/G4 patients are given delayed, risk-adapted radiation.

High-Grade Gliomas in infancy

Among the brain tumors diagnosed during infancy, gliomas are the most common. Pediatric high-grade gliomas (pHGG) are diagnostically and clinically challenging during infancy. pHGGs have a better prognosis in infants, but predicting individual outcomes is elusive.

In a study comprising 56 infants with pHGG, it was identified that infant type hemispheric glioma (IHG) is a type of pHGG that is volumetrically large and hemorrhagic but primarily drives the better prognosis in this age group. Molecular studies of IHG have shown distinct methylation profiles and genetic drivers that consist of receptor tyrosine kinase (RTK) fusion (ALK, ROS1, NTRK1/2/3, and MET). The RTK fusions can be targeted by unique tyrosine kinase inhibitors that cause rapid and sustained shrinkage of these tumors, making them safe for surgical resection.

As a next step in this work, I am developing a frontline clinical trial that will test the use of the tyrosine kinase inhibitor as primary therapy. The objective of this trial is to improve the survival of patients but also mitigate the toxicities of chemotherapy and aggressive surgeries that are currently being used to treat these tumors.

A large part of my clinical research involves seeing patients in the St. Jude Brain Tumor Clinic. I see about 25 new patients per year and serve as a consultant across the U.S. for patients with rare infantile brain tumors. Each opportunity to care for a patient informs the next step in clinical research as we seek to improve survival rates and quality-of-life measures for patients with infantile brain tumors.