In a FLASH: reducing toxicity and enhancing cure for pediatric brain tumors

Dr. Sahaja Acharya, M.D. – Johns Hopkins University School of Medicine, Baltimore, MD

Although treatment advancements have increased survival rates for pediatric brain tumors, side effects remain a major issue. Recalling new information (memory), promptly completing mental tasks (processing speed), and maintaining focus (attention) are particularly affected in patients treated with radiation therapy (RT). We will address this problem by investigating FLASH, a method of delivering RT quickly, which has been shown to reduce short- and long-term neurocognitive problems in young mice compared to conventional RT. Originally, FLASH was delivered using electrons and X-rays, but these methods cannot reach deep parts of the brain where most brain tumors are located. A new technique, pencil beam scanning proton therapy, uses protons to deliver FLASH (pFLASH) to treat brain tumors. While promising, this approach cannot be translated to clinical practice because the correct dose for curing tumors and the best delivery method are still unknown. We aim to characterize the toxicity, cognitive function, and survival after p-FLASH compared to conventional RT in healthy mice and in mice with metastatic medulloblastoma and atypical teratoid/rhabdoid tumor, both of which are aggressive pediatric brain tumors. Our study will define optimal radiation doses and schedules to protect cognition and effectively treat these aggressive pediatric brain tumors with the long-term goal of translating this new technique into clinical practice.