Abstract Body

Tumors of the central nervous system are the most common solid tumor in childhood. Radiation therapy regularly has a pivotal role in their treatment. Technological advancements have dramatically improved the ability to deliver radiation in a more focused manner, but despite this, side effects remain a concern. Over the world, medulloblastoma (MB) is the most frequent malignant central nervous system tumor in childhood. Currently, post-operative craniospinal radiation is considered the standard of care. Treatment increases survival considerably, but treatment-related cognitive, neurologic, and endocrinologic effects can severely affect children’s quality of life. In different animal models, Ultra-High Dose rate radiotherapy has recently been shown to produce the Flash Effect, meaning that it maintains anti-tumor efficacy without the normal tissue complications associated with standard dose rates. In this talk, the most recent pre-clinical results exploring the Flash Effect on the brain of juvenile mice will be presented. First, flash radiotherapy (FLASH-RT) has been shown to protect from neurocognitive decrements induced by conventional radiotherapy (CONV-RT). Better cognitive outcomes can be related to the fact that, after FLASH-RT, the neurogenesis and vasculature are preserved, and neuroinflammation is reduced. More recently it has been proved that FLASH-RT can also protect synaptic integrity and preserve long term potentiation (LTP), which is considered an electrophysiological basis of memory and cognition. On the other hand, using orthotopic cerebellar injections of MB human cells (UW-228 cells) in juvenile mice, we assessed tumor volumes after both FLASH-RT and CONV-RT by contrast-enhanced cone beam CT (CBCT).We used the electron eRT6/Oriatron/CHUV/6 MeV to deliver 3 Fx of 10 Gy, both CONV-RT at 0.01Gy/pulse 100ms between pulses (mean dose rate 0.1 Gy/s) and FLASH-RT at 5.6x10⁶ Gy/s delivered in a single 1.8 μs pulse. We found that both irradiation modalities were iso-effective in controlling tumor growth and increasing survival. This demonstrates for the first time that FLASH-RT, while may offer protection from cognitive impairments and improvements in quality of life, can preserve the efficacy against brain pediatric tumors. In summary, pre-clinical results suggest that the flash effect is plausible in pediatric brain tumors and can be considered a future alternative to treat brain tumors in pediatric patients.
Works presented were supported by FNS/SPIRIT grant IZSTZ0_198747/1, NCI grants P01CA244091 and CONACYT/CCINSHAE scholarship.