Differential and regionally distinct molecular responses distinguish FLASH and conventional RT in a medulloblastoma model while preserving therapeutic outcomes

Hypofractionated FLASH-RT (3×10 Gy at 5.5×10 Gy/s) and conventional RT (3×10 Gy at 0.1 Gy/s) both produce long-lasting anti-tumor effects in orthotopic UW228-MB mice.

• Why it matters: The clinical translation of FLASH depends on whether it preserves therapeutic outcomes while altering molecular and region-specific tissue responses linked to treatment complications.
• What they did: Juvenile UW228-MB-bearing nude mice received 3×10 Gy (BED10 = 60 Gy) with 48 h between fractions; molecular profiling used digital spatial profiling and immunofluorescence 24 h post-RT, with long-term tumor response, cognition, and neuroinflammation tracked in additional cohorts.
• The result: Neuroinflammatory markers were statistically reduced after FLASH, with sustained microglial activation in the cerebellar tumor micro-environment and hippocampal astrocyte–neuron transcriptional crosstalk, including enhanced MCT4 expression, while NOR performance remained preserved.

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