The potential and risks of FLASH radiotherapy in pediatric patients

Irradiation at ultra-high dose rates, also termed as 'FLASH' radiotherapy, has generated great interest in radiation oncology due to its potential to preferentially spare healthy tissue without compromising tumor control. Over the past decade, studies on the potential benefits of FLASH radiotherapy (FLASH-RT) have grown rapidly, yet the underlying mechanisms of this differential effect remain poorly understood. Nonetheless, compelling preclinical data, particularly the preservation of cognitive function after whole-brain irradiation, suggest that FLASH-RT may significantly improve quality of life, especially for pediatric patients. Early preclinical (large animal) and adult clinical trials are underway, prompting consideration of how and when to translate this modality to pediatric populations. This review summarizes the current state of FLASH-RT, with a special focus on pediatric CNS applications. We discuss disease-specific opportunities and limitations, how biological and clinical differences between adults and children may influence the FLASH effect, and key factors that must be evaluated before safe and effective pediatric translation.