KEY POINTS
- This guest editorial reviews preclinical, veterinary, technical, and early clinical evidence on ultrahigh dose-rate radiotherapy, emphasizing that reported normal-tissue protection varies by tissue, dose, fractionation, irradiated volume, oxygenation, and beam delivery conditions.
- Representative studies report dose-modifying effects corresponding to approximately 20%–30% normal-tissue sparing, but other models show negligible benefit, inconsistent protection, or greater toxicity than conventional dose-rate irradiation.
- In a veterinary study of feline nasal planum carcinoma, 3 of 7 cats (43%) treated with single-fraction 30 Gyelectron ultrahigh dose-rate radiotherapy developed severe maxillary bone necrosis, compared with no such events after conventional fractionated treatment.
- Mini-pigs treated with a single 31 Gy electron ultrahigh dose-rate field developed severe late skin necrosis at 7–9 months, with larger irradiated volumes associated with greater toxicity.
- Proton-based approaches currently offer the strongest pathway toward conformal ultrahigh dose-rate delivery, but substantial uncertainties remain regarding dose-rate definition, large-volume treatment, real-time dosimetry, quality assurance, and prediction of biological response.
CLINICAL TAKEAWAY
Ultrahigh dose-rate delivery should not be treated as a substitute for established dose-volume constraints, conformal planning, or the principle of keeping exposure as low as reasonably achievable. This editorial provides an important caution for investigators and early adopters, but it is an expert synthesis rather than comparative clinical evidence and does not establish treatment recommendations.