Clinical translation of ultra-high dose rate flash radiotherapy: Opportunities, challenges, and prospects

Table 1 Key parameters from ultra-high dose rate flash radiotherapy clinical trials

Trial phase	Tumor type	Dose rate (Gy/s)	Total dose (Gy)	Normal tissue toxicity	Tumor control	Follow-up
I	Cutaneous	166	15-35	Reduced skin fibrosis	Comparable	24 months
I	Bone metastases	200	8	Minimal myelopathy	Partial	9 months

Table 2 Summary of clinical trials and application scenarios for ultra-high dose rate flash radiotherapy with different beam devices

Beam type	Energy/characteristics	Clinical application scenarios	Current trial phase	Key advantages	Limitations
Low-energy electrons	≤ 10 MeV	Superficial tumors (e.g., skin cancers, cutaneous lesions)	Phase I trials ongoing	Mimics pre-clinical conditions for safety validation. Minimal normal tissue damage	Limited penetration depth (approximately 3 cm-5 cm). Restricted to accessible tumors
FLASH-VHEE	50-250 MeV	Deep-seated tumors (e.g., lung, brain, abdominal)	Pre-clinical development	Higher penetration depth (up to 20 cm-30 cm). Potential for homogeneous dose distribution	Requires specialized accelerators. Technical challenges in beam control
Protons	70-250 MeV	Deep-seated tumors with critical organ proximity	Prototype development	Combines flash dose rates with Bragg peak precision. Enhanced normal tissue sparing	High infrastructure costs. Limited availability of flash-enabled systems
X-rays (linac-based)	6-20 MV	Broad applications (superficial and deep tumors)	Early feasibility studies	Utilizes existing linear accelerators with modifications. Flexible energy adjustments	Requires beam parameter optimization (dose rate ≥ 40 Gy/second). Limited clinical data

VHEE: Very high-energy electrons.