While spatial dose conformity delivered to a target volume has been pushed to its practical limits with advanced treatment planning and delivery, investigations in novel temporal dose delivery are unfolding new mechanisms. Recent advances in ultra-high dose radiotherapy, abbreviated as FLASH, indicate the potential for reduction in healthy tissue damage while preserving tumor control. FLASH therapy relies on very high dose rate of > 40Gy/s with sub-second temporal beam modulation, taking a seemingly opposite direction from the conventional paradigm of fractionated therapy. FLASH brings unique challenges to dosimetry, beam control, and verification, as well as complexity of radiobiological effective dose through altered tissue response. In this review, we compare the dosimetric methods capable of operating under high dose rate environments. Due to excellent dose-rate independence, superior spatial (∼ <1 mm) and temporal (∼ns) resolution achievable with Cherenkov and scintillation-based detectors, we show that luminescent detectors have a key role to play in the development of FLASH, as the field rapidly progresses toward clinical adaptation. Additionally, we show that the unique ability of certain luminescence-based methods to provide tumor oxygenation maps in real-time with submillimeter resolution can elucidate the radiobiological mechanisms behind the FLASH effect. In particular, such techniques will be crucial for understanding the role of oxygen in mediating the FLASH effect.

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Objective. Existing ultra-high dose rate (UHDR) electron sources lack dose rate independent dosimeters and a calibrated dose control system for accurate delivery. In this study, we aim to develop a custom single-pulse dose monitoring and a real-time dose-based control system for a FLASH enabled clinical linear accelerator (Linac). Approach. A commercially available point scintillator detector was coupled to a gated integrating amplifier and a real-time controller for dose monitoring and feedback control loop. The controller was programmed to integrate dose for each radiation pulse and stop the radiation beam when the prescribed dose was delivered. Additionally, the scintillator was mounted in a solid water phantom and placed underneath mice skin for in vivo dose monitoring. The scintillator was characterized in terms of its radiation stability, mean dose-rate ( D ̇ m ), and dose per pulse (D p) dependence. Main results. The D p exhibited a consistent ramp-up period across ∼4–5 pulse. The plastic scintillator was shown to be linear with D ̇ m (40–380 Gy s−1) and D p (0.3–1.3 Gy Pulse−1) to within +/− 3%. However, the plastic scintillator was subject to significant radiation damage (16%/kGy) for the initial 1 kGy and would need to be calibrated frequently. Pulse-counting control was accurately implemented with one-to-one correspondence between the intended and the actual delivered pulses. The dose-based control was sufficient to gate on any pulse of the Linac. In vivo dosimetry monitoring with a 1 cm circular cut-out revealed that during the ramp-up period, the average D p was ∼0.045 ± 0.004 Gy Pulse−1, whereas after the ramp-up it stabilized at 0.65 ± 0.01 Gy Pulse−1. Significance. The tools presented in this study can be used to determine the beam parameter space pertinent to the FLASH effect. Additionally, this study is the first instance of real-time dose-based control for a modified Linac at ultra-high dose rates, which provides insight into the tool required for future clinical translation of FLASH-RT.