A potential revolution in cancer treatment: A topical review of FLASH radiotherapy

Abstract

FLASH radiotherapy (RT) is a novel technique in which the ultrahigh dose rate (UHDR) (≥40 Gy/s) is delivered to the entire treatment volume. Recent outcomes of in vivo studies show that the UHDR RT has the potential to spare normal tissue without sacrificing tumor control. There is a growing interest in the application of FLASH RT, and the ultrahigh dose irradiation delivery has been achieved by a few experimental and modified linear accelerators. The underlying mechanism of FLASH effect is yet to be fully understood, but the oxygen depletion in normal tissue providing extra protection during FLASH irradiation is a hypothesis that attracts most attention currently. Monte Carlo simulation is playing an important role in FLASH, enabling the understanding of its dosimetry calculations and hardware design. More advanced Monte Carlo simulation tools are under development to fulfill the challenge of reproducing the radiolysis and radiobiology processes in FLASH irradiation. FLASH RT may become one of standard treatment modalities for tumor treatment in the future. This paper presents the history and status of FLASH RT studies with a focus on FLASH irradiation delivery modalities, underlying mechanism of FLASH effect, in vivo and vitro experiments, and simulation studies. Existing challenges and prospects of this novel technique are discussed in this manuscript.

Characterization of 250 MeV Protons from the Varian ProBeam PBS System for FLASH Radiation Therapy

“…Investigations have shown the FLASH effect with x-rays in the kilovolt range [ 6 – 9 ] and efforts to achieve the FLASH effect with megavoltage x-rays [ 6 , 10 ]. Regardless, an attractive and readily available option to deliver a FLASH beam is cyclotron-based protons, specifically pencil beam scanning (PBS), because PBS can be better controlled in terms of position and intensity [ 11 ].…”

Mass density estimation based on single-energy computed tomography via deep learning

“…Note that DL models were trained with phantom data, while the SECT stoichiometric method and DECT empirical data were optimized for clinical use with both phantom and human tissue, which might lead to a worse performance than DL models on anthropomorphic phantoms mass density and RSP estimation. Improving the mass density estimation accuracy and reducing proton range uncertainty and margin may also help the proton ultra-high dose rate therapy which are actively investigated in research field [24].…”

Feasibility study of hybrid inverse planning with transmission beams and single‐energy spread‐out Bragg peaks for proton FLASH radiotherapy

“…The maximum number of spots to be removed each time was limited as N M prior to the spot reduction process. In each iteration, the N R least weighted spots were firstly removed from the planning, and the corresponding weights, w R , were excluded from w. Then, w were updated by the optimal weights, w * , acquired from solving the optimization problem formulated in (5). At last, the number of spots, N s , of weights ≥ w min was obtained and the minimum value between N R and N M was assigned to N R .…”

“…[1][2][3][4][5] Normal tissue sparing by the FLASH effect has been observed in several in vivo small animal studies using electron, photon, and proton beams. [1][2][3][4][5][6][7][8] The radiobiological mechanisms contributing to the FLASH effect have not yet been fully clarified, however, oxygen depletion and reactive oxygen species production are currently the most supported hypothesis. 9,10 The FLASH treatment of a first patient with T-cell cutaneous lymphoma using an electron beam has been shown to achieve promising outcomes both on normal skin and the tumor.…”