Ultra-high dose-rates, the FLASH effect, and hydrogen peroxide yields: do experiments and simulations really disagree?

Abstract Radiation chemistry of model systems irradiated with ultra-high dose-rates (UHDR) is the key to obtain a mechanistic understanding of the observed sparing of healthy tissue. This sparing under isodose conditions is called the FLASH effect. It is envisioned to be used for more efficient treatment of cancer by FLASH radiotherapy . However, it seems that even the most simple model systems, namely water irradiated with varying dose-rates, pose a challenge. This became evident recently, as differences within measured and predicted hydrogen peroxide ( $$\hbox {H}_{{2}}\hbox {O}_{{2}}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mtext>H</mml:mtext> <mml:mn>2</mml:mn> </mml:msub> <mml:msub> <mml:mtext>O</mml:mtext> <mml:mn>2</mml:mn> </mml:msub> </mml:mrow> </mml:math> ) yields (G values) for exposure of liquid samples to conventional dose-rates and UHDR were reported. Many of the recently reported values contradict older experimental studies and current Monte-Carlo simulations (MCS). In the present work, we aim to identify possible underlying reasons of these discrepancies and propose ways to overcome this issue. Hereby a short review of recent and classical literature concerning experimental and simulational studies is performed. The studies cover different radiation sources, from gamma rays, high-energy electrons, heavy particles, such as protons and ions, with low and high linear energy transfer (LET), and samples of hypoxic and oxygenated water, with and without added cosolutes such as bovine-serum albumine (BSA). Results are compared in terms of additional experimental parameters, such as solvent, sample container and analysis methods used to determine the respective G values of $$\hbox {H}_{{2}}\hbox {O}_{{2}}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mtext>H</mml:mtext> <mml:mn>2</mml:mn> </mml:msub> <mml:msub> <mml:mtext>O</mml:mtext> <mml:mn>2</mml:mn> </mml:msub> </mml:mrow> </mml:math> . Similarly the parameter governing the outcome of the MCS by the step-by-step (SBS) approach, or the independent-reaction time (IRT) method are discussed. Here, UHDR induced modification of the radical–radical interaction and dynamics, not governed by diffusion processes, may cause problems. Approaches to test these different models are highlighted to allow progress: by making the step from a purely descriptive discourse of the effects observed, toward testable models, which should clarify the reasons of how and why such a disagreement came to light in the first place. Graphical abstract