Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology | 2021

May oxygen depletion explain the FLASH effect? A chemical track structure analysis.

 
 
 
 
 

Abstract


BACKGROUND AND PURPOSE\nRecent observations in animal models show that ultra-high dose rate ( FLASH ) radiation treatment significantly reduces normal tissue toxicity maintaining an equivalent tumor control. The dependence of this FLASH effect on target oxygenation has led to the assumption that oxygen depletion could be its major driving force.\n\n\nMATERIALS AND METHODS\nIn a bottom-up approach starting from the chemical track evolution of 1 MeV electrons in oxygenated water simulated with the TRAX-CHEM Monte Carlo code, we determine the oxygen consumption and radiolytic reactive oxygen species production following a short radiation pulse. Based on these values, the effective dose weighted by oxygen enhancement ratio (OER) or the in vitro cell survival under dynamic oxygen pressure is calculated and compared to that of conventional exposures, at constant OER.\n\n\nRESULTS\nWe find an excellent agreement of our Monte Carlo predictions with the experimental value for radiolytic oxygen removal from oxygenated water. However, the application of the present model to published radiobiological experiment conditions shows that oxygen depletion can only have a negligible impact on radiosensitivity through oxygen enhancement, especially at typical experimental oxygenations where a FLASH effect has been observed.\n\n\nCONCLUSION\nWe show that the magnitude and dependence of the oxygen depletion hypothesis are not consistent with the observed biological effects of FLASH irradiation. While oxygenation plays an undoubted role in mediating the FLASH effect, we conclude that state-of-the-art radiation chemistry models do not support oxygen depletion and radiation-induced transient hypoxia as the main mechanism.

Volume None
Pages None
DOI 10.1016/j.radonc.2021.06.031
Language English
Journal Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

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