Toxicity of Pulsed Beams in Radiation Therapy from a Physio-Chemical Perspective

Abstract: A significant portion of cancer patients receive radiotherapy as part of their curative or palliative treatment plan. Radiotherapy is however greatly limited by radiation induced toxicities in healthy tissue surrounding the tumour, which can lead to long-term or acute complications for a patient. In response to this issue, recent studies have considered a new technique called FLASH radiotherapy, where ultra-high dose rates have been shown to effectively reduce toxicity in normal cells whilst maintaining a tumour response equivalent to conventional dose rates. However, the exact mechanism for this effect is not yet well understood. This project seeks to investigate if certain dose delivery patterns exist where there is an increase or reduction of concentration of the toxic radical hydroxyl, which is known to play a key role in the damage of DNA in the cell, for unchanged total dose. This was done by simulating the chemical reactions which take place when water is irradiated with ionizing radiation using a simple model system consisting of water with free oxygen dissolved into it, called RadChemModel. Using basic reaction laws from chemistry, the concentration of each chemical species involved was solved for from a system of linear and non-linear ordinary differential equations. The concentration of hydroxyl was calculated as a function of time for a range of irradiation beam patterns. This model supports that there could be a difference in toxicity between FLASH and conventional beam parameters. Furthermore, a shift in the behaviour of hydroxyl suggesting reduced toxicity was observed at FLASH dose rates with very high beam pulse frequencies. However, the results obtained do not provide enough information to confirm that the concentration of hydroxyl is reduced with FLASH beam parameters.