Abstract
FLASH radiotherapy is a rapidly developing field which promises improved normal tissue protection compared to conventional irradiation and no compromise on tumour control. The transient hypoxic state induced by the depletion of oxygen at high dose rates provides one possible explanation. However, studies have mostly focused on uniform fields of dose and there is a lack of investigation into the spatial and temporal variation of dose from proton pencil-beam scanning (PBS). A model of oxygen reaction and diffusion in tissue has been extended to simulate proton PBS delivery and its impact on oxygen levels. This provides a tool to predict oxygen effects from various PBS treatments, and explore potential delivery strategies. Here we present a number of case applications to demonstrate the use of this tool for FLASH-related investigations. We show that levels of oxygen depletion could vary significantly across a large parameter space for PBS treatments, and highlight the need for in silico models such as this to aid in the development and optimisation of FLASH radiotherapy.
Highlights
The development of proton pencil-beam scanning (PBS) was a major breakthrough in particle therapy [1]
Nodes at a distance of approximately 20–30 μm were found to undergo the greatest reduction in oxygen enhancement ratio (OER) in this example; this is roughly expected from the quasi-hyperbolic variation of OER with oxygen tension [26], where there exists an initial tension at which a maximum change in OER is achieved for a given depletion
As expected from the four beams in the treatment simulation, there is a gross structure in the OER curves consisting of four troughs where the nodes, in the cases of the GTV and brainstem, experience prolonged oxygen depletion from consecutive spots
Summary
The development of proton pencil-beam scanning (PBS) was a major breakthrough in particle therapy [1]. The exploration of ultra-high dose rates during the 1970s and 1980s led to promising results demonstrating improved sparing of normal tissue compared to conventional dose rates [3,4]. This was attributed to a depletion of molecular oxygen, at a rate too fast for cells to be re-oxygenated via diffusion of oxygen from nearby blood vessels, resulting in a state of transient hypoxia to produce the apparent sparing effect [5,6]. Despite the major advantages of each of these breakthrough treatment modalities, the avenue that exists from combining the techniques remains under-explored
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