Modeling of the FLASH effect for ion beam radiation therapy

Song, Hanhyeon; Kim, Yeseul; Sung, Wonmo

doi:10.1016/j.ejmp.2023.102553

Cited by 3 publications

(1 citation statement)

References 21 publications

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“…Different in vivo and in-vitro endpoints are modeled; defining for example different RBE quantities for survival and/or mutation induction [10]. In most cases, molecular oxygen is believed to be a strong mediator for the FLASH effect, discussing the role of oxygen tension in tissues [18,19] and the impact of hypoxia on LET and RBE relationships, namely at the oxygen enhancement ratio [20], 12].…”

Section: Introductionmentioning

confidence: 99%

Phenomenological toy model for flash effect in proton therapy

García,

Llorena,

Illescas

et al. 2024

Eur. Phys. J. Plus

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We present a simple model based on general assumptions for the FLASH effect in radiotherapy, leading to a rate equation with only three free parameters. The model can predict the biological effect ratio between healthy and tumoral tissue for arbitrary input treatments, given as a dose rate versus time function. We analyze the behavior of the model and its sensitivity to its free parameters, and decide on suitable parameter values in accordance with available experimental data from the literature. Then we apply our model to study different sets of treatments, modeled as square pulse periodic functions with different pulse peak dose rate, pulse width and repetition period, in order to illustrate how it may be used to guide future experiment design. The model predicts that, for a given average dose rate above the FLASH threshold, a more prominent FLASH effect would be observed for continuous beams than for ultra-pulsated beams with an infinitely short irradiation time. This finding needs to be validated with suitable experiments.

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Section: Introductionmentioning

confidence: 99%

Phenomenological toy model for flash effect in proton therapy

García,

Llorena,

Illescas

et al. 2024

Eur. Phys. J. Plus

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A microscopic oxygen transport model for ultra‐high dose rate radiotherapy in vivo: The impact of physiological conditions on FLASH effect

Guo,

Medin,

Wang

2024

Medical Physics

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BackgroundUltra‐high dose rate irradiation (≥40 Gy/s, FLASH) has been shown to reduce normal tissue toxicity, while maintaining tumor control compared to conventional dose‐rate radiotherapy. The radiolytic oxygen (O2) depletion (ROD) resulting from FLASH has been proposed to explain the normal tissue protection effect; however, in vivo experiments have not confirmed that FLASH induced global tissue hypoxia. Nonetheless, the experiments reported are based on volume‐averaged measurement, which have inherent limitations in detecting microscopic phenomena, including the potential preservation of stem cells niches due to local FLASH‐induced O2 depletion. Computational modeling offers a complementary approach to understand the ROD caused by FLASH at the microscopic level.PurposeWe developed a comprehensive model to describe the spatial and temporal dynamics of O2 consumption and transport in response to irradiation in vivo. The change of oxygen enhancement ratio (OER) was used to quantify and investigate the FLASH effect as a function of physiological and radiation parameters at microscopic scale.MethodsWe considered time‐dependent O2 supply and consumption in a 3D cylindrical geometry, incorporating blood flow linking the O2 concentration ([O2]) in the capillary to that within the tissue through the Hill equation, radial and axial diffusion of O2, metabolic and zero‐order radiolytic O2 consumption, and a pulsed radiation structure. Time‐evolved distributions of [O2] were obtained by numerically solving perfusion‐diffusion equations. The model enables the computation of dynamic O2 distribution and the relative change of OER (δROD) under various physiological and radiation conditions in vivo.ResultsInitial [O2] level and the subsequent changes during irradiation determined δROD distribution, which strongly depends on physiological parameters, i.e., intercapillary spacing, ultimately determining the tissue area with enhanced radioresistance. We observed that the δROD/FLASH effect is affected by and sensitive to the interplay effect among physiological and radiation parameters. It renders that the FLASH effect can be tissue environment dependent. The saturation of FLASH normal tissue protection upon dose and dose rate was shown. Beyond ∼60 Gy/s, no significant decrease in radiosensitivity within tissue region was observed. In turn, for a given dose rate, the change of radiosensitivity became saturated after a certain dose level. Pulse structures with the same dose and instantaneous dose rate but with different delivery times were shown to have distinguishable δROD thus tissue sparing, suggesting the average dose rate could be a metric assessing the FLASH effect and demonstrating the capability of our model to support experimental findings.ConclusionOn a macroscopic scale, the modeling results align with the experimental findings in terms of dose and dose rate thresholds, and it also indicates that pulse structure can vary the FLASH effect. At the microscopic level, this model enables us to examine the spatially resolved FLASH effect based on physiological and irradiation parameters. Our model thus provides a complementary approach to experimental methods for understanding the underlying mechanism of FLASH radiotherapy. Our results show that physiological conditions can potentially determine the FLASH efficacy in tissue protection. The FLASH effect may be observed under optimal combination of physiological parameters, not limited to radiation conditions alone.

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