A computational model of radiolytic oxygen depletion during FLASH irradiation and its effect on the oxygen enhancement ratio

Pratx, Guillem; Kapp, Daniel S.

doi:10.1088/1361-6560/ab3769

Cited by 137 publications

(173 citation statements)

References 54 publications

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“…maintained tumor control is proposed in a recent paper by Spitz et al They hypothesized that higher levels of redox-active iron (labile iron) in tumor compared to normal tissue and differences in oxidative metabolism between normal and tumor tissues, with the more rapid removal and decay of the organic hydroperoxides and free radicals derived from peroxidation chain reactions in normal tissue, defines the beneficial therapeutic index of the FLASH effect (50). Interestingly, a recent computational model of oxygen depletion induced by FLASH-RT concluded that radiochemical oxygen depletion at an expected rate of 0.42 mmHg/Gy would be sufficient to confer radioresistance (51). However, this conclusion was predicated on the basis that radioresistance would only be conferred to already hypoxic tissues.…”

Section: Hypotheses To Explain the Flash Effect Oxygen Depletion Hypomentioning

confidence: 99%

Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?

et al. 2020

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Radiotherapy is a cornerstone of both curative and palliative cancer care. However, radiotherapy is severely limited by radiation-induced toxicities. If these toxicities could be reduced, a greater dose of radiation could be given therefore facilitating a better tumor response. Initial pre-clinical studies have shown that irradiation at dose rates far exceeding those currently used in clinical contexts reduce radiation-induced toxicities whilst maintaining an equivalent tumor response. This is known as the FLASH effect. To date, a single patient has been subjected to FLASH radiotherapy for the treatment of subcutaneous T-cell lymphoma resulting in complete response and minimal toxicities. The mechanism responsible for reduced tissue toxicity following FLASH radiotherapy is yet to be elucidated, but the most prominent hypothesis so far proposed is that acute oxygen depletion occurs within the irradiated tissue. This review examines the tissue response to FLASH radiotherapy, critically evaluates the evidence supporting hypotheses surrounding the biological basis of the FLASH effect, and considers the potential for FLASH radiotherapy to be translated into clinical contexts.

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Section: Hypotheses To Explain the Flash Effect Oxygen Depletion Hypomentioning

confidence: 99%

Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?

et al. 2020

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“…Nevertheless, there are still many questions to be addressed, before using the FLASH effect in the clinical practice. The radiobiological mechanism underlying the FLASH effect is still unknown [11]; oxygen consumption has been proposed as a possible explanation [12][13][14] but other works underlined the limits of this explanation attempt and the need of further investigations [11,13].…”

Section: Introductionmentioning

confidence: 99%

FLASH Radiotherapy With Electrons: Issues Related to the Production, Monitoring, and Dosimetric Characterization of the Beam

Martino

Barca

Barone³

et al. 2020

Front. Phys.

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Various in vivo experimental works carried out on different animals and organs have shown that it is possible to reduce the damage caused to healthy tissue still preserving the therapeutic efficacy on the tumor tissue, by drastically reducing the total time of dose delivery (<200 ms). This effect, called the FLASH effect, immediately attracted considerable attention within the radiotherapy community, due to the possibility of widening the therapeutic window and treating effectively tumors which appear radioresistant to conventional techniques. Despite the experimental evidence, the radiobiological mechanisms underlying the FLASH effect and the beam parameters contributing to its optimization are not yet known in details. In order to fully understand the FLASH effect, it might be worthy to investigate some alternatives which can further improve the tools adopted so far, in terms of both linac technology and dosimetric systems. This work investigates the problems and solutions concerning the realization of an electron accelerator dedicated to FLASH therapy and optimized for in vivo experiments. Moreover, the work discusses the saturation problems of the most common radiotherapy dosimeters when used in the very high dose-per-pulse FLASH conditions and provides some preliminary experimental data on their behavior.

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“…The investigation of the influence of target oxygenation and LET on radiation-induced radical production and oxygen consumption opens the way for applications where these factors are being discussed to enable a differential radioprotective effect. This includes e.g., ultra-high dose rate (FLASH) conditions [39,41,42] where high instantaneous concentrations of ROS are produced and replenishment of oxygen through diffusion is too slow to maintain stable oxygenation.…”

Section: When Considering the Correlation Between The Production Yielmentioning

confidence: 99%

Impact of Target Oxygenation on the Chemical Track Evolution of Ion and Electron Radiation

Boscolo

Krämer

Fuß

et al. 2020

IJMS

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The radiosensitivity of biological systems is strongly affected by the system oxygenation. On the nanoscopic scale and molecular level, this effect is considered to be strongly related to the indirect damage of radiation. Even though particle track radiolysis has been the object of several studies, still little is known about the nanoscopic impact of target oxygenation on the radical yields. Here we present an extension of the chemical module of the Monte Carlo particle track structure code TRAX, taking into account the presence of dissolved molecular oxygen in the target material. The impact of the target oxygenation level on the chemical track evolution and the yields of all the relevant chemical species are studied in water under different irradiation conditions: different linear energy transfer (LET) values, different oxygenation levels, and different particle types. Especially for low LET radiation, a large production of two highly toxic species ( HO 2 • and O 2 • − ), which is not produced in anoxic conditions, is predicted and quantified in oxygenated solutions. The remarkable correlation between the HO 2 • and O 2 • − production yield and the oxygen enhancement ratio observed in biological systems suggests a direct or indirect involvement of HO 2 • and O 2 • − in the oxygen sensitization effect. The results are in agreement with available experimental data and previous computational approaches. An analysis of the oxygen depletion rate in different radiation conditions is also reported. The radiosensitivity of biological systems is strongly affected by the system oxygenation. On the nanoscopic scale and molecular level, this effect is considered to be strongly related to the indirect damage of radiation. Even though particle track radiolysis has been the object of several studies, still little is known about the nanoscopic impact of target oxygenation on the radical yields. Here we present an extension of the chemical module of the Monte Carlo particle track structure code TRAX, taking into account the presence of dissolved molecular oxygen in the target material. The impact of the target oxygenation level on the chemical track evolution and the yields of all the relevant chemical species are studied in water under different irradiation conditions: different linear energy transfer (LET) values, different oxygenation levels, and different particle types. Especially for low LET radiation, a large production of two highly toxic species ( HO 2 • and O 2 • − ), which is not produced in anoxic conditions, is predicted and quantified in oxygenated solutions. The remarkable correlation between the HO 2 • and O 2 • − production yield and the oxygen enhancement ratio observed in biological systems suggests a direct or indirect involvement of HO 2 • and O 2 • − in the oxygen sensitization effect. The results are in agreement with available experimental data and previous computational approaches. An analysis of the oxygen depletion rate in different radiation conditions is also reported.

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A computational model of radiolytic oxygen depletion during FLASH irradiation and its effect on the oxygen enhancement ratio

Cited by 137 publications

References 54 publications

Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?

Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?

FLASH Radiotherapy With Electrons: Issues Related to the Production, Monitoring, and Dosimetric Characterization of the Beam

Impact of Target Oxygenation on the Chemical Track Evolution of Ion and Electron Radiation

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