High dose‐per‐pulse electron beam dosimetry: Commissioning of the Oriatron eRT6 prototype linear accelerator for preclinical use

Jaccard, Maud; Durán, M. Teresa; Petersson, Kristoffer; Germond, Jean‐François; Liger, Philippe; Vozenin, Marie-Catherine; Bourhis, Jean; Bochud, François; Bailat, Claude

doi:10.1002/mp.12713

Cited by 163 publications

(189 citation statements)

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“…Irradiation Devices. Irradiation was performed using a prototype 6MeV electron beam linear accelerator (LINAC) of type Oriatron 6e (eRT6; PMB-Alcen), available at Lausanne University Hospital and described previously (43). Physical dosimetry has been extensively described and published to ensure reproducible and reliable biological studies (19,(43)(44)(45).…”

Section: Methodsmentioning

confidence: 99%

“…Irradiation was performed using a prototype 6MeV electron beam linear accelerator (LINAC) of type Oriatron 6e (eRT6; PMB-Alcen), available at Lausanne University Hospital and described previously (43). Physical dosimetry has been extensively described and published to ensure reproducible and reliable biological studies (19,(43)(44)(45). This LINAC is able to produce pulsed electron beams at a mean dose rate ranging from 0.1 Gy·s −1 (i.e., comparable to conventional dose rates used in RT) up to 1,000 Gy·s −1 , corresponding to a dose, in each electron pulse, ranging from 0.01 up to 10 Gy.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species

Montay‐Gruel

Acharya

Petersson

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Here, we highlight the potential translational benefits of delivering FLASH radiotherapy using ultra-high dose rates (>100 Gy·s −1 ). Compared with conventional dose-rate (CONV; 0.07-0.1 Gy·s −1 ) modalities, we showed that FLASH did not cause radiation-induced deficits in learning and memory in mice. Moreover, 6 months after exposure, CONV caused permanent alterations in neurocognitive end points, whereas FLASH did not induce behaviors characteristic of anxiety and depression and did not impair extinction memory. Mechanistic investigations showed that increasing the oxygen tension in the brain through carbogen breathing reversed the neuroprotective effects of FLASH, while radiochemical studies confirmed that FLASH produced lower levels of the toxic reactive oxygen species hydrogen peroxide. In addition, FLASH did not induce neuroinflammation, a process described as oxidative stress-dependent, and was also associated with a marked preservation of neuronal morphology and dendritic spine density. The remarkable normal tissue sparing afforded by FLASH may someday provide heretofore unrealized opportunities for dose escalation to the tumor bed, capabilities that promise to hasten the translation of this groundbreaking irradiation modality into clinical practice.ultra-high dose-rate irradiation | cognitive dysfunction | neuronal morphology | neuroinflammation | reactive oxygen species R adiation therapy (RT) remains an essential part of cancer treatment, and, today, the benefit of RT would increase dramatically if normal tissues surrounding the tumor could tolerate higher doses of radiation (1-3). In the last decade, major advances in high-precision treatment delivery and multimodal imaging have improved tolerance to RT (4), but the selective protection of normal tissue remains a significant clinical challenge and the radiation-induced toxicities still adversely impact the patient's quality of life. This latter fact largely remains an unmet medical need, and points to the urgency of developing improved RT modalities for combating those cancers refractory to treatment.This issue is especially critical for those afflicted with brain tumors, including glioblastoma multiforme (GBM), for which standard treatment consists of surgical resection followed by RT and concomitant chemotherapy (temozolomide). Typical radiotherapeutic protocols for GBM induce neurocognitive complications, including impairments in learning and memory, attention, and executive function and a variety of mood disorders (5-8). A breadth of past work from our laboratories has linked adverse neurocognitive outcomes following cranial irradiation to a range of neuropathologies, including reductions in dendritic complexity and spine density (9-12), reductions in microvascular density (13-15), reduced myelination and synapse density, and increased neuroinflammation (16,17). These changes are persistent and problematic in the conventionally irradiated brain and have prompted efforts to more fully develop a truly innovative approach to RT, where we have concept...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species

Montay‐Gruel

Acharya

Petersson

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

382

447

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“…To date, preclinical FLASH irradiation of small animals and small superficial targets in larger animals has been possible using modifications of existing irradiation systems that are capable of producing FLASH dose rates when limited to small volumes (of up to a few cubic centimeters), including electron linear accelerators, a synchrotron light source producing kilovoltage energy x rays, and certain proton accelerators …”

Section: For the Proposition: Peter G Maxim Phdmentioning

confidence: 99%

FLASH radiotherapy: Newsflash or flash in the pan?

Maxim

Keall

Cai³

2019

Medical Physics

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“…To meet this demand, we propose a means of using existing technologies to enable more accessible in vitro FLASH experiments. To date, achieving FLASH‐capable dose rates has typically relied upon access to specialized electron sources (i.e., Oriatron eRT6), and few other commercial devices yet exist which are readily suited for FLASH therapy despite the growing demand for preclinical research in this domain . In principal, modern clinical linacs can be made suitable for FLASH therapy, but this requires substantial modification to these clinically optimized systems .…”

Section: Introductionmentioning

confidence: 99%

“…To date, achieving FLASH-capable dose rates has typically relied upon access to specialized electron sources (i.e., Oriatron eRT6), and few other commercial devices yet exist which are readily suited for FLASH therapy despite the growing demand for preclinical research in this domain. 13,15 In principal, modern clinical linacs can be made suitable for FLASH therapy, but this requires substantial modification to these clinically optimized systems. 16,17 Moreover, while synchrotrons, notable for their superior beam intensities, 14,18,19 and high-energy cyclotron-accelerated protons are also capable of achieving the requisite dose rates, 20 limited accessibility and high costs remain barriers to their widespread application.…”

Section: Introductionmentioning

confidence: 99%

On the capabilities of conventional x‐ray tubes to deliver ultra‐high (FLASH) dose rates

Bazalova‐Carter

Esplen

2019

Medical Physics

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Purpose By means of Monte Carlo (MC) simulations and indirect measurements, we have evaluated the maximum dose rates achievable with conventional x‐ray tubes and related them to FLASH therapy dose rates of >40 Gy/s. Methods Monte Carlo models of two 160 kV x‐ray tubes, the 3‐kW MXR‐160/22 and the 6‐kW MXR‐165, were built in the EGSnrc/BEAMnrc code. The dose rate in a water phantom placed against the x‐ray tube surface, located at 3.7 and 3.5 cm from the focal spot for the MXR‐160/22 and MXR‐165 x‐ray tube, respectively, was calculated with DOSXYZnrc. Dose delivered with the 120‐kV beam in a plastic water phantom for the MXR‐160/22 was measured and calculated. Gafchromic EBT3 films were placed at 15 and 18 mm depths in the plastic water phantom that was irradiated with a low tube current of 0.2 mA for 30 s. Results The maximum 160‐kV phantom surface dose rate was determined to be FLASH capable, calculated as (114.3 ± 0.6) Gy/s and (160.0 ± 0.8) Gy/s for the MXR‐160/22 and MXR‐165 x‐ray tubes, respectively. The dose rate in a 1‐cm diameter region was found to be (110.6 ± 2.8) Gy/s and (151.9 ± 2.6) Gy/s and remained FLASH capable to depths of 1.4 and 2.0 mm for the MXR‐160/22 and MXR‐165 x‐ray tube, respectively. The 120‐kV dose profiles measured with EBT3 films agreed with MC simulations to within 3.6% for regions outside of heel effect and at both measurement depths; this presented a good validation data set for the simulations of phantom surface dose rate using the 160‐kV beam. Conclusions We have indirectly determined that, with a careful experimental design, conventional x‐ray tubes can be made suitable for use in FLASH radiotherapy and dosimetry experiments.

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High dose‐per‐pulse electron beam dosimetry: Commissioning of the Oriatron eRT6 prototype linear accelerator for preclinical use

Abstract: The Oriatron eRT6 was successfully commissioned for preclinical use and is currently in full operation, with studies being performed on the radiobiological effects of high dose-per-pulse irradiation.

Cited by 163 publications

References 22 publications

Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species

Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species

FLASH radiotherapy: Newsflash or flash in the pan?

On the capabilities of conventional x‐ray tubes to deliver ultra‐high (FLASH) dose rates

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