Dosimetric and preparation procedures for irradiating biological models with pulsed electron beam at ultra-high dose-rate

Jorge, Patrik Gonçalves; Jaccard, Maud; Petersson, Kristoffer; Gondré, Maude; Durán, M. Teresa; Desorgher, L.; Germond, Jean François; Liger, Philippe; Vozenin, Marie-Catherine; Bourhis, Jean; Bochud, François; Moeckli, Raphaël; Bailat, Claude

doi:10.1016/j.radonc.2019.05.004

Cited by 106 publications

(135 citation statements)

References 15 publications

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“…The roles of dose-per-pulse, instantaneous dose per pulse (dose per pulse divided by pulse duration), and pulse duration and frequency still remain to be understood. This is essentially due to the fact that the accelerators used up to now for in vivo FLASH experiments are electron accelerators designed for industrial use [18][19][20] or modified medical accelerators, where diffuser filters and monitor chambers have been mechanically dismounted and removed from the beam path [21]. Therefore, such accelerators are not able to perform beam parameters real-time monitoring as well as provide an accurate and reproducible output.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the dosimetry is complicated by the saturation problems typical of all clinical dosimeters which provide online information to these dose-per-pulse values. In all the experimental works published so far [18][19][20][21], the dosimetry was performed using independent dose-rate dosimeters, in most cases radiochromic films. Radiochromic films do not have the same accuracy of other detectors (for example ionization chambers), they do not provide online dosimetric information, and they are not able to control any changes in the output during the experiment.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 99%

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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“…Irradiation was performed using a prototype 6 MeV electron beam, LINAC, of the Oriatron type 6e (eRT6; PMB Alcen), available at Lausanne University Hospital and described previously [62]. Physical dosimetry has been extensively described and published to ensure reproducible and reliable biological studies [13,[63][64][65]. This LINAC was able to produce a pulsed electron beam at a mean dose rate ranging from 0.1 Gy/s (i.e., comparable to CONV used in RT) up to 4.4 × 10 6 Gy/s (at standard distance), corresponding to a dose, in each electron pulse, ranging from 0.01 up to 8 Gy.…”

Section: Whole Brain Irradiationsmentioning

confidence: 99%

Neuroprotection of Radiosensitive Juvenile Mice by Ultra-High Dose Rate FLASH Irradiation

Alaghband

Cheeks

Allen

et al. 2020

Cancers

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Major advances in high precision treatment delivery and imaging have greatly improved the tolerance of radiotherapy (RT); however, the selective sparing of normal tissue and the reduction of neurocognitive side effects from radiation-induced toxicities remain significant problems for pediatric patients with brain tumors. While the overall survival of pediatric patients afflicted with medulloblastoma (MB), the most common type primary brain cancer in children, remains high (≥80%), lifelong neurotoxic side-effects are commonplace and adversely impact patients’ quality of life. To circumvent these clinical complications, we have investigated the capability of ultra-high dose rate FLASH-radiotherapy (FLASH-RT) to protect the radiosensitive juvenile mouse brain from normal tissue toxicities. Compared to conventional dose rate (CONV) irradiation, FLASH-RT was found to ameliorate radiation-induced cognitive dysfunction in multiple independent behavioral paradigms, preserve developing and mature neurons, minimize microgliosis and limit the reduction of the plasmatic level of growth hormone. The protective “FLASH effect” was pronounced, especially since a similar whole brain dose of 8 Gy delivered with CONV-RT caused marked reductions in multiple indices of behavioral performance (objects in updated location, novel object recognition, fear extinction, light-dark box, social interaction), reductions in the number of immature (doublecortin+) and mature (NeuN+) neurons and increased neuroinflammation, adverse effects that were not found with FLASH-RT. Our data point to a potentially innovative treatment modality that is able to spare, if not prevent, many of the side effects associated with long-term treatment that disrupt the long-term cognitive and emotional well-being of medulloblastoma survivors.

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“…on the dose-rate, which is the quantity to be measured. Although specific models have been recently developed to characterize the saturation and compute the absolute dose, this saturation effect may vary depending on the beam characteristics and irradiation setup, which makes the establishment of the correction factors inaccurate and time-consuming [13]. Additionally, ionization chambers need several tens of µs (30-300 µs for 0.5-5 mm air gap) to collect the charges and are too slow to monitor a FLASH beam, which delivers tens of Gy in a few µs.…”

Section: Beam Monitors In Conventional Radiotherapymentioning

confidence: 99%

Beam Monitors for Tomorrow: The Challenges of Electron and Photon FLASH RT

et al. 2020

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The emergent FLASH RadioTherapy (RT) uses ultrahigh dose-rate irradiation (up to 10 7 Gy/s instantaneous dose-rate in each µs pulse) to deliver a single high dose of irradiation in a very short time (<200 ms). Pre-clinical studies at ultrahigh dose-rates recently showed an increased ratio between tumoricidal effect and normal tissue toxicity (therapeutic index), compared to conventional RT at standard Gy/min dose-rates. If confirmed by biological in vivo validations, this could represent a breakthrough in cancer treatment. However, the reliability and the accuracy of experimental studies are nowadays limited by the lack of detectors able to measure online the beam fluence at FLASH dose-rates. The behavior of standard beam monitors (gas-filled ionization chambers) is compromised by the volume recombination caused by the amount of charges created per unit volume and unit time, due to the large dose-rate. Moreover, due to the lack of proper monitoring devices and to the uncertainties of its future applications, very few facilities are able to deliver at present FLASH irradiations. In this contribution, we report about the physical and technological challenges of monitoring high and ultra-high dose-rates with electrons and photon beams, starting from the pre-clinical and clinical constraints for new devices. Based on the extensive experience in silicon detectors for monitoring applications in RT with external beams, the work then investigates silicon sensors as a possible option to tackle such extreme requirements and a rugged thin and large (e.g., 10 × 10 cm 2) flat detector (silicon-based sensor + readout electronics) is therefore outlined. This study aims at presenting the FLASH-RT dosimetry problem and analyzing the possibilities for a silicon sensor to be employed as sensing device for several FLASH scenarios, including some ideas on the readout part. However, more detailed simulations and studies are demanded to delineate more precisely the technical choices to be undertaken in order to tackle the clinical accuracy required on the beam fluence, typically a few %, during photon and electron high and ultra-high irradiations, the required minimal perturbation of the beam and the high level of radiation resistance.

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Dosimetric and preparation procedures for irradiating biological models with pulsed electron beam at ultra-high dose-rate

Cited by 106 publications

References 15 publications

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

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

Neuroprotection of Radiosensitive Juvenile Mice by Ultra-High Dose Rate FLASH Irradiation

Beam Monitors for Tomorrow: The Challenges of Electron and Photon FLASH RT

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