Transfer of Minibeam Radiation Therapy into a cost-effective equipment for radiobiological studies: a proof of concept

Prezado, Yolanda; Santos, M. Dos; González, Wilfredo; Jouvion, Grégory; Guardiola, Consuelo; Heinrich, Sophie; Labiod, Dalila; Juchaux, Marjorie; Jourdain, Laurène; Sebrié, Catherine; Pouzoulet, F.

doi:10.1038/s41598-017-17543-3

Cited by 55 publications

(111 citation statements)

References 37 publications

(53 reference statements)

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“…Photon MBRT, pMBRT, and eMBRT were simulated using the irradiation configurations currently used for our theoretical or experimental studies …”

Section: Methodsmentioning

confidence: 99%

“…Photon MBRT, pMBRT, and eMBRT were simulated using the irradiation configurations currently used for our theoretical or experimental studies. 5,14,31 In the present study, for xMBRT, three minibeams of 600 µm 9 5 mm with a center-to-center distance of 1200 µm were simulated. The effective energy of the photon beam was 69 keV, based on the photon energy spectrum of the SAARP facility.…”

Section: B Simulation Details Of Irradiation Configurations Geomementioning

confidence: 99%

“…The therapeutic index of radiation therapy (RT) treatments can be notably improved by changing the dose delivery methods, such as the temporal or spatial fractionation of the dose . Minibeam RT (MBRT) is a promising example of how the spatial modulation of the dose can lead to a net reduction in neurotoxicity while providing equivalent or superior tumor control to standard RT for high‐grade gliomas …”

Section: Introductionmentioning

confidence: 99%

“…The therapeutic index of radiation therapy (RT) treatments can be notably improved by changing the dose delivery methods, such as the temporal 1 or spatial fractionation of the dose. [2][3][4][5][6][7][8] Minibeam RT (MBRT) is a promising example of how the spatial modulation of the dose can lead to a net reduction in neurotoxicity [2][3][4][5]7 while providing equivalent or superior tumor control to standard RT for high-grade gliomas. 6,8 Although photon MBRT (xMBRT) was originally developed in synchrotrons, 2 it was recently implemented on a cost-effective preclinical installation, the Small Animal Radiation Research Platform (SARRP, XSTRAHL Ltd., UK), available at the Experimental Radiotherapy Platform of the Institut Curie (Orsay, France).…”

Section: Introductionmentioning

confidence: 99%

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Minibeam radiation therapy: A micro‐ and nano‐dosimetry Monte Carlo study

et al. 2020

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Purpose Minibeam radiation therapy (MBRT) is an innovative strategy based on a distinct dose delivery method that is administered using a series of narrow (submillimetric) parallel beams. To shed light on the biological effects of MBRT irradiation, we explored the micro‐ and nanodosimetric characteristics of three promising MBRT modalities (photon, electron, and proton) using Monte Carlo (MC) calculations. Methods Irradiation with proton (100 MeV), electron (300 MeV), and photon (effective energy of 69 keV) minibeams were simulated using Geant4 MC code and the Geant4‐DNA extension, which allows the simulation of energy transfer points with nanometric accuracy. As the target of the simulations, cells containing spherical nuclei with or without a detailed description of the DNA (deoxyribonucleic acid) geometry were placed at different depths in peak and valley regions in a water phantom. The energy deposition and number of events in the cell nuclei were recorded in the microdosimetry study, and the number of DNA breaks and their complexity were determined in the nanodosimetric study, where a multi‐scale simulation approach was used for the latter. For DNA damage assessment, an adapted DBSCAN clustering algorithm was used. To compare the photon MBRT (xMBRT), electron MBRT (eMBRT), and proton MBRT (pMBRT) approaches, we considered the treatment of a brain tumor located at a depth of 75 mm. Results Both mean energy deposition at micrometric scale and DNA damage in the “valley” cell nuclei were very low as compared with these parameters in the peak region at all depths for xMBRT and at depths of 0 to 30 mm and 0 to 50 mm for eMBRT and pMBRT, respectively. Only the charged minibeams were favorable for tumor control by producing similar effects in peak and valley cells after 70 mm. At the micrometer scale, the energy deposited per event pointed to a potential advantage of proton beams for tumor control, as more aggressive events could be expected at the end of their tracks. At the nanometer scale, all three MBRT modalities produced direct clustered DNA breaks, although the majority of damage (>93%) was composed of isolated single strand breaks. The pMBRT led to a significant increase in the proportion of clustered single strand breaks and double‐strand breaks at the end of its range as compared to the entrance (7% at 75 mm vs 3% at 10 mm) in contrast to eMBRT and xMBRT. In the latter cases, the proportions of complex breaks remained constant, irrespective of the depth and region (peak or valley). Conclusions Enhanced normal tissue sparing can be expected with these three MBRT techniques. Among the three modalities, pMBRT offers an additional gain for radioresistant tumors, as it resulted in a higher number of complex DNA damage clusters in the tumor region. These results can aid understanding of the biological mechanisms of MBRT.

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“…Photon MBRT, pMBRT, and eMBRT were simulated using the irradiation configurations currently used for our theoretical or experimental studies …”

Section: Methodsmentioning

confidence: 99%

Section: B Simulation Details Of Irradiation Configurations Geomementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Minibeam radiation therapy: A micro‐ and nano‐dosimetry Monte Carlo study

et al. 2020

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“…One of the main advantages of pMBRT is the fact that dose homogenization can be obtained in the target with a single array, while normal tissues at the entrance profit from a PVDR high enough to ensure sparing effects. 1,11 However, dose homogenization is not strictly needed in pMBRT for tumor control. 13,14 Provided the same c-t-c distance, helium ions also yield a higher PVDR than protons which would be beneficial for tissue sparing.…”

Section: B Dose Distributionsmentioning

confidence: 99%

Improving the dose distributions in minibeam radiation therapy: Helium ions vs protons

2019

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Purpose Charged particle minibeam radiation therapy is a novel therapeutic strategy aiming at reducing the normal tissue complication probability by combining the normal tissue sparing of submillimetric, spatially fractionated beams with the improved dose deposition of ions. This may allow a safe dose escalation in the tumor and other targets. In particular, proton minibeam radiation therapy has already proven a remarkable increase of the therapeutic index for high‐grade gliomas in animal experiments. The reduced multiple Coulomb scattering and nuclear fragmentation of helium ions compared to protons and heavier ions, respectively, make them a good candidate for minibeam radiation therapy (MBRT). The purpose of the present work was to perform a comprehensive dosimetric comparison between proton and helium MBRT (pMBRT and HeMBRT). Methods Proton and helium minibeams of the same range (7.7 cm) have been simulated in a water phantom and in CT images of an anonymized human head. The Monte Carlo simulation toolkit GATE v8.0 was used. Different beam sizes (1 and 3 mm) and multiple beam spacings were evaluated. Depth dose curves, lateral profiles, peak‐to‐valley dose ratios (PVDR), and dose‐averaged linear energy transfer (LET) were assessed. Furthermore, evaluations of the secondary products in the valley regions were carried out and a basic example of a treatment plan in pMBRT and HeMBRT was considered. Results Compared to protons, helium ions yield a significantly improved Bragg‐peak‐to‐entrance dose ratio (BEDR) and higher PVDR at equal minibeam spacing. At the same time, due to the lower lateral scattering, dose homogenization in the target becomes more difficult for helium ions than for protons. To achieve a homogeneous target dose in HeMBRT, the minibeam spacing has to be reduced which in turn decreases the PVDR in normal tissues to values lower than those observed for protons. LET maps show up to 20%–30% higher values in the valley regions than in the peak regions for all evaluated cases. Helium ions lead to higher LET than protons at all depths, including the entrance region. However, this is compensated by a lower dose at shallow depths thanks to the improved BEDR of HeMBRT. Conclusions Helium ions might offer a good choice for minibeam radiation therapy. They provide a more pronounced spatial fractionation than protons without the possible drawbacks linked to nuclear fragmentation of heavier ions. However, biological experiments are needed to evaluate whether the higher dose heterogeneity in the target volume in HeMBRT would still lead to an efficient tumor control, as in the case of pMBRT.

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Technical and dosimetric realization of in vivo x‐ray microbeam irradiations at the Munich Compact Light Source

et al. 2020

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Purpose: X-ray microbeam radiation therapy is a preclinical concept for tumor treatment promising tissue sparing and enhanced tumor control. With its spatially separated, periodic micrometer-sized pattern, this method requires a high dose rate and a collimated beam typically available at large synchrotron radiation facilities. To treat small animals with microbeams in a laboratory-sized environment, we developed a dedicated irradiation system at the Munich Compact Light Source (MuCLS). Methods: A specially made beam collimation optic allows to increase x-ray fluence rate at the position of the target. Monte Carlo simulations and measurements were conducted for accurate microbeam dosimetry. The dose during irradiation is determined by a calibrated flux monitoring system. Moreover, a positioning system including mouse monitoring was built. Results: We successfully commissioned the in vivo microbeam irradiation system for an exemplary xenograft tumor model in the mouse ear. By beam collimation, a dose rate of up to 5.3 Gy/min at 25 keV was achieved. Microbeam irradiations using a tungsten collimator with 50 lm slit size and 350 lm center-to-center spacing were performed at a mean dose rate of 0.6 Gy/min showing a high peak-to-valley dose ratio of about 200 in the mouse ear. The maximum circular field size of 3.5 mm in diameter can be enlarged using field patching.

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Transfer of Minibeam Radiation Therapy into a cost-effective equipment for radiobiological studies: a proof of concept

Cited by 55 publications

References 37 publications

Minibeam radiation therapy: A micro‐ and nano‐dosimetry Monte Carlo study

Minibeam radiation therapy: A micro‐ and nano‐dosimetry Monte Carlo study

Improving the dose distributions in minibeam radiation therapy: Helium ions vs protons

Technical and dosimetric realization of in vivo x‐ray microbeam irradiations at the Munich Compact Light Source

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