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Open accessJournal ArticleDOI: 10.3390/APP11052170

FLASH Irradiation with Proton Beams: Beam Characteristics and Their Implications for Beam Diagnostics

02 Mar 2021-Applied Sciences (MDPI AG)-Vol. 11, Iss: 5, pp 2170
Abstract: FLASH irradiations use dose-rates orders of magnitude higher than commonly used in patient treatments. Such irradiations have shown interesting normal tissue sparing in cell and animal experiments, and, as such, their potential application to clinical practice is being investigated. Clinical accelerators used in proton therapy facilities can potentially provide FLASH beams; therefore, the topic is of high interest in this field. However, a clear FLASH effect has so far been observed in presence of high dose rates (>40 Gy/s), high delivered dose (tens of Gy), and very short irradiation times (<300 ms). Fulfilling these requirements poses a serious challenge to the beam diagnostics system of clinical facilities. We will review the status and proposed solutions, from the point of view of the beam definitions for FLASH and their implications for beam diagnostics. We will devote particular attention to the topics of beam monitoring and control, as well as absolute dose measurements, since finding viable solutions in these two aspects will be of utmost importance to guarantee that the technique can be adopted quickly and safely in clinical practice.

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Topics: Proton therapy (52%), Flash (photography) (51%), Dose profile (51%)
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6 results found


Open accessDOI: 10.18429/JACOW-IPAC2021-FRXC05
01 Aug 2021-
Abstract: Medical applications of charged particle beams require a full online characterisation of the beam to ensure patient safety, treatment efficacy, and facility efficiency. In-vivo dosimetry, measurement of delivered dose during treatment, is a significant part of this characterisation. Current methods offer limited information or are invasive to the beam, meaning measurements must be done offline. This contribution presents the development of a non-invasive gas jet in-vivo dosimeter for treatment facilities. The technique is based on the interaction between a particle beam and a supersonic gas jet curtain, which was originally developed for the high luminosity upgrade of the large hadron collider (HL-LHC). To demonstrate the medical application of this technique, an existing HL-LHC test system with minor modifications will be installed at the University of Birmingham’s 35 MeV proton cyclotron, which has properties comparable to that of a treatment beam. This contribution presents the design and development of this test setup, plans for initial benchmarking measurements, and plans for a future optimised medical accelerator gas jet in-vivo dosimeter.

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Topics: Jet (fluid) (65%), Particle beam (53%)

1 Citations


Journal ArticleDOI: 10.1016/J.CLON.2021.08.013
Kevin L.M. Chua1, Pek Lim Chu1, D.J.H. Tng, K.C. Soo  +1 moreInstitutions (1)
08 Sep 2021-Clinical Oncology
Abstract: Despite improvements in radiotherapy, radioresistance remains an important clinical challenge. Radioresistance can be mediated through enhanced DNA damage response mechanisms within the tumour or through selective pressures exerted by the tumour microenvironment (TME). The effects of the TME have in recent times gained increased attention, in part due to the success of immune modulating strategies, but also through improved understanding of the downstream effects of hypoxia and dysregulated wound healing processes on mediating radioresistance. Although we have a better appreciation of these molecular mechanisms, efforts to address them through novel combination approaches have been scarce, owing to limitations of photon therapy and concerns over toxicity. At the same time, proton beam therapy (PBT) represents an advancement in radiotherapy technologies. However, early clinical results have been mixed and the clinical strategies around optimal use and patient selection for PBT remain unclear. Here we highlight the role that PBT can play in addressing radioresistance, through better patient selection, and by providing an improved toxicity profile for integration with novel agents. We will also describe the developments around FLASH PBT. Through close examination of its normal tissue-sparing effects, we will highlight how FLASH PBT can facilitate combination strategies to tackle radioresistance by further improving toxicity profiles and by directly mediating the mechanisms of radioresistance.

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Topics: Radioresistance (55%)

1 Citations


Open accessPosted Content
Abstract: The physical and clinical benefits of charged particle therapy (CPT) are well recognised and recent developments have led to the rapid emergence of facilities, resulting in wider adoption worldwide. Nonetheless, the availability of CPT and complete exploitation of dosimetric advantages are still limited by high facility costs and technological challenges. There are extensive ongoing efforts to improve upon these, which will lead to greater accessibility, superior delivery, and therefore better treatment outcomes. Several of these aspects can be addressed by developments to the beam delivery system (BDS) which determine the overall shaping and timing capabilities to provide high quality treatments. Modern delivery techniques are necessary but are limited by extended treatment times. The energy layer switching time (ELST) is a limiting constraint of the BDS and a determinant of the beam delivery time (BDT), along with the accelerator and other factors. This review evaluates the delivery process in detail, presenting the limitations and developments for the BDS and related accelerator technology, toward decreasing the BDT. As extended BDT impacts motion and has dosimetric implications for treatment, we discuss avenues to minimise the ELST and overview the clinical benefits and feasibility of a large energy acceptance BDS. These developments support the possibility of delivering advanced methodologies such as volumetric rescanning, FLASH and arc therapy and can further reduce costs given a faster delivery for a greater range of treatment indications. Further work to realise multi-ion, image guided and adaptive therapies is also discussed. In this review we examine how increased treatment efficiency and efficacy could be achieved with an improved BDS and how this could lead to faster and higher quality treatments for the future of CPT.

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Journal ArticleDOI: 10.1002/MP.15278
Vivek Maradia1, Vivek Maradia2, David Meer2, Damien C. Weber3  +6 moreInstitutions (4)
29 Oct 2021-Medical Physics
Abstract: PURPOSE In proton therapy, the potential of using high dose rates in cancer treatment is being explored. High dose rates could improve efficiency and throughput in standard clinical practice, allow efficient utilization of motion mitigation techniques for moving targets, and potentially enhance normal tissue sparing due to the so-called FLASH effect. However, high dose rates are difficult to reach when lower energy beams are applied in cyclotron-based proton therapy facilities, because they result in large beam sizes and divergences downstream of the degrader, incurring large losses from the cyclotron to the patient position (isocenter). In current facilities the emittance after the degrader is reduced using circular collimators; this however does not provide an optimal matching to the acceptance of the following beamline, causing a low transmission for these energies. We, therefore, propose to use a collimation system, asymmetric in both beam size and divergence, resulting in symmetric emittance in both beam transverse planes as required for a gantry system. This new emittance selection, together with a new optics design for the following beamline and gantry, allows a better matching to the beamline acceptance and an improvement of the transmission. METHODS We implemented a custom method to design the collimator sizes and shape required to select high emittance, to be transported by the following beamline using new beam optics (designed with TRANSPORT) to maximize acceptance matching. For predicting the transmission in the new configuration (new collimators + optics) we used Monte Carlo simulations implemented in BDSIM, implementing a model of PSI Gantry 2 which we benchmarked against measurements taken in the current clinical scenario (circular collimators + clinical optics). RESULTS From the BDSIM simulations, we found that the new collimator system and matching beam optics we propose results in an overall transmission from the cyclotron to the isocenter for a 70 MeV beam of 0.72%. This is an improvement of almost a factor of 6 over the current clinical performance (0.13% transmission). The new optics satisfies clinical beam requirements at the isocenter. CONCLUSIONS We developed a new emittance collimation system for PSI's PROSCAN beamline which, by carefully selecting beam size and divergence asymmetrically, increases the beam transmission for low energy beams in current state-of-the-art cyclotron-based proton therapy gantries. With these improvements, we could predict almost 1% transmission for low-energy beams at PSI's Gantry 2. Such a system could be easily be implemented in facilities interested in increasing dose rates for efficient motion mitigation and FLASH experiments alike. This article is protected by copyright. All rights reserved.

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Topics: Thermal emittance (54%), Collimator (54%), Proton therapy (53%) ... show more

Journal ArticleDOI: 10.1002/MP.15276
26 Oct 2021-Medical Physics
Abstract: We review the current status of proton FLASH experimental systems, including preclinical physical and biological results. Technological limitations on preclinical investigation of FLASH biological mechanisms and determination of clinically relevant parameters are discussed. A review of the biological data reveals no reproduced proton FLASH effect in vitro and a significant in vivo FLASH sparing effect of normal tissue toxicity observed with multiple proton FLASH irradiation systems. Importantly, multiple studies suggest little or no difference in tumor growth delay for proton FLASH when compared to conventional dose rate proton radiation. A discussion follows on future areas of development with a focus on the determination of the optimal parameters for maximizing the therapeutic ratio between tumor and normal tissue response and ultimately clinical translation of proton FLASH radiation.

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Topics: Flash (photography) (53%)

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51 results found


Journal ArticleDOI: 10.1016/0168-9002(93)91335-K
Abstract: Beams of heavy ions have favourable physical and biological properties for the use in radiotherapy. These advantages are most pronoucced if the beam is delivered in a tumor-conform way by active beam scanning. A magnetic scanning technique is used to spread the beam laterally. The range of the particles in tissue is controlled by the variation of the beam energy in the accelerator. Computer simulations were used to compare a discrete scan mode (pixel scan) with a continous scan mode (raster scan). It was found that both methods lead to nearly identical results. The design and technical realization of the magnetic scanning system at GSI combines features of both scan techniques. First results using the lateral beam scanning method as well as the combination of the active energy variation with the magnetic beam scanning are presented.

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Topics: Laser beam quality (61%), Raster scan (57%), Beam (structure) (55%)

691 Citations


Journal ArticleDOI: 10.1118/1.597522
Eros Pedroni1, Reinhard Bacher1, Hans Blattmann1, T Böhringer1  +7 moreInstitutions (1)
01 Jan 1995-Medical Physics
Abstract: The new proton therapy facility is being assembled at the Paul Scherrer Institute (PSI). The beam delivered by the PSI sector cyclotron can be split and brought into a new hall where it is degraded from 590 MeV down to an energy in the range of 85-270 MeV. A new beam line following the degrader is used to clean the low-energetic beam in phase space and momentum band. The analyzed beam is then injected into a compact isocentric gantry, where it is applied to the patient using a new dynamic treatment modality, the so-called spot-scanning technique. This technique will permit full three-dimensional conformation of the dose to the target volume to be realized in a routine way without the need for individualized patient hardware like collimators and compensators. By combining the scanning of the focused pencil beam within the beam optics of the gantry and by mounting the patient table eccentrically on the gantry, the diameter of the rotating structure has been reduced to only 4 m. In the article the degrees of freedom available on the gantry to apply the beam to the patient (with two rotations for head treatments) are also discussed. The devices for the positioning of the patient on the gantry (x rays and proton radiography) and outside the treatment room (the patient transporter system and the modified mechanics of the computer tomograph unit) are briefly presented. The status of the facility and first experimental results are introduced for later reference.

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Topics: Pencil-beam scanning (56%), Proton therapy (53%), Beam (structure) (50%)

609 Citations


Journal ArticleDOI: 10.1126/SCITRANSLMED.3008973
Abstract: In vitro studies suggested that sub-millisecond pulses of radiation elicit less genomic instability than continuous, protracted irradiation at the same total dose. To determine the potential of ultrahigh dose-rate irradiation in radiotherapy, we investigated lung fibrogenesis in C57BL/6J mice exposed either to short pulses (≤500 ms) of radiation delivered at ultrahigh dose rate (≥40 Gy/s, FLASH) or to conventional dose-rate irradiation (≤0.03 Gy/s, CONV) in single doses. The growth of human HBCx-12A and HEp-2 tumor xenografts in nude mice and syngeneic TC-1 Luc + orthotopic lung tumors in C57BL/6J mice was monitored under similar radiation conditions. CONV (15 Gy) triggered lung fibrosis associated with activation of the TGF-b (transforming growth factor–b) cascade, whereas no complications developed after doses of FLASH below 20 Gy for more than 36 weeks after irradiation. FLASH irradiation also spared normal smooth muscle and epithelial cells from acute radiation-induced apoptosis, which could be reinduced by administrationofsystemicTNF-a(tumornecrosisfactor–a)beforeirradiation.Incontrast,FLASHwasasefficientasCONVinthe repression of tumor growth. Together, these results suggest that FLASH radiotherapy might allow complete eradication of lung tumors and reduce the occurrence and severity of early and late complications affecting normal tissue.

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364 Citations


Journal ArticleDOI: 10.1016/J.RADONC.2017.05.003
Abstract: This study shows for the first time that normal brain tissue toxicities after WBI can be reduced with increased dose rate Spatial memory is preserved after WBI with mean dose rates above 100Gy/s, whereas 10Gy WBI at a conventional radiotherapy dose rate (01Gy/s) totally impairs spatial memory

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199 Citations


Open accessJournal ArticleDOI: 10.1016/J.EJMP.2012.10.001
01 Nov 2013-Physica Medica
Abstract: Purpose: To evaluate the uncertainties and characteristics of radiochromic film-based dosimetry system using the EBT3 model Gafchromic ® film in therapy photon, electron and proton beams. Material and methods: EBT3 films were read using an EPSON Expression 10000XL/PRO scanner. They were irradiated in five beams, an Elekta SL25 6 MV and 18 MV photon beam, an IBA 100 MeV 5 × 5 cm 2 proton beam delivered by pencil-beam scanning, a 60 MeV fixed proton beam and an Elekta SL25 6 MeV electron beam. Reference dosimetry was performed using a FC65-G chamber (Elekta beam), a PPC05 (IBA beam) and both Markus 1916 and PPC40 Roos ion-chambers (60 MeV proton beam). Calibration curves of the radiochromic film dosimetry system were acquired and compared within a dose range of 0.4-10 Gy. An uncertainty budget was estimated on films irradiated by Elekta SL25 by measuring intra-film and inter-film reproducibility and uniformity; scanner uniformity and reproducibility; room light and film reading delay influences. Results: The global uncertainty on acquired optical densities was within 0.55% and could be reduced to 0.1% by placing films consistently at the center of the scanner. For all beam types, the calibration curves are within uncertainties of measured dose and optical densities. The total uncertainties on calibration curve due to film reading and fitting were within 1.5% for photon and proton beams. For electrons, the uncertainty was within 2% for dose superior to 0.8 Gy. Conclusions: The low combined uncertainty observed and low beam and energy-dependence make EBT3 suitable for dosimetry in various applications. © 2012 Associazione Italiana di Fisica Medica.

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Topics: Dosimetry (55%), Proton therapy (54%), Beam (structure) (51%)

158 Citations


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