Beam characterization and feasibility study for a small animal irradiation platform at clinical proton therapy facilities

Gerlach, Sonja; Pinto, M.; Kurichiyanil, Neeraj; Grau, Cai; Hérault, J.; Hillbrand, Martin; Poulsen, P.R.; Safai, Sairos; Schippers, Jacobus Maarten; Schwarz, Marco; Søndergaard, Claus S.; Tommasino, Francesco; Verroi, Enrico; Vidal, M.; Yohannes, Indra; Schreiber, Jörg; Parodi, Katia

doi:10.1088/1361-6560/abc832

Cited by 12 publications

(14 citation statements)

References 36 publications

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“…Small animal irradiators that incorporate imaging and robotic stage alignment are ideal for this use when placed on a fixed proton beam line. 13,14,41,42 The isocenter of the X-ray irradiator can be aligned with the proton beam axis, and the imaging capabilities of the irradiator used to identify targets and shift a robotic stage to precisely align the proton beam. Nevertheless, in principle, all clinical proton therapy beam lines have a patient positioning system with X-rays and typically six degrees of freedom couch platforms, as well as large in room cone-beam computed tomography (CBCT) that can be used for accurate alignment.…”

Section: Beam Alignment/imagingmentioning

confidence: 99%

The current status of preclinical proton FLASH radiation and future directions

et al. 2021

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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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Section: Beam Alignment/imagingmentioning

confidence: 99%

The current status of preclinical proton FLASH radiation and future directions

et al. 2021

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“…Here, precise and reproducible positioning is key, especially for 3D targets inside the animal body. Elaborated positioning for animal experiments is realized at the different proton centers [31,[42][43][44][45][46][47][48], which is, however, difficult to standardize. In a first attempt, Gerlach et al developed a portable setup for animal studies with protons [46]; some facilities installed small animal irradiators, enabling in situ CT imaging and precise positioning of target volumes [49,50].…”

Section: The Physicist's Point Of Viewmentioning

confidence: 99%

“…Elaborated positioning for animal experiments is realized at the different proton centers [31,[42][43][44][45][46][47][48], which is, however, difficult to standardize. In a first attempt, Gerlach et al developed a portable setup for animal studies with protons [46]; some facilities installed small animal irradiators, enabling in situ CT imaging and precise positioning of target volumes [49,50]. Besides positioning, small animals are also challenging for absolute dosimetry, due to a lack of standardized dosimeters for such volumes.…”

Section: The Physicist's Point Of Viewmentioning

confidence: 99%

Models for Translational Proton Radiobiology—From Bench to Bedside and Back

Suckert

Nexhipi

Dietrich

et al. 2021

Cancers

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The number of proton therapy centers worldwide are increasing steadily, with more than two million cancer patients treated so far. Despite this development, pending questions on proton radiobiology still call for basic and translational preclinical research. Open issues are the on-going discussion on an energy-dependent varying proton RBE (relative biological effectiveness), a better characterization of normal tissue side effects and combination treatments with drugs originally developed for photon therapy. At the same time, novel possibilities arise, such as radioimmunotherapy, and new proton therapy schemata, such as FLASH irradiation and proton mini-beams. The study of those aspects demands for radiobiological models at different stages along the translational chain, allowing the investigation of mechanisms from the molecular level to whole organisms. Focusing on the challenges and specifics of proton research, this review summarizes the different available models, ranging from in vitro systems to animal studies of increasing complexity as well as complementing in silico approaches.

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“…In the studies on biological effectiveness, Guan et al 12 and Patel et al 13 used energy-attenuating components to produce low-energy spectra with high LET from a clinical beam line. An in-silico dosimetric characterization to study degraded proton energies for a small animal irradiation platform was presented by Gerlach et al 14 The procedure of energy-degrading of clinical proton beams to a few MeV by placing an absorber in the beam path is, however, nontrivial, due to range straggling and decreasing fluence: Both effects become more pronounced with absorber thickness. In addition, the large number of scattering events results in a broad energy spectrum.…”

Section: Introductionmentioning

confidence: 99%

“…used energy‐attenuating components to produce low‐energy spectra with high LET from a clinical beam line. An in‐silico dosimetric characterization to study degraded proton energies for a small animal irradiation platform was presented by Gerlach et al 14 …”

Section: Introductionmentioning

confidence: 99%

Technical note: Providing proton fields down to the few‐MeV level at clinical pencil beam scanning facilities for radiobiological experiments

et al. 2021

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The adequate performance of radiobiological experiments using clinical proton beams typically requires substantial preparations to provide the appropriate setup for specific experiments. Providing radiobiologically interesting low-energy protons is a particular challenge, due to various physical effects that become more pronounced with larger absorber thickness and smaller proton energy. This work demonstrates the generation of decelerated low-energy protons from a clinical proton beam. Methods: Monte Carlo simulations of proton energy spectra were performed for energy absorbers with varying thicknesses to reduce the energy of the clinical proton beam down to the few-MeV level corresponding to μm-ranges. In this way, a setup with an optimum thickness of the absorber with a maximum efficiency of the proton fluence for the provisioning of low-energy protons is supposed to be found. For the specific applications of 2.5-3.3 MeV protons and 𝛼-particle range equivalent protons, the relative depth dose was measured and simulated together with the dose-averaged linear energy transfer (LETd) distribution. Results:The resulting energy spectra from Monte Carlo simulations indicate an optimal absorber thickness for providing low-energy protons with maximum efficiency of proton fluence at an user-requested energy range for experiments. For instance, providing energies lower than 5 MeV, an energy spectrum with a relative total efficiency of 38.6% to the initial spectrum was obtained with the optimal setup. The measurements of the depth dose, compared to the Monte Carlo simulations, showed that the dosimetry of low-energy protons works and protons with high LETd down to the range of 𝛼-particles can be produced. Conclusions: This work provides a method for generating all clinically and radiobiologically relevant energies -especially down to the few-MeV levelat one clinical facility with pencil beam scanning. Thereby, it enables radiobiological experiments under environmentally uniform conditions.

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Beam characterization and feasibility study for a small animal irradiation platform at clinical proton therapy facilities

Cited by 12 publications

References 36 publications

The current status of preclinical proton FLASH radiation and future directions

The current status of preclinical proton FLASH radiation and future directions

Models for Translational Proton Radiobiology—From Bench to Bedside and Back

Technical note: Providing proton fields down to the few‐MeV level at clinical pencil beam scanning facilities for radiobiological experiments

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