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Background: Proton spatially fractionated RT (SFRT) can potentially synergize the unique advantages of using proton Bragg peak and SFRT peak-valley dose ratio (PVDR) to reduce the radiation-induced damage for normal tissues. Uniform-target-dose (UTD) proton GRID is a proton SFRT modality that can be clinically desirable and conveniently adopted since its UTD resembles target dose distribution in conventional proton RT (CONV). However, UTD proton GRID is not used clinically, which is likely due to the lack of an effective treatment planning method., Purpose: This work will develop a novel treatment planning method using scissor beams (SB) for UTD proton GRID, with the joint optimization of PVDR and dose objectives., Methods: The SB method for spatial dose modulation in normal tissues with UTD has two steps: (1) a primary beam (PB) is halved with interleaved beamlets, to generate spatial dose modulation in normal tissues; (2) a complementary beam (CB) is added to fill in previously valley-dose positions in the target to generate UTD, while the CB is angled slightly from the PB, to maintain spatial dose modulation in normal tissues. A treatment planning method with PVDR optimization via the joint total variation and L1 (TVL1) regularization is developed to jointly optimize PVDR and dose objectives. The plan optimization solution is obtained using an iterative convex relaxation algorithm., Results: The new methods SB and SB-TVL1 were validated in comparison with CONV. Compared to CONV of relatively homogeneous dose distribution, SB had modulated spatial dose pattern in normal tissues with UTD and comparable plan quality. Compared to SB, SB-TVL1 further maximized PVDR, with comparable dose-volume parameters., Conclusions: A novel SB method is proposed that can generate modulated spatial dose pattern in normal tissues to achieve UTD proton GRID. A treatment planning method with PVDR optimization capability via TVL1 regularization is developed that can jointly optimize PVDR and dose objectives for proton GRID., (© 2024 American Association of Physicists in Medicine.)

Background: Minibeam represents a preclinical spatially fractionated radiotherapy modality with great translational potential. The advantage lies in its high therapeutic index (compared to GRID and LATTICE) and ability to treat at greater depth (compared to microbeam). Proton minibeam radiotherapy (pMBRT) is a synergy of proton and minibeam. While the single-gantry proton facility has gained popularity due to its affordability and compact design, it often has limited beam time available for research purposes. Conversely, given the current requirement of pMBRT on specific minibeam hardware collimators, necessitates a reproducible and fast setup to minimize pMBRT treatment time and streamline the switching time between pMBRT and conventional treatment for clinically translation., Purpose: The contribution of this work is the development and characterization of the first pMBRT system tailored for single-gantry proton facility. The system allows for efficient and reproducible plug-and-play setup, achievable within minutes., Methods: The single room pMBRT system is constructed based on IBA ProteusONE proton machine. The end of nozzle is attached with beam modifying accessories though an accessory drawer. A small snout is attached to the accessory drawer and used to hold apertures and range shifters. The minibeam aperture consists of two components: a fitting ring and an aperture body. Three minibeam apertures were manufactured. The first-generation apertures underwent qualitatively analysis with film, and the second generation aperture underwent more comprehensive quantitative measurement. The reproducibility of the setup is accessed, and the film measurements are performed to characterize the pMBRT system in cross validation with Monte Carlo (MC) simulations., Results: We presented initial results of large field pMBRT aperture and the film measurements indicates the effect of source-to-isocenter distance = 930 cm in Y proton scanning direction. Consistent with TOPAS MC simulation, the dose uniformity of pMBRT field <2 cm is demonstrated to be better than 2%, rendering its suitability for pre-clinical studies. Subsequently, we developed the second generation of aperture with five slits and characterized the aperture with film dosimetry studies and compared the results to the benchmark MC. Comprehensive film measurements were also performed to evaluate the effect of divergence, air gap and gantry-angle dependency and repeatability and revealing a consistent performance within 5%. Furthermore, the 2D gamma analysis indicated a passing rate exceeding 99% using 3% dose difference and 0.2 mm distance agreement criteria. We also establish the peak valley dose ratio and the depth dose profile measurements, and the results are within 10% from MC simulation., Conclusions: We have developed the first pMBRT system tailored for a single-gantry proton facility, which has demonstrated accuracy in benchmark with MC simulations, and allows for efficient plug-and-play setup, emphasizing efficiency., (© 2024 American Association of Physicists in Medicine.)

Purpose: Proton minibeam radiation therapy (pMBRT) is a new radiotherapy approach that has shown a significant increase in the therapeutic window in glioma‐bearing rats compared to conventional proton therapy. The dosimetry of pMBRT is challenging and error prone due to the submillimetric beamlet sizes used. The aim of this study was to perform a robustness analysis on the setup parameters utilized in current preclinical trials and provide guidelines for reproducible dosimetry. The results of this work are intended to guide upcoming implementations of pMBRT worldwide, as well as pave the way for future clinical implementations. Methods: Monte Carlo simulations and experimental data were used to evaluate the impact of variations in setup parameters and uncertainties in collimator specifications on lateral pMBRT dose distributions. The value of each parameter was modified individually to evaluate their effect on dose distributions. Experimental dosimetry was performed by means of high‐resolution detectors, that is, radiochromic films, the IBA Razor and the Microdiamond detector. New guidelines were proposed to optimize the experimental setup in pMBRT studies and perform reproducible dosimetry. Results: The sensitivity of dose distributions to uncertainties and variations in setup parameters was quantified. Quantities that define pMBRT lateral profiles (i.e., the peak‐to‐valley dose ratio [PVDR], peak and valley doses, and peak width) are significantly influenced by small‐scale fluctuations in several of those parameters. The setup implemented at the Orsay proton therapy center for pMBRT irradiation was optimized to increase PVDRs and peak symmetry. In addition, we proposed guidelines to perform accurate and reproducible dosimetry in preclinical studies. Conclusions: This study revealed the importance of adopting guidelines and protocols tailored to the distinct dose delivery method and dose distributions in pMBRT. This new methodology leads to reproducible dosimetry, which is imperative in preclinical trials. The results and guidelines presented in this manuscript can ease the initiation of pMBRT investigations in other centers. [ABSTRACT FROM AUTHOR]

Ultra‐high‐dose rate "FLASH" radiotherapy (FLASH‐RT) has been shown to drastically reduce normal tissue toxicities while being as efficacious as conventional dose rate radiotherapy to treat tumors. A large number of preclinical studies describing this so‐called FLASH effect have led to the clinical translation of FLASH‐RT using ultra‐high‐dose rate electron and proton beams. Although the vast majority of radiation therapy treatments are delivered using X‐rays, few preclinical data using ultra‐high‐dose rate X‐ray irradiation have been published. This review focuses on different methods that can be used to generate ultra‐high‐dose rate X‐rays and their beam characteristics along with their effect on the biological tissues and the perspectives for the development of FLASH‐RT with X‐rays. [ABSTRACT FROM AUTHOR]

Background: Proton minibeam radiation therapy (pMBRT) is a new radiotherapy approach that has shown a significant increase in the therapeutic window in glioma-bearing rats compared to conventional proton therapy. Such preclinical results encourage the preparation of clinical trials., Purpose: In this study, the potential of pMBRT for treating clinical indications candidates for the first clinical trials (i.e., brain, lung, and liver metastases) was evaluated., Methods: Four clinical cases, initially treated with stereotactic radiotherapy (SRT), were selected for this study. pMBRT, SRT, and conventional proton therapy (PT) dose distributions were compared by using three main criteria: (i) the tumor coverage, (ii) the mean dose to organs-at-risk, and (iii) the possible adverse effects in normal tissues by considering valley doses as the responsible for tissue sparing. pMBRT plans consisted of one fraction and one-two fields. Dose calculations were computed by means of Monte Carlo simulations., Results: pMBRT treatments provide a similar or superior target coverage than SRT, even using fewer fields. pMBRT also significantly reduces the biologically effective dose (BED) to organs-at-risk. In addition, valley and mean doses to normal tissues remain below tolerance limits when treatments are delivered in a single fraction, contrary to PT treatments., Conclusions: This work provides a first insight into the possibility of treating metastases with pMBRT. More favorable dose distributions and treatment delivery regimes may be expected from this new approach than SRT. The advantages of pMBRT would need to be confirmed by means of Phase I clinical trials., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

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. [ABSTRACT FROM AUTHOR]

Purpose: Microbeam radiation therapy is an innovative treatment approach in radiation therapy that uses arrays of a few tens of micrometer wide and a few hundreds of micrometer spaced planar x-ray beams as treatment fields. In preclinical studies these fields efficiently eradicated tumors while normal tissue could effectively be spared. However, development and clinical application of microbeam radiation therapy is impeded by a lack of suitable small scale sources. Until now, only large synchrotrons provide appropriate beam properties for the production of microbeams. Methods: In this work, a conventional x-ray tube with a small focal spot and a specially designed collimator are used to produce microbeams for preclinical research. The applicability of the developed source is demonstrated in a pilot in vitro experiment. The properties of the produced radiation field are characterized by radiochromic film dosimetry. Results: 50 μm wide and 400 µm spaced microbeams were produced in a 20×20 mm² sized microbeam field. The peak to valley dose ratio ranged from 15.5 to 30, which is comparable to values obtained at synchrotrons. A dose rate of up to 300 mGy/s was achieved in the microbeam peaks. Analysis of DNA double strand repair and cell cycle distribution after in vitro exposures of pancreatic cancer cells (Panc1) at the x-ray tube and the European Synchrotron leads to similar results. In particular, a reduced G2 cell cycle arrest is observed in cells in the microbeam peak region. Conclusions: At its current stage, the source is restricted to in vitro applications. However, moderate modifications of the setup may soon allow in vivo research in mice and rats. [ABSTRACT FROM AUTHOR]