TY - JOUR AU - Almeida, A. AU - Togno, M. AU - Ballesteros-Zebadua, P. AU - Franco-Perez, J. AU - Geyer, R. AU - Schaefer, R. AU - Petit, B. AU - Grilj, V. AU - Meer, D. AU - Safai, S. AU - Lomax, T. AU - Weber, D.C. AU - Bailat, C. AU - Psoroulas, S. AU - Vozenin, M.-C. TI - Dosimetric and biologic intercomparison between electron and proton FLASH beams JF - RADIOTHERAPY AND ONCOLOGY J2 - RADIOTHER ONCOL VL - 190 PY - 2024 SN - 0167-8140 DO - 10.1016/j.radonc.2023.109953 UR - https://m2.mtmt.hu/api/publication/34327444 ID - 34327444 N1 - Laboratory of Radiation Oncology/Radiation Oncology Service/Department of Oncology/CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland Center for Proton Therapy, Paul Scherrer Institute, Villigen, 5323, Switzerland Department of Radiation Oncology, lnselspital, Bern University Hospital, University of Bern, Switzerland Department of Radiation Oncology, University Hospital of Zurich, Switzerland Institute of Radiation Physics (IRA)/CHUV, Lausanne University Hospital, Lausanne, Switzerland Instituto Nacional de Neurología y Neurocirugía MVS, Mexico City, Mexico Radiotherapy and Radiobiology sector, Radiation Therapy service, University hospital of Geneva, Geneva, Switzerland Export Date: 14 November 2023 CODEN: RAOND Correspondence Address: Vozenin, M.-C.; Laboratory of Radiation Oncology/Radiation Oncology Service/Department of Oncology/CHUV, Switzerland; email: marie-catherine.vozenin@chuv.ch Chemicals/CAS: proton, 12408-02-5, 12586-59-3 Funding details: National Institutes of Health, NIH, P01CA244091-01 Funding details: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNF, IZSTZ0_198747/1, MAGIC - FNS CRS II5_186369 Funding details: Consejo Nacional de Ciencia y Tecnología, CONACYT Funding text 1: Funding was provided by National Institutes of Health grant P01CA244091-01 (to MCV supporting AA, VG); Swiss National Science Foundation grant Spirit IZSTZ0_198747/1 (to MCV and PBZ supporting JFC) and MAGIC - FNS CRS II5_186369 (to MCV and supporting VG); and CONACYT for supporting PBZ sabbatical in Switzerland. We also thank the Lausanne core facilities including the Animal facility, In vivo imaging facility, Mouse pathology facility at Epalinges. AB - Background and purpose: The FLASH effect has been validated in different preclinical experiments with electrons (eFLASH) and protons (pFLASH) operating at an average dose rate above 40 Gy/s. However, no systematic intercomparison of the FLASH effect produced by eFLASH vs. pFLASH has yet been performed and constitutes the aim of the present study. Materials and methods: The electron eRT6/Oriatron/CHUV/5.5 MeV and proton Gantry1/PSI/170 MeV were used to deliver conventional (0.1 Gy/s eCONV and pCONV) and FLASH (≥110 Gy/s eFLASH and pFLASH) dose rates. Protons were delivered in transmission. Dosimetric and biologic intercomparisons were performed using previously validated dosimetric approaches and experimental murine models. Results: The difference between the average absorbed dose measured at Gantry 1 with PSI reference dosimeters and with CHUV/IRA dosimeters was −1.9 % (0.1 Gy/s) and + 2.5 % (110 Gy/s). The neurocognitive capacity of eFLASH and pFLASH irradiated mice was indistinguishable from the control, while both eCONV and pCONV irradiated cohorts showed cognitive decrements. Complete tumor response was obtained after an ablative dose of 20 Gy delivered with the two beams at CONV and FLASH dose rates. Tumor rejection upon rechallenge indicates that anti-tumor immunity was activated independently of the beam-type and the dose-rate. Conclusion: Despite major differences in the temporal microstructure of proton and electron beams, this study shows that dosimetric standards can be established. Normal brain protection and tumor control were produced by the two beams. More specifically, normal brain protection was achieved when a single dose of 10 Gy was delivered in 90 ms or less, suggesting that the most important physical parameter driving the FLASH sparing effect might be the mean dose rate. In addition, a systemic anti-tumor immunological memory response was observed in mice exposed to high ablative dose of electron and proton delivered at CONV and FLASH dose rate. © 2023 The Authors LA - English DB - MTMT ER - TY - JOUR AU - Angelou, Christina AU - Patallo, Ileana Silvestre AU - Doherty, Daniel AU - Romano, Francesco AU - Schettino, Giuseppe TI - A review of diamond dosimeters in advanced radiotherapy techniques JF - MEDICAL PHYSICS J2 - MED PHYS PY - 2024 PG - 20 SN - 0094-2405 DO - 10.1002/mp.17370 UR - https://m2.mtmt.hu/api/publication/35257343 ID - 35257343 N1 - Funding Agency and Grant Number: University of Surrey; Micron Semiconductor Ltd Funding text: University of Surrey; Micron Semiconductor Ltd AB - This review article synthesizes key findings from studies on the use of diamond dosimeters in advanced radiotherapy techniques, showcasing their applications, challenges, and contributions to enhancing dosimetric accuracy. The article explores various dosimeters, highlighting synthetic diamond dosimeters as potential candidates especially due to their high spatial resolution and negligible ion recombination effect. The clinically validated commercial dosimeter, PTWmicro Diamond (mD),faces limitations in small fields, proton and hadron therapy and ultra-high dose per pulse (UHDPP) conditions. Variability in reported valuesfor field sizes <2x2cm(2) is noted, reflecting the competition between volume averaging and density perturbation effects. PTW's introduction of flash Diamond(fD) holds promise for dosimetric measurements in UHDPP conditions and is reliable for commissioning ultra-high dose rate (UHDR) electron beam systems, pending the clinical validation of the device. Other advancements in diamond detectors, such as in 3D configurations and real-time dose per pulse x-ray detectors, are considered valuable in overcoming challenges posed by modern radiotherapy techniques, alongside relative dosimetry and pre-treatment verifications. The studies discussed collectively provide a comprehensive overview of the evolving landscape of diamond dosimetry in the field of radiotherapy, and offer insights into future directions for research and development in the field. LA - English DB - MTMT ER - TY - JOUR AU - Borghini, A. AU - Labate, L. AU - Piccinini, S. AU - Panaino, C.M.V. AU - Andreassi, M.G. AU - Gizzi, L.A. TI - FLASH Radiotherapy: Expectations, Challenges, and Current Knowledge JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 5 SN - 1661-6596 DO - 10.3390/ijms25052546 UR - https://m2.mtmt.hu/api/publication/34750077 ID - 34750077 N1 - CNR Institute of Clinical Physiology, Pisa, 56124, Italy Intense Laser Irradiation Laboratory (ILIL), CNR Istituto Nazionale di Ottica, Pisa, 56124, Italy Export Date: 21 March 2024 Correspondence Address: Borghini, A.; CNR Institute of Clinical PhysiologyItaly; email: andrea.borghini@cnr.it Funding details: 101079773, CUP B53C22001750006, D2B8D520, CUP B83C22003930001, IR0000016 Funding details: ECS_00000017 Funding text 1: We acknowledge financial support from the Project “Tuscany Health Ecosystem—THE” “Spoke 1—Advanced Radiotherapies and Diagnostics in Oncology” funded by the NextGenerationEU (PNRR), Codice progetto ECS_00000017, D.D. MUR No. 1055 23 May 2022- http://www.pi.ino.cnr.it/sites/the/ - (accessed on 18 February 2024). Funding text 2: All the figures in this manuscript were created with biorender.com. We acknowledge the Horizon Europe Research and Innovation Programme “EuPRAXIA PP” under Grant Agreement No. 101079773 (CUP B83C22003930001) and NextGeneration EU Integrated Infrastructure I-PHOQS—Initiative in Photonic and Quantum Sciences- (CUP B53C22001750006, ID D2B8D520, IR0000016). AB - Major strides have been made in the development of FLASH radiotherapy (FLASH RT) in the last ten years, but there are still many obstacles to overcome for transfer to the clinic to become a reality. Although preclinical and first-in-human clinical evidence suggests that ultra-high dose rates (UHDRs) induce a sparing effect in normal tissue without modifying the therapeutic effect on the tumor, successful clinical translation of FLASH-RT depends on a better understanding of the biological mechanisms underpinning the sparing effect. Suitable in vitro studies are required to fully understand the radiobiological mechanisms associated with UHDRs. From a technical point of view, it is also crucial to develop optimal technologies in terms of beam irradiation parameters for producing FLASH conditions. This review provides an overview of the research progress of FLASH RT and discusses the potential challenges to be faced before its clinical application. We critically summarize the preclinical evidence and in vitro studies on DNA damage following UHDR irradiation. We also highlight the ongoing developments of technologies for delivering FLASH-compliant beams, with a focus on laser-driven plasma accelerators suitable for performing basic radiobiological research on the UHDR effects. © 2024 by the authors. LA - English DB - MTMT ER - TY - JOUR AU - Byrne, K.E. AU - Poirier, Y. AU - Xu, J. AU - Gerry, A. AU - Foley, M.J. AU - Jackson, I.L. AU - Sawant, A. AU - Jiang, K. TI - Technical note: A small animal irradiation platform for investigating the dependence of the FLASH effect on electron beam parameters JF - MEDICAL PHYSICS J2 - MED PHYS VL - 51 PY - 2024 IS - 2 SP - 1421 EP - 1432 PG - 12 SN - 0094-2405 DO - 10.1002/mp.16909 UR - https://m2.mtmt.hu/api/publication/34572862 ID - 34572862 N1 - Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, United States Department of Physics, School of Natural Sciences, University of Galway, Galway, Ireland Export Date: 12 February 2024 CODEN: MPHYA Correspondence Address: Byrne, K.E.; Division of Translational Radiation Sciences, 685 W. Baltimore Street, United States; email: kbyrne@som.umaryland.edu Funding text 1: The authors declare no acknowledgments. This work was conducted without financial support from external sources. AB - Background: The recent rediscovery of the FLASH effect, a normal tissue sparing phenomenon observed in ultra-high dose rate (UHDR) irradiations, has instigated a surge of research endeavors aiming to close the gap between experimental observation and clinical treatment. However, the dependences of the FLASH effect and its underpinning mechanisms on beam parameters are not well known, and large-scale in vivo studies using murine models of human cancer are needed for these investigations. Purpose: To commission a high-throughput, variable dose rate platform providing uniform electron fields (≥15 cm diameter) at conventional (CONV) and UHDRs for in vivo investigations of the FLASH effect and its dependences on pulsed electron beam parameters. Methods: A murine whole-thoracic lung irradiation (WTLI) platform was constructed using a 1.3 cm thick Cerrobend collimator forming a 15 × 1.6 cm2 slit. Control of dose and dose rate were realized by adjusting the number of monitor units and couch vertical position, respectively. Achievable doses and dose rates were investigated using Gafchromic EBT-XD film at 1 cm depth in solid water and lung-density phantoms. Percent depth dose (PDD) and dose profiles at CONV and various UHDRs were also measured at depths from 0 to 2 cm. A radiation survey was performed to assess radioactivation of the Cerrobend collimator by the UHDR electron beam in comparison to a precision-machined copper alternative. Results: This platform allows for the simultaneous thoracic irradiation of at least three mice. A linear relationship between dose and number of monitor units at a given UHDR was established to guide the selection of dose, and an inverse-square relationship between dose rate and source distance was established to guide the selection of dose rate between 20 and 120 Gy·s−1. At depths of 0.5 to 1.5 cm, the depth range relevant to murine lung irradiation, measured PDDs varied within ±1.5%. Similar lateral dose profiles were observed at CONV and UHDRs with the dose penumbrae widening from 0.3 mm at 0 cm depth to 5.1 mm at 2.0 cm. The presence of lung-density plastic slabs had minimal effect on dose distributions as compared to measurements made with only solid water slabs. Instantaneous dose rate measurements of the activated copper collimator were up to two orders of magnitude higher than that of the Cerrobend collimator. Conclusions: A high-throughput, variable dose rate platform has been developed and commissioned for murine WTLI electron FLASH radiotherapy. The wide field of our UHDR-enabled linac allows for the simultaneous WTLI of at least three mice, and for the average dose rate to be modified by changing the source distance, without affecting dose distribution. The platform exhibits uniform, and comparable dose distributions at CONV and UHDRs up to 120 Gy·s−1, owing to matched and flattened 16 MeV CONV and UHDR electron beams. Considering radioactivation and exposure to staff, Cerrobend collimators are recommended above copper alternatives for electron FLASH research. This platform enables high-throughput animal irradiation, which is preferred for experiments using a large number of animals, which are required to effectively determine UHDR treatment efficacies. © 2024 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine. LA - English DB - MTMT ER - TY - JOUR AU - Cengel, Keith A. AU - Kim, Michele M. AU - Diffenderfer, Eric S. AU - Busch, Theresa M. TI - FLASH Radiotherapy: What Can FLASH's Ultra High Dose Rate Offer to the Treatment of Patients With Sarcoma? JF - SEMINARS IN RADIATION ONCOLOGY J2 - SEMIN RADIAT ONCOL VL - 34 PY - 2024 IS - 2 SP - 218 EP - 228 PG - 11 SN - 1053-4296 DO - 10.1016/j.semradonc.2024.02.001 UR - https://m2.mtmt.hu/api/publication/34878223 ID - 34878223 N1 - Funding Agency and Grant Number: NIH/NCI [P01CA257904]; Abramson Cancer Center's Translational Center of Excellence in Radiation Oncology Funding text: This manuscript was supported by an NIH/NCI grant P01CA257904 and Institutional and Departmental funding including from the Abramson Cancer Center's Translational Center of Excellence in Radiation Oncology. AB - FLASH is an emerging treatment paradigm in radiotherapy (RT) that utilizes ultra -high dose rates (UHDR; > 40 Gy)/s) of radiation delivery. Developing advances in technology support the delivery of UHDR using electron and proton systems, as well as some ion beam units (eg, carbon ions), while methods to achieve UHDR with photons are under investigation. The major advantage of FLASH RT is its ability to increase the therapeutic index for RT by shifting the dose response curve for normal tissue toxicity to higher doses. Numerous preclinical studies have been conducted to date on FLASH RT for murine sarcomas, alongside the investigation of its effects on relevant normal tissues of skin, muscle, and bone. The tumor control achieved by FLASH RT of sarcoma models is indistinguishable from that attained by treatment with standard RT to the same total dose. FLASH 's high dose rates are able to mitigate the severity or incidence of RT side effects on normal tissues as evaluated by endpoints ranging from functional sparing to histological damage. Large animal studies and clinical trials of canine patients show evidence of skin sparing by FLASH vs. standard RT, but also caution against delivery of high single doses with FLASH that exceed those safely applied with standard RT. Also, a human clinical trial has shown that FLASH RT can be delivered safely to bone metastasis. Thus, data to date support continued investigations of clinical translation of FLASH RT for the treatment of patients with sarcoma. Toward this purpose, hypofractionated irradiation schemes are being investigated for FLASH effects on sarcoma and relevant normal tissues. LA - English DB - MTMT ER - TY - JOUR AU - Clements, Nathan AU - Esplen, Nolan AU - Bateman, Joseph AU - Robertson, Cameron AU - Dosanjh, Manjit AU - Korysko, Pierre AU - Farabolini, Wilfrid AU - Corsini, Roberto AU - Bazalova-Carter, Magdalena TI - Mini-GRID radiotherapy on the CLEAR very-high-energy electron beamline: collimator optimization, film dosimetry, and Monte Carlo simulations JF - PHYSICS IN MEDICINE AND BIOLOGY J2 - PHYS MED BIOL VL - 69 PY - 2024 IS - 5 PG - 17 SN - 0031-9155 DO - 10.1088/1361-6560/ad247d UR - https://m2.mtmt.hu/api/publication/34746004 ID - 34746004 N1 - Funding Agency and Grant Number: Canada Research Chairshttps://doi.org/10.13039/501100001804; NSERC Discovery Grant; Canada Research Chairs program; WestGrid; Digital Research Alliance of Canada Funding text: This work was funded in part by an NSERC Discovery Grant as well as the Canada Research Chairs program. This research was enabled in part by support provided by WestGrid (www.westgrid.ca) and The Digital Research Alliance of Canada (formerly known as Compute Canada) (www.alliancecan.ca). AB - Objective. Spatially-fractionated radiotherapy (SFRT) delivered with a very-high-energy electron (VHEE) beam and a mini-GRID collimator was investigated to achieve synergistic normal tissue-sparing through spatial fractionation and the FLASH effect. Approach. A tungsten mini-GRID collimator for delivering VHEE SFRT was optimized using Monte Carlo (MC) simulations. Peak-to-valley dose ratios (PVDRs), depths of convergence (DoCs, PVDR <= 1.1), and peak and valley doses in a water phantom from a simulated 150 MeV VHEE source were evaluated. Collimator thickness, hole width, and septal width were varied to determine an optimal value for each parameter that maximized PVDR and DoC. The optimized collimator (20 mm thick rectangular prism with a 15 mm x 15 mm face with a 7 x 7 array of 0.5 mm holes separated by 1.1 mm septa) was 3D-printed and used for VHEE irradiations with the CERN linear electron accelerator for research beam. Open beam and mini-GRID irradiations were performed at 140, 175, and 200 MeV and dose was recorded with radiochromic films in a water tank. PVDR, central-axis (CAX) and valley dose rates and DoCs were evaluated. Main results. Films demonstrated peak and valley dose rates on the order of 100 s of MGy/s, which could promote FLASH-sparing effects. Across the three energies, PVDRs of 2-4 at 13 mm depth and DoCs between 39 and 47 mm were achieved. Open beam and mini-GRID MC simulations were run to replicate the film results at 200 MeV. For the mini-GRID irradiations, the film CAX dose was on average 15% higher, the film valley dose was 28% higher, and the film PVDR was 15% lower than calculated by MC. Significance. Ultimately, the PVDRs and DoCs were determined to be too low for a significant potential for SFRT tissue-sparing effects to be present, particularly at depth. Further beam delivery optimization and investigations of new means of spatial fractionation are warranted. LA - English DB - MTMT ER - TY - JOUR AU - Darsan, A.S. AU - Pandikumar, A. TI - Recent research progress on metal halide perovskite based visible light active photoanode for photoelectrochemical water splitting JF - MATERIALS SCIENCE IN SEMICONDUCTOR PROCESSING J2 - MAT SCI SEMICON PROC VL - 174 PY - 2024 SN - 1369-8001 DO - 10.1016/j.mssp.2024.108203 UR - https://m2.mtmt.hu/api/publication/34746073 ID - 34746073 N1 - Electrochemical Power Sources Division, CSIR-Central Electrochemical Research Institute, Tamil Nadu, Karaikudi, 630003, India Electro-Organic and Materials Electrochemistry Division, CSIR-Central Electrochemical Research Institute, Tamil Nadu, Karaikudi, 630003, India Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India Export Date: 19 March 2024 Correspondence Address: Pandikumar, A.; Electro-Organic and Materials Electrochemistry Division, Tamil Nadu, India; email: pandikumarinbox@gmail.com Funding details: Department of Science and Technology, Ministry of Science and Technology, India, DST, CECRI/PESVC/Pubs/2023-014, IF200282 Funding details: Council of Scientific and Industrial Research, India, CSIR, MLP0319 Funding text 1: Dr. A. Pandikumar thanks CSIR, New Delhi for the financial support through FBR-E 2 D theme ( MLP0319 ). Ms. Ardra S Darsan thanks to DST-Inspire Fellowship ( IF200282 ). CSIR-CECRI manuscript communication number: CECRI/PESVC/Pubs/2023-014(A). Funding text 2: Dr. A. Pandikumar thanks CSIR, New Delhi for the financial support through FBR-E2D theme (MLP0319). Ms. Ardra S Darsan thanks to DST-Inspire Fellowship (IF200282). CSIR-CECRI manuscript communication number: CECRI/PESVC/Pubs/2023-014(A). AB - The wheels of the future generation will be driven by hydrogen fuel. Hydrogen is the potential, sustainable and clean energy vector, with high energy density, high heating value, and greenhouse gas-free combustion. Artificial photosynthesis especially photoelectrocatalytic (PEC) and photocatalytic (PC) water splitting reactions are widely investigated over gasification, electrolysis, thermochemical and photobiological systems for green hydrogen production. Metal Halide Perovskites (MHPs) with ABX3 stoichiometry have piqued researcher's curiosity because of their peculiar electronic, thermal and optical properties, including long carrier diffusion lengths, outstanding tolerance factors, high light absorption coefficients, large thermal expansion coefficient and ultralow thermal conductivity. The optoelectronic properties of MHPs can be modified using band-gap tuning and defect engineering techniques, and they can be used for photocatalytic and photoelectrocatalytic applications in water splitting, nitrogen fixation, and CO2 reduction. Many review articles have summarized the synthesis, properties and application in the above-mentioned area by using MHPs. Few review articles exclusively focused on MHP based photocatalytic systems for water splitting and there is no dedicated review article is available to date for MHP-based PEC water splitting. In this article, we reviewed the latest research trends and developments in the field of PEC water splitting using MHPs. This also provides details about the optical, electronic, and thermal aspects of MHPs, along with feasible changes, limitations, and stability concerns, as well as viable ways to overcome such hurdles. © 2024 Elsevier Ltd LA - English DB - MTMT ER - TY - JOUR AU - El, Khatib M. AU - Motlagh, A.O. AU - Beyer, J.N. AU - Troxler, T. AU - Allu, S.R. AU - Sun, Q. AU - Burslem, G.M. AU - Vinogradov, S.A. TI - Direct Measurements of FLASH-Induced Changes in Intracellular Oxygenation JF - INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS J2 - INT J RADIAT ONCOL VL - 118 PY - 2024 IS - 3 SP - 781 EP - 789 PG - 9 SN - 0360-3016 DO - 10.1016/j.ijrobp.2023.09.019 UR - https://m2.mtmt.hu/api/publication/34327447 ID - 34327447 N1 - Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, United States Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States Export Date: 14 November 2023 CODEN: IOBPD Correspondence Address: El Khatib, M.; Department of Biochemistry and Biophysics, United States; email: elmirna@pennmedicine.upenn.edu Funding details: EB028941, HL145092, P01CA257904 Funding details: National Science Foundation, NSF, 2019272859 Funding details: National Institutes of Health, NIH Funding text 1: Disclosures: S.A.V. has partial ownership of Oxygen Enterprises Ltd, which owns the intellectual property for the Oxyphor technology (US patent No. 9,556,213; US, 2017/0137449 A1). All other authors declare no competing interests. Support of the grants HL145092 (M.E.K.), P01CA257904, and EB028941 (S.A.V.) from the National Institutes of Health USA and of NSF Graduate Research Fellowship #2019272859 (J.N.B.) is gratefully acknowledged. Funding text 2: Disclosures: S.A.V. has partial ownership of Oxygen Enterprises Ltd, which owns the intellectual property for the Oxyphor technology (US patent No. 9,556,213; US, 2017/0137449 A1). All other authors declare no competing interests. Support of the grants HL145092 (M.E.K.), P01CA257904, and EB028941 (S.A.V.) from the National Institutes of Health USA and of NSF Graduate Research Fellowship #2019272859 (J.N.B.) is gratefully acknowledged. AB - Purpose: The goal of our study was to characterize the dynamics of intracellular oxygen during application of radiation at conventional (CONV) and FLASH dose rates and obtain evidence for or against the oxygen depletion hypothesis as a mechanism of the FLASH effect. Methods and Materials: The measurements were performed by the phosphorescence quenching method using probe Oxyphor PtG4, which was delivered into the cellular cytosol by electroporation. Results: Intracellular radiochemical oxygen depletion (ROD) g-value for a dose rate of 100 Gy/s in the normoxic range was found to be 0.58 ± 0.03 μM/Gy. Intracellular ROD g-values for FLASH and CONV dose rates in the normoxic range were found to be nearly equal. As in solution-based studies, intracellular ROD was found to exhibit strong dependence on oxygen concentration in the range of 0 to ∼40 μM [O2]. Conclusions: Depletion of oxygen in cells in vitro by a clinical dose of proton radiation delivered as FLASH is unable to produce a transient state of hypoxia and, therefore, unable to induce radioprotection. The difference between ROD g-values for FLASH and CONV dose rates, detected previously in solutions-based experiments, disappears when measurements are conducted inside cells. Understanding this phenomenon should provide additional insight into the role of oxygen in FLASH radiation therapy and help to decipher the mechanism of the FLASH effect. © 2023 Elsevier Inc. LA - English DB - MTMT ER - TY - JOUR AU - Fenwick, John D. AU - Mayhew, Christopher AU - Jolly, Simon AU - Amos, Richard A. AU - Hawkins, Maria A. TI - Navigating the straits: realizing the potential of proton FLASH through physics advances and further pre-clinical characterization JF - FRONTIERS IN ONCOLOGY J2 - FRONT ONCOL VL - 14 PY - 2024 PG - 14 SN - 2234-943X DO - 10.3389/fonc.2024.1420337 UR - https://m2.mtmt.hu/api/publication/35155416 ID - 35155416 N1 - Funding Agency and Grant Number: Radiation Research Unit at the Cancer Research UK City of London Centre Award [C7893/A28990]; National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre Funding text: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. JF is supported by the Radiation Research Unit at the Cancer Research UK City of London Centre Award (C7893/A28990). CM is supported by the Radiation Research Unit at the Cancer Research UK City of London Centre Award (C7893/A28990). MH is supported by the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre. AB - Ultra-high dose-rate 'FLASH' radiotherapy may be a pivotal step forward for cancer treatment, widening the therapeutic window between radiation tumour killing and damage to neighbouring normal tissues. The extent of normal tissue sparing reported in pre-clinical FLASH studies typically corresponds to an increase in isotoxic dose-levels of 5-20%, though gains are larger at higher doses. Conditions currently thought necessary for FLASH normal tissue sparing are a dose-rate >= 40 Gy s-1, dose-per-fraction >= 5-10 Gy and irradiation duration <= 0.2-0.5 s. Cyclotron proton accelerators are the first clinical systems to be adapted to irradiate deep-seated tumours at FLASH dose-rates, but even using these machines it is challenging to meet the FLASH conditions. In this review we describe the challenges for delivering FLASH proton beam therapy, the compromises that ensue if these challenges are not addressed, and resulting dosimetric losses. Some of these losses are on the same scale as the gains from FLASH found pre-clinically. We therefore conclude that for FLASH to succeed clinically the challenges must be systematically overcome rather than accommodated, and we survey physical and pre-clinical routes for achieving this. LA - English DB - MTMT ER - TY - JOUR AU - Gu, Runqiu AU - Wang, Jianlin AU - Wang, Pan AU - Mao, Xin AU - Lin, Binwei AU - Tan, Wanchao AU - Du, Xiaobo AU - Gao, Feng AU - Wang, Tingting TI - Alanine/electron spin resonance dosimetry for FLASH radiotherapy JF - RADIATION PHYSICS AND CHEMISTRY: THE JOURNAL FOR RADIATION PHYSICS RADIATION CHEMISTRY AND RADIATION PROCESSING J2 - RADIAT PHYS CHEM VL - 225 PY - 2024 PG - 8 SN - 0969-806X DO - 10.1016/j.radphyschem.2024.112113 UR - https://m2.mtmt.hu/api/publication/35192051 ID - 35192051 N1 - Funding Agency and Grant Number: Sichuan Science and Technology Program [2023NSFSC1454, 2023NSFSC1453]; Talent Introduction Research Project Mianyang Central Hospital [2022YJRC-002]; NHC Key Laboratory of Nuclear Technology Medical Transformation [2021HYX014] Funding text: This work was supported by the Sichuan Science and Technology Program (Grant No.2023NSFSC1454 and 2023NSFSC1453) and the Talent Introduction Research Project Mianyang Central Hospital (Grant No. 2022YJRC-002) , by the NHC Key Laboratory of Nuclear Technology Medical Transformation (Grant No. 2021HYX014) . AB - The purpose of this study is to systematically study and analyse the dose calibration and measurement of the alanine/electron spin resonance dosimetry system in FLASH radiotherapy. The dose calibration curve of the alanine dosimeter ranged from 0 to 50 Gy, and the best linear fit to the data shows a correlation coefficient close to 1. In the stability experiment, the preset irradiation values for the alanine dosimeter and radiochromic film were 14.34 Gy and 13.38 Gy, respectively, and the results of a stability experiment results showed that the alanine dosimeter exhibited superior stability, compared with radiochromic film, with a deviation of less than 1% in repeated measurements. The results of X-ray FLASH irradiation experiments on mice showed that the maximum standard errors of the alanine dosimeter between the measured results and the preset dose values were 4.57% (chest experiment) and 3.22% (abdomen experiment), whereas those for the radiochromic film were 6.03% (chest experiment) and 6.50% (abdomen experiment). Additionally, X-ray and electron-beam FLASH radiotherapy experiments on mice verified that the alanine dosimeter showed no dose-rate dependence and provided more accurate measurement results compared to the radiochromic film. LA - English DB - MTMT ER - TY - JOUR AU - Horst, F. AU - Bodenstein, E. AU - Brand, M. AU - Hans, S. AU - Karsch, L. AU - Lessmann, E. AU - Löck, S. AU - Schürer, M. AU - Pawelke, J. AU - Beyreuther, E. TI - Dose and dose rate dependence of the tissue sparing effect at ultra-high dose rate studied for proton and electron beams using the zebrafish embryo model JF - RADIOTHERAPY AND ONCOLOGY J2 - RADIOTHER ONCOL VL - 194 PY - 2024 SN - 0167-8140 DO - 10.1016/j.radonc.2024.110197 UR - https://m2.mtmt.hu/api/publication/34750076 ID - 34750076 N1 - Helmholtz-Zentrum Dresden – Rossendorf, Institute of Radiooncology – OncoRay, Dresden, Germany OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden – Rossendorf, Dresden, Germany Center for Regenerative Therapies TU Dresden and Cluster of Excellence 'Physics of Life', Technische Universität Dresden, Dresden, Germany Helmholtz-Zentrum Dresden – Rossendorf, Institute of Radiation Physics, Dresden, Germany Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Germany National Center for Tumor Diseases Dresden (NCT/UCC), Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany Export Date: 21 March 2024 CODEN: RAOND Correspondence Address: Beyreuther, E.; Helmholtz-Zentrum Dresden – Rossendorf, Bautzener Landstraße 400, Germany; email: E.Beyreuther@hzdr.de Funding details: Horizon 2020 Funding details: Helmholtz Association Funding details: Horizon 2020 Framework Programme, H2020, 730983 Funding text 1: We would like to thank Till Tobias Böhlen for sharing his data collection with us and for fruitful discussions. Part of this research was carried out at ELBE at the Helmholtz-Zentrum Dresden – Rossendorf e. V. a member of the Helmholtz Association. We would like to thank especially Rico Schurig, Pavel Evtushenko, Ulf Lehnert, Christoph Schneider and Peter Michel from the ELBE crew for support and their ongoing interest in our high-dose rate electron experiments. We thank Daniela Zöller for help with zebrafish embryo transfer and Marika Fischer, Judith Konantz, Sylvio Kunadt and Daniela Mögel from the animal facility for dedicated zebrafish care. We are thankful to Marit Wondrak for sample preparation for our zebrafish experiments. The experimental part of the UPTD proton facility has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No.730983 (INSPIRE). We also thank the local IBA team for supporting our proton Flash experiments. Funding text 2: The experimental part of the UPTD proton facility has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No.730983 (INSPIRE). Funding text 3: We would like to thank Till Tobias Böhlen for sharing his data collection with us and for fruitful discussions. Part of this research was carried out at ELBE at the Helmholtz-Zentrum Dresden – Rossendorf e. V., a member of the Helmholtz Association. We would like to thank especially Rico Schurig, Pavel Evtushenko, Ulf Lehnert, Christoph Schneider and Peter Michel from the ELBE crew for support and their ongoing interest in our high-dose rate electron experiments. We thank Daniela Zöller for help with zebrafish embryo transfer and Marika Fischer, Judith Konantz, Sylvio Kunadt and Daniela Mögel from the animal facility for dedicated zebrafish care. We are thankful to Marit Wondrak for sample preparation for our zebrafish experiments. The experimental part of the UPTD proton facility has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No.730983 (INSPIRE). We also thank the local IBA team for supporting our proton Flash experiments. AB - Purpose: A better characterization of the dependence of the tissue sparing effect at ultra-high dose rate (UHDR) on physical beam parameters (dose, dose rate, radiation quality) would be helpful towards a mechanistic understanding of the FLASH effect and for its broader clinical translation. To address this, a comprehensive study on the normal tissue sparing at UHDR using the zebrafish embryo (ZFE) model was conducted. Methods: One-day-old ZFE were irradiated over a wide dose range (15–95 Gy) in three different beams (proton entrance channel, proton spread out Bragg peak and 30 MeV electrons) at UHDR and reference dose rate. After irradiation the ZFE were incubated for 4 days and then analyzed for four different biological endpoints (pericardial edema, curved spine, embryo length and eye diameter). Results: Dose-effect curves were obtained and a sparing effect at UHDR was observed for all three beams. It was demonstrated that proton relative biological effectiveness and UHDR sparing are both relevant to predict the resulting dose response. Dose dependent FLASH modifying factors (FMF) for ZFE were found to be compatible with rodent data from the literature. It was found that the UHDR sparing effect saturates at doses above ∼ 50 Gy with an FMF of ∼ 0.7–0.8. A strong dose rate dependence of the tissue sparing effect in ZFE was observed. The magnitude of the maximum sparing effect was comparable for all studied biological endpoints. Conclusion: The ZFE model was shown to be a suitable pre-clinical high-throughput model for radiobiological studies on FLASH radiotherapy, providing results comparable to rodent models. This underlines the relevance of ZFE studies for FLASH radiotherapy research. © 2024 The Author(s) LA - English DB - MTMT ER - TY - JOUR AU - Malidarreh, Roya Boudaghi AU - Zakaly, Hesham M. H. TI - FLASH Radiation Therapy - Key physical irradiation parameters and beam characteristics JF - JOURNAL OF INSTRUMENTATION J2 - J INSTRUM VL - 19 PY - 2024 IS - 2 PG - 19 SN - 1748-0221 DO - 10.1088/1748-0221/19/02/P02035 UR - https://m2.mtmt.hu/api/publication/34833278 ID - 34833278 N1 - Funding Agency and Grant Number: Ministry of Science and Higher Education of the Russian Federation (Ural Federal University Program of Development within the Priority-2030 Program) Funding text: The research partially funding from the Ministry of Science and Higher Education of the Russian Federation (Ural Federal University Program of Development within the Priority-2030 Program) is gratefully acknowledged. AB - FLASH-RT represents a novel therapeutic radiation modality that holds remarkable potential for mitigating radiation therapy's adverse side effects. This cutting -edge technology allows for sparing healthy tissue while precisely targeting cancerous cells. This is possible by administering an ultra -high -dose -rate in less than a few hundred milliseconds. FLASH-RT has demonstrated impressive results in small -animal models, prompting scientists to adapt and advance existing technologies to make it a viable treatment option for humans. However, producing the ultra -high -dose -rate radiation required for the therapy remains a significant challenge. Several radiation sources, such as very high energy electrons (VHEEs), low energy electrons, x-rays, and protons, have been studied for their ability to deliver the necessary dose. Among them, FLASH -x-ray has gained the most attention owing to its capacity to penetrate deep-seated tumors. Despite the complexity of the process, the potential advantages of FLASH-RT made it an exciting area of research. To achieve the FLASH effect, high -frequency, pulsed irradiated accelerator technology can be employed. Sparing healthy tissue may allow for more aggressive and effective cancer treatments, leading to a better quality of life for patients. Ongoing research and development will be necessary to refine and optimize this approach to radiation therapy. LA - English DB - MTMT ER - TY - JOUR AU - McGarrigle, J.M. AU - Long, K.R. AU - Prezado, Y. TI - The FLASH effect—an evaluation of preclinical studies of ultra-high dose rate radiotherapy JF - FRONTIERS IN ONCOLOGY J2 - FRONT ONCOL VL - 14 PY - 2024 SN - 2234-943X DO - 10.3389/fonc.2024.1340190 UR - https://m2.mtmt.hu/api/publication/34849941 ID - 34849941 N1 - Department of Physics, Imperial College London, London, United Kingdom Science and Technology Facilities Council (STFC), Rutherford Appleton Laboratory, Oxford, United Kingdom Institut Curie, Universite Paris-Saclay, Centre national de la recherche scientifique (CNRS) UMR3347, Inserm U1021, Signalisation radiobiologie et cancer, Orsay, France Universite Paris-Saclay, Centre national de la recherche scientifique (CNRS) UMR3347, Inserm U1021, Signalisation radiobiologie et cancer, Orsay, France Export Date: 13 May 2024 Correspondence Address: McGarrigle, J.M.; Department of Physics, United Kingdom; email: jmm119@ic.ac.uk Correspondence Address: Long, K.R.; Department of Physics, United Kingdom; email: k.long@imperial.ac.uk Correspondence Address: Prezado, Y.; Institut Curie, France; email: yolanda.prezado@curie.fr Funding details: Imperial College London, ICL Funding details: Centre National de la Recherche Scientifique, CNRS Funding details: European Research Council, ERC Funding details: UK Research and Innovation, UKRI Funding details: Horizon 2020 Framework Programme, H2020, 817908 Funding text 1: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The work described here was carried out within the joint National de la Recherche Scientifique (CNRS)-Imperial College London (ICL) International Research Centre. The research was made possible by grants from CNRS, ICL and the UKRI Science and Technology Facilities Council and received funding from the European Research Council (ERC) under the European Union\\u2019s Horizon 2020 research and innovation program (Grant Agreement No 817908). Acknowledgments AB - FLASH radiotherapy (FLASH-RT) is a novel radiotherapy approach based on the use of ultra-high dose radiation to treat malignant cells. Although tumours can be reduced or eradicated using radiotherapy, toxicities induced by radiation can compromise healthy tissues. The FLASH effect is the observation that treatment delivered at an ultra-high dose rate is able to reduce adverse toxicities present at conventional dose rates. While this novel technique may provide a turning point for clinical practice, the exact mechanisms underlying the causes or influences of the FLASH effect are not fully understood. The study presented here uses data collected from 41 experimental investigations (published before March 2024) of the FLASH effect. Searchable databases were constructed to contain the outcomes of the various experiments in addition to values of beam parameters that may have a bearing on the FLASH effect. An in-depth review of the impact of the key beam parameters on the results of the experiments was carried out. Correlations between parameter values and experimental outcomes were studied. Pulse Dose Rate had positive correlations with almost all end points, suggesting viability of FLASH-RT as a new modality of radiotherapy. The collective results of this systematic review study suggest that beam parameter qualities from both FLASH and conventional radiotherapy can be valuable for tissue sparing and effective tumour treatment. Copyright © 2024 McGarrigle, Long and Prezado. LA - English DB - MTMT ER - TY - JOUR AU - Mossahebi, Sina AU - Byrne, Kevin AU - Jiang, Kai AU - Gerry, Andrew AU - Deng, Wei AU - Repetto, Carlo AU - Jackson, Isabel L. AU - Sawant, Amit AU - Poirier, Yannick TI - A high-throughput focused collimator for OAR-sparing preclinical proton FLASH studies: commissioning and validation JF - PHYSICS IN MEDICINE AND BIOLOGY J2 - PHYS MED BIOL VL - 69 PY - 2024 IS - 14 PG - 15 SN - 0031-9155 DO - 10.1088/1361-6560/ad589f UR - https://m2.mtmt.hu/api/publication/35155494 ID - 35155494 N1 - Funding text: The authors declare no acknowledgments. AB - Objective. To fabricate and validate a novel focused collimator designed to spare normal tissue in a murine hemithoracic irradiation model using 250 MeV protons delivered at ultra-high dose rates (UHDRs) for preclinical FLASH radiation therapy (FLASH-RT) studies. Approach. A brass collimator was developed to shape 250 MeV UHDR protons from our Varian ProBeam. Six 13 mm apertures, of equivalent size to kV x-ray fields historically used to perform hemithorax irradiations, were precisely machined to match beam divergence, allowing concurrent hemithoracic irradiation of six mice while sparing the contralateral lung and abdominal organs. The collimated field profiles were characterized by film dosimetry, and a radiation survey of neutron activation was performed to ensure the safety of staff positioning animals. Main results. The brass collimator produced 1.2 mm penumbrae radiation fields comparable to kV x-rays used in preclinical studies. The penumbrae in the six apertures are similar, with full-width half-maxima of 13.3 mm and 13.5 mm for the central and peripheral apertures, respectively. The collimator delivered a similar dose at an average rate of 52 Gy s(-1) for all apertures. While neutron activation produces a high (0.2 mSv h(-1)) initial ambient equivalent dose rate, a parallel work-flow in which imaging and setup are performed without the collimator ensures safety to staff. Significance. Scanned protons have the greatest potential for future translation of FLASH-RT in clinical treatments due to their ability to treat deep-seated tumors with high conformality. However, the Gaussian distribution of dose in proton spots produces wider lateral penumbrae compared to other modalities. This presents a challenge in small animal pre-clinical studies, where millimeter-scale penumbrae are required to precisely target the intended volume. Offering high-throughput irradiation of mice with sharp penumbrae, our novel collimator-based platform serves as an important benchmark for enabling large-scale, cost-effective radiobiological studies of the FLASH effect in murine models. LA - English DB - MTMT ER - TY - JOUR AU - Schneider, M. AU - Schilz, J.D. AU - Schürer, M. AU - Gantz, S. AU - Dreyer, A. AU - Rothe, G. AU - Tillner, F. AU - Bodenstein, E. AU - Horst, F. AU - Beyreuther, E. TI - SAPPHIRE —establishment of small animal proton and photon image-guided radiation experiments JF - PHYSICS IN MEDICINE AND BIOLOGY J2 - PHYS MED BIOL VL - 69 PY - 2024 IS - 9 SN - 0031-9155 DO - 10.1088/1361-6560/ad3887 UR - https://m2.mtmt.hu/api/publication/34849940 ID - 34849940 N1 - OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine, University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiation Physics, Dresden, Germany National Center for Tumor Diseases (NCT/UCC), Dresden, Germany German Cancer Research Center (DKFZ), Heidelberg, Germany Medizinische Fakultät and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology-OncoRay, Dresden, Germany Department of Radiotherapy and Radiation Oncology, Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany Export Date: 13 May 2024 CODEN: PHMBA Correspondence Address: Schneider, M.; OncoRay, Germany; email: m.schneider@hzdr.de Chemicals/CAS: proton, 12408-02-5, 12586-59-3; Protons AB - The in vivo evolution of radiotherapy necessitates innovative platforms for preclinical investigation, bridging the gap between bench research and clinical applications. Understanding the nuances of radiation response, specifically tailored to proton and photon therapies, is critical for optimizing treatment outcomes. Within this context, preclinical in vivo experimental setups incorporating image guidance for both photon and proton therapies are pivotal, enabling the translation of findings from small animal models to clinical settings. The SAPPHIRE project represents a milestone in this pursuit, presenting the installation of the small animal radiation therapy integrated beamline (SmART+ IB, Precision X-Ray Inc., Madison, Connecticut, USA) designed for preclinical image-guided proton and photon therapy experiments at University Proton Therapy Dresden. Through Monte Carlo simulations, low-dose on-site cone beam computed tomography imaging and quality assurance alignment protocols, the project ensures the safe and precise application of radiation, crucial for replicating clinical scenarios in small animal models. The creation of Hounsfield lookup tables and comprehensive proton and photon beam characterizations within this system enable accurate dose calculations, allowing for targeted and controlled comparison experiments. By integrating these capabilities, SAPPHIRE bridges preclinical investigations and potential clinical applications, offering a platform for translational radiobiology research and cancer therapy advancements. © 2024 The Author(s). Published on behalf of Institute of Physics and Engineering in Medicine by IOP Publishing Ltd LA - English DB - MTMT ER - TY - JOUR AU - Schoenauen, L. AU - Stubbe, F.-X. AU - Van, Gestel D. AU - Penninckx, S. AU - Heuskin, A.-C. TI - C. elegans: A potent model for high-throughput screening experiments investigating the FLASH effect JF - CLINICAL AND TRANSLATIONAL RADIATION ONCOLOGY J2 - CLIN TRANSL RADIAT ONCOL (CTRO) VL - 45 PY - 2024 SN - 2405-6308 DO - 10.1016/j.ctro.2023.100712 UR - https://m2.mtmt.hu/api/publication/34502368 ID - 34502368 N1 - NAmur Research Insitute for Life Sciences, University of Namur, Belgium Department of Radiation Oncology, Institut Jules Bordet, Hopital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles, Brussels, Belgium Export Date: 15 January 2024 Correspondence Address: Schoenauen, L.; Physics department (LARN), Rue de Bruxelles 61, Belgium; email: lucas.schoenauen@unamur.be Tradenames: Farmer, PTW, Germany; ImageJ; Mobetron, IntraOp, United States; Prism 10.0.0, Graphpad, United States; X-Rad 225XL, Precision X-Ray, United States Manufacturers: PTW, Germany; Altais, United States; Graphpad, United States; IntraOp, United States; Precision X-Ray, United States Funding details: Université de Namur, UNamur Funding text 1: The authors thank the laboratory of Molecular Genetics (GÉMO) and Damien Hermand from University of Namur for the C. elegans strain and maintenance, and Christophe Vandekerkhove for the technical help during the electron irradiations at Bordet Institute. AB - This study explores the effects of UHDR irradiation on Caenorhabditis elegans embryos. UHDR proton and electron beams demonstrate a sparing effect, aligning with literature findings. This highlights C. elegans suitability as a screening model for studying the LET impact on the FLASH effect, reinforcing its potential in radiation research. © 2023 The Author(s) LA - English DB - MTMT ER - TY - JOUR AU - Schoenauen, L. AU - Coos, R. AU - Colaux, J.L. AU - Heuskin, A.-C. TI - Design and optimization of a dedicated Faraday cup for UHDR proton dosimetry: Implementation in a UHDR irradiation station JF - NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT J2 - NUCL INSTRUM METH A VL - 1064 PY - 2024 SN - 0168-9002 DO - 10.1016/j.nima.2024.169411 UR - https://m2.mtmt.hu/api/publication/35012913 ID - 35012913 N1 - NAmur Research Insitute for Life Sciences (NARILIS), University of Namur, Belgium Namur Institute of Structured Matter (NISM), University of Namur, Belgium Export Date: 13 June 2024 CODEN: NIMAE Correspondence Address: Schoenauen, L.; NAmur Research Insitute for Life Sciences (NARILIS), Belgium; email: lucas.schoenauen@unamur.be AB - We describe in detail an Ultra High Dose Rate (UHDR) setup on a 2 MV tandem accelerator for investigating the FLASH effect in radiotherapy. Addressing UHDR dosimetry challenges, we have developed a specialized Faraday Cup (FC) as a dose rate-independent solution. Utilizing Monte Carlo simulations, the geometry and materials used for the FC's design has been optimized for a 4 MeV proton beam. According to the simulations, the virtual error on the charge collection is negligible. This three-part UHDR setup also integrates a beam profiler to ensure the beam homogeneity and an electrostatic chopper to irradiate for precise short times (down to 10 μs), replicating the macro beam structure of typical clinical proton accelerator structures such as the S2C2 and C230 (IBA, Louvain-la-Neuve). The integrated setup ensures dose deposition with an error ≤ 5% for dose rate from 140 to 1000 Gy/s. © 2024 Elsevier B.V. LA - English DB - MTMT ER - TY - JOUR AU - Tavakkoli, A.D. AU - Clark, M.A. AU - Kheirollah, A. AU - Sloop, A.M. AU - Soderholm, H.E. AU - Daniel, N.J. AU - Petusseau, A.F. AU - Huang, Y.H. AU - Thomas, C.R. Jr AU - Jarvis, L.A. AU - Zhang, R. AU - Pogue, B.W. AU - Gladstone, D.J. AU - Hoopes, P.J. TI - Anesthetic Oxygen Use and Sex Are Critical Factors in the FLASH Sparing Effect JF - ADVANCES IN RADIATION ONCOLOGY J2 - ADV RADIAT ONCOL VL - 9 PY - 2024 IS - 6 SN - 2452-1094 DO - 10.1016/j.adro.2024.101492 UR - https://m2.mtmt.hu/api/publication/34849939 ID - 34849939 N1 - Department of Radiation Oncology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, United States Department of Immunology and Microbiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States Department of Radiation Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, United States Department of Radiation Medicine, New York Medical College, Valhalla, New York, United States Department of Medical Physics, University of Wisconsin School of Medicine, Madison, WI, United States Export Date: 13 May 2024 Correspondence Address: Hoopes, P.J.; Department of Radiation Oncology, United States; email: p.jack.hoopes@dartmouth.edu Funding details: National Institutes of Health, NIH Funding details: Dartmouth Cancer Center, DCC, 5P30CA023108-37 Funding details: National Cancer Institute, NCI, U01CA260446 Funding text 1: Sources of support: This research was supported by the Dartmouth Cancer Center CCSG: 5P30CA023108-37 (Irradiation and Imaging Shared Resource, Genomics Shared Resource, Pathology Shared Resource), NIH/NCI grant: U01CA260446, and the Dartmouth Radiation Oncology Medical Student Research Fellowship. AB - Purpose: Ultra High Dose-Rate (UHDR) radiation has been reported to spare normal tissue, compared with Conventional Dose-Rate (CDR) radiation. However, important work remains to be done to improve the reproducibility of the FLASH effect. A better understanding of the biologic factors that modulate the FLASH effect may shed light on the mechanism of FLASH sparing. Here, we evaluated whether sex and/or the use of 100% oxygen as a carrier gas during irradiation contribute to the variability of the FLASH effect. Methods and Materials: C57BL/6 mice (24 male, 24 female) were anesthetized using isoflurane mixed with either room air or 100% oxygen. Subsequently, the mice received 27 Gy of either 9 MeV electron UHDR or CDR to a 1.6 cm2 diameter area of the right leg skin using the Mobetron linear accelerator. The primary postradiation endpoint was time to full thickness skin ulceration. In a separate cohort of mice (4 male, 4 female), skin oxygenation was measured using PdG4 Oxyphor under identical anesthesia conditions. Results: Neither supplemental oxygen nor sex affected time to ulceration in CDR irradiated mice. In the UHDR group, skin damage occured earlier in male and female mice that received 100% oxygen compared room air and female mice ulcerated sooner than male mice. However, there was no significant difference in time to ulceration between male and female UHDR mice that received room air. Oxygen measurements showed that tissue oxygenation was significantly higher when using 100% oxygen as the anesthesia carrier gas than when using room air, and female mice showed higher levels of tissue oxygenation than male mice under 100% oxygen. Conclusions: The skin FLASH sparing effect is significantly reduced when using oxygen during anesthesia rather than room air. FLASH sparing was also reduced in female mice compared to male mice. Both tissue oxygenation and sex are likely sources of variability in UHDR studies. These results suggest an oxygen-based mechanism for FLASH, as well as a key role for sex in the FLASH skin sparing effect. © 2024 The Author(s) LA - English DB - MTMT ER - TY - JOUR AU - Tessonnier, T. AU - Verona-Rinati, G. AU - Rank, L. AU - Kranzer, R. AU - Mairani, A. AU - Marinelli, M. TI - Diamond detectors for dose and instantaneous dose-rate measurements for ultra-high dose-rate scanned helium ion beams JF - MEDICAL PHYSICS J2 - MED PHYS VL - 51 PY - 2024 IS - 2 SP - 1450 EP - 1459 PG - 10 SN - 0094-2405 DO - 10.1002/mp.16757 UR - https://m2.mtmt.hu/api/publication/34199443 ID - 34199443 N1 - Heidelberg Ion Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany Clinical Cooperation Unit Translational Radiation Oncology, German Cancer Consortium (DKTK) Core-Center Heidelberg, National Center for Tumor Diseases (NCT), Heidelberg University Hospital (UKHD) and German Cancer Research Center (DKFZ), Heidelberg, Germany Industrial Engineering Department, University of Rome Tor Vergata, Rome, Italy Faculty of Physics, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany PTW-Freiburg, Freiburg, Germany University Clinic for Medical Radiation Physics, Carl von Ossietzky University, Oldenburg, Medical Campus Pius Hospital, Germany Medical Physics department, National Centre of Oncological Hadrontherapy (CNAO), Pavia, Italy Export Date: 16 October 2023 CODEN: MPHYA Correspondence Address: Tessonnier, T.; Heidelberg Ion Beam Therapy Center (HIT), Germany; email: thomas.tessonnier@med.uni-heidelberg.de Funding details: Horizon 2020 Funding text 1: This work was supported in part by NIH‐1P01CA257904‐01A1. This project 18HLT04 UHDpulse has received funding from the EMPIR programme co‐financed by the Participating States and from the European Union's Horizon 2020 research and innovation programme. AB - Background: The possible emergence of the FLASH effect—the sparing of normal tissue while maintaining tumor control—after irradiations at dose-rates exceeding several tens of Gy per second, has recently spurred a surge of studies attempting to characterize and rationalize the phenomenon. Investigating and reporting the dose and instantaneous dose-rate of ultra-high dose-rate (UHDR) particle radiotherapy beams is crucial for understanding and assessing the FLASH effect, towards pre-clinical application and quality assurance programs. Purpose: The purpose of the present work is to investigate a novel diamond-based detector system for dose and instantaneous dose-rate measurements in UHDR particle beams. Methods: Two types of diamond detectors, a microDiamond (PTW 60019) and a diamond detector prototype specifically designed for operation in UHDR beams (flashDiamond), and two different readout electronic chains, were investigated for absorbed dose and instantaneous dose-rate measurements. The detectors were irradiated with a helium beam of 145.7 MeV/u under conventional and UHDR delivery. Dose-rate delivery records by the monitoring ionization chamber and diamond detectors were studied for single spot irradiations. Dose linearity at 5 cm depth and in-depth dose response from 2 to 16 cm were investigated for both measurement chains and both detectors in a water tank. Measurements with cylindrical and plane-parallel ionization chambers as well as Monte-Carlo simulations were performed for comparisons. Results: Diamond detectors allowed for recording the temporal structure of the beam, in good agreement with the one obtained by the monitoring ionization chamber. A better time resolution of the order of few μs was observed as compared to the approximately 50 μs of the monitoring ionization chamber. Both diamonds detectors show an excellent linearity response in both delivery modalities. Dose values derived by integrating the measured instantaneous dose-rates are in very good agreement with the ones obtained by the standard electrometer readings. Bragg peak curves confirmed the consistency of the charge measurements by the two systems. Conclusions: The proposed novel dosimetric system allows for a detailed investigation of the temporal evolution of UHDR beams. As a result, reliable and accurate determinations of dose and instantaneous dose-rate are possible, both required for a comprehensive characterization of UHDR beams and relevant for FLASH effect assessment in clinical treatments. © 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine. LA - English DB - MTMT ER - TY - JOUR AU - Tsai, Pingfang AU - Yang, Yunjie AU - Wu, Mengjou AU - Chen, Chin-Cheng AU - Yu, Francis AU - Simone II, Charles B. AU - Choi, Jehee Isabelle AU - Tome, Wolfgang A. AU - Lin, Haibo TI - A comprehensive pre-clinical treatment quality assurance program using unique spot patterns for proton pencil beam scanning FLASH radiotherapy JF - JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS J2 - J APPL CLIN MED PHYS PY - 2024 PG - 11 SN - 1526-9914 DO - 10.1002/acm2.14400 UR - https://m2.mtmt.hu/api/publication/34976368 ID - 34976368 LA - English DB - MTMT ER - TY - JOUR AU - Yan, Ouying AU - Wang, Shang AU - Wang, Qiaoli AU - Wang, Xin TI - FLASH Radiotherapy: Mechanisms of Biological Effects and the Therapeutic Potential in Cancer JF - BIOMOLECULES J2 - BIOMOLECULES VL - 14 PY - 2024 IS - 7 PG - 16 SN - 2218-273X DO - 10.3390/biom14070754 UR - https://m2.mtmt.hu/api/publication/35160499 ID - 35160499 N1 - Funding Agency and Grant Number: National Natural Science Foundation of China [82073338]; Sichuan Science and Technology Support Project [2021YFSY0039, 22ZDYF0499]; The 135 Project for Disciplines of Excellence-Clinical Research Incubation Project, West China Hospital, Sichuan University [2020HXFH002] Funding text: This work was supported by the National Natural Science Foundation of China (82073338), Sichuan Science and Technology Support Project (2021YFSY0039 and 22ZDYF0499), and the 135 Project for Disciplines of Excellence-Clinical Research Incubation Project, West China Hospital, Sichuan University (2020HXFH002). AB - Radiotherapy is an important treatment for many unresectable advanced malignant tumors, and radiotherapy-associated inflammatory reactions to radiation and other toxic side effects are significant reasons which reduce the quality of life and survival of patients. FLASH-radiotherapy (FLASH-RT), a prominent topic in recent radiation therapy research, is an ultra-high dose rate treatment known for significantly reducing therapy time while effectively targeting tumors. This approach minimizes radiation side effects on at-risk organs and maximally protects surrounding healthy tissues. Despite decades of preclinical exploration and some notable achievements, the mechanisms behind FLASH effects remain debated. Standardization is still required for the type of FLASH-RT rays and dose patterns. This review addresses the current state of FLASH-RT research, summarizing the biological mechanisms behind the FLASH effect. Additionally, it examines the impact of FLASH-RT on immune cells, cytokines, and the tumor immune microenvironment. Lastly, this review will discuss beam characteristics, potential clinical applications, and the relevance and applicability of FLASH-RT in treating advanced cancers. LA - English DB - MTMT ER - TY - JOUR AU - Atkinson, Jake AU - Bezak, Eva AU - Le, Hien AU - Kempson, Ivan TI - The current status of FLASH particle therapy: a systematic review JF - PHYSICAL AND ENGINEERING SCIENCES IN MEDICINE J2 - PHYS ENG SCI MED VL - 46 PY - 2023 SP - 529 EP - 560 PG - 32 SN - 2662-4729 DO - 10.1007/s13246-023-01266-z UR - https://m2.mtmt.hu/api/publication/33937484 ID - 33937484 N1 - Funding Agency and Grant Number: CAUL Funding text: Open Access funding enabled and organized by CAUL and its Member Institutions AB - Particle therapies are becoming increasingly available clinically due to their beneficial energy deposition profile, sparing healthy tissues. This may be further promoted with ultra-high dose rates, termed FLASH. This review comprehensively summarises current knowledge based on studies relevant to proton- and carbon-FLASH therapy. As electron-FLASH literature presents important radiobiological findings that form the basis of proton and carbon-based FLASH studies, a summary of key electron-FLASH papers is also included. Preclinical data suggest three key mechanisms by which proton and carbon-FLASH are able to reduce normal tissue toxicities compared to conventional dose rates, with equipotent, or enhanced, tumour kill efficacy. However, a degree of caution is needed in clinically translating these findings as: most studies use transmission and do not conform the Bragg peak to tumour volume; mechanistic understanding is still in its infancy; stringent verification of dosimetry is rarely provided; biological assays are prone to limitations which need greater acknowledgement. LA - English DB - MTMT ER - TY - JOUR AU - Aylward, J. D. AU - Henthorn, N. AU - Manger, S. AU - Warmenhoven, J. W. AU - Merchant, M. J. AU - Taylor, M. J. AU - Mackay, R. I AU - Kirkby, K. J. TI - Characterisation of the UK high energy proton research beamline for high and ultra-high dose rate (FLASH) irradiation JF - BIOMEDICAL PHYSICS AND ENGINEERING EXPRESS J2 - BIOMED PHYS ENGINEERING EXPRESS VL - 9 PY - 2023 IS - 5 PG - 10 SN - 2057-1976 DO - 10.1088/2057-1976/acef25 UR - https://m2.mtmt.hu/api/publication/34143219 ID - 34143219 N1 - Funding Agency and Grant Number: We thank John Gordon from Pyramid Technical Consultants (Waltham MA, USA) as well as Matt Clarke, David Lines, and Shaun Atherton from The Christie Proton Beam Therapy Centre (Manchester, UK) for their support. Funding text: This research was funded by the Science and Technology Facilities Council STFC [ST/T506217/1] and supported by Cancer Research UK RadNet Manchester [C1994/A28701], NIHR Manchester Biomedical Research Centre[grant number: BRC-1215-20007], European Union's Horizon 2020 Research and Innovation Programme, INSPIRE [730983], the Engineering and Physical Sciences Research Council [EP/R023220/1], STFC Impact Acceleration Account, and the Christie Charitable Fund.r We thank John Gordon from Pyramid Technical Consultants (Waltham MA, USA) as well as Matt Clarke, David Lines, and Shaun Atherton from The Christie Proton Beam Therapy Centre (Manchester, UK) for their support. AB - Objective. This work sets out the capabilities of the high energy proton research beamline developed in the Christie proton therapy centre for Ultra-High Dose Rate (UHDR) irradiation and FLASH experiments. It also characterises the lower limits of UHDR operation for this Pencil Beam Scanning (PBS) proton hardware. Approach. Energy dependent nozzle transmission was measured using a Faraday Cup beam collector. Spot size was measured at the reference plane using a 2D scintillation detector. Integrated depth doses (IDDs) were measured. EBT3 Gafchromic film was used to compare UHDR and conventional dose rate spots. Our beam monitor calibration methodolgy for UHDR is described. A microDiamond detector was used to determine dose rates at zref. Instantaneous depth dose rates were calculated for 70-245 MeV. PBS dose rate distributions were calculated using Folkerts and Van der Water definitions. Main results. Transmission of 7.05 & PLUSMN; 0.1% is achieveable corresponding to a peak instantaneous dose rate of 112.7 Gy s-1. Beam parameters are comparable in conventional and UHDR mode with a spot size of & sigma; x = 4.6 mm, & sigma; y = 6.6 mm. Dead time in the beam monitoring electonics warrants a beam current dependent MU correction in the present configuration. Fast beam scanning of 26.4 m s-1 (X) and 12.1 m s-1 (Y) allows PBS dose rates of the order tens of Grays per second. Significance. UHDR delivery is possible for small field sizes and high energies enabling research into the FLASH effect with PBS protons at our facility. To our knowledge this is also the first thorough characterisation of UHDR irradiation using the hardware of this clinical accelerator at energies less than 250 MeV. The data set out in this publication can be used for designing experiments at this UK research facility and inform the possible future clinical translation of UHDR PBS proton therapy. LA - English DB - MTMT ER - TY - CHAP AU - Ballesteros-Zebadua, P. AU - Franco-Perez, J. AU - Vozenin, M.-C. ED - Morales-Barcenas, J.H. ED - Aguirre, O.L.A. ED - Ruiz-Trejo, C. ED - Massillon-J.L., G. ED - Torres-Garcia, E. ED - Brandan, M.-E. ED - Garcia-Pelagio, K.P. TI - How flash-RT can change the way we treat cancer T2 - 17th Mexican Symposium on Medical Physics 2022, MSMP 2022 VL - 2947 PB - American Institute of Physics (AIP) CY - Melville (NY) SN - 9780735446564 T3 - AIP Conference Proceedings, ISSN 0094-243X ; 2947. PY - 2023 IS - 1 DO - 10.1063/5.0161154 UR - https://m2.mtmt.hu/api/publication/34496095 ID - 34496095 N1 - Facultad de Fisica, and Instituto de Investigaciones Medico Biologicas, Universidad Veracruzana (UV); General Electric; The Medical Physics Division of the Mexican Physics Society Radiation Oncology Laboratory, Department of Radiation Oncology, Lausanne University Hospital, University of Lausanne, Bugnon 46, Lausanne, 1011, Switzerland National Institute of Neurology and Neurosurgery, Manuel Velasco Suarez. Insurgentes Sur 3877, La Fama, Mexico City, 14269, Mexico Conference code: 193360 Export Date: 11 January 2024 Correspondence Address: Vozenin, M.-C.; Radiation Oncology Laboratory, Bugnon 46, Switzerland; email: marie-catherine.vozenin@chuv.ch AB - In recent years, we have conceptualized and implemented a new irradiation modality at ultra-high dose rates, named FLASH-RT. Performed studies on different organs of several animal species have shown that this irradiation at ultra-high dose rates induces a remarkable FLASH effect. This effect is characterized by preserving normal tissue integrity but maintaining anti-tumor efficacy. The FLASH effect was first described using electron beams; however, evidence now indicates that similar findings are observed after the treatment of animal models with photon and proton beams. FLASH-RT has rapidly become a new field of research and consequently points towards translational medicine. Experimental evidence supports the clinical translation of FLASH; however, it is undeniable that several technological, physical, and biological aspects remain to be investigated before safe application in human patients. © 2023 AIP Publishing LLC. LA - English DB - MTMT ER - TY - JOUR AU - Bélanger-Champagne, C. AU - Roddy, D. AU - Penner, C. AU - Tattenberg, S. AU - Trinczek, M. AU - Yen, S. AU - Blackmore, E. AU - Hoehr, C. TI - Delivery of proton FLASH at the TRIUMF Proton Therapy Research Centre JF - NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT J2 - NUCL INSTRUM METH A VL - 1052 PY - 2023 SN - 0168-9002 DO - 10.1016/j.nima.2023.168243 UR - https://m2.mtmt.hu/api/publication/33810126 ID - 33810126 N1 - TRIUMF, 4004 Wesbrook Mall, Vancouver, BC V6T 2A3, Canada University of Edinburgh, Edinburgh, EH9 3FD, United Kingdom NOSM University, Sudbury, ON P3E 2C6, Canada Export Date: 11 May 2023 CODEN: NIMAE Correspondence Address: Hoehr, C.; TRIUMF, 4004 Wesbrook Mall, Canada; email: choehr@triumf.ca Funding details: National Research Council Canada, NRC Funding text 1: TRIUMF receives funding via a contribution agreement with the National Research Council of Canada. D. Roddy received funding from the UK government's Turing scheme. The authors would like to thank Kimmo Kotajärvi, Chelsey Currie, and Scott Kellogg for the use of their 3D printers. AB - The TRIUMF particle accelerator center in Vancouver, British Columbia, Canada houses a proton therapy beam line formerly used for the treatment of ocular cancer. This existing Proton Therapy Research Centre (PTRC) was upgraded to deliver protons at ultra-high dose rates which would be required for FLASH radiotherapy treatments. A peak dose rate of 110 Gy/s over an area of 20 mm2 was delivered at a beam energy of 21 MeV. This was achieved by degrading the cyclotron extracted beam energy of 70 MeV using polymethyl methacrylate (PMMA) plates. In addition, a fast, versatile and reliable method for producing static ridge filters has been developed to spread the proton beam to the entirety of the target axially (i.e., in depth). FLASH dose rates were maintained with a spread-out Bragg peak of 0.5 cm. © 2023 Elsevier B.V. LA - English DB - MTMT ER - TY - CHAP AU - Bertho, A. AU - Iturri, L. AU - Prezado, Y. TI - Radiation-induced immune response in novel radiotherapy approaches FLASH and spatially fractionated radiotherapies T2 - Ionizing Radiation and the Immune Response - Part A VL - 376 PB - Elsevier CY - [s.l.] SN - 9780323955232 T3 - International Review of Cell and Molecular Biology, ISSN 1937-6448 ; 376. PY - 2023 SP - 37 EP - 68 PG - 32 DO - 10.1016/bs.ircmb.2022.11.005 UR - https://m2.mtmt.hu/api/publication/33810135 ID - 33810135 N1 - Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, France Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, France Export Date: 11 May 2023 Correspondence Address: Prezado, Y.; Institut Curie, France; email: yolanda.prezado@curie.fr Funding details: European Research Council, ERC Funding details: Horizon 2020, 817908 Funding text 1: This project received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant Agreement No 817908). AB - The last several years have revealed increasing evidence of the immunomodulatory role of radiation therapy. Radiotherapy reshapes the tumoral microenvironment can shift the balance toward a more immunostimulatory or immunosuppressive microenvironment. The immune response to radiation therapy appears to depend on the irradiation configuration (dose, particle, fractionation) and delivery modes (dose rate, spatial distributions). Although an optimal irradiation configuration (dose, temporal fractionation, spatial dose distribution, etc.) has not yet been determined, temporal schemes employing high doses per fraction appear to favor radiation-induced immune response through immunogenic cell death. Through the release of damage-associated molecular patterns and the sensing of double-stranded DNA and RNA breaks, immunogenic cell death activates the innate and adaptive immune response, leading to tumor infiltration by effector T cells and the abscopal effect. Novel radiotherapy approaches such as FLASH and spatially fractionated radiotherapies (SFRT) strongly modulate the dose delivery method. FLASH-RT and SFRT have the potential to trigger the immune system effectively while preserving healthy surrounding tissues. This manuscript reviews the current state of knowledge on the immunomodulation effects of these two new radiotherapy techniques in the tumor, healthy immune cells and non-targeted regions, as well as their therapeutic potential in combination with immunotherapy. © 2023 Elsevier Inc. LA - English DB - MTMT ER - TY - JOUR AU - Cuitiño, M.C. AU - Fleming, J.L. AU - Jain, S. AU - Cetnar, A. AU - Ayan, A.S. AU - Woollard, J. AU - Manring, H. AU - Meng, W. AU - McElroy, J.P. AU - Blakaj, D.M. AU - Gupta, N. AU - Chakravarti, A. TI - Comparison of Gonadal Toxicity of Single-Fraction Ultra-High Dose Rate and Conventional Radiation in Mice JF - ADVANCES IN RADIATION ONCOLOGY J2 - ADV RADIAT ONCOL VL - 8 PY - 2023 IS - 4 SN - 2452-1094 DO - 10.1016/j.adro.2023.101201 UR - https://m2.mtmt.hu/api/publication/33810127 ID - 33810127 N1 - Department of Radiation Oncology, Arthur G. James Hospital, Comprehensive Cancer Center, Columbus, OH, United States Department of Biomedical Informatics, Center for Biostatistics, Ohio State University, Columbus, OH, United States Export Date: 11 May 2023 Correspondence Address: Chakravarti, A.; Department of Radiation Oncology, United States; email: Arnab.Chakravarti@osumc.edu Funding details: National Cancer Institute, NCI Funding details: Ohio State University, OSU Funding details: American Association of Physicists in Medicine, AAPM Funding text 1: Sources of support: This work was supported by grants R01CA108633, R01CA169368, RC2CA148190, and U10CA180850-01 (National Cancer Institute) and the Ohio State University Comprehensive Cancer Center (all to Dr Chakravarti). The histology and immunohistochemistry work was supported by the Comparative Pathology and Digital Imaging Shared Resource at the Ohio State University. Funding text 2: We thank Johanna Rawlings and Kevin Thorburn for assistance with histology and immunohistochemistry. Sources of support: This work was supported by grants R01CA108633, R01CA169368, RC2CA148190, and U10CA180850-01 (National Cancer Institute) and the Ohio State University Comprehensive Cancer Center (all to Dr Chakravarti). The histology and immunohistochemistry work was supported by the Comparative Pathology and Digital Imaging Shared Resource at the Ohio State University. Disclosures: Dr Chakravarti reports a relationship with Varian Medical Systems that includes funding grants. Dr Blakaj reports a relationship with IntraOp Medical that includes funding grants. Dr Cetnar reports a relationship with the American Association of Physicists in Medicine that includes travel reimbursement and a board membership and serves as Associate Section Editor for Advances in Radiation Oncology. Dr McElroy reports a relationship with the Ohio State University Department of Radiation Oncology that includes employment and nonfinancial support. Dr Fleming serves as Associate Senior Editor for Advances in Radiation Oncology. Dr Ayan serves as Associate Section Editor for Advances in Radiation Oncology. No other disclosures were reported. AB - Purpose: Increasing evidence suggests that ultra-high-dose-rate (UHDR) radiation could result in similar tumor control as conventional (CONV) radiation therapy (RT) while reducing toxicity to surrounding healthy tissues. Considering that radiation toxicity to gonadal tissues can cause hormone disturbances and infertility in young patients with cancer, the purpose of this study was to assess the possible role of UHDR-RT in reducing toxicity to healthy gonads in mice compared with CONV-RT. Methods and Materials: Radiation was delivered to the abdomen or pelvis of female (8 or 16 Gy) and male (5 Gy) C57BL/6J mice, respectively, at conventional (∼0.4 Gy/s) or ultrahigh (>100 Gy/s) dose rates using an IntraOp Mobetron linear accelerator. Organ weights along with histopathology and immunostaining of irradiated gonads were used to compare toxicity between radiation modalities. Results: CONV-RT and UHDR-RT induced a similar decrease in uterine weights at both studied doses (∼50% of controls), which indicated similarly reduced ovarian follicular activity. Histologically, ovaries of CONV- and UHDR-irradiated mice exhibited a comparable lack of follicles. Weights of CONV- and UHDR-irradiated testes were reduced to ∼30% of controls, and the percentage of degenerate seminiferous tubules was also similar between radiation modalities (∼80% above controls). Pairwise comparisons of all quantitative data indicated statistical significance between irradiated (CONV or UHDR) and control groups (from P ≤ .01 to P ≤ .0001) but not between radiation modalities. Conclusions: The data presented here suggest that the short-term effects of UHDR-RT on the mouse gonads are comparable to those of CONV-RT. © 2023 The Authors LA - English DB - MTMT ER - TY - JOUR AU - Espinosa-Rodriguez, A. AU - Villa-Abaunza, A. AU - Diaz, N. AU - Perez-Diaz, M. AU - Sanchez-Parcerisa, D. AU - Udias, J. M. AU - Ibanez, P. TI - Design of an X-ray irradiator based on a standard imaging X-ray tube with FLASH dose-rate capabilities for preclinical research JF - RADIATION PHYSICS AND CHEMISTRY: THE JOURNAL FOR RADIATION PHYSICS RADIATION CHEMISTRY AND RADIATION PROCESSING J2 - RADIAT PHYS CHEM VL - 206 PY - 2023 PG - 8 SN - 0969-806X DO - 10.1016/j.radphyschem.2023.110760 UR - https://m2.mtmt.hu/api/publication/33809995 ID - 33809995 N1 - Funding Agency and Grant Number: Comunidad de Madrid [B2017/BMD-3888 PRONTO-CM]; Spanish Government [RTI 2018-098868-B-I00, RTC-2015-3772-1, CPP 2021-008751 NEW-MBI]; European Regional and Resilience Funds; European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [793576]; UCM; EU Regional Funds; Moncloa Campus of International Excellence, "Grupo de Fisica Nuclear-UCM" [910059] Funding text: This work was funded by Comunidad de Madrid under project B2017/BMD-3888 PRONTO-CM "Protontherapy and nuclear techniques for oncology". Support by the Spanish Government (RTI 2018-098868-B-I00, RTC-2015-3772-1, XPHASE-LASER, CPP 2021-008751 NEW-MBI) , as well as European Regional and Resilience Funds, and the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 793576 (CAP-PERAM) is acknowledged. This is a contribution for the Moncloa Campus of International Excellence, "Grupo de Fisica Nuclear-UCM", Ref. 910059. Part of the calculations of this work were performed in the "Cluster de Calculo para Tecnicas Fisicas", funded in part by UCM and in part by EU Regional Funds. AB - We propose a new concept of small animal X-ray irradiator based on a conventional imaging X-ray tube for preclinical research. In this work we assessed its feasibility to deliver FLASH dose rates. Our design puts the imaging X-ray tube into a shielded cabinet, which makes the system affordable and suitable to use without disruption in existing laboratories and with minimum regulatory burden. Two conventional 150 kVp X-ray tubes were characterized with Gafchromic films for dose rates and dose uniformity. Monte Carlo simulations were also performed to model the irradiator, and the efficiencies of the tube and dose rates (with and without additional filtration) were calculated and compared with measurements. The feasibility of achieving ultra-high dose rates was determined from the rating charts provided by the manufacturer and measurements. The small animal irradiator proposed in this work was able to deliver conventional dose rate irradiation (0.5-1 Gy/min) at 150 kVp at 20 cm distance with minimum amount of filtration. FLASH irradiations (a 10 Gy dose delivered at >40 Gy/s) were also possible at the maximum capabilities of the tubes by placing the samples at the closest possible distances from the sources. A first prototype has already been built and characterized. LA - English DB - MTMT ER - TY - JOUR AU - Farokhi, F. AU - Shirani, B. AU - Fattori, S. AU - Ali, Asgarian M. AU - Cuttone, G. AU - Jia, S.B. AU - Petringa, G. AU - Sciuto, A. AU - Pablo, Cirrone G.A. TI - Effects of the Oxygen depletion in FLASH irradiation investigated through Geant4-DNA toolkit JF - RADIATION PHYSICS AND CHEMISTRY: THE JOURNAL FOR RADIATION PHYSICS RADIATION CHEMISTRY AND RADIATION PROCESSING J2 - RADIAT PHYS CHEM VL - 212 PY - 2023 SN - 0969-806X DO - 10.1016/j.radphyschem.2023.111184 UR - https://m2.mtmt.hu/api/publication/34136192 ID - 34136192 N1 - Faculty of Physics, University of Isfahan, Isfahan, Iran Istituto Nazionale di Fisica Nucleare (INFN), Laboratori Nazionali del Sud, Catania, Italy Department of Physics, University of Bojnord, Bojnord, Iran Centro Siciliano di Fisica Nucleare e Struttura della Materia, Catania, Italy Dipartimento di FISICA ED ASTRONOMIA “Ettore Majorana” - Università degli Studi di Catania, Catania, Italy Export Date: 12 September 2023 CODEN: RPCHD Correspondence Address: Shirani, B.; Faculty of Physics, Iran; email: b.shirani@ast.ui.ac.ir Correspondence Address: Fattori, S.; Istituto Nazionale di Fisica Nucleare (INFN), Italy; email: dr.serena.fattori@gmail.com Funding details: Instituto Nazionale di Fisica Nucleare, INFN Funding details: University of Isfahan, UI Funding text 1: This work was supported by Isfahan University, Iran . Moreover, it was performed in the framework of the MC-INFN (Monte Carlo at INFN) initiative, also funded by the Interdisciplinary Committee V of INFN . The authors want to thank F. Chappuis, L. Desorgher, S. Incerti, H. N. Tran, E. Scifoni, D. Boscolo and M. C. Fuss for all the valuable discussions and advice. F. Farokhi wants to thank V. R. Sharma (Dept. of Radiation Oncology, SoM-UMB, MD, USA) for all his support during the realization of this manuscript. Funding text 2: This work was supported by Isfahan University, Iran. Moreover, it was performed in the framework of the MC-INFN (Monte Carlo at INFN) initiative, also funded by the Interdisciplinary Committee V of INFN. The authors want to thank F. Chappuis, L. Desorgher, S. Incerti, H. N. Tran, E. Scifoni, D. Boscolo and M. C. Fuss for all the valuable discussions and advice. F. Farokhi wants to thank V. R. Sharma (Dept. of Radiation Oncology, SoM-UMB, MD, USA) for all his support during the realization of this manuscript. AB - FLASH radiotherapy (or FLASH-RT) is a novel radiotherapy technology consisting of radiation delivery at dose rates several orders of magnitude higher (≥40Gy/s) than the currently used in conventional clinical radiotherapy. Many recent in-vivo preclinical studies indicate that FLASH-RT can greatly spare healthy tissues while maintaining unchanged tumour control. The generally acknowledged, though not entirely substantiated, explanation for the FLASH effect relates to the oxygen depletion that occurs after the radiation passage. On the other hand, oxygen depletion or, more in general, oxygen-related effects are still not fully clarified. Different research groups carried out the Monte Carlo simulations of electron and proton irradiations in oxygenated water to evaluate the oxygen-concentration-related effects at the cell-scale level. We analysed and compared the simulation results of the oxygen effect under the FLASH condition (considering the time-dependent G-values and the oxygen enhancement ratio-weighted dose) we obtained with GEANT4-DNA against TRAX-CHEM code results in the literature. Our results indicate that oxygen depletion has a negligible effect on radiosensitivity via oxygen enhancement, showing a close agreement with the TRAX-CHEM code. The conclusion is that the Geant4-DNA toolkit can be a valid instrument to study the FLASH effect. © 2023 Elsevier Ltd LA - English DB - MTMT ER - TY - JOUR AU - Horst, Felix AU - Beyreuther, Elke AU - Bodenstein, Elisabeth AU - Gantz, Sebastian AU - Misseroni, Diego AU - Pugno, Nicola M. AU - Schuy, Christoph AU - Tommasino, Francesco AU - Weber, Uli AU - Pawelke, Joerg TI - Passive SOBP generation from a static proton pencil beam using 3D-printed range modulators for FLASH experiments JF - FRONTIERS IN PHYSICS J2 - FRONT PHYS-LAUSANNE VL - 11 PY - 2023 PG - 12 SN - 2296-424X DO - 10.3389/fphy.2023.1213779 UR - https://m2.mtmt.hu/api/publication/34089796 ID - 34089796 N1 - Funding Agency and Grant Number: FRIDA project - INFN CSN5 Funding text: The range modulator studies performed in Trento were partially supported by the FRIDA project, funded by INFN CSN5. AB - The University Proton Therapy facility in Dresden (UPTD), Germany, is equipped with an experimental room with a beamline providing a static pencil beam. High proton beam currents can be achieved at this beamline which makes it suitable for FLASH experiments. However, the established experimental setup uses only the entrance channel of the proton Bragg curve. In this work, a set of 3D-printed range modulators designed to generate spread out Bragg peaks (SOBPs) for radiobiological experiments at ultra-high dose rate at this beamline is described. A new method to optimize range modulators specifically for the case of a static pencil beam based on the central depth dose profile is introduced. Modulators for two different irradiation setups were produced and characterized experimentally by measurements of lateral and depth dose distributions using different detectors. In addition, Monte Carlo simulations were performed to assess profiles of the dose averaged linear energy transfer (LETD) in water. These newly produced range modulators will allow future proton FLASH experiments in the SOBP at UPTD with two different experimental setups. LA - English DB - MTMT ER - TY - JOUR AU - Jeon, Chanil AU - Ahn, Sunghwan AU - Amano, Daizo AU - Kamiguchi, Nagaaki AU - Cho, Sungkoo AU - Sheen, Heesoon AU - Park, Hee Chul AU - Han, Youngyih TI - FLASH dose rate calculation based on log files in proton pencil beam scanning therapy JF - MEDICAL PHYSICS J2 - MED PHYS VL - 50 PY - 2023 IS - 11 SP - 7154 EP - 7166 PG - 13 SN - 0094-2405 DO - 10.1002/mp.16575 UR - https://m2.mtmt.hu/api/publication/34089795 ID - 34089795 N1 - Funding Agency and Grant Number: National Research Foundation of Korea (NRF) - Korean government (MSIT) [2021M2E8A1048108]; National Research Foundation of Korea [2021M2E8A1048108] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS) Funding text: ACKNOWLEDGMENTS This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2021M2E8A1048108). AB - BackgroundIn radiation therapy, irradiating healthy normal tissues in the beam trajectories is inevitable. This unnecessary dose means that patients undergoing treatment risk developing side effects. Recently, FLASH radiotherapy delivering ultra-high-dose-rate beams has been re-examined because of its normal-tissue-sparing effect. To confirm the mean and instantaneous dose rates of the FLASH beam, stable and accurate dosimetry is required. PurposeDetailed verification of the FLASH effect requires dosimeters and a method to measure the average and instantaneous dose rate stably for 2- or 3-dimensional dose distributions. To verify the delivered FLASH beam, we utilized machine log files from the built-in monitor chamber to develop a dosimetry method to calculate the dose and average/instantaneous dose rate distributions in two or three dimensions in a phantom. MethodsTo create a spread-out Bragg peak (SOBP) and deliver a uniform dose in a target, a mini-ridge filter was created with a 3D printer. Proton pencil beam line scanning plans of 2 x 2 cm(2), 3 x 3 cm(2), 4 x 4 cm(2), and round shapes with 2.3 cm diameter patterns delivering 230 MeV energy protons were created. The absorbed dose in the solid water phantom of each plan was measured using a PPC05 ionization chamber (IBA Dosimetry, Virginia, USA) in the SOBP region, and the log files for each plan were exported from the treatment control system console. Using these log files, the delivered dose and average dose rate were calculated using two methods: a direct method and a Monte Carlo (MC) simulation method that uses log file information. The computed and average dose rates were compared with the ionization chamber measurements. Additionally, instantaneous dose rates in user-defined volumes were calculated using the MC simulation method with a temporal resolution of 5 ms. ResultsCompared to ionization chamber dosimetry, 10 of 12 cases using the direct calculation method and 9 of 11 cases using the MC method had a dose difference below & PLUSMN;3%. Nine of 12 cases using the direct calculation method and 8 of 11 cases using the MC method had dose rate differences below & PLUSMN;3%. The average and maximum dose differences for the direct calculation and MC method were-0.17, +0.72%, and -3.15, +3.32%, respectively. For the dose rate difference, the average and maximum for the direct calculation and MC method were +1.26, +1.12%, and +3.75, +3.15%, respectively. In the instantaneous dose rate calculation with the MC simulation, a large fluctuation with a maximum of 163 Gy/s and a minimum of 4.29 Gy/s instantaneous dose rate was observed in a specific position, whereas the mean dose rate was 62 Gy/s. ConclusionsWe successfully developed methods in which machine log files are used to calculate the dose and the average and instantaneous dose rates for FLASH radiotherapy and demonstrated the feasibility of verifying the delivered FLASH beams. LA - English DB - MTMT ER - TY - JOUR AU - José, Santo R. AU - Habraken, S.J.M. AU - Breedveld, S. AU - Hoogeman, M.S. TI - Pencil-beam Delivery Pattern Optimization Increases Dose Rate for Stereotactic FLASH Proton Therapy JF - INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS J2 - INT J RADIAT ONCOL VL - 115 PY - 2023 IS - 3 SP - 759 EP - 767 PG - 9 SN - 0360-3016 DO - 10.1016/j.ijrobp.2022.08.053 UR - https://m2.mtmt.hu/api/publication/33810129 ID - 33810129 N1 - Erasmus MC Cancer Institute, University Medical Center Rotterdam, Department of Radiotherapy, Rotterdam, Radiotherapy, Netherlands Instituto Superior Técnico, Universidade, de Lisboa, Lisbon, Portugal Holland Proton Therapy Center, Department of Medical Physics & Informatics, Delft, Netherlands Cited By :1 Export Date: 11 May 2023 CODEN: IOBPD Correspondence Address: Habraken, S.J.M.; Erasmus MC Cancer Institute, Rotterdam, Netherlands; email: s.habraken@erasmusmc.nl Chemicals/CAS: dimpylate, 333-41-5; proton, 12408-02-5, 12586-59-3 AB - Purpose: FLASH dose rates >40 Gy/s are readily available in proton therapy (PT) with cyclotron-accelerated beams and pencil-beam scanning (PBS). The PBS delivery pattern will affect the local dose rate, as quantified by the PBS dose rate (PBS-DR), and therefore needs to be accounted for in FLASH-PT with PBS, but it is not yet clear how. Our aim was to optimize patient-specific scan patterns for stereotactic FLASH-PT of early-stage lung cancer and lung metastases, maximizing the volume irradiated with PBS-DR >40 Gy/s of the organs at risk voxels irradiated to >8 Gy (FLASH coverage). Methods and Materials: Plans to 54 Gy/3 fractions with 3 equiangular coplanar 244 MeV proton shoot-through transmission beams for 20 patients were optimized with in-house developed software. Planning target volume-based planning with a 5 mm margin was used. Planning target volume ranged from 4.4 to 84 cc. Scan-pattern optimization was performed with a Genetic Algorithm, run in parallel for 20 independent populations (islands). Mapped crossover, inversion, swap, and shift operators were applied to achieve (local) optimality on each island, with migration between them for global optimality. The cost function was chosen to maximize the FLASH coverage per beam at >8 Gy, >40 Gy/s, and 40 nA beam current. The optimized patterns were evaluated on FLASH coverage, PBS-DR distribution, and population PBS-DR-volume histograms, compared with standard line-by-line scanning. Robustness against beam current variation was investigated. Results: The optimized patterns have a snowflake-like structure, combined with outward swirling for larger targets. A population median FLASH coverage of 29.0% was obtained for optimized patterns compared with 6.9% for standard patterns, illustrating a significant increase in FLASH coverage for optimized patterns. For beam current variations of 5 nA, FLASH coverage varied between –6.1%-point and 2.2%-point for optimized patterns. Conclusions: Significant improvements on the PBS-DR and, hence, on FLASH coverage and potential healthy-tissue sparing are obtained by sequential scan-pattern optimization. The optimizer is flexible and may be further fine-tuned, based on the exact conditions for FLASH. © 2022 The Authors LA - English DB - MTMT ER - TY - JOUR AU - Kim, K.-T. AU - Choi, Y. AU - Cho, G.-S. AU - Jang, W.-I. AU - Yang, K.-M. AU - Lee, S.-S. AU - Bahng, J. TI - Evaluation of the water-equivalent characteristics of the SP34 plastic phantom for film dosimetry in a clinical linear accelerator JF - PLOS ONE J2 - PLOS ONE VL - 18 PY - 2023 IS - 10 October PG - 16 SN - 1932-6203 DO - 10.1371/journal.pone.0293191 UR - https://m2.mtmt.hu/api/publication/34327445 ID - 34327445 N1 - Neuroscience Research Institute, Seoul National University Medical Research Center, Seoul, South Korea Research and Development team, Radexel Inc., Seoul, South Korea Department of Accelerator Science, Korea University Sejong Campus, Sejong, South Korea Research Team of Radiological Physics & Engineering, Korea Institute of Radiological & Medical Sciences, Seoul, South Korea Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, South Korea Department of Radiation Oncology, Kangwon National University hospital, Chuncheon-si, South Korea Export Date: 14 November 2023 CODEN: POLNC Correspondence Address: Lee, S.-S.; Research Team of Radiological Physics & Engineering, South Korea; email: dubidubab87@kirams.re.kr Correspondence Address: Bahng, J.; Research and Development team, South Korea; email: bahngjb@knuh.or.kr Chemicals/CAS: polystyrene, 9003-53-6; water, 7732-18-5; Polystyrenes; Water Tradenames: DoseLab, Mobius Medical Systems, United States; TANDEM; TM31010, PTW, Germany; Varian Clinic iX, Varian, United States; vernier, Mitutoyo, Japan Manufacturers: PTW, Germany; Mitutoyo, Japan; Mobius Medical Systems, United States; Varian, United States Funding details: Ministry of Science, ICT and Future Planning, MSIP, 1711149774 Funding text 1: The authors wish to acknowledge financial support of the Innopolis Foundation of Korea funded by the Ministry of Science and ICT (Grant No. 1711149774), Daejeon, Korea. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to extend my gratitude to the authors Kyo-Tae Kim, Yona Choi, Gyu-Seok Cho, Won-il Jang, Kwang-Mo Yang, Soon-Sung Lee and Jungbae Bahng for their contributions to this project." AB - In this study, some confusing points about electron film dosimetry using white polystyrene suggested by international protocols were verified using a clinical linear accelerator (LINAC). According to international protocol recommendations, ionometric measurements and film dosimetry were performed on an SP34 slab phantom at various electron energies. Scaling factor analysis using ionometric measurements yielded a depth scaling factor of 0.923 and a fluence scaling factor of 1.019 at an electron beam energy of <10 MeV (i.e., R50 < 4.0 g/cm2). It was confirmed that the water-equivalent characteristics were similar because they have values similar to white polystyrene (i.e., depth scaling factor of 0.922 and fluence scaling factor of 1.019) presented in international protocols. Furthermore, percentage depth dose (PDD) curve analysis using film dosimetry showed that when the density thickness of the SP34 slab phantom was assumed to be water-equivalent, it was found to be most similar to the PDD curve measured using an ionization chamber in water as a reference medium. Therefore, we proved that the international protocol recommendation that no correction for measured depth dose is required means that no scaling factor correction for the plastic phantom is necessary. This study confirmed two confusing points that could occur while determining beam characteristics using electron film dosimetry, and it is expected to be used as basic data for future research on clinical LINACs. © 2023 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. LA - English DB - MTMT ER - TY - JOUR AU - Kneepkens, Esther AU - Wolfs, Cecile AU - Wanders, Roel-Germ AU - Traneus, Erik AU - Eekers, Danielle AU - Verhaegen, Frank TI - Shoot-through proton FLASH irradiation lowers linear energy transfer in organs at risk for neurological tumors and is robust against density variations JF - PHYSICS IN MEDICINE AND BIOLOGY J2 - PHYS MED BIOL VL - 68 PY - 2023 IS - 21 PG - 11 SN - 0031-9155 DO - 10.1088/1361-6560/ad0280 UR - https://m2.mtmt.hu/api/publication/34328495 ID - 34328495 AB - Objective. The goal of the study was to test the hypothesis that shoot-through FLASH proton beams would lead to lower dose-averaged LET (LETD) values in critical organs, while providing at least equal normal tissue sparing as clinical proton therapy plans. Approach. For five neurological tumor patients, pencil beam scanning (PBS) shoot-through plans were made, using the maximum energy of 227 MeV and assuming a hypothetical FLASH protective factor (FPF) of 1.5. The effect of different FPF ranging from 1.2 to 1.8 on the clinical goals were also considered. LETD was calculated for the clinical plan and the shoot-through plan, applying a 2 Gy total dose threshold (RayStation 8 A/9B and 9A-IonRPG). Robust evaluation was performed considering density uncertainty (+/- 3% throughout entire volume). Main results. Clinical plans showed large LETD variations compared to shoot-through plans and the maximum LETD in OAR is 1.2-8 times lower for the latter. Although less conformal, shoot-through plans met the same clinical goals as the clinical plans, for FLASH protection factors above 1.4. The FLASH shoot-through plans were more robust to density uncertainties with a maximum OAR D2% increase of 0.6 Gy versus 5.7 Gy in the clinical plans. Significance. Shoot-through proton FLASH beams avoid uncertainties in LETD distributions and proton range, provide adequate target coverage, meet planning constraints and are robust to density variations. LA - English DB - MTMT ER - TY - JOUR AU - Lascaud, Julie AU - Parodi, Katia TI - On the potential biological impact of radiation-induced acoustic emissions during ultra-high dose rate electron radiotherapy: a preliminary study JF - PHYSICS IN MEDICINE AND BIOLOGY J2 - PHYS MED BIOL VL - 68 PY - 2023 IS - 5 PG - 7 SN - 0031-9155 DO - 10.1088/1361-6560/acb9ce UR - https://m2.mtmt.hu/api/publication/33809992 ID - 33809992 N1 - Funding Agency and Grant Number: European Research Council [725 539]; LMUexcellent - Federal Ministry of Education and Research (BMBF); Free State of Bavaria under the Excellence Strategy of the Federal Government Funding text: The authors acknowledge the financial support from the European Research Council (SIRMIO, Grant number 725 539). This research project was supported by LMUexcellent, funded by the Federal Ministry of Education and Research (BMBF) and the Free State of Bavaria under the Excellence Strategy of the Federal Government and the Laender. AB - Ionizing radiation pulses delivered at ultra-high dose rates in emerging FLASH radiotherapy can result in high-intensity low-frequency thermoacoustic emissions that may have a biological impact. This study aims at providing insights into the thermoacoustic emissions expected during FLASH radiotherapy and their likelihood of inducing acoustic cavitation. The characteristics of acoustic waves induced by the energy deposition of a pulsed electron beam similar to previous pre-clinical FLASH radiotherapy studies and their propagation in murine head-like phantoms are investigated in-silico. The results show that the generated pressures are sufficient to produce acoustic cavitation due to resonance in the irradiated object. It suggests that thermoacoustics may, in some irradiation scenarios, contribute to the widely misunderstood FLASH effect or cause adverse effects if not taken into account at the treatment planning stage. LA - English DB - MTMT ER - TY - JOUR AU - Lattery, G. AU - Kaulfers, T. AU - Cheng, C. AU - Zhao, X. AU - Selvaraj, B. AU - Lin, H. AU - Simone, C.B. II AU - Choi, J.I. AU - Chang, J. AU - Kang, M. TI - Pencil Beam Scanning Bragg Peak FLASH Technique for Ultra-High Dose Rate Intensity-Modulated Proton Therapy in Early-Stage Breast Cancer Treatment JF - CANCERS J2 - CANCERS VL - 15 PY - 2023 IS - 18 SN - 2072-6694 DO - 10.3390/cancers15184560 UR - https://m2.mtmt.hu/api/publication/34199442 ID - 34199442 N1 - Department of Physics and Astronomy, Hofstra University, 1000 Hempstead Turnpike, Hempstead, NY 11549, United States Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, United States Beijing Key Laboratory of Medical Physics and Engineering, Peking University, Beijing, 100871, China New York Proton Center, 225 E 126th Street, New York, NY 10035, United States Radiation Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 450 Lakeville Road, Lake SuccessNY 11042, United States Export Date: 16 October 2023 Correspondence Address: Chang, J.; Department of Physics and Astronomy, 1000 Hempstead Turnpike, United States; email: jchang24@northwell.edu Correspondence Address: Kang, M.; New York Proton Center, 225 E 126th Street, United States; email: mkang@nyproton.com Funding details: Hofstra University, HU, 2022–2023 PRAP, 2023–2024 Funding text 1: This research was funded by Varian Research Grant (Recipient: Minglei Kang), Hofstra University, 2022–2023 FRDG award, 2022–2023 PRAP award, and 2023–2024 FRDG award (Recipient: Jenghwa Chang). AB - Bragg peak FLASH-RT can deliver highly conformal treatment and potentially offer improved normal tissue protection for radiotherapy patients. This study focused on developing ultra-high dose rate (≥40 Gy × RBE/s) intensity-modulated proton therapy (IMPT) for hypofractionated treatment of early-stage breast cancer. A novel tracking technique was developed to enable pencil beaming scanning (PBS) of single-energy protons to adapt the Bragg peak (BP) to the target distally. Standard-of-care PBS treatment plans of consecutively treated early-stage breast cancer patients using multiple energy layers were reoptimized using this technique, and dose metrics were compared between single-energy layer BP FLASH and conventional IMPT plans. FLASH dose rate coverage by volume (V40Gy/s) was also evaluated for the FLASH sparing effect. Distal tracking can precisely stop BP at the target distal edge. All plans (n = 10) achieved conformal IMPT-like dose distributions under clinical machine parameters. No statistically significant differences were observed in any dose metrics for heart, ipsilateral lung, most ipsilateral breast, and CTV metrics (p > 0.05 for all). Conventional plans yielded slightly superior target and skin dose uniformities with 4.5% and 12.9% lower dose maxes, respectively. FLASH-RT plans reached 46.7% and 61.9% average-dose rate FLASH coverage for tissues receiving more than 1 and 5 Gy plan dose total under the 250 minimum MU condition. Bragg peak FLASH-RT techniques achieved comparable plan quality to conventional IMPT while reaching adequate dose rate ratios, demonstrating the feasibility of early-stage breast cancer clinical applications. © 2023 by the authors. LA - English DB - MTMT ER - TY - JOUR AU - Leite, A.M.M. AU - Cavallone, M. AU - Ronga, M.G. AU - Trompier, F. AU - Ristic, Y. AU - Patriarca, A. AU - De, Marzi L. TI - Ion recombination correction factors and detector comparison in a very-high dose rate proton scanning beam JF - PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS J2 - PHYS MEDICA VL - 106 PY - 2023 SN - 1120-1797 DO - 10.1016/j.ejmp.2022.102518 UR - https://m2.mtmt.hu/api/publication/33810131 ID - 33810131 N1 - Institut Curie, PSL Research University, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay, 91898, France Institut Curie, PSL Research University, Radiation Oncology Department, Proton Therapy Center, Centre Universitaire, Orsay, 91898, France Institut de Radioprotection et de Sûreté Nucléaire, Service de Dosimétrie, Laboratoire de Dosimétrie des Rayonnements Ionisants, Fontenay-aux-Roses Cedex, 92262, France Institut Curie, PSL Research University, Université Paris-Saclay, INSERM LITO, Orsay, 91898, France Cited By :1 Export Date: 11 May 2023 CODEN: PHYME Correspondence Address: Leite, A.M.M.; Institut Curie, Proton Therapy Center, Centre Universitaire, France; email: amelia.leite@ijclab.in2p3.fr Chemicals/CAS: proton, 12408-02-5, 12586-59-3; Protons Tradenames: Advanced Markus, PTW, Germany; CC01, IBA Dosimetry, Germany; PPC05, IBA Dosimetry, Germany; Razor Nano-chamber CC003, IBA Dosimetry, Germany Manufacturers: IBA Dosimetry, Germany; PTW, Germany Funding details: Horizon 2020 Framework Programme, H2020 Funding details: European Metrology Programme for Innovation and Research, EMPIR Funding details: International Association for Bear Research and Management, IBA Funding details: Horizon 2020, 730983 Funding details: Grand Équipement National De Calcul Intensif, GENCI Funding text 1: The authors acknowledge IBA for the support in using the machine in FLASH mode. This work was partly funded by the European Union’s Horizon 2020 research and innovation program under grant agreement No. 730983 (INSPIRE). This work was partly done in the framework of the project 18HLT04 UHDpulse, which has received funding from the EMPIR program, co-financed by the Participating States and from the European Union’s Horizon 2020 research and innovation program. The simulations for this work were carried out using the access to the HPC resources of TGCC under the allocation 2021-A0100312448 made by GENCI. Funding text 2: The authors acknowledge IBA for the support in using the machine in FLASH mode. This work was partly funded by the European Union's Horizon 2020 research and innovation program under grant agreement No. 730983 (INSPIRE). This work was partly done in the framework of the project 18HLT04 UHDpulse, which has received funding from the EMPIR program, co-financed by the Participating States and from the European Union's Horizon 2020 research and innovation program. The simulations for this work were carried out using the access to the HPC resources of TGCC under the allocation 2021-A0100312448 made by GENCI. AB - Purpose: Accurate dosimetry is paramount to study the FLASH biological effect since dose and dose rate are critical dosimetric parameters governing its underlying mechanisms. With the goal of assessing the suitability of standard clinical dosimeters in a very-high dose rate (VHDR) experimental setup, we evaluated the ion collection efficiency of several commercially available air-vented ionization chambers (IC) in conventional and VHDR proton irradiation conditions. Methods: A cyclotron at the Orsay Proton Therapy Center was used to deliver VHDR pencil beam scanning irradiation. Ion recombination correction factors (ks) were determined for several detectors (Advanced Markus, PPC05, Nano Razor, CC01) at the entrance of the plateau and at the Bragg peak, using the Niatel model, the Two-voltage method and Boag's analytical formula for continuous beams. Results: Mean dose rates ranged from 4 Gy/s to 385 Gy/s, and instantaneous dose rates up to 1000 Gy/s were obtained with the experimental set-up. Recombination correction factors below 2 % were obtained for all chambers, except for the Nano Razor, at VHDRs with variations among detectors, while ks values were significantly smaller (0.8 %) for conventional dose rates. Conclusions: While the collection efficiency of the probed ICs in scanned VHDR proton therapy is comparable to those in the conventional regime with recombination coefficiens smaller than 1 % for mean dose rates up to 177 Gy/s, the reduction in collection efficiency for higher dose rates cannot be ignored when measuring the absorbed dose in pre-clinical proton scanned FLASH experiments and clinical trials. © 2023 Associazione Italiana di Fisica Medica e Sanitaria LA - English DB - MTMT ER - TY - JOUR AU - Lin, Binwei AU - Fan, Mi AU - Niu, Tingting AU - Liang, Yuwen AU - Xu, Haonan AU - Tang, Wenqiang AU - Du, Xiaobo TI - Key changes in the future clinical application of ultra-high dose rate radiotherapy JF - FRONTIERS IN ONCOLOGY J2 - FRONT ONCOL VL - 13 PY - 2023 PG - 10 SN - 2234-943X DO - 10.3389/fonc.2023.1244488 UR - https://m2.mtmt.hu/api/publication/34421171 ID - 34421171 N1 - Funding Agency and Grant Number: This work was financially supported by the National Natural Science Foundation of China Academy of Engineering Physics and jointly set up quot;NSAFquot; joint fund (grant no. U2330122) and Natural Science Foundation of Sichuan Province (grant no. 2022NSF [U2330122]; National Natural Science Foundation of China Academy of Engineering Physics and jointly set up quot;NSAFquot; joint fund [2022NSFSC0849]; Natural Science Foundation of Sichuan Province Funding text: This work was financially supported by the National Natural Science Foundation of China Academy of Engineering Physics and jointly set up & quot;NSAF & quot; joint fund (grant no. U2330122) and Natural Science Foundation of Sichuan Province (grant no. 2022NSFSC0849). AB - Ultra-high dose rate radiotherapy (FLASH-RT) is an external beam radiotherapy strategy that uses an extremely high dose rate (>= 40 Gy/s). Compared with conventional dose rate radiotherapy (<= 0.1 Gy/s), the main advantage of FLASH-RT is that it can reduce damage of organs at risk surrounding the cancer and retain the anti-tumor effect. An important feature of FLASH-RT is that an extremely high dose rate leads to an extremely short treatment time; therefore, in clinical applications, the steps of radiotherapy may need to be adjusted. In this review, we discuss the selection of indications, simulations, target delineation, selection of radiotherapy technologies, and treatment plan evaluation for FLASH-RT to provide a theoretical basis for future research. LA - English DB - MTMT ER - TY - JOUR AU - Luo, H.-T. AU - Shi, J. AU - Liu, R.-F. AU - Liu, Z.-Q. AU - Sun, S.-L. AU - Zhang, Q.-N. AU - Wang, X.-H. TI - Visualization of the current research status of FLASH radiotherapy JF - CHINESE JOURNAL OF CANCER PREVENTION AND TREATMENT J2 - CHIN J CANCER PREV TREATM VL - 30 PY - 2023 IS - 2 SP - 104 EP - 113 PG - 10 SN - 1673-5269 DO - 10.16073/j.cnki.cjcpt.2023.02.07 UR - https://m2.mtmt.hu/api/publication/33810133 ID - 33810133 N1 - Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China Heavy Ion Medical Center, Lanzhou Heavy Ion Hospital, Lanzhou, 730010, China Export Date: 11 May 2023 Correspondence Address: Zhang, Q.-N.; Institute of Modern Physics, China; email: zhangqn@impcas.ac.cn Correspondence Address: Wang, X.-H.; Institute of Modern Physics, China; email: xhwang@impcas.ac.cn Chemicals/CAS: water, 7732-18-5 AB - Objective To visually analyze the current research status, hotspots and trends in the field of FLASH radiotherapy by bibliometric methods based on the web of science (WOS). Methods Using " FLASH radiotherapy OR ultrahigh dose-rate radiotherapy OR FLASH irradiation" as the subject terms, the relevant literature of FLASH radiotherapy were searched in the core collection of WOS database from the inception of database to January 18, 2022. The included literature were visually analyzed the trend, country, institution of the publications and research hotspots using WOS self-contained citation analysis function and CiteSpace (5. 8. R3) software. The corresponding visual knowledge map was drawn. Results A total of 144 articles and 22 reviews were included in the analysis, and the literature were mainly published m 2019-2021 with 22, 48, and 76 papers published in each year, respectively. The United States has the largest number of papers published (61), and China ranks the seventh (15). The University Hospital of Lausanne published the largest number of papers (15). Vozenin MC published the most papers (17). Eight clusters were formed based on key words, including electron beams, beam, liquid water, ultra-high dose rate, proton therapy, radiation therapy, immune system, ionization chamber, preclinical models. The frontier of FLASH radiotherapy focused on the biological mechanism exploration, physical technology development and FLASH radiotherapy equipment development. The trend in the field of FLASH radiotherapy is to transform into clinical application. Conclusion FLASH radiotherapy is expected to be one of the revolutionary new techniques in radiotherapy. The clinical transformation of this technique still faces many problems to be solved. Chinese scholars should strengthen internal cooperation and actively cooperate with external scientific research institutions to promote the safe transformation of this technology in clinical practice. © 2023 Chinese Journal of Cancer Prevention and Treatment, Editorial board. All rights reserved. LA - Chinese DB - MTMT ER - TY - JOUR AU - Motta, S. AU - Christensen, J. B. AU - Togno, M. AU - Schafer, R. AU - Safai, S. AU - Lomax, A. J. AU - Yukihara, E. G. TI - Characterization of LiF:Mg,Ti thermoluminescence detectors in low-LET proton beams at ultra-high dose rates JF - PHYSICS IN MEDICINE AND BIOLOGY J2 - PHYS MED BIOL VL - 68 PY - 2023 IS - 4 PG - 13 SN - 0031-9155 DO - 10.1088/1361-6560/acb634 UR - https://m2.mtmt.hu/api/publication/33809994 ID - 33809994 N1 - Funding Agency and Grant Number: Swiss Federal Nuclear Safety Inspectorate ENSI [CTR00836] Funding text: AcknowledgmentsThis work was funded by the Swiss Federal Nuclear Safety Inspectorate ENSI, contract no. CTR00836. AB - Objective. This work aims at characterizing LiF:Mg,Ti thermoluminescence detectors (TLDs) for dosimetry of a 250 MeV proton beam delivered at ultra-high dose rates (UHDR). Possible dose rate effects in LiF:Mg,Ti, as well as its usability for dosimetry of narrow proton beams are investigated. Approach. LiF:Mg,Ti (TLD-100 (TM) Microcubes, 1 mm x 1 mm x 1 mm) was packaged in matrices of 5 x 5 detectors. The center of each matrix was irradiated with single-spot low-LET (energy > 244 MeV) proton beam in the (1-4500) Gy s(-1) average dose rates range. A beam reconstruction procedure was applied to the detectors irradiated at the highest dose rate (Gaussian beam sigma < 2 mm) to correct for volumetric averaging effects. Reference dosimetry was carried out with a diamond detector and radiochromic films. The delivered number of protons was measured by a Faraday cup, which was employed to normalize the detector responses. Main results. The lateral beam spread obtained from the beam reconstruction agreed with the one derived from the radiochromic film measurements. No dose rates effects were observed in LiF:Mg,Ti for the investigated dose rates within 3% (k = 1). On average, the dose response of the TLDs agreed with the reference detectors within their uncertainties. The largest deviation (-5%) was measured at 4500 Gy s(-1). Significance. The dose rate independence of LiF:Mg,Ti TLDs makes them suitable for dosimetry of UHDR proton beams. Additionally, the combination of a matrix of TLDs and the beam reconstruction can be applied to determine the beam profile of narrow proton beams. LA - English DB - MTMT ER - TY - JOUR AU - Motta, S. AU - Christensen, J. B. AU - Frei, F. AU - Peier, P. AU - Yukihara, E. G. TI - Investigation of TL and OSL detectors in ultra-high dose rate electron beams JF - PHYSICS IN MEDICINE AND BIOLOGY J2 - PHYS MED BIOL VL - 68 PY - 2023 IS - 14 PG - 16 SN - 0031-9155 DO - 10.1088/1361-6560/acdfb2 UR - https://m2.mtmt.hu/api/publication/34089794 ID - 34089794 N1 - Funding Agency and Grant Number: Swiss Federal Nuclear Safety Inspectorate ENSI [CTR00836] Funding text: AcknowledgmentsThis work was funded by the Swiss Federal Nuclear Safety Inspectorate ENSI, contract no. CTR00836. AB - Objective. This work aims at investigating the response of various thermally stimulated luminescence detectors (TLDs) and optically stimulated luminescence detectors (OSLDs) for dosimetry of ultra-high dose rate electron beams. The study was driven by the challenges of dosimetry at ultra-high dose rates and the importance of dosimetry for FLASH radiotherapy and radiobiology experiments. Approach. Three types of TLDs (LiF:Mg,Ti; LiF:Mg,Cu,P; CaF2:Tm) and one type of OSLD (Al2O3:C) were irradiated in a 15 MeV electron beam with instantaneous dose rates in the (1-324) kGy s(-1) range. Reference dosimetry was carried out with an integrating current transformer, which was calibrated in absorbed dose to water against a reference ionization chamber. Additionally, dose rate independent BeO OSLDs were employed as a reference. Beam non-uniformity was addressed using a matrix of TLDs/OSLDs. Main results. The investigated TLDs were shown to be dose rate independent within the experimental uncertainties, which take into account the uncertainty of the dosimetry protocol and the irradiation uncertainty. The relative deviation between the TLDs and the reference dose was lower than 4 % for all dose rates. A decreasing response with the dose rate was observed for Al2O3:C OSLDs, but still within 10 % from the reference dose. Significance. The precision of the investigated luminescence detectors make them suitable for dosimetry of ultra-high dose rate electron beams. Specifically, the dose rate independence of the TLDs can support the investigation of the beam uniformity as a function of the dose rate, which is one of the challenges of the employed beam. Al2O3:C OSLDs provided high precision measurements, but the decreasing response with the dose rate needs to be confirmed by additional experiments. LA - English DB - MTMT ER - TY - JOUR AU - Petoukhova, Anna AU - Snijder, Roland AU - Vissers, Thomas AU - Ceha, Heleen AU - Struikmans, Henk TI - In vivo dosimetry in cancer patients undergoing intraoperative radiation therapy JF - PHYSICS IN MEDICINE AND BIOLOGY J2 - PHYS MED BIOL VL - 68 PY - 2023 IS - 18 PG - 22 SN - 0031-9155 DO - 10.1088/1361-6560/acf2e4 UR - https://m2.mtmt.hu/api/publication/34170015 ID - 34170015 N1 - Funding Agency and Grant Number: The authors are grateful to Ko van Wingerden for his advises about this manuscript. Funding text: The authors are grateful to Ko van Wingerden for his advises about this manuscript. AB - In vivo dosimetry (IVD) is an important tool in external beam radiotherapy (EBRT) to detect major errors by assessing differences between expected and delivered dose and to record the received dose by individual patients. Also, in intraoperative radiation therapy (IORT), IVD is highly relevant to register the delivered dose. This is especially relevant in low-risk breast cancer patients since a high dose of IORT is delivered in a single fraction. In contrast to EBRT, online treatment planning based on intraoperative imaging is only under development for IORT. Up to date, two commercial treatment planning systems proposed intraoperative ultrasound or in-room cone-beam CT for real-time IORT planning. This makes IVD even more important because of the possibility for real-time treatment adaptation. Here, we summarize recent developments and applications of IVD methods for IORT in clinical practice, highlighting important contributions and identifying specific challenges such as a treatment planning system for IORT. HDR brachytherapy as a delivery technique was not considered. We add IVD for ultrahigh dose rate (FLASH) radiotherapy that promises to improve the treatment efficacy, when compared to conventional radiotherapy by limiting the rate of toxicity while maintaining similar tumour control probabilities. To date, FLASH IORT is not yet in clinical use. LA - English DB - MTMT ER - TY - JOUR AU - Polevoy, Georgiy Georgievich AU - Kumar, Devika S. AU - Daripelli, Sushma AU - Prasanna Sr, Muthu TI - Flash Therapy for Cancer: A Potentially New Radiotherapy Methodology JF - CUREUS J2 - CUREUS VL - 15 PY - 2023 IS - 10 PG - 8 SN - 2168-8184 DO - 10.7759/cureus.46928 UR - https://m2.mtmt.hu/api/publication/34328496 ID - 34328496 AB - In traditional treatment modalities and standard clinical practices, FLASH radiotherapy (FL-RT) administers radiation therapy at an exceptionally high dosage rate. When compared to standard dose rate radiation therapy, numerous preclinical investigations have demonstrated that FL-RT provides similar benefits in conserving normal tissue while maintaining equal antitumor efficacy, a phenomenon possible due to the 'FLASH effect' (FE) of FL-RT. The methodologies involve proton radiotherapy, intensity-modulated radiation treatment, and managing high-throughput damage by radiation to solid tissues. Recent results from animal studies indicate that FL-RT can reduce radiation-induced tissue damage, significantly enhancing anticancer potency. Focusing on the potential benefits of FL proton beam treatment in the years to come, this review details the FL-RT research that has been done so far and the existing theories illuminating the FL effects. This subject remains of interest, with many issues still needing to be answered. We offer a brief review to emphasize a few of the key efforts and difficulties in moving FL radiation research forward. The existing research state of FL-RT, its affecting variables, and its different specific impacts are presented in this current review. Key topics discussed include the biochemical mechanism during FL therapy, beam sources for FL therapy, the FL effect on immunity, clinical and preclinical studies on the protective effect of FL therapy, and parameters for effective FL therapy. LA - English DB - MTMT ER - TY - JOUR AU - Romano, Francesco AU - Milluzzo, Giuliana AU - Di, Martino Fabio AU - D'Oca, Maria Cristina AU - Felici, Giuseppe AU - Galante, Federica AU - Gasparini, Alessia AU - Mariani, Giulia AU - Marrale, Maurizio AU - Medina, Elisabetta AU - Pacitti, Matteo AU - Sangregorio, Enrico AU - Vanreusel, Verdi AU - Verellen, Dirk AU - Vignati, Anna AU - Camarda, Massimo TI - First Characterization of Novel Silicon Carbide Detectors with Ultra-High Dose Rate Electron Beams for FLASH Radiotherapy JF - APPLIED SCIENCES-BASEL J2 - APPL SCI-BASEL VL - 13 PY - 2023 IS - 5 PG - 12 SN - 2076-3417 DO - 10.3390/app13052986 UR - https://m2.mtmt.hu/api/publication/33809993 ID - 33809993 N1 - Export Date: 31 October 2023 AB - Ultra-high dose rate (UHDR) beams for FLASH radiotherapy present significant dosimetric challenges. Although novel approaches for decreasing or correcting ion recombination in ionization chambers are being proposed, applicability of ionimetric dosimetry to UHDR beams is still under investigation. Solid-state sensors have been recently investigated as a valuable alternative for real-time measurements, especially for relative dosimetry and beam monitoring. Among them, Silicon Carbide (SiC) represents a very promising candidate, compromising between the maturity of Silicon and the robustness of diamond. Its features allow for large area sensors and high electric fields, required to avoid ion recombination in UHDR beams. In this study, we present simulations and experimental measurements with the low energy UHDR electron beams accelerated with the ElectronFLASH machine developed by the SIT Sordina company (IT). The response of a newly developed 1 x 1 cm(2) SiC sensor in charge as a function of the dose-per-pulse and its radiation hardness up to a total delivered dose of 90 kGy, was investigated during a dedicated experimental campaign, which is, to our knowledge, the first characterization ever done of SiC with UHDR-pulsed beams accelerated by a dedicated ElectronFLASH LINAC. Results are encouraging and show a linear response of the SiC detector up to 2 Gy/pulse and a variation in the charge per pulse measured for a cumulative delivered dose of 90 kGy, within +/- 0.75%. LA - English DB - MTMT ER - TY - JOUR AU - Saade, G. AU - Bogaerts, E. AU - Chiavassa, S. AU - Blain, G. AU - Delpon, G. AU - Evin, M. AU - Ghannam, Y. AU - Haddad, F. AU - Haustermans, K. AU - Koumeir, C. AU - Macaeva, E. AU - Maigne, L. AU - Mouchard, Q. AU - Servagent, N. AU - Sterpin, E. AU - Supiot, S. AU - Potiron, V. TI - Ultrahigh-Dose-Rate Proton Irradiation Elicits Reduced Toxicity in Zebrafish Embryos JF - ADVANCES IN RADIATION ONCOLOGY J2 - ADV RADIAT ONCOL VL - 8 PY - 2023 IS - 2 SN - 2452-1094 DO - 10.1016/j.adro.2022.101124 UR - https://m2.mtmt.hu/api/publication/33699713 ID - 33699713 N1 - Nantes Université, Nantes, France Department of Oncology, KU Leuven, Leuven, Belgium IMT Atlantique, Nantes Université, Subatech, Nantes, France Institut de Cancérologie de l'Ouest, Saint-Herblain, France GIP ARRONAX, Saint-Herblain, France Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Woluwé-Saint-Lambert, Belgium Université Clermont Auvergne, Clermont-Ferrand, France Export Date: 14 March 2023 Correspondence Address: Potiron, V.; Nantes UniversitéFrance; email: vincent.potiron@univ-nantes.fr Funding details: Ligue Contre le Cancer Funding details: Stichting Tegen Kanker, D7.21214.014-P, ZKD6219 Funding text 1: Sources of support: This work was supported by Inserm Cancer, the Ligue Contre le Cancer, IRC Transformed, Institut de Cancérologie de l'Ouest, the Stichting Tegen Kanker (STK) grant ZKD6219, and the Walloon region EPT grant D7.21214.014-P. AB - Purpose: Recently, ultrahigh-dose-rate radiation therapy (UHDR-RT) has emerged as a promising strategy to increase the benefit/risk ratio of external RT. Extensive work is on the way to characterize the physical and biological parameters that control the so-called “Flash” effect. However, this healthy/tumor differential effect is observable in in vivo models, which thereby drastically limits the amount of work that is achievable in a timely manner. Methods and Materials: In this study, zebrafish embryos were used to compare the effect of UHDR irradiation (8-9 kGy/s) to conventional RT dose rate (0.2 Gy/s) with a 68 MeV proton beam. Viability, body length, spine curvature, and pericardial edema were measured 4 days postirradiation. Results: We show that body length is significantly greater after UHDR-RT compared with conventional RT by 180 µm at 30 Gy and 90 µm at 40 Gy, while pericardial edema is only reduced at 30 Gy. No differences were obtained in terms of survival or spine curvature. Conclusions: Zebrafish embryo length appears as a robust endpoint, and we anticipate that this model will substantially fasten the study of UHDR proton-beam parameters necessary for “Flash.” © 2022 The Authors LA - English DB - MTMT ER - TY - JOUR AU - Schaefer, R. AU - Psoroulas, S. AU - Weber, D. C. TI - In situ correction of recombination effects in ultra-high dose rate irradiations with protons JF - PHYSICS IN MEDICINE AND BIOLOGY J2 - PHYS MED BIOL VL - 68 PY - 2023 IS - 10 PG - 11 SN - 0031-9155 DO - 10.1088/1361-6560/accf5c UR - https://m2.mtmt.hu/api/publication/33937488 ID - 33937488 AB - Background. At the Center for Proton Therapy at the Paul Scherrer Institute (PSI) the delivery of proton radiation is controlled via gas-based ionization chambers: the beam is turned off when a certain amount of preset charge has been collected. At low dose rates the charge collection efficiency in these detectors is unity, at ultra-high dose rates it is less due to induced charge recombination effects. If not corrected, the latter would lead to an overdosage. Purpose. In the scope of this work, we developed a novel approach to an in situ charge recombination correction for our dose defining detectors, when irradiated with a proton beam at ultra-high dose rates. This approach is based on the Two-Voltage-Method. Methods. We have translated this method to two separate devices operated simultaneously at different conditions. By doing so, the charge collection losses can be corrected directly and without the need for empirical correction values. This approach has been tested at ultra-high dose rates; proton beam was delivered by the COMET cyclotron to Gantry 1 at PSI. Results. We were able to correct the charge losses caused by recombination effects at local beam currents of approximately 700 nA (i.e. instantaneous dose rate of 3600 Gy s(-1) at isocenter). The corrected collected charges in our gaseous detectors were compared against recombination-free measurements with a Faraday cup. The ratio of both quantities shows no significant dose rate dependence within their respective combined uncertainties. Conclusions. Correcting recombination effects in our gas-based detectors with the novel method greatly eases the handling of Gantry 1 as 'FLASH test bench'. Not only is the application of a preset dose more accurate compared to using an empirical correction curve, also the re-determination of empirical correction curves in the case of a beam phase space change can be omitted. LA - English DB - MTMT ER - TY - JOUR AU - Schieferecke, J. AU - Gantz, S. AU - Hoffmann, A. AU - Pawelke, J. TI - Investigation of contrast mechanisms for MRI phase signal-based proton beam visualization in water phantoms JF - MAGNETIC RESONANCE IN MEDICINE J2 - MAGN RESON MED VL - 90 PY - 2023 IS - 5 SP - 1776 EP - 1788 PG - 13 SN - 0740-3194 DO - 10.1002/mrm.29752 UR - https://m2.mtmt.hu/api/publication/34059892 ID - 34059892 N1 - OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology–OncoRay, Dresden, Germany Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany Export Date: 12 July 2023 CODEN: MRMEE Correspondence Address: Pawelke, J.; OncoRay – National Center for Radiation Research in Oncology, Fetscherstr. 74/PF 41, Germany; email: joerg.pawelke@oncoray.de Funding details: Horizon 2020, 730983 Funding text 1: The authors thank Andrea Serra and Marco Battiston (ASG Superconductors S.p.A., Genoa, Italy) for assistance in MRI sequence programming and contrast interpretation, Andrea Bínová (OncoRay, Dresden, Germany) for assistance in conducting experiments, Benjamin Gebauer (OncoRay, Dresden, Germany) for assistance in film evaluation, Elke Beyreuther (OncoRay, Dresden, Germany) for sharing film calibration data, Daniela Kunath (University Hospital Carl Gustav Carus, Dresden, Germany) for providing PMMA water equivalent path length data, and Ion Beam Applications S.A. (Louvain‐la‐Neuve, Belgium) for their technical support. The experimental part of the University Proton Therapy Dresden facility has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement 730983 (INSPIRE). Open Access funding enabled and organized by Projekt DEAL. AB - Purpose: The low sensitivity and limitation to water phantoms of convection-dependent MRI magnitude signal-based proton beam visualization hinder its in vivo applicability in MR-integrated proton beam therapy. The purpose of the present study was, therefore, to assess possible contrast mechanisms for MRI phase signal-based proton beam visualization that can potentially be exploited to enhance the sensitivity of the method and extend its applicability to tissue materials. Methods: To assess whether proton beam-induced magnetic field perturbations, changes in material susceptibility or convection result in detectable changes in the MRI phase signal, water phantom characteristics, experiment timing, and imaging parameters were varied in combined irradiation and imaging experiments using a time-of-flight angiography pulse sequence on a prototype in-beam MRI scanner. Velocity encoding was used to further probe and quantify beam-induced convection. Results: MRI phase signal-based proton beam visualization proved feasible. The observed phase difference contrast was evoked by beam-induced buoyant convection with flow velocities in the mm/s range. Proton beam-induced magnetic field perturbations or changes in magnetic susceptibility did not influence the MRI phase signal. Velocity encoding was identified as a means to enhance the detection sensitivity. Conclusion: Because the MRI phase difference contrast observed during proton beam irradiation of water phantoms is caused by beam-induced convection, this method will unlikely be transferable to tightly compartmentalized tissue wherein flow effects are restricted. However, strong velocity encoded pulse sequences were identified as promising candidates for the future development of MRI-based methods for water phantom-based geometric quality assurance in MR-integrated proton beam therapy. © 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine. LA - English DB - MTMT ER - TY - JOUR AU - Schieferecke, Juliane AU - Gantz, Sebastian AU - Karsch, Leonhard AU - Pawelke, Joerg AU - Hoffmann, Aswin TI - MRI magnitude signal-based proton beam visualisation in water phantoms reflects composite effects of beam-induced buoyant convection and radiation chemistry JF - PHYSICS IN MEDICINE AND BIOLOGY J2 - PHYS MED BIOL VL - 68 PY - 2023 IS - 18 PG - 17 SN - 0031-9155 DO - 10.1088/1361-6560/acf2e0 UR - https://m2.mtmt.hu/api/publication/34170016 ID - 34170016 N1 - Funding Agency and Grant Number: European Union [730983] Funding text: The authors thank Andrea Serra (ASG Superconductors S.p.A., Genoa, Italy) and Paul Anders (OncoRay, Dresden, Germany) for support with the MR image acquisition, Andrea Binova (OncoRay, Dresden, Germany) for assistance during experiments, Benjamin Gebauer (OncoRay, Dresden, Germany) for assistance in film evaluation, Elke Beyreuther (OncoRay, Dresden, Germany) for providing film calibration data, Sonja Schellhammer (OncoRay, Dresden, Germany) for sharing range calibration data, Daniela Kunath (University Hospital Carl Gustav Carus, Dresden, Germany) for providing PMMA WEPL data and Ion Beam Applications S.A. (Louvain-la-Neuve, Belgium) for their technical support. The experimental part of the University Proton Therapy Dresden facility has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 730983 (INSPIRE). AB - Objective. Local magnetic resonance (MR) signal loss was previously observed during proton beam irradiation of free-floating water phantoms at ambient temperature using a research prototype in-beam magnetic resonance imaging (MRI) scanner. The emergence of this MR signal loss was hypothesised to be dependent on beam-induced convection. The aim of this study was therefore to unravel whether physical conditions allowing the development of convection must prevail for the beam-induced MRI signatures to emerge. Approach. The convection dependence of MRI magnitude signal-based proton beam visualisation was investigated in combined irradiation and imaging experiments using a gradient echo (GE)-based time-of-flight (ToF) angiography pulse sequence, which was first tested for its suitability for proton beam visualisation in free-floating water phantoms at ambient temperature. Subsequently, buoyant convection was selectively suppressed in water phantoms using either mechanical barriers or temperature control of water expansivity. The underlying contrast mechanism was further assessed using sagittal imaging and variation of T1 relaxation time-weighting. Main results. In the absence of convection-driven water flow, weak beam-induced MR signal changes occurred, whereas strong changes did occur when convection was not mechanically or thermally inhibited. Moreover, the degree of signal loss was found to change with the variation of T1-weighting. Consequently, beam-induced MR signal loss in free-floating water phantoms at ambient temperature does not exclusively originate from buoyant convection, but is caused by local composite effects of beam-induced motion and radiation chemistry resulting in a local change in the water T1 relaxation time. Significance. The identification of ToF angiography sequence-based proton beam visualisation in water phantoms to result from composite effects of beam-induced motion and radiation chemistry represents the starting point for the future elucidation of the currently unexplained motion-based MRI contrast mechanism and the identification of the proton beam-induced material change causing T1 relaxation time lengthening. LA - English DB - MTMT ER - TY - JOUR AU - Schulte, R. AU - Johnstone, C. AU - Boucher, S. AU - Esarey, E. AU - Geddes, C.G.R. AU - Kravchenko, M. AU - Kutsaev, S. AU - Loo, B.W. Jr. AU - Méot, F. AU - Mustapha, B. AU - Nakamura, K. AU - Nanni, E.A. AU - Obst-Huebl, L. AU - Sampayan, S.E. AU - Schroeder, C.B. AU - Sheng, K. AU - Snijders, A.M. AU - Snively, E. AU - Tantawi, S.G. AU - Van, Tilborg J. TI - Transformative Technology for FLASH Radiation Therapy JF - APPLIED SCIENCES-BASEL J2 - APPL SCI-BASEL VL - 13 PY - 2023 IS - 8 SN - 2076-3417 DO - 10.3390/app13085021 UR - https://m2.mtmt.hu/api/publication/33823658 ID - 33823658 N1 - Division of Biomedical Engineering Sciences, Loma Linda University, Loma Linda, CA 92350, United States Fermi National Accelerator Laboratory, Batavia, IL 60510, United States RadiaBeam Technologies, LLC, Santa Monica, CA 90404, United States Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States Department of Radiation Oncology, Stanford University School of Medicine, StanfordCA 94305, United States Brookhaven National Laboratory, UptonNY 11973, United States Argonne National Laboratory, Lemont, IL 60439, United States SLAC National Accelerator Laboratory, Menlo Park, CA 94025, United States Lawrence Livermore National Laboratory, Livermore, CA 94551, United States Opcondys, Inc, Manteca, CA 95336, United States Department of Radiation Oncology, University of California, San Francisco, CA 94115, United States Export Date: 15 May 2023 Correspondence Address: Schulte, R.; Division of Biomedical Engineering Sciences, United States; email: rschulte@llu.edu Funding details: DE-AC02-05CH11231 Funding details: National Science Foundation, NSF, 1519964 Funding details: National Institutes of Health, NIH, R01CA255432 Funding details: U.S. Department of Energy, USDOE Funding details: National Cancer Institute, NCI, 2R44CA217607 Funding details: California Energy Commission, CEC, 17-01-03 Funding details: Stanford University, SU Funding details: Advanced Research Projects Agency - Energy, ARPA-E, DE-AR0000907 Funding details: Lawrence Livermore National Laboratory, LLNL, DE-AC52-07NA27344 Funding details: Lawrence Berkeley National Laboratory, LBNL Funding details: Small Business Innovation Research, SBIR Funding details: Laboratory Directed Research and Development, LDRD, DE-AC02-76SF00515 Funding details: Seattle Translational Tumor Research, STTR, 0000219678, DE-SC0015717, DE-SC0020009 Funding text 1: Billy W. Loo Jr. is an employee of Stanford University School of Medicine. Dr. Billy W. Loo Jr. has received research support from Varian Medical Systems. He is a co-founder and board member of TibaRay. Reinhard Schulte is employed by Loma Linda University, School of Medicine. Dr. Schulte has received research funding by Grant R44CA257178 “Ultrafast and Precise External Beam Monitor for FLASH and Other Advanced Radiation Therapy Modalities” from the National Cancer Institute awarded to Peter Friedman (PI), Integrated Sensors, LLC. The funder had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. The United States Government has rights to patents pursuant to Contract No. DE-AC52-07NA27344 between the United States Department of Energy and Lawrence Livermore National Security, LLC for the operation of Lawrence Livermore National Laboratory. For SES, Opcondys, Inc. is a for-profit company and may profit from the technologies described in this paper. Funding text 2: The work on ACCIL was supported in part by the U.S. Department of Energy, Office of High Energy AQ:2 Physics, through SBIR/STTR under Grant DE-SC0015717, and in part by the AQ:3 Accelerator Stewardship under Grant 0000219678. The work on non-scaling FFGA was partially supported by the U.S. Department of Energy under SBIR Grant DE-SC0020009. The PHASER research is supported by the NIH/NCI Grant 2R44CA217607, Stanford University Department of Radiation Oncology, and philanthropic donors to the Stanford University Department of Radiation Oncology. The ROAD project is funded by the National Institutes of Health (NIH), award number NIH R01CA255432. The LIA work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. Work performed by Opcondys, Inc. was funded separately by the United States Government under ARPA-E (Contract No. DE-AR0000907), the National Science Foundation (Grant No. 1519964), and the California Energy Commission CalSEED Program (Grant No. 17-01-03). Emma Snively and the mm-wave VHEE development at SLAC were supported by the Department of Energy, Laboratory Directed Research and Development program at SLAC National Accelerator Laboratory, under Contract DE-AC02-76SF00515, and the LaserNetUS. Authors from LBNL acknowledge support from the Laboratory Directed Research and Development (LDRD) funding from LBNL provided by the Director, the U.S. Department of Energy Office of Science Offices of High Energy Physics and Fusion Energy Sciences, under Contract No. DE-AC02-05CH11231, and the LaserNetUS. AB - Featured Application: We report on new accelerator technology that has applications in FLASH radiation therapy. FLASH radiation therapy may have profound implications in cancer therapy because it may significantly spare normal tissues and solve the problem of tumors in motion due to the short time interval (sub-second) during which it is delivered. The general concept of radiation therapy used in conventional cancer treatment is to increase the therapeutic index by creating a physical dose differential between tumors and normal tissues through precision dose targeting, image guidance, and radiation beams that deliver a radiation dose with high conformality, e.g., protons and ions. However, the treatment and cure are still limited by normal tissue radiation toxicity, with the corresponding side effects. A fundamentally different paradigm for increasing the therapeutic index of radiation therapy has emerged recently, supported by preclinical research, and based on the FLASH radiation effect. FLASH radiation therapy (FLASH-RT) is an ultra-high-dose-rate delivery of a therapeutic radiation dose within a fraction of a second. Experimental studies have shown that normal tissues seem to be universally spared at these high dose rates, whereas tumors are not. While dose delivery conditions to achieve a FLASH effect are not yet fully characterized, it is currently estimated that doses delivered in less than 200 ms produce normal-tissue-sparing effects, yet effectively kill tumor cells. Despite a great opportunity, there are many technical challenges for the accelerator community to create the required dose rates with novel compact accelerators to ensure the safe delivery of FLASH radiation beams. © 2023 by the authors. LA - English DB - MTMT ER - TY - JOUR AU - Shi, Ying AU - Zhang, Man-Zhou AU - Ou-Yang, Lian-Hua AU - Chen, Zhi-Ling AU - Li, Xiu-Fang AU - Li, De-Ming TI - Design of a rapid-cycling synchrotron for flash proton therapy JF - NUCLEAR SCIENCE AND TECHNIQUES J2 - NUCL SCI TECH VL - 34 PY - 2023 IS - 10 PG - 11 SN - 1001-8042 DO - 10.1007/s41365-023-01283-3 UR - https://m2.mtmt.hu/api/publication/34222211 ID - 34222211 N1 - Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China University of Chinese Academy of Sciences, Beijing, 100049, China Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China Export Date: 30 May 2024 CODEN: NSETE Correspondence Address: Zhang, M.-Z.; Shanghai Advanced Research Institute, China; email: zhangmanzhou@sinap.ac.cn AB - The purpose of this study was to design a rapid-cycling synchrotron, making it capable of proton beam ultrahigh dose rate irradiation, inspired by laser accelerators. The design had to be cheap and simple. We consider our design from six aspects: the lattice, injection, extraction, space charge effects, eddy current effects and energy switching. Efficiency and particle quantity must be addressed when injected. The space charge effects at the injection could affect particles' number. The eddy current effects in the vacuum chambers would affect the magnetic field itself and generate heat, all of which need to be taken into account. Fast extraction can obtain 10(10) protons/pulse, equal to instantaneous dose rate up to 10(7) Gy/s in a very short time, while changing various extraction energies rapidly and easily to various deposition depths. In the further research, we expect to combine a delivery system with this accelerator to realize the FLASH irradiation. LA - English DB - MTMT ER - TY - JOUR AU - Tan, Y. AU - Zhou, S. AU - Haefner, J. AU - Chen, Q. AU - Mazur, T.R. AU - Darafsheh, A. AU - Zhang, T. TI - Simulation study of a novel small animal FLASH irradiator (SAFI) with integrated inverse-geometry CT based on circularly distributed kV X-ray sources JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 13 PY - 2023 IS - 1 SN - 2045-2322 DO - 10.1038/s41598-023-47421-0 UR - https://m2.mtmt.hu/api/publication/34496094 ID - 34496094 N1 - Department of Radiation Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, United States Department of Physics, Washington University in St. Louis, St. Louis, MO 63130, United States Center for Radiological Research, Columbia University, New York, NY 10032, United States Export Date: 11 January 2024 Correspondence Address: Zhang, T.; Department of Radiation Oncology, United States; email: tiezhizhang@wustl.edu Chemicals/CAS: tungsten, 7440-33-7; Tungsten Funding details: National Institutes of Health, NIH, 41DE029727 Funding text 1: We acknowledge the support from the National Institutes of Health under grant #R41DE029727. AB - Ultra-high dose rate (UHDR) radiotherapy (RT) or FLASH-RT can potentially reduce normal tissue toxicity. A small animal irradiator that can deliver FLASH-RT treatments similar to clinical RT treatments is needed for pre-clinical studies of FLASH-RT. We designed and simulated a novel small animal FLASH irradiator (SAFI) based on distributed x-ray source technology. The SAFI system comprises a distributed x-ray source with 51 focal spots equally distributed on a 20 cm diameter ring, which are used for both FLASH-RT and onboard micro-CT imaging. Monte Carlo simulation was performed to estimate the dosimetric characteristics of the SAFI treatment beams. The maximum dose rate, which is limited by the power density of the tungsten target, was estimated based on finite-element analysis (FEA). The maximum DC electron beam current density is 2.6 mA/mm2, limited by the tungsten target's linear focal spot power density. At 160 kVp, 51 focal spots, each with a dimension of 2 × 20 mm2 and 10° anode angle, can produce up to 120 Gy/s maximum DC irradiation at the center of a cylindrical water phantom. We further demonstrate forward and inverse FLASH-RT planning, as well as inverse-geometry micro-CT with circular source array imaging via numerical simulations. © 2023, The Author(s). LA - English DB - MTMT ER - TY - JOUR AU - Trotter, J. AU - Lin, A. TI - Advances in Proton Therapy for the Management of Head and Neck Tumors JF - SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA J2 - SURG ONCOL CLIN N AM VL - 32 PY - 2023 IS - 3 SP - 587 EP - 598 PG - 12 SN - 1055-3207 DO - 10.1016/j.soc.2023.03.003 UR - https://m2.mtmt.hu/api/publication/33810132 ID - 33810132 N1 - Export Date: 11 May 2023 CODEN: SOCAF Correspondence Address: Lin, A.; Department of Radiation Oncology, 3400 Civic Center Boulevard, United States; email: Alexander.Lin2@pennmedicine.upenn.edu LA - English DB - MTMT ER - TY - JOUR AU - Tubin, S. AU - Vozenin, M.C. AU - Prezado, Y. AU - Durante, M. AU - Prise, K.M. AU - Lara, P.C. AU - Greco, C. AU - Massaccesi, M. AU - Guha, C. AU - Wu, X. AU - Mohiuddin, M.M. AU - Vestergaard, A. AU - Bassler, N. AU - Gupta, S. AU - Stock, M. AU - Timmerman, R. TI - Novel unconventional radiotherapy techniques: Current status and future perspectives – Report from the 2nd international radiation oncology online seminar JF - CLINICAL AND TRANSLATIONAL RADIATION ONCOLOGY J2 - CLIN TRANSL RADIAT ONCOL (CTRO) VL - 40 PY - 2023 SN - 2405-6308 DO - 10.1016/j.ctro.2023.100605 UR - https://m2.mtmt.hu/api/publication/33744730 ID - 33744730 N1 - Medaustron Center for Ion Therapy, Marie-Curie Strasse 5, Wiener Neustadt, 2700, Austria Radiation Oncology Laboratory, Radiation Oncology Service, Oncology Department, Lausanne University Hospital and University of Lausanne, Switzerland Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, 91400, France Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, 91400, France Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung, Planckstraße 1, Darmstadt, 64291, Germany Technsiche Universität Darmstadt, Institute for Condensed Matter Physics, Darmstadt, Germany Patrick G Johnston Centre for Cancer Research Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7AE, United Kingdom Canarian Comprehensive Cancer Center, San Roque University Hospital & Fernando Pessoa Canarias University, C/Dolores de la Rocha 9, Las Palmas GC, 35001, Spain Department of Radiation Oncology Champalimaud Foundation, Av. Brasilia, Lisbon, 1400-038, Portugal UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy Montefiore Medical Center Radiation Oncology, 111 E 210th St, New York, NY, United States Executive Medical Physics Associates, 19470 NE 22nd Road, Miami, FL 33179, United States Northwestern Medicine Cancer Center Warrenville and Northwestern Medicine Proton Center, 4455 Weaver Pkwy, Warrenville, IL 60555, United States Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark The Loop Immuno-Oncology Laboratory, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, United States Karl Landsteiner University of Health Sciences, Marie-Curie Strasse 5, Wiener Neustadt, 2700, Austria Department of Radiation Oncology, University of Texas, Southwestern Medical Center, Inwood Road Dallas, TX 2280, United States Export Date: 11 October 2023 Correspondence Address: Tubin, S.; Medaustron Center for Ion Therapy, Marie-Curie Strasse 5, Austria; email: slavisa.tubin@medaustron.at LA - English DB - MTMT ER - TY - JOUR AU - Yogo, Katsunori AU - Kodaira, Satoshi AU - Kusumoto, Tamon AU - Kitamura, Hisashi AU - Toshito, Toshiyuki AU - Iwata, Hiromitsu AU - Umezawa, Masumi AU - Yamada, Masashi AU - Miyoshi, Takuto AU - Komori, Masataka AU - Yasuda, Hiroshi AU - Kataoka, Jun AU - Yamamoto, Seiichi TI - Luminescence imaging of water irradiated by protons under FLASH radiation therapy conditions JF - PHYSICS IN MEDICINE AND BIOLOGY J2 - PHYS MED BIOL VL - 68 PY - 2023 IS - 15 PG - 10 SN - 0031-9155 DO - 10.1088/1361-6560/ace60b UR - https://m2.mtmt.hu/api/publication/34092629 ID - 34092629 N1 - Funding Agency and Grant Number: JSPS KAKENHI [JP18K07679, JP21K07699, JPMJER2102]; NU-AIST alliance project; Radiation Effects Association; Foundation of Public Interest of Tatematsu; Aichi Cancer Research Foundation; JSTERATO [22H03019] Funding text: This research was partially funded by JSPS KAKENHI (grant numbers JP18K07679 and JP21K07699) Program of the Network-Type Joint Usage/Research Center for Radiation Disaster Medical Science of Hiroshima University, NU-AIST alliance project, a grant from the Radiation Effects Association, Foundation of Public Interest of Tatematsu, and the Aichi Cancer Research Foundation. This work was also partly supported by JSTERATO Grant Number JPMJER2102 and JSPS KAKENHI Grant Number 22H03019 AB - Objective. FLASH radiation therapy with ultrahigh dose rates (UHDR) has the potential to reduce damage to normal tissue while maintaining anti-tumor efficacy. However, rapid and precise dose distribution measurements remain difficult for FLASH radiation therapy with proton beams. To solve this problem, we performed luminescence imaging of water following irradiation by a UHDR proton beam captured using a charge-coupled device camera. Approach. We used 60 MeV proton beams with dose rates of 0.03-837 Gy s(-1) from a cyclotron. Therapeutic 139.3 MeV proton beams with dose rates of 0.45-4320 Gy s(-1) delivered by a synchrotron-based proton therapy system were also tested. The luminescent light intensity induced by the UHDR beams was compared with that produced by conventional beams to compare the dose rate dependency of the light intensity and its profile. Main results. Luminescence images of water were clearly visualized under UHDR conditions, with significantly shorter exposure times than those with conventional beams. The light intensity was linearly proportional to the delivered dose, which is similar to that of conventional beams. No significant dose-rate dependency was observed for 0.03-837 Gy s(-1). The light-intensity profiles of the UHDR beams agreed with those of conventional beams. The results did not differ between accelerators (synchrotron or cyclotron) and beam energies. Significance. Luminescence imaging of water is achievable with UHDR proton beams as well as with conventional beams. The proposed method should be suitable for rapid and easy quality assurance investigations for proton FLASH therapy, because it facilitates real-time, filmless measurements of dose distributions, and is useful for rapid feedback. LA - English DB - MTMT ER - TY - JOUR AU - Zeng, Yiling AU - Quan, Hong TI - Considerations and current status of treatment planning for proton FLASH radiotherapy JF - KEXUE TONGBAO / CHINESE SCIENCE BULLETIN J2 - KEXUE TONGBAO / CHINESE SCIENCE BULLETIN VL - 68 PY - 2023 IS - 31 SP - 4231 EP - 4244 PG - 14 SN - 0023-074X DO - 10.1360/TB-2023-0291 UR - https://m2.mtmt.hu/api/publication/34638788 ID - 34638788 LA - Chinese DB - MTMT ER - TY - JOUR AU - Zhu, Hongyu AU - Xie, Dehuan AU - Wang, Ying AU - Huang, Runda AU - Chen, Xi AU - Yang, Yiwei AU - Wang, Bin AU - Peng, Yinglin AU - Wang, Jianxin AU - Xiao, Dexin AU - Wu, Dai AU - Qian, Chao-Nan AU - Deng, Xiaowu TI - Comparison of intratumor and local immune response between MV X-ray FLASH and conventional radiotherapies JF - CLINICAL AND TRANSLATIONAL RADIATION ONCOLOGY J2 - CLIN TRANSL RADIAT ONCOL (CTRO) VL - 38 PY - 2023 SP - 138 EP - 146 PG - 9 SN - 2405-6308 DO - 10.1016/j.ctro.2022.11.005 UR - https://m2.mtmt.hu/api/publication/33809997 ID - 33809997 N1 - Funding Agency and Grant Number: National Key R&D Program of China; National Natural Science Foundation of China; Science and Technology Planning Project of Guangzhou; [2022YFC2402300]; [82073220]; [81872384]; [81672872]; [11975218]; [202201011076] Funding text: Funding: This work was funded by grants from the National Key R&D Program of China (No. 2022YFC2402300 to X. Deng) , National Natural Science Foundation of China (No. 82073220, No. 81872384, and No. 81672872 to CN. Qian, No. 11975218 to D. Wu) , Science and Technology Planning Project of Guangzhou (202201011076, H. Zhu) . AB - Background/Purpose: Investigating the antitumor effect and intratumor as well as local immune response in breast cancer-bearing mice after MV X-ray ultra-high dose rate radiotherapy (FLASH-RT) and conventional dose rate radiotherapy (CONV-RT). Materials/Methods: Six-week-old female C57BL/6 mice were inoculated subcutaneously with Py8119 and Py230 breast tumor cells in the inguinal mammary gland and administered 10 Gy abdominal 6 MV X-ray FLASH-RT (125 Gy/s) or CONV-RT (0.2 Gy/s) 15 days after tumor inoculation. Tumor and spleen tissues were obtained at different time points post-irradiation (PI) for analysis of immune cell infiltration using flow cytometry and immunohistochemical (IHC) staining. Intestine tissues were collected 3 days PI to evaluate normal tissue damage and immune cell infiltration.Results: Both FLASH-RT and CONV-RT significantly delayed tumor growth. Flow cytometry showed increased CD8+/CD3 + and CD8+/CD4 + ratios, and IHC confirmed a similar increased CD8 + T cell infiltration at 2 weeks PI in Py8119 tumor tissues in both irradiation groups. No statistical difference was observed between the irradiation groups in terms of tumor growth and increased T cell infiltration in the tumor. Unexpectedly, significantly smaller spleen weight and substantially higher CD8+/CD3 + and lower CD4+/CD3 + ratios were observed in the spleens of the FLASH-RT group than in the spleens of the non-irradiated control and CONV-RT groups 4 weeks PI. Pathological analysis revealed severe red pulp expansion in several spleens from the CONV-RT group, but not in the spleens of the FLASH-RT group. Reduced intestinal damage, macrophage and neutrophil infiltration were observed in the FLASH-RT group compared with CONV-RT group.Conclusions: FLASH-RT and CONV-RT effectively suppressed tumor growth and promoted CD8 + T cell influx into tumors. FLASH-RT can induce different splenic immune responses and reduce radiation-induced damage in the spleen and intestine, which may potentially enhance the therapeutic ratio of FLASH-RT. LA - English DB - MTMT ER - TY - JOUR AU - Zou, W. AU - Zhang, R. AU - Schüler, E. AU - Taylor, P.A. AU - Mascia, A.E. AU - Diffenderfer, E.S. AU - Zhao, T. AU - Ayan, A.S. AU - Sharma, M. AU - Yu, S.-J. AU - Lu, W. AU - Bosch, W.R. AU - Tsien, C. AU - Surucu, M. AU - Pollard-Larkin, J.M. AU - Schuemann, J. AU - Moros, E.G. AU - Bazalova-Carter, M. AU - Gladstone, D.J. AU - Li, H. AU - Simone, C.B. II AU - Petersson, K. AU - Kry, S.F. AU - Maity, A. AU - Loo, B.W. Jr AU - Dong, L. AU - Maxim, P.G. AU - Xiao, Y. AU - Buchsbaum, J.C. TI - Framework for Quality Assurance of Ultrahigh Dose Rate Clinical Trials Investigating FLASH Effects and Current Technology Gaps JF - INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS J2 - INT J RADIAT ONCOL VL - 116 PY - 2023 IS - 5 SP - 1202 EP - 1217 PG - 16 SN - 0360-3016 DO - 10.1016/j.ijrobp.2023.04.018 UR - https://m2.mtmt.hu/api/publication/34092633 ID - 34092633 N1 - Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, United States Department of Radiation Oncology, Geisel School of Medicine, Dartmouth College, Hanover, NH, United States Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States Cincinnati Children's Hospital, Cincinnati, OH, United States Department of Radiation Oncology, Washington University, St. Louis, MO, United States Department of Radiation Oncology, Ohio State University, Columbus, OH, United States Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, United States Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, United States Department of Radiation Oncology, University of Texas Southwestern, Dallas, TX, United States Department of Radiation Oncology, McGill University Health Center, Montreal, QC, Canada Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, United States Department of Physics and Astronomy, University of Victoria, Victoria, BC, Canada Department of Radiation Oncology, Johns Hopkins University, Baltimore, MD, United States Department of Radiation Oncology, New York Proton Center, New York, NY, United States Department of Radiation Oncology, MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK, Oxford, United Kingdom Department of Radiation Oncology, University of California Irvine, Irvine, CA, United States Radiation Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institute of Health, Bethesda, MD, United States Cited By :1 Export Date: 10 August 2023 CODEN: IOBPD Correspondence Address: Zou, W.email: wei.zou@pennmedicine.upenn.edu Funding details: 180803, U24CA180803-06 Funding details: MC_UU_00001/9, MR/X006611/1 Funding details: U01 CA260446 Funding details: R01HL-148272-01A1, R01HL152707 Funding details: National Institutes of Health, NIH, 1P01CA210944-04, 2U10CA180868-06, NIH/NCI1P01CA257904-01A1, P01CA244091 Funding details: National Cancer Institute, NCI, 2U24CA180803-06, U10 CA 180833 Funding details: Massachusetts General Hospital, MGH Funding details: Patient-Centered Outcomes Research Institute, PCORI, PCS-1403-12804, PCS-2017C1-0422 Funding details: University of Pennsylvania, P01CA257904 Funding details: Varian Medical Systems, PO1CA244091 Funding details: University of Texas MD Anderson Cancer Center Funding details: American Association of Physicists in Medicine, AAPM, 1P01CA257904-01A1, 2/12/2019, 9R44CA254844-02, CPRIT-MIRA RP160661, NCIP30CA023108, R01 CA218402, R01 CA235723-01, R01EB023909, R42CA224646-02, RR200042, SBIR 75N91021C00031, SRA202201-0021, U01 CA260446-01A1, US20140114150 A1, WO2016176265 A1 Funding details: Medical Research Council, MRC Funding details: Cancer Research UK, CRUK, C6078/A28736, P30 CA016672 Funding details: Brain Tumour Charity Funding text 1: This research was funded by the National Institutes of Health ( 2U24CA180803-06 , 2U10CA180868-06 , and P01CA257904-01A1 ). This article represents the opinions of the authors. It does not represent the opinion or policy of the National Institutes of Health of the United States government. Funding text 2: Disclosures: M.B.-C. declares in the past 36 months grants or contracts from New Frontiers in Research Fund – Exploration – Canadian Tri-Council Canada Research Chairs Program. W.R.B. declares in the past 36 months grants or contracts from the Patient-Centered Outcomes Research Institute (PCS-1403-12804 and PCS-2017C1-0422), Massachusetts General Hospital Consortium Agreement (Efstathiou) PARTIQoL, and the National Cancer Institute (NCI; U24 CA 180803, U10 CA 180833) and a service contract from the American Association of Physicists in Medicine. E.S.D. declares in the past 36 months grants from the National Institutes of Health (NIH)/NCI (1P01CA210944-04 and NIH/NCI1P01CA257904-01A1). W.L. declares in the past 36 months Grants or contracts from CPRIT RR200042, NIH R01 CA235723-01, NIH R01 CA218402, SBIR 75N91021C00031, SBIR 9R44CA254844-02, CPRIT-MIRA RP160661 and RefleXion SRA202201-0021. L.D. declares in the past 36 months a grant from NIH (1P01CA257904-01A1), IBA-sponsored research on FLASH proton therapy, and speaker fees from Varian Medical Systems. D.J.G. declares in the past 36 months grants from NCI (NCIP30CA023108, R01EB023909, U01 CA260446-01A1, R42CA224646-02) and United States patent numbers US10,201,718 B2, 2/12/2019, WO2016176265 A1, and US20140114150 A1. B.W.L. declares, since the initial planning of the work, a grant from NCI (P01CA244091) and in the past 36 months grants from Varian Medical Systems to Stanford University and is cofounder and board member of TibaRay. A.M. declares in the past 36 months a grant from the University of Pennsylvania (P01CA257904) for “Translational Studies in FLASH Particle Radiotherapy” and honoraria from the University of Pennsylvania for giving the lecture “Proton FLASH Radiotherapy at Penn” at an IBA Proton Therapy conference in September 2019. A.E.M. declares in the past 36 months grants or contracts from Varian Medical Systems–sponsored research projects, speaker fees paid to the institution, and payment to the institution from Varian Medical Systems. P.G.M. declares in the past 36 months a grant from NCI (PO1CA244091) and is the founder (no payments) of TibaRay, Inc. E.G.M. declares in the past 36 months a submitted R01 grant in fall 2021 to NCI on the application of radiation-induced acoustics to FLASH monitoring. K.P. declares, since the initial planning of the work, grants from Medical Research Council (MRCMRC [MC_UU_00001/9] and MR/X006611/1) and Cancer Research UK (RadNet Grant [C6078/A28736]) and declares in the past 36 months membership in the scientific advisory board on FLASH for IBA (unpaid position). J.M.P.-L. declares in the past 36 months membership in the American Association of Physicists in Medicine's board of directors. E.S. declares in the past 36 months a Cancer Center Support Grant (P30 CA016672) from NCI/NIH to the University of Texas MD Anderson Cancer Center, University Cancer Foundation via the Institutional Research Grant program at the University of Texas MD Anderson Cancer Center, Division of Radiation Oncology and support from both Varian Medical Systems and IntraOp Medical for travel. J.S. declares in the past 36 months grants or contracts from NIH/NCI, the Brain Tumor Charity, and the Damon Runyon Foundation as well as a leadership or fiduciary role in the Radiation Research Society. M.Sh. declares in the past 36 months a sponsored research project from Sientra. C.B.S. declares in the past 36 months an honorarium from and a position as FlashForward Consortium Clinical Chair of Varian Medical Systems. P.A.T. declares in the past 36 months a grant from NCI (180803) as well as a leadership or fiduciary role at Healthcare for the Homeless-Houston. C.T. declares in the past 36 months payment or honoraria from Varian Medical Systems in 2021 and support for attending meetings and travel from Zeiss in 2022. Y.X. declares in the past 36 months grants from NCI (U24CA180803-06 [Imaging and Radiation Oncology Core], 2U10CA180868-06 [NRG]). R.Z. declares in the past 36 months a grant from NCI (U01 CA260446). T.Z. declares in the past 36 months grants from Varian Medical Systems, Mevion, and NIH paid to their institution and is a data safety monitoring volunteer for Mevion. W.Z. declares in the past 36 months grants from NCI (P01CA257904), NIH (R01HL-148272-01A1, R01HL152707), and Varian Medical Systems. No other disclosures were reported. Funding text 3: This research was funded by the National Institutes of Health (2U24CA180803-06, 2U10CA180868-06, and P01CA257904-01A1). This article represents the opinions of the authors. It does not represent the opinion or policy of the National Institutes of Health of the United States government. Disclosures: M.B.-C. declares in the past 36 months grants or contracts from New Frontiers in Research Fund – Exploration – Canadian Tri-Council Canada Research Chairs Program. W.R.B. declares in the past 36 months grants or contracts from the Patient-Centered Outcomes Research Institute (PCS-1403-12804 and PCS-2017C1-0422), Massachusetts General Hospital Consortium Agreement (Efstathiou) PARTIQoL, and the National Cancer Institute (NCI; U24 CA 180803, U10 CA 180833) and a service contract from the American Association of Physicists in Medicine. E.S.D. declares in the past 36 months grants from the National Institutes of Health (NIH)/NCI (1P01CA210944-04 and NIH/NCI1P01CA257904-01A1). W.L. declares in the past 36 months Grants or contracts from CPRIT RR200042, NIH R01 CA235723-01, NIH R01 CA218402, SBIR 75N91021C00031, SBIR 9R44CA254844-02, CPRIT-MIRA RP160661 and RefleXion SRA202201-0021. L.D. declares in the past 36 months a grant from NIH (1P01CA257904-01A1), IBA-sponsored research on FLASH proton therapy, and speaker fees from Varian Medical Systems. D.J.G. declares in the past 36 months grants from NCI (NCIP30CA023108, R01EB023909, U01 CA260446-01A1, R42CA224646-02) and United States patent numbers US10,201,718 B2, 2/12/2019, WO2016176265 A1, and US20140114150 A1. B.W.L. declares, since the initial planning of the work, a grant from NCI (P01CA244091) and in the past 36 months grants from Varian Medical Systems to Stanford University and is cofounder and board member of TibaRay. A.M. declares in the past 36 months a grant from the University of Pennsylvania (P01CA257904) for “Translational Studies in FLASH Particle Radiotherapy” and honoraria from the University of Pennsylvania for giving the lecture “Proton FLASH Radiotherapy at Penn” at an IBA Proton Therapy conference in September 2019. A.E.M. declares in the past 36 months grants or contracts from Varian Medical Systems–sponsored research projects, speaker fees paid to the institution, and payment to the institution from Varian Medical Systems. P.G.M. declares in the past 36 months a grant from NCI (PO1CA244091) and is the founder (no payments) of TibaRay, Inc. E.G.M. declares in the past 36 months a submitted R01 grant in fall 2021 to NCI on the application of radiation-induced acoustics to FLASH monitoring. K.P. declares, since the initial planning of the work, grants from Medical Research Council (MRCMRC [MC_UU_00001/9] and MR/X006611/1) and Cancer Research UK (RadNet Grant [C6078/A28736]) and declares in the past 36 months membership in the scientific advisory board on FLASH for IBA (unpaid position). J.M.P.-L. declares in the past 36 months membership in the American Association of Physicists in Medicine's board of directors. E.S. declares in the past 36 months a Cancer Center Support Grant (P30 CA016672) from NCI/NIH to the University of Texas MD Anderson Cancer Center, University Cancer Foundation via the Institutional Research Grant program at the University of Texas MD Anderson Cancer Center, Division of Radiation Oncology and support from both Varian Medical Systems and IntraOp Medical for travel. J.S. declares in the past 36 months grants or contracts from NIH/NCI, the Brain Tumor Charity, and the Damon Runyon Foundation as well as a leadership or fiduciary role in the Radiation Research Society. M.Sh. declares in the past 36 months a sponsored research project from Sientra. C.B.S. declares in the past 36 months an honorarium from and a position as FlashForward Consortium Clinical Chair of Varian Medical Systems. P.A.T. declares in the past 36 months a grant from NCI (180803) as well as a leadership or fiduciary role at Healthcare for the Homeless-Houston. C.T. declares in the past 36 months payment or honoraria from Varian Medical Systems in 2021 and support for attending meetings and travel from Zeiss in 2022. Y.X. declares in the past 36 months grants from NCI (U24CA180803-06 [Imaging and Radiation Oncology Core], 2U10CA180868-06 [NRG]). R.Z. declares in the past 36 months a grant from NCI (U01 CA260446). T.Z. declares in the past 36 months grants from Varian Medical Systems, Mevion, and NIH paid to their institution and is a data safety monitoring volunteer for Mevion. W.Z. declares in the past 36 months grants from NCI (P01CA257904), NIH (R01HL-148272-01A1, R01HL152707), and Varian Medical Systems. No other disclosures were reported. AB - FLASH radiation therapy (FLASH-RT), delivered with ultrahigh dose rate (UHDR), may allow patients to be treated with less normal tissue toxicity for a given tumor dose compared with currently used conventional dose rate. Clinical trials are being carried out and are needed to test whether this improved therapeutic ratio can be achieved clinically. During the clinical trials, quality assurance and credentialing of equipment and participating sites, particularly pertaining to UHDR-specific aspects, will be crucial for the validity of the outcomes of such trials. This report represents an initial framework proposed by the NRG Oncology Center for Innovation in Radiation Oncology FLASH working group on quality assurance of potential UHDR clinical trials and reviews current technology gaps to overcome. An important but separate consideration is the appropriate design of trials to most effectively answer clinical and scientific questions about FLASH. This paper begins with an overview of UHDR RT delivery methods. UHDR beam delivery parameters are then covered, with a focus on electron and proton modalities. The definition and control of safe UHDR beam delivery and current and needed dosimetry technologies are reviewed and discussed. System and site credentialing for large, multi-institution trials are reviewed. Quality assurance is then discussed, and new requirements are presented for treatment system standard analysis, patient positioning, and treatment planning. The tables and figures in this paper are meant to serve as reference points as we move toward FLASH-RT clinical trial performance. Some major questions regarding FLASH-RT are discussed, and next steps in this field are proposed. FLASH-RT has potential but is associated with significant risks and complexities. We need to redefine optimization to focus not only on the dose but also on the dose rate in a manner that is robust and understandable and that can be prescribed, validated, and confirmed in real time. Robust patient safety systems and access to treatment data will be critical as FLASH-RT moves into the clinical trials. © 2023 The Authors LA - English DB - MTMT ER - TY - JOUR AU - Boehlen, Till Tobias AU - Germond, Jean-Francois AU - Bourhis, Jean AU - Vozenin, Marie-Catherine AU - Ozsahin, Esat Mahmut AU - Bochud, Francois AU - Bailat, Claude AU - Moeckli, Raphael TI - Normal Tissue Sparing by FLASH as a Function of Single-Fraction Dose: A Quantitative Analysis JF - INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS J2 - INT J RADIAT ONCOL VL - 114 PY - 2022 IS - 5 SP - 1032 EP - 1044 PG - 13 SN - 0360-3016 DO - 10.1016/j.ijrobp.2022.05.038 UR - https://m2.mtmt.hu/api/publication/33809999 ID - 33809999 N1 - Funding Agency and Grant Number: ISREC Foundation; Fondation pour le Soutien de la Recherche et du Developpement de l'Oncologie (FSRDO) Funding text: This research was partially funded by the ISREC Foundation from a Biltema donation and by the Fondation pour le Soutien de la Recherche et du Developpement de l'Oncologie (FSRDO). AB - Purpose: The FLASH effect designates normal tissue sparing by ultra-high dose rate (UHDR) compared with conventional dose rate irradiation without compromising tumor control. Understanding the magnitude of this effect and its dependency on dose are essential requirements for an optimized clinical translation of FLASH radiation therapy. In this context, we evaluated available experimental data on the magnitudes of normal tissue sparing provided by the FLASH effect as a function of dose, and followed a phenomenological data-driven approach for its parameterization. Methods and Materials: We gathered available in vivo data of normal tissue sparing of conventional (CONV) versus UHDR single-fraction doses and converted these to a common scale using isoeffect dose ratios, hereafter referred to as FLASH-modifying factors (FMF= (DCONV/DUHDR)|isoeffect). We then evaluated the suitability of a piecewise linear function with 2 pieces to parametrize FMF pound DUHDR as a function of dose DUHDR. Results: We found that the magnitude of FMF generally decreases (ie, sparing increases) as a function of single-fraction dose, and that individual data series can be described by the piecewise linear function. The sparing magnitude appears organ-specific, and pooled skin-reaction data followed a consistent trend as a function of dose. Average FMF values and their standard deviations were 0.95 0.11 for all data <10 Gy, 0.92
0.06 for mouse gut data between 10 and 25 Gy, and 0.96 0.07 and 0.71 0.06 for mammalian skin-reaction data between 10 and 25 Gy and >25 Gy, respectively. Conclusions: The magnitude of normal tissue sparing by FLASH increases with dose and is dependent on the irradiated tissue. A piecewise linear function can parameterize currently available individual data series. (c) 2022 Elsevier Inc. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Calvo, Felipe A. AU - Ayestaran, Adriana AU - Serrano, Javier AU - Cambeiro, Mauricio AU - Palma, Jacobo AU - Meirino, Rosa AU - Morcillo, Miguel A. AU - Lapuente, Fernando AU - Chiva, Luis AU - Aguilar, Borja AU - Azcona, Diego AU - Pedrero, Diego AU - Pascau, Javier AU - Delgado, Jose Miguel AU - Aristu, Javier AU - Prezado, Yolanda TI - Practice-oriented solutions integrating intraoperative electron irradiation and personalized proton therapy for recurrent or unresectable cancers: Proof of concept and potential for dual FLASH effect JF - FRONTIERS IN ONCOLOGY J2 - FRONT ONCOL VL - 12 PY - 2022 PG - 15 SN - 2234-943X DO - 10.3389/fonc.2022.1037262 UR - https://m2.mtmt.hu/api/publication/33423748 ID - 33423748 N1 - Department of Radiation Oncology, Clinica Universidad de Navarra, Madrid, Spain Medical Applications Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain Department of Surgery, Clinica Universidad de Navarra, Madrid, Spain Department of Gynecology and Obstretics, Clinica Universidad de Navarra, Madrid, Spain Department of Medical Physics, Clinica Universidad de Navarra, Madrid, Spain Department of Bioengineering and Aerospace Engineering, Universidad Carlos III de Madrid, Madrid, Spain Translational Research Department, Institut Curie, Université PSL, CNRS UMR, Inserm, Signalisation, Radiobiologie et Cancer, Orsay, France Université Paris-Saclay, CNRS UMR, Inserm, Signalisation, Radiobiologie et Cancer, Orsay, France Export Date: 11 May 2023 Correspondence Address: Calvo, F.A.; Department of Radiation Oncology, Spain; email: fcalvom@unav.es Chemicals/CAS: bevacizumab, 216974-75-3, 1438851-35-4; doxorubicin, 23214-92-8, 25316-40-9; ifosfamide, 3778-73-2; irinotecan, 100286-90-6, 97682-44-5 Funding details: European Commission, EC Funding details: Federación Española de Enfermedades Raras, FEDER, PID 2019-104558RB-100 Funding details: Instituto de Salud Carlos III, ISCIII, AC20/00102, AC20/00123 Funding details: Ministerio de Ciencia e Innovación, MICINN Funding text 1: This research was supported through the project PerPlanRT by Instituto de Salud Carlos III (ISCIII) (AC20/00123 and AC20/00102), FCAECC, and co-funded by the European Union, FEDER funds under the ERA PerMed ERA-NET Program, and the project PID 2019-104558RB-100 by Ministry of Science and Innovation. AB - Background: Oligo-recurrent disease has a consolidated evidence of long-term surviving patients due to the use of intense local cancer therapy. The latter combines real-time surgical exploration/resection with high-energy electron beam single dose of irradiation. This results in a very precise radiation dose deposit, which is an essential element of contemporary multidisciplinary individualized oncology. Methods: Patient candidates to proton therapy were evaluated in Multidisciplinary Tumor Board to consider improved treatment options based on the institutional resources and expertise. Proton therapy was delivered by a synchrotron-based pencil beam scanning technology with energy levels from 70.2 to 228.7 MeV, whereas intraoperative electrons were generated in a miniaturized linear accelerator with dose rates ranging from 22 to 36 Gy/min (at Dmax) and energies from 6 to 12 MeV. Results: In a period of 24 months, 327 patients were treated with proton therapy: 218 were adults, 97 had recurrent cancer, and 54 required re-irradiation. The specific radiation modalities selected in five cases included an integral strategy to optimize the local disease management by the combination of surgery, intraoperative electron boost, and external pencil beam proton therapy as components of the radiotherapy management. Recurrent cancer was present in four cases (cervix, sarcoma, melanoma, and rectum), and one patient had a primary unresectable locally advanced pancreatic adenocarcinoma. In re-irradiated patients (cervix and rectum), a tentative radical total dose was achieved by integrating beams of electrons (ranging from 10- to 20-Gy single dose) and protons (30 to 54-Gy Relative Biological Effectiveness (RBE), in 10-25 fractions). Conclusions: Individual case solution strategies combining intraoperative electron radiation therapy and proton therapy for patients with oligo-recurrent or unresectable localized cancer are feasible. The potential of this combination can be clinically explored with electron and proton FLASH beams. LA - English DB - MTMT ER - TY - JOUR AU - Diffenderfer, E.S. AU - Sørensen, B.S. AU - Mazal, A. AU - Carlson, D.J. TI - The current status of preclinical proton FLASH radiation and future directions JF - MEDICAL PHYSICS J2 - MED PHYS VL - 49 PY - 2022 IS - 3 SP - 2039 EP - 2054 PG - 16 SN - 0094-2405 DO - 10.1002/mp.15276 UR - https://m2.mtmt.hu/api/publication/32672622 ID - 32672622 N1 - Cited By :2 Export Date: 14 February 2022 CODEN: MPHYA Correspondence Address: Diffenderfer, E.S.; Department of Radiation Oncology, United States; email: Eric.Diffenderfer@pennmedicine.upenn.edu LA - English DB - MTMT ER - TY - JOUR AU - El Khatib, Mirna AU - van Slyke, Alexander L. AU - Velalopoulou, Anastasia AU - Kim, Michele M. AU - Shoniyozov, Khayrullo AU - Allu, Srinivasa Rao AU - Diffenderfer, Eric E. AU - Busch, Theresa M. AU - Wiersma, Rodney D. AU - Koch, Cameron J. AU - Vinogradov, Sergei A. TI - Ultrafast Tracking of Oxygen Dynamics During Proton FLASH JF - INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS J2 - INT J RADIAT ONCOL VL - 113 PY - 2022 IS - 3 SP - 624 EP - 634 PG - 11 SN - 0360-3016 DO - 10.1016/j.ijrobp.2022.03.016 UR - https://m2.mtmt.hu/api/publication/33423772 ID - 33423772 N1 - Department of Biochemistry and Biophysics, Perelman School of Medicine Department of Chemistry, School of Arts and Sciences Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania Cited By :6 Export Date: 11 May 2023 CODEN: IOBPD Correspondence Address: Vinogradov, S.A.; Department of Biochemistry and Biophysics, email: vinograd.upenn@gmail.com Chemicals/CAS: oxygen, 7782-44-7; phosphate, 14066-19-4, 14265-44-2; proton, 12408-02-5, 12586-59-3; Oxygen; Protons Funding details: National Institutes of Health, NIH Funding details: Perelman School of Medicine, University of Pennsylvania Funding text 1: Support of the grants HL145092 (M.E.K.), EB027397, and EB028941 (S.A.V.) from the National Institutes of Health and developmental funds from the Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, is gratefully acknowledged. AB - Purpose: Radiation therapy delivered at ultrafast dose rates, known as FLASH RT, has been shown to provide a therapeutic advantage compared with conventional radiation therapy by selectively protecting normal tissues. Radiochemical depletion of oxygen has been proposed to underpin the FLASH effect; however, experimental validation of this hypothesis has been lacking, in part owing to the inability to measure oxygenation at rates compatible with FLASH.Methods and Materials: We present a new variant of the phosphorescence quenching method for tracking oxygen dynamics with rates reaching up to similar to 3.3 kHz. Using soluble Oxyphor probes we were able to resolve, both in vitro and in vivo, oxygen dynamics during the time of delivery of proton FLASH.Results: In vitro in solutions containing bovine serum albumin the O-2 depletion g values (moles/L of O-2 depleted per radiation dose, eg, mu M/Gy) are higher for conventional irradiation (by similar to 13% at 75 mM [O-2]) than for FLASH, and in the low-oxygen region (<25 mu M [O-2]) they decrease with oxygen concentration. In vivo, depletion of oxygen by a single FLASH is insufficient to achieve severe hypoxia in initially well-oxygenated tissue, and the g values measured appear to correlate with baseline oxygen levels.Conclusions: The developed method should be instrumental in radiobiological studies, such as studies aimed at unraveling the mechanism of the FLASH effect. The FLASH effect could in part originate from the difference in the oxygen dependencies of the oxygen consumption g values for conventional versus FLASH RT. (C) 2022 Elsevier Inc. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Esplen, Nolan AU - Egoriti, Luca AU - Paley, Bill AU - Planche, Thomas AU - Hoehr, Cornelia AU - Gottberg, Alexander AU - Bazalova-Carter, Magdalena TI - Design optimization of an electron-to-photon conversion target for ultra-high dose rate x-ray (FLASH) experiments at TRIUMF JF - PHYSICS IN MEDICINE AND BIOLOGY J2 - PHYS MED BIOL VL - 67 PY - 2022 IS - 10 PG - 24 SN - 0031-9155 DO - 10.1088/1361-6560/ac5ed6 UR - https://m2.mtmt.hu/api/publication/33423779 ID - 33423779 N1 - Department of Physics and Astronomy, University of Victoria, Victoria, BC, Canada Department of Chemistry, University of British Columbia, Vancouver, BC, Canada TRIUMF, Vancouver, BC, Canada Cited By :3 Export Date: 11 May 2023 CODEN: PHMBA Correspondence Address: Esplen, N.; Department of Physics and Astronomy, Canada; email: nolane@uvic.ca Chemicals/CAS: aluminum, 7429-90-5; tantalum, 7440-25-7; water, 7732-18-5; Aluminum; Tantalum; Water Funding details: Natural Sciences and Engineering Research Council of Canada, NSERC Funding details: Canada Research Chairs Funding text 1: The authors would like to acknowledge the TRIUMF lab for supporting this developmental work and for provision of its technical and scientific resources, including trained personnel and facilities. In particular, the authors thank Doug Preddy for offering his consistent technical support and expertise to the project. We also thank Chris Secord, Mike Wicken and the TRIUMF machine shop for their practical inputs and target fabrication, Jericho O’Connell of the UVic XCITE lab for work on the motion stage apparatus, and the UVic Center for Advanced Materials and Related Technology (CAMTEC). This work was funded in part by NFRF (NFRFE-2018-00102) and NSERC Discovery grants as well as the Canada Research Chairs program. AB - Objective. To develop a bremsstrahlung target and megavoltage (MV) x-ray irradiation platform for ultrahigh dose-rate (UHDR) irradiation of small-animals on the Advanced Rare Isotope Laboratory (ARIEL) electron linac (e-linac) at TRIUMF. Approach. An electron-to-photon converter design for UHDR radiotherapy (RT) was centered around optimization of a tantalum-aluminum (Ta-Al) explosion-bonded target. Energy deposition within a homogeneous water-phantom and the target itself were evaluated using EGSnrc and FLUKA MC codes, respectively, for various target thicknesses (0.5-1.5 mm), beam energies (Ee- = 8, 10 MeV) and electron (Gaussian) beam sizes (2 sigma = 2-10 mm). Depth dose-rates in a 3D-printed mouse phantom were also calculated to infer the compatibility of the 10 MV dose distributions for FLASH-RT in small-animal models. Coupled thermo-mechanical FEA simulations in ANSYS were subsequently used to inform the stress-strain conditions and fatigue life of the target assembly. Main results. Dose-rates of up to 128 Gy s(-1) at the phantom surface, or 85 Gy s(-1) at 1 cm depth, were obtained for a 1 x 1 cm(2) field size, 1 mm thick Ta target and 7.5 cm source-to-surface distance using the FLASH-mode beam (Ee- = 10 MeV, 2 sigma = 5 mm, P = 1 kW); furthermore, removal of the collimation assembly and using a shorter (3.5 cm) SSD afforded doserates >600 Gy s(-1), albeit at the expense of field conformality. Target temperatures were maintained below the tantalum, aluminum and cooling-water thresholds of 2000 degrees C, 300 degrees C and 100 degrees C, respectively, while the aluminum strain behavior remained everywhere elastic and helped ensure the converter survives its prescribed 5 yr operational lifetime. Significance. Effective design iteration, target cooling and failure mitigation have culminated in a robust target compatible with intensive transient (FLASH) and steady-state (diagnostic) applications. The ARIEL UHDR photon source will facilitate FLASH-RT experiments concerned with sub-second, pulsed or continuous beam irradiations at dose rates in excess of 40 Gy s(-1). LA - English DB - MTMT ER - TY - JOUR AU - Gao, F. AU - Yang, Y. AU - Zhu, H. AU - Wang, J. AU - Xiao, D. AU - Zhou, Z. AU - Dai, T. AU - Zhang, Y. AU - Feng, G. AU - Li, J. AU - Lin, B. AU - Xie, G. AU - Ke, Q. AU - Zhou, K. AU - Li, P. AU - Shen, X. AU - Wang, H. AU - Yan, L. AU - Lao, C. AU - Shan, L. AU - Li, M. AU - Lu, Y. AU - Chen, M. AU - Feng, S. AU - Zhao, J. AU - Wu, D. AU - Du, X. TI - First demonstration of the FLASH effect with ultrahigh dose rate high-energy X-rays JF - RADIOTHERAPY AND ONCOLOGY J2 - RADIOTHER ONCOL VL - 166 PY - 2022 SP - 44 EP - 50 PG - 7 SN - 0167-8140 DO - 10.1016/j.radonc.2021.11.004 UR - https://m2.mtmt.hu/api/publication/32672606 ID - 32672606 N1 - Departmant of Oncology, Nuclear Medicine Laboratory of Mianyang Central Hospital, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang, China Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China Institute of Applied Electronics, China Academy of Engineering Physics, Mianyang, China Department of Pathology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China School of Nuclear Science and Technology, University of South China, Hengyang, China Export Date: 14 February 2022 CODEN: RAOND Correspondence Address: Wu, D.; Institute of Applied Electronics, China; email: wudai04@caep.cn LA - English DB - MTMT ER - TY - JOUR AU - Gao, Yuan AU - Liu, Ruirui AU - Chang, Chih-Wei AU - Charyyev, Serdar AU - Zhou, Jun AU - Bradley, Jeffrey D. AU - Liu, Tian AU - Yang, Xiaofeng TI - A potential revolution in cancer treatment: A topical review of FLASH radiotherapy JF - JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS J2 - J APPL CLIN MED PHYS VL - 23 PY - 2022 IS - 10 PG - 21 SN - 1526-9914 DO - 10.1002/acm2.13790 UR - https://m2.mtmt.hu/api/publication/33423764 ID - 33423764 N1 - Cited By :5 Export Date: 11 May 2023 Correspondence Address: Yang, X.; Department of Radiation Oncology and Winship Cancer Institute, United States; email: xiaofeng.yang@emory.edu Chemicals/CAS: oxygen, 7782-44-7; Oxygen Funding details: National Institutes of Health, NIH, R01CA215718 Funding details: National Cancer Institute, NCI Funding text 1: This research is supported in part by the National Cancer Institute of the National Institutes of Health under Award Number R01CA215718. AB - FLASH radiotherapy (RT) is a novel technique in which the ultrahigh dose rate (UHDR) (>= 40 Gy/s) is delivered to the entire treatment volume. Recent outcomes of in vivo studies show that the UHDR RT has the potential to spare normal tissue without sacrificing tumor control. There is a growing interest in the application of FLASH RT, and the ultrahigh dose irradiation delivery has been achieved by a few experimental and modified linear accelerators. The underlying mechanism of FLASH effect is yet to be fully understood, but the oxygen depletion in normal tissue providing extra protection during FLASH irradiation is a hypothesis that attracts most attention currently. Monte Carlo simulation is playing an important role in FLASH, enabling the understanding of its dosimetry calculations and hardware design. More advanced Monte Carlo simulation tools are under development to fulfill the challenge of reproducing the radiolysis and radiobiology processes in FLASH irradiation. FLASH RT may become one of standard treatment modalities for tumor treatment in the future. This paper presents the history and status of FLASH RT studies with a focus on FLASH irradiation delivery modalities, underlying mechanism of FLASH effect, in vivo and vitro experiments, and simulation studies. Existing challenges and prospects of this novel technique are discussed in this manuscript. LA - English DB - MTMT ER - TY - JOUR AU - Goff, Kevin M. AU - Zheng, Chuqi AU - Alonso-Basanta, Michelle TI - Proton radiotherapy for glioma and glioblastoma JF - CHINESE CLINICAL ONCOLOGY J2 - CHIN CLIN ONCOL VL - 11 PY - 2022 IS - 6 PG - 10 SN - 2304-3865 DO - 10.21037/cco-22-92 UR - https://m2.mtmt.hu/api/publication/33810000 ID - 33810000 N1 - Medical Scientist Training Program (MSTP), The University of Pennsylvania Perelman, School of Medicine, Philadelphia, PA, United States Department of Radiation Oncology, The University of Pennsylvania Perelman, School of Medicine, Philadelphia, PA, United States Cited By :1 Export Date: 11 May 2023 Correspondence Address: Alonso-Basanta, M.; Perelman Center for Advanced Medicine, 3400 Civic Center Boulevard, United States; email: michelle.alonso-basanta@pennmedicine.upenn.edu Chemicals/CAS: proton, 12408-02-5, 12586-59-3; Protons Funding text 1: We would like to acknowledge Dr. Robert A. Lustig for his meaningful review of the manuscript. AB - Radiotherapy (RT) continues to be an important component of treatment of glioma, particularly high-grade glioma and glioblastoma multiforme (GBM). GBM is one of the most aggressive central nervous system (CNS) tumors, with high rates of recurrence and very low rates of long-term survival. However, outcomes in these patients are improving with modern genetic profiling and multimodal therapy, which leads to more consideration for the risk for toxicities associated with traditional photon-based RT. Proton therapy (PT) is an increasingly available method to reduce off-target irradiation in CNS tumors due to the intrinsic properties of heavy-particle irradiation. Here, we review currently available data examining the used of PT in glioma patients, including dose escalation for GBM, re-irradiation (reRT) of recurrent glioma, and the potential cognitive sparing effects of conventional dose PT. We discuss the incorporation of PT into the multimodal therapy of GBM patients, and how the aggressive nature of the disease poses a unique challenge to PT study design. We also describe how PT may provide the most feasible method for implementing high rate 'FLASH' RT and the implications for glioma patients. We conclude with a discussion of ongoing clinical trials, the necessity of continued research, and how we interpret and incorporate available data into our current practice. LA - English DB - MTMT ER - TY - CHAP AU - Grilj, V. AU - Vozenin, M.-C. TI - The biology of FLASH-a critical appraisal for clinical translation T2 - Spatially Fractionated, Microbeam and Flash Radiation Therapy: Physics and Multidisciplinary Approach PB - Institute of Physics Publishing SN - 9780750340441 T3 - Spatially Fractionated, Microbeam and Flash Radiat. Therapy: Phys. and Multidiscip. Approach PY - 2022 SP - 4.1 EP - 4.20 DO - 10.1088/978-0-7503-4046-5ch4 UR - https://m2.mtmt.hu/api/publication/34327448 ID - 34327448 N1 - Export Date: 14 November 2023 Correspondence Address: Grilj, V.; Institute of Radiation Physics/Department of Radiology/CHUV, Switzerland AB - Grilj and Vozenin critically appraise the technological basis, experimental data and emerging clinical investigations of FLASH therapy in chapter 4. © IOP Publishing Ltd 2023. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Habraken, Steven AU - Breedveld, Sebastiaan AU - Groen, Jort AU - Nuyttens, Joost AU - Hoogeman, Mischa TI - Trade-off in healthy tissue sparing of FLASH and fractionation in stereotactic proton therapy of lung lesions with transmission beams JF - RADIOTHERAPY AND ONCOLOGY J2 - RADIOTHER ONCOL VL - 175 PY - 2022 SP - 231 EP - 237 PG - 7 SN - 0167-8140 DO - 10.1016/j.radonc.2022.08.015 UR - https://m2.mtmt.hu/api/publication/33423754 ID - 33423754 N1 - Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, Netherlands Holland Proton Therapy Center, Department of Medical Physics & Informatics, Delft, Netherlands Holland Proton Therapy Center, Department Radiation Oncology, Delft, Netherlands Cited By :2 Export Date: 11 May 2023 CODEN: RAOND Correspondence Address: Habraken, S.; Erasmus University Medical Center, Postbus 2040, Netherlands; email: s.habraken@erasmusmc.nl Chemicals/CAS: proton, 12408-02-5, 12586-59-3; Protons Funding details: Elekta Funding details: Accuray Funding details: KWF Kankerbestrijding, DCS Funding text 1: The department of radiotherapy of the Erasmus MC Cancer Institute received a research grant from the Dutch cancer society and has research collaborations with Elekta AB, Stockholm, Sweden and Accuray Inc., Sunnyvale, USA. HollandPTC has a research collaboration with Varian, Palo Alto, USA. AB - Purpose and objective: Besides a dose-rate threshold of 40-100 Gy/s, the FLASH effect may require a dose > 3.5-7 Gy. Even in hypofractioned treatments, with all beams delivered in each fraction (ABEF), most healthy tissue is irradiated to a lower fraction dose. This can be circumvented by single-beamper-fraction (SBPF) delivery, with a loss of healthy tissue sparing by fractionation. We investigated the trade-off between FLASH and loss of fractionation in SBPF stereotactic proton therapy of lung cancer and determined break-even FLASH-enhancement ratios (FERs).Materials and Methods: Treatment plans for 12 patients were generated. GTV delineations were available and a 5 mm GTV-PTV margin was applied. Equiangular arrangements of 3, 5, 7, and 9 244 MeV proton transmission beams were used. To facilitate SBPF, the number of fractions was equal to the number of beams. Iso-effective fractionation schedules with a single field uniform dose prescription were used: D95%,PTV = 100%Dpres per beam. All plans were evaluated in terms of dose to lung and conformity of dose to target of FLASH-enhanced biologically equivalent dose (EQD2).Results: Compared to ABEF, SBPF resulted in a median increase of EQD2mean to healthy lung of 56%, 58%, 55% and 54% in plans with 3, 5, 7 and 9 fractions respectively and of 236%, 78%, 50% and 41% in V100% EQD2, quantifying conformity. This can be compensated for by FERs of at least 1.28, 1.32, 1.30 and 1.23 respectively for EQD2mean and 1.29, 1.18, 1.28 and 1.15 for V100%,EQD2.Conclusion: A FLASH effect outweighing the loss of fractionation in SBPF may be achieved in stereotactic lung treatments. The trade-off with fractionation depends on the conditions under which the FLASH effect occurs. Better understanding of the underlying biology and the impact of delivery conditions is needed.(c) 2022 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 175 (2022) 231-237 LA - English DB - MTMT ER - TY - JOUR AU - Hageman, Eline AU - Che, Pei-Pei AU - Dahele, Max AU - Slotman, Ben J. AU - Sminia, Peter TI - Radiobiological Aspects of FLASH Radiotherapy JF - BIOMOLECULES J2 - BIOMOLECULES VL - 12 PY - 2022 IS - 10 PG - 18 SN - 2218-273X DO - 10.3390/biom12101376 UR - https://m2.mtmt.hu/api/publication/33423760 ID - 33423760 N1 - Amsterdam UMC Location Vrije Universiteit Amsterdam, Radiation Oncology, Boelelaan 1117, Amsterdam, 1081 HV, Netherlands Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, 1081 HV, Netherlands Cited By :1 Export Date: 30 March 2023 Correspondence Address: Sminia, P.; Amsterdam UMC Location Vrije Universiteit Amsterdam, Boelelaan 1117, Netherlands; email: p.sminia@amsterdamumc.nl Funding details: Stichting Zabawas, #CCA 2019-5-55 Funding details: Cancer Center Amsterdam, CCA, 2006784 Funding text 1: This work was supported by the Zabawas Foundation (Grant #CCA 2019-5-55), Cancer Center Amsterdam (Project #2006784). AB - Radiotherapy (RT) is one of the primary treatment modalities for cancer patients. The clinical use of RT requires a balance to be struck between tumor effect and the risk of toxicity. Sparing normal tissue is the cornerstone of reducing toxicity. Advances in physical targeting and dose-shaping technology have helped to achieve this. FLASH RT is a promising, novel treatment technique that seeks to exploit a potential normal tissue-sparing effect of ultra-high dose rate irradiation. A significant body of in vitro and in vivo data has highlighted a decrease in acute and late radiation toxicities, while preserving the radiation effect in tumor cells. The underlying biological mechanisms of FLASH RT, however, remain unclear. Three main mechanisms have been hypothesized to account for this differential FLASH RT effect between the tumor and healthy tissue: the oxygen depletion, the DNA damage, and the immune-mediated hypothesis. These hypotheses and molecular mechanisms have been evaluated both in vitro and in vivo. Furthermore, the effect of ultra-high dose rate radiation with extremely short delivery times on the dynamic tumor microenvironment involving circulating blood cells and immune cells in humans is essentially unknown. Therefore, while there is great interest in FLASH RT as a means of targeting tumors with the promise of an increased therapeutic ratio, evidence of a generalized FLASH effect in humans and data to show that FLASH in humans is safe and at least effective against tumors as standard photon RT is currently lacking. FLASH RT needs further preclinical investigation and well-designed in-human studies before it can be introduced into clinical practice. LA - English DB - MTMT ER - TY - JOUR AU - Kacem, H. AU - Almeida, A. AU - Cherbuin, N. AU - Vozenin, M.-C. TI - Understanding the FLASH effect to unravel the potential of ultra-high dose rate irradiation JF - INTERNATIONAL JOURNAL OF RADIATION BIOLOGY J2 - INT J RADIAT BIOL VL - 98 PY - 2022 IS - 3 SP - 506 EP - 516 PG - 11 SN - 0955-3002 DO - 10.1080/09553002.2021.2004328 UR - https://m2.mtmt.hu/api/publication/32672620 ID - 32672620 N1 - Department of Oncology, Laboratory of Radiation Oncology, Radiation Oncology Service, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland Department of Medical Radiology, Institute of Radiation Physics, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland Export Date: 14 February 2022 CODEN: IJRBA Correspondence Address: Vozenin, M.-C.; Department of Oncology, Switzerland; email: marie-catherine.vozenin@chuv.ch LA - English DB - MTMT ER - TY - JOUR AU - Kacem, Houda AU - Psoroulas, Serena AU - Boivin, Gael AU - Folkerts, Michael AU - Grilj, Veljko AU - Lomax, Tony AU - Martinotti, Adrien AU - Meer, David AU - Ollivier, Jonathan AU - Petit, Benoit AU - Safai, Sairos AU - Sharma, Ricky A. AU - Togno, Michele AU - Vilalta, Marta AU - Weber, Damien C. AU - Vozenin, Marie -Catherine TI - Comparing radiolytic production of H2O2 and development of Zebrafish embryos after ultra high dose rate exposure with electron and transmission proton beams JF - RADIOTHERAPY AND ONCOLOGY J2 - RADIOTHER ONCOL VL - 175 PY - 2022 SP - 197 EP - 202 PG - 6 SN - 0167-8140 DO - 10.1016/j.radonc.2022.07.011 UR - https://m2.mtmt.hu/api/publication/33423759 ID - 33423759 N1 - Radiation Oncology Laboratory, Service of Radiation Oncology, Department of Oncology. Lausanne, University Hospital and University of Lausanne, Switzerland Paul Scherrer Institut-Centre for Proton Therapy, Villigen, Switzerland Varian, a Siemens Healthineers Company, 3120 Hansen Way, Palo Alto, CA 94304, United States Institute of Radiation Physics, University Hospital and University of Lausanne, Switzerland Cited By :5 Export Date: 11 May 2023 CODEN: RAOND Correspondence Address: Vozenin, M.-C.; Radiation Oncology Laboratory, Switzerland; email: marie-catherine.vozenin@chuv.ch Chemicals/CAS: hydrogen peroxide, 7722-84-1; proton, 12408-02-5, 12586-59-3; Hydrogen Peroxide; Protons Funding details: National Institutes of Health, NIH, PO1CA244091 Funding details: Université de Lausanne, UNIL Funding details: Centre Hospitalier Universitaire Vaudois, CHUV Funding text 1: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [The proton studies were funded by a research grant from Varian, a Healthineers company (Palo Alto, CA, USA) (to MCV, SP and TL).] Funding text 2: HK and electron studies were funded by MAGIC-FNS CRS II5_186369 (to MCV) and proton studies were funded by a research grant from Varian, a Healthineers company (Palo Alto, CA, USA) (to MCV, SP and TL), VG was funded by NIH program project grant PO1CA244091 (to MCV). We would like to thank Drs P Froidevaux and C Bailat for their critical contribution; Paula Barrera-Gomez and the PTZ from UNIL for ZF breading and well as Dr A Benechet from IVIF/UNIL/CHUV and Dr F Morgenthaler from CIF for help in imaging procedures. AB - The physico-chemical and biological response to conventional and UHDR electron and proton beams was investigated, along with conventional photons. The temporal structure and nature of the beam affected both, with electron beam at >= 1400 Gy/s and proton beam at 0.1 and 1260 Gy/s found to be isoefficient at sparing zebrafish embryos.(c) 2022 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 175 (2022) 197-202 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). LA - English DB - MTMT ER - TY - JOUR AU - Karsch, Leonhard AU - Pawelke, Jörg AU - Brand, Michael AU - Hans, Stefan AU - Hideghéty, Katalin AU - Jansen, Jeannette AU - Lessmann, Elisabeth AU - Löck, Steffen AU - Schürer, Michael AU - Schurig, Rico AU - Seco, Joao AU - Szabó, Emilia Rita AU - Beyreuther, Elke TI - Beam pulse structure and dose rate as determinants for the flash effect observed in zebrafish embryo JF - RADIOTHERAPY AND ONCOLOGY J2 - RADIOTHER ONCOL VL - 173 PY - 2022 SP - 49 EP - 54 PG - 6 SN - 0167-8140 DO - 10.1016/j.radonc.2022.05.025 UR - https://m2.mtmt.hu/api/publication/32868094 ID - 32868094 N1 - Helmholtz-Zentrum Dresden – Rossendorf (HZDR), Institute of Radiooncology - OncoRay, Germany OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden – Rossendorf, Germany Center for Regenerative Therapies TU Dresden (CRTD), Cluster of Excellence 'Physics of Life', Technische Universität Dresden, Germany ELI-ALPS, ELI-HU Non-Profit Ltd., Szeged, Hungary Oncotherapy Department, University of Szeged, Hungary Division of Biomedical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany Helmholtz-Zentrum Dresden – Rossendorf, Institute of Radiation Physics, Germany Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany National Center for Tumor Diseases Dresden (NCT/UCC), Germany, German Cancer Research Center (DKFZ), Heidelberg, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Helmholtz-Zentrum Dresden – Rossendorf, Dresden, Germany Faculty of Physics and Astronomy, Heidelberg University, Germany Cited By :10 Export Date: 14 March 2023 CODEN: RAOND Correspondence Address: Beyreuther, E.; OncoRay – National Center for Radiation Research in Oncology, Bautzner Landstraße 400, Germany; email: E.Beyreuther@hzdr.de Chemicals/CAS: proton, 12408-02-5, 12586-59-3; Protons Funding details: Horizon 2020 Framework Programme, H2020 Funding details: European Commission, EC Funding details: European Research Council, ERC Funding details: Deutsche Forschungsgemeinschaft, DFG, BR 1746/3, BR 1746/6 Funding details: Horizon 2020, 730983, 871124, GINOP-2.3.6-15-2015-00001 Funding details: European Regional Development Fund, ERDF Funding details: Helmholtz Association Funding text 1: This research was carried out at ELBE at the Helmholtz-Zentrum Dresden – Rossendorf e. V. a member of the Helmholtz Association. We would like to thank especially Pavel Evtushenko, Ulf Lehnert, Christoph Schneider and Peter Michel from the ELBE crew for support and their ongoing interest in our high-dose rate electron experiments. We thank Daniela Zöller for help with zebrafish embryo transfer and Marika Fischer, Sylvio Kunadt and Daniela Mögel from the animal facility for dedicated zebrafish care. Work by SH and MB is supported by project grants to MB of the German Research Foundation (Deutsche Forschungsgemeinschaft, project numbers BR 1746/3 and BR 1746/6), and an ERC advanced grant (Zf-BrainReg). The experimental part of the UPTD proton facility has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No.730983 (INSPIRE). We also thank the local IBA Team for supporting our proton Flash experiments. The ELI-ALPS project (GINOP-2.3.6-15-2015-00001) is supported by the European Union and co-financed by the European Regional Development Fund. KH and ERS has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no 871124 Laserlab-Europe. JJ was supported by grants of the German-Israeli Helmholtz Research School in Cancer Biology – Cancer Transitional and Research Exchange Program (Cancer-TRAX) and by the Weizmann-Helmholtz Laboratory for Laser Matter Interaction (WHELMI). Funding text 2: This research was carried out at ELBE at the Helmholtz-Zentrum Dresden – Rossendorf e. V., a member of the Helmholtz Association. We would like to thank especially Pavel Evtushenko, Ulf Lehnert, Christoph Schneider and Peter Michel from the ELBE crew for support and their ongoing interest in our high-dose rate electron experiments. We thank Daniela Zöller for help with zebrafish embryo transfer and Marika Fischer, Sylvio Kunadt and Daniela Mögel from the animal facility for dedicated zebrafish care. Work by SH and MB is supported by project grants to MB of the German Research Foundation (Deutsche Forschungsgemeinschaft, project numbers BR 1746/3 and BR 1746/6), and an ERC advanced grant (Zf-BrainReg). The experimental part of the UPTD proton facility has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No.730983 (INSPIRE). We also thank the local IBA Team for supporting our proton Flash experiments. The ELI-ALPS project (GINOP-2.3.6-15-2015-00001) is supported by the European Union and co-financed by the European Regional Development Fund. KH and ERS has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no 871124 Laserlab-Europe. JJ was supported by grants of the German-Israeli Helmholtz Research School in Cancer Biology – Cancer Transitional and Research Exchange Program (Cancer-TRAX) and by the Weizmann-Helmholtz Laboratory for Laser Matter Interaction (WHELMI). LA - English DB - MTMT ER - TY - JOUR AU - Kim, Michele M. AU - Darafsheh, Arash AU - Schuemann, Jan AU - Dokic, Ivana AU - Lundh, Olle AU - Zhao, Tianyu AU - Ramos-Mendez, Jose AU - Dong, Lei AU - Petersson, Kristoffer TI - Development of Ultra-High Dose-Rate (FLASH) Particle Therapy JF - IEEE TRANSACTIONS ON RADIATION AND PLASMA MEDICAL SCIENCES J2 - IEEE T RADIAT PLASMA VL - 6 PY - 2022 IS - 3 SP - 252 EP - 262 PG - 11 SN - 2469-7311 DO - 10.1109/TRPMS.2021.3091406 UR - https://m2.mtmt.hu/api/publication/33423789 ID - 33423789 N1 - Cited By :11 Export Date: 11 May 2023 Correspondence Address: Kim, M.M.; Department of Radiation Oncology, United States; email: michele.kim@pennmedicine.upenn.edu AB - Research efforts in FLASH radiotherapy (FLASH-RT) have increased at an accelerated pace recently. FLASH-RT involves ultra-high dose rates and has been shown to reduce toxicity to normal tissue while maintaining tumor response in preclinical studies when compared to conventional dose rate radiotherapy. The goal of this review is to summarize the studies performed to date with proton, electron, and heavy-ion FLASH-RT, with particular emphasis on the physical aspects of each study and the advantages and disadvantages of each modality. Beam delivery parameters, experimental setup, and the dosimetry tools used are described for each FLASH modality. In addition, modeling efforts and treatment planning for FLASH-RT are discussed along with potential drawbacks when translated into the clinical setting. The final section concludes with further questions that have yet to be answered before safe clinical implementation of FLASH-RT. LA - English DB - MTMT ER - TY - JOUR AU - Krieger, M. AU - van, de Water S. AU - Folkerts, M.M. AU - Mazal, A. AU - Fabiano, S. AU - Bizzocchi, N. AU - Weber, D.C. AU - Safai, S. AU - Lomax, A.J. TI - A quantitative FLASH effectiveness model to reveal potentials and pitfalls of high dose rate proton therapy JF - MEDICAL PHYSICS J2 - MED PHYS VL - 49 PY - 2022 IS - 3 SP - 2026 EP - 2038 PG - 13 SN - 0094-2405 DO - 10.1002/mp.15459 UR - https://m2.mtmt.hu/api/publication/32672604 ID - 32672604 N1 - Varian Medical Systems Particle Therapy GmbH & Co. KG, Troisdorf, Germany Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland Varian Medical Systems, Inc., Palo Alto, CA, United States Centro de Protonterapia Quironsalud, Madrid, Spain Department of Physics, ETH Zurich, Zurich, Switzerland Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland Export Date: 14 February 2022 CODEN: MPHYA Correspondence Address: Krieger, M.; Varian Medical Systems Particle Therapy GmbH & Co. KGGermany; email: Miriam.krieger@psi.ch LA - English DB - MTMT ER - TY - JOUR AU - Kroll, Florian AU - Brack, Florian-Emanuel AU - Bernert, Constantin AU - Bock, Stefan AU - Bodenstein, Elisabeth AU - Bruechner, Kerstin AU - Cowan, Thomas E. AU - Gaus, Lennart AU - Gebhardt, Rene AU - Helbig, Uwe AU - Karsch, Leonhard AU - Kluge, Thomas AU - Kraft, Stephan AU - Krause, Mechthild AU - Lessmann, Elisabeth AU - Masood, Umar AU - Meister, Sebastian AU - Metzkes-Ng, Josefine AU - Nossula, Alexej AU - Pawelke, Joerg AU - Pietzsch, Jens AU - Pueschel, Thomas AU - Reimold, Marvin AU - Rehwald, Martin AU - Richter, Christian AU - Schlenvoigt, Hans-Peter AU - Schramm, Ulrich AU - Umlandt, Marvin E. P. AU - Ziegler, Tim AU - Zeil, Karl AU - Beyreuther, Elke TI - Tumour irradiation in mice with a laser-accelerated proton beam JF - NATURE PHYSICS J2 - NAT PHYS VL - 18 PY - 2022 IS - 3 SP - 316 EP - + PG - 10 SN - 1745-2473 DO - 10.1038/s41567-022-01520-3 UR - https://m2.mtmt.hu/api/publication/33361716 ID - 33361716 N1 - Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany Technische Universität Dresden, Dresden, Germany OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany German Cancer Consortium (DKTK), Partner Site Dresden, Dresden, Germany National Center for Tumor Diseases (NCT), Partner Site Dresden: German Cancer Research Center (DKFZ), Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany, Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany Department for Radiotherapy and Radiooncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany Cited By :24 Export Date: 13 March 2023 Correspondence Address: Kroll, F.; Helmholtz-Zentrum Dresden-RossendorfGermany; email: florian.kroll@hzdr.de Funding details: Horizon 2020 Framework Programme, H2020, 730983 Funding details: Laserlab-Europe, 871124 Funding text 1: We thank T. Hermannsdörfer, S. Zherlitsyn and the workshop of the Dresden High Magnetic Field Laboratory for advice and magnet manufacturing. We acknowledge M. Pfeifer of the Institut of Forensic Medicine (TU Dresden) and W. Eicheler of OncoRay for verification of the tumour model and thank the animal husbandry staff at OncoRay and HZDR. We recognize the support of the Weizmann-Helmholtz Laboratory for Laser Matter Interaction (WHELMI). We are very grateful for the long-lasting support of R. Sauerbrey and W. Enghardt. The work was supported by Laserlab Europe V (PRISES, contract no. 871124). The research infrastructure at the University Proton Therapy Dresden (UPTD) has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement no. 730983 (INSPIRE). Funding text 2: We thank T. Hermannsdörfer, S. Zherlitsyn and the workshop of the Dresden High Magnetic Field Laboratory for advice and magnet manufacturing. We acknowledge M. Pfeifer of the Institut of Forensic Medicine (TU Dresden) and W. Eicheler of OncoRay for verification of the tumour model and thank the animal husbandry staff at OncoRay and HZDR. We recognize the support of the Weizmann-Helmholtz Laboratory for Laser Matter Interaction (WHELMI). We are very grateful for the long-lasting support of R. Sauerbrey and W. Enghardt. The work was supported by Laserlab Europe V (PRISES, contract no. 871124). The research infrastructure at the University Proton Therapy Dresden (UPTD) has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement no. 730983 (INSPIRE). AB - Recent oncological studies identified beneficial properties of radiation applied at ultrahigh dose rates, several orders of magnitude higher than the clinical standard of the order of Gy min(-1). Sources capable of providing these ultrahigh dose rates are under investigation. Here we show that a stable, compact laser-driven proton source with energies greater than 60 MeV enables radiobiological in vivo studies. We performed a pilot irradiation study on human tumours in a mouse model, showing the concerted preparation of mice and laser accelerator, dose-controlled, tumour-conform irradiation using a laser-driven as well as a clinical reference proton source, and the radiobiological evaluation of irradiated and unirradiated mice for radiation-induced tumour growth delay. The prescribed homogeneous dose of 4 Gy was precisely delivered at the laser-driven source. The results demonstrate a complete laser-driven proton research platform for diverse user-specific small animal models, able to deliver tunable single-shot doses up to around 20 Gy to millimetre-scale volumes on nanosecond timescales, equivalent to around 10(9) Gy s(-1), spatially homogenized and tailored to the sample. The platform provides a unique infrastructure for translational research with protons at ultrahigh dose rates.A laser-plasma accelerator provides proton beams for the precise irradiation of human tumours in a mouse model. This work advances translational research with ultrahigh proton dose rates at laser-driven sources. LA - English DB - MTMT ER - TY - JOUR AU - Kusumoto, Tamon AU - Inaniwa, Taku AU - Mizushima, Kota AU - Sato, Shinji AU - Hojo, Satoru AU - Kitamura, Hisashi AU - Konishi, Teruaki AU - Kodaira, Satoshi TI - Radiation Chemical Yields of 7-Hydroxy-Coumarin-3-Carboxylic Acid for Proton- and Carbon-Ion Beams at Ultra-High Dose Rates: Potential Roles in FLASH Effects JF - RADIATION RESEARCH J2 - RADIAT RES VL - 198 PY - 2022 IS - 3 SP - 255 EP - 262 PG - 8 SN - 0033-7587 DO - 10.1667/RADE-21-00.230.1 UR - https://m2.mtmt.hu/api/publication/33423768 ID - 33423768 N1 - Cited By :4 Export Date: 11 May 2023 CODEN: RAREA Correspondence Address: Kodaira, S.; National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Japan; email: kodaira.satoshi@qst.go.jp Chemicals/CAS: carbon, 7440-44-0; proton, 12408-02-5, 12586-59-3; oxygen, 7782-44-7; Carbon; coumarin-3-carboxylic acid; Coumarins; Ions; Oxygen; Protons Funding details: Japan Society for the Promotion of Science, KAKEN, 21H02874 Funding text 1: The authors express our thanks to the NIRS-Cyclotron and HIMAC crews for providing excellent beams. This work was supported by JSPS KAKENHI grant 21H02874. AB - It has been observed that healthy tissues are spared at ultra-high dose rate (UHDR:.40 Gy/s), so called FLASH effect. To elucidate the mechanism of FLASH effect, we evaluate changes in radiation chemical yield (G value) of 7-hydroxy-coumarin-3-carboxylic acid (7OH-C3CA), which is formed by the reaction of hydroxyl radicals with coumarin-3- carboxylic acid (C3CA), under carbon ions (140 MeV/u) and protons (27.5 and 55 MeV) in a wide-dose-rate range up to 100 Gy/s. The relative G value, which is the G value at each dose rate normalized by that at the conventional dose (CONV: 0.1 Gy/s.), 140 MeV/u carbon-ion beam is almost equivalent to 27.5 and 55 MeV proton beams. This finding implies that UHDR irradiations using carbon-ion beams have a potential to spare healthy tissues. Furthermore, we evaluate the G value of 7OH-C3CA under the de-oxygenated condition to investigate roles of oxygen to the generation of 7OH-C3CA effect. The G value of 7OH-C3CA under the deoxygenated condition is lower than that under the oxygenated condition. The G value of 7OH-C3CA under the deoxygenated condition is higher than those under UHDR irradiations. By direct measurements of the oxygen concentration during 55 MeV proton irradiations, the oxygen concentration drops by 0.1%/Gy, which is independent of the dose rate. When the oxygen concentration directly affects to yields of 7OH-C3CA, the rate of decrease in the oxygen concentration may be correlated with that of decrease in the G value of 7OH-C3CA. However, the reduction rate of G value under UHDR is significantly higher than the oxygen consumption. This finding implied that the influence of the reaction between water radiolysis species formed by neighborhood tracks could be strongly related to the mechanisms of UHDR effect. (C) 2022 by Radiation Research Society LA - English DB - MTMT ER - TY - JOUR AU - Li, L. AU - Yuan, Y. AU - Zuo, Y. TI - A review of the impact of FLASH radiotherapy on the central nervous system and glioma JF - RADIATION MEDICINE AND PROTECTION J2 - RADIAT MED PROT VL - 3 PY - 2022 IS - 4 SP - 208 EP - 212 PG - 5 SN - 2097-0439 DO - 10.1016/j.radmp.2022.10.002 UR - https://m2.mtmt.hu/api/publication/33810139 ID - 33810139 N1 - Export Date: 11 May 2023 Correspondence Address: Zuo, Y.; China Institute for Radiation ProtectionChina; email: yahuiz@163.com Funding details: 20210302124283 Funding text 1: This work was funded by the Shanxi Provincial Youth Research Fund (No. 20210302124283 ), China. AB - Glioma has received considerable attention because of its potential of inducing high rates of morbidity, disability, and mortality. FLASH radiotherapy (FLASH-RT) has emerged as a popular topic in current research because of its ability to protect normal tissues. The present review summarized the current development of FLASH-RT in both the central nervous system and glioblastomas, explored the potential mechanisms underlying FLASH-RT-mediated protective effects on the central nervous system, and revealed the advantages of this new technique for glioma therapy. This study highlights the benefits and challenges of the present research and provides a reference for future research. © 2022 Chinese Medical Association LA - English DB - MTMT ER - TY - JOUR AU - Lv, Yinghao AU - Lv, Yue AU - Wang, Zhen AU - Lan, Tian AU - Feng, Xuping AU - Chen, Hao AU - Zhu, Jiang AU - Ma, Xiao AU - Du, Jinpeng AU - Hou, Guimin AU - Liao, Wenwei AU - Yuan, Kefei AU - Wu, Hong TI - FLASH radiotherapy: A promising new method for radiotherapy JF - ONCOLOGY LETTERS J2 - ONCOL LETT VL - 24 PY - 2022 IS - 6 PG - 14 SN - 1792-1074 DO - 10.3892/ol.2022.13539 UR - https://m2.mtmt.hu/api/publication/33423762 ID - 33423762 N1 - Department of Liver Surgery and Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, Collaborative Innovation Center of Biotherapy, West China Hospital, China Laboratory of Liver Surgery, West China Hospital, Sichuan University, Sichuan, Chengdu, 610000, China Cited By :1 Export Date: 11 May 2023 Correspondence Address: Kefei, Y.; Department of Liver Surgery and Liver Transplantation, 1 Keyuan 4th Road, Gaopeng Avenue, Sichuan, China; email: ykf13@163.com Correspondence Address: Hong, W.; Department of Liver Surgery and Liver Transplantation, 1 Keyuan 4th Road, Gaopeng Avenue, Sichuan, China; email: wuhong@scu.edu.cn Funding details: Key Technologies Research and Development Program, 2018YFC1106800 Funding text 1: This work was supported by grants from the National Key Technologies R&D Program (grant no. 2018YFC1106800). AB - Among the treatments for malignant tumors, radiotherapy is of great significance both as a main treatment and as an adjuvant treatment. Radiation therapy damages cancer cells with ionizing radiation, leading to their death. However, radiation-induced toxicity limits the dose delivered to the tumor, thereby constraining the control effect of radiotherapy on tumor growth. In addition, the delayed toxicity caused by radiotherapy significantly harms the physical and mental health of patients. FLASH-RT, an emerging class of radiotherapy, causes a phenomenon known as the 'FLASH effect', which delivers radiotherapy at an ultra-high dose rate with lower toxicity to normal tissue than conventional radiotherapy to achieve local tumor control. Although its mechanism remains to be fully elucidated, this modality constitutes a potential new approach to treating malignant tumors. In the present review, the current research progress of FLASH-RT and its various particular effects are described, including the status of research on FLASH-RT and its influencing factors. The hypothetic mechanism of action of FLASH-RT is also summarized, providing insight into future tumor treatments. LA - English DB - MTMT ER - TY - JOUR AU - Matuszak, Natalia AU - Suchorska, Wiktoria Maria AU - Milecki, Piotr AU - Kruszyna-Mochalska, Marta AU - Misiarz, Agnieszka AU - Pracz, Jacek AU - Malicki, Julian TI - FLASH radiotherapy: an emerging approach in radiation therapy JF - REPORTS OF PRACTICAL ONCOLOGY AND RADIOTHERAPY J2 - REP PRACT ONCOL RADI VL - 27 PY - 2022 IS - 2 SP - 344 EP - 351 PG - 8 SN - 1507-1367 DO - 10.5603/RPOR.a2022.0038 UR - https://m2.mtmt.hu/api/publication/33423766 ID - 33423766 N1 - Electroradiology Department, Poznan University of Medical Sciences, Poznan, Poland Radiobiology Lab. Medical Physics Department, The Greater Poland Cancer Centre, Poznan, Poland Department of Radiotherapy I, The Greater Poland Cancer Centre, Poznan, Poland Medical Physics Department, The Greater Poland Cancer Centre, Poznan, Poland Department of Nuclear Techniques and Equipment, National Centre for Nuclear Research, Otwock, Poland Centre of High Technology HITEC, Swierk, Otwock, Poland Cited By :3 Export Date: 11 May 2023 CODEN: RPORA Correspondence Address: Matuszak, N.; Electroradiology Department, Poland; email: natalia.matuszak@wco.pl Funding details: 2015/19/B/NZ7/03811 Funding details: Narodowe Centrum Nauki, NCN Funding text 1: This work was supported by the Nation al Science Centre of Poland under grant no 2015/19/B/NZ7/03811. Funding text 2: This work was supported by the National Science Centre of Poland under grant no 2015/19/B/NZ7/03811. AB - FLASH radiotherapy (RT) is a technique involving the delivery of ultra-high dose rate radiation to the target. FLASH-RT has been shown to reduce radiation-induced toxicity in healthy tissues without compromising the anti-cancer effects of treatment compared to conventional radiation therapy. In the present article, we review the published data on FLASH-RT and discuss the current state of knowledge of this novel approach. We also highlight the technological constraints and complexity of FLASH-RT and describe the physics underlying this modality, particularly how technology supports energy transfer by ionising radiation (e.g., beam on/off sequence, pulse-energy load, intervals). We emphasise that current preclinical experience is mostly based on FLASH electrons and that clinical application of FLASH-RT is very limited. The incorporation of FLASH-RT into routine clinical radiotherapy will require the development of devices capable of producing FLASH photon beams. LA - English DB - MTMT ER - TY - JOUR AU - Qi, Y. AU - Gao, N. AU - Lu, X. AU - Qian, D. AU - Xu, X. TI - Research progresses of Flash radiotherapy technique JF - ZHONGGUO YIXUE YINGXIANG JISHU / CHINESE JOURNAL OF MEDICAL IMAGING TECHNOLOGY J2 - CHINESE J MED IMAG TECH VL - 38 PY - 2022 IS - 1 SP - 146 EP - 149 PG - 4 SN - 1003-3289 DO - 10.13929/j.issn.1003-3289.2022.01.035 UR - https://m2.mtmt.hu/api/publication/33810144 ID - 33810144 N1 - Export Date: 11 May 2023 Correspondence Address: Xu, X.; School of Nuclear Science and Technology, China; email: xgxu@ustc.edu.cn Correspondence Address: Xu, X.; Department of Radiotherapy, China; email: xgxu@ustc.edu.cn AB - Flash radiotherapy (Flash-RT) has become a hot topic in the field of radiotherapy owing to its unique radiobiological characteristics and potentials in clinical application, yet researches of mechanism and clinical application of Flash-RT remained in preliminary stage. The progresses of Flash-RT were reviewed in this paper. Copyright © 2022 by the Press of Chinese Journal of Medical Imaging and Technology. LA - Chinese DB - MTMT ER - TY - JOUR AU - Romano, Francesco AU - Bailat, Claude AU - Jorge, Patrik Goncalves AU - Lerch, Michael Lloyd Franz AU - Darafsheh, Arash TI - Ultra-high dose rate dosimetry: Challenges and opportunities for FLASH radiation therapy JF - MEDICAL PHYSICS J2 - MED PHYS VL - 49 PY - 2022 IS - 7 SP - 4912 EP - 4932 PG - 21 SN - 0094-2405 DO - 10.1002/mp.15649 UR - https://m2.mtmt.hu/api/publication/33423781 ID - 33423781 N1 - Istituto Nazionale di Fisica Nucleare, Sezione di Catania, Catania, Italy Institute of Radiation Physics, Lausanne University Hospital Lausanne University, Lausanne, Switzerland Department of Radiation Oncology, Lausanne University Hospital, Lausanne, Switzerland Radio-Oncology Laboratory, DO/CHUV, Lausanne University Hospital, Lausanne, Switzerland Centre for Medical Radiation Physics, University of WollongongNSW, Australia Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, United States Cited By :13 Export Date: 11 May 2023 CODEN: MPHYA Correspondence Address: Romano, F.; Istituto Nazionale di Fisica Nucleare, Italy; email: francesco.romano@ct.infn.it Funding details: Horizon 2020 Framework Programme, H2020 Funding details: European Metrology Programme for Innovation and Research, EMPIR Funding text 1: The authors wish to thank their colleagues who contributed in this manuscript through informal discussions and exchange of views. CB and PGJ received support from the project 18HLT04 UHDpulse, which has received funding from the EMPIR programme co‐financed by the Participating States and from the European Union’s Horizon 2020 research and innovation programme. Funding text 2: informationThe authors received no funding for this work.The authors wish to thank their colleagues who contributed in this manuscript through informal discussions and exchange of views. CB and PGJ received support from the project 18HLT04 UHDpulse, which has received funding from the EMPIR programme co-financed by the Participating States and from the European Union’s Horizon 2020 research and innovation programme. AB - The clinical translation of FLASH radiotherapy (RT) requires challenges related to dosimetry and beam monitoring of ultra-high dose rate (UHDR) beams to be addressed. Detectors currently in use suffer from saturation effects under UHDR regimes, requiring the introduction of correction factors. There is significant interest from the scientific community to identify the most reliable solutions and suitable experimental approaches for UHDR dosimetry. This interest is manifested through the increasing number of national and international projects recently proposed concerning UHDR dosimetry. Attaining the desired solutions and approaches requires further optimization of already established technologies as well as the investigation of novel radiation detection and dosimetry methods. New knowledge will also emerge to fill the gap in terms of validated protocols, assessing new dosimetric procedures and standardized methods. In this paper, we discuss the main challenges coming from the peculiar beam parameters characterizing UHDR beams for FLASH RT. These challenges vary considerably depending on the accelerator type and technique used to produce the relevant UHDR radiation environment. We also introduce some general considerations on how the different time structure in the production of the radiation beams, as well as the dose and dose-rate per pulse, can affect the detector response. Finally, we discuss the requirements that must characterize any proposed dosimeters for use in UDHR radiation environments. A detailed status of the current technology is provided, with the aim of discussing the detector features and their performance characteristics and/or limitations in UHDR regimes. We report on further developments for established detectors and novel approaches currently under investigation with a view to predict future directions in terms of dosimetry approaches, practical procedures, and protocols. Due to several on-going detector and dosimetry developments associated with UHDR radiation environment for FLASH RT it is not possible to provide a simple list of recommendations for the most suitable detectors for FLASH RT dosimetry. However, this article does provide the reader with a detailed description of the most up-to-date dosimetric approaches, and describes the behavior of the detectors operated under UHDR irradiation conditions and offers expert discussion on the current challenges which we believe are important and still need to be addressed in the clinical translation of FLASH RT. LA - English DB - MTMT ER - TY - CHAP AU - Samanta, S. AU - Mossahebi, S. AU - Miller, R.C. TI - FLASH Radiotherapy T2 - Principles and Practice of Particle Therapy PB - Wiley SN - 9781119707516 T3 - Principles and Practice of Particle Therapy PY - 2022 SP - 115 EP - 120 PG - 6 DO - 10.1002/9781119707530.ch8 UR - https://m2.mtmt.hu/api/publication/33810145 ID - 33810145 N1 - Export Date: 11 May 2023 Correspondence Address: Miller, R.C.; University of Tennessee Medical Center, 1926 Alcoa Highway, Building F,Suite #130, United States AB - Ionizing radiation with ultrahigh dose rates (>40 Gy/s), known as FLASH radiotherapy, has been recently shown to markedly reduce radiation toxicity to normal healthy tissues while inhibiting tumor growth with similar efficacy as compared to conventional dose-rate radiation. The two major hypotheses to explain FLASH include the oxygen depletion hypothesis and the immune hypothesis. Bourhis et al. conducted the first human patient study to demonstrate feasibility and safety with favorable outcomes using FLASH-RT therapy. FLASH-RT involves dose delivery at ultrahigh dose rates generally several thousand times higher than the ones currently used in routine clinical practice. The clinical translation of FLASH-RT has been substantiated by multiple experiments that confirm the differential effect between the tumors and the normal tissue, as compared to conventional dose-rate radiation. Recent clinical studies further validate the potential benefits of FLASH-RT. © 2022 John Wiley and Sons Ltd. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Schneider, Tim AU - Fernandez-Palomo, Cristian AU - Bertho, Annaig AU - Fazzari, Jennifer AU - Iturri, Lorea AU - Martin, Olga A. AU - Trappetti, Verdiana AU - Djonov, Valentin AU - Prezado, Yolanda TI - Combining FLASH and spatially fractionated radiation therapy: The best of both worlds JF - RADIOTHERAPY AND ONCOLOGY J2 - RADIOTHER ONCOL VL - 175 PY - 2022 SP - 169 EP - 177 PG - 9 SN - 0167-8140 DO - 10.1016/j.radonc.2022.08.004 UR - https://m2.mtmt.hu/api/publication/33423756 ID - 33423756 N1 - Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, 91400, France Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, Orsay, 91400, France Institute of Anatomy, University of Bern, Baltzerstrasse 2, Bern, 3012, Switzerland Division of Radiation Oncology, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, VIC 3000, Australia University of Melbourne, Parkville, VIC 3010, Australia Cited By :3 Export Date: 11 May 2023 CODEN: RAOND Correspondence Address: Prezado, Y.; Institut Curie, France; email: Yolanda.prezado@curie.fr Funding details: Horizon 2020 Framework Programme, H2020 Funding details: European Research Council, ERC Funding details: Horizon 2020, 817908 Funding text 1: Y. Prezado acknowledges the funding from European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 817908). Funding text 2: Y. Prezado acknowledges the funding from European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 817908). AB - FLASH radiotherapy (FLASH-RT) and spatially fractionated radiation therapy (SFRT) are two new thera-peutical strategies that use non-standard dose delivery methods to reduce normal tissue toxicity and increase the therapeutic index. Although likely based on different mechanisms, both FLASH-RT and SFRT have shown to elicit radiobiological effects that significantly differ from those induced by conven-tional radiotherapy. With the therapeutic potential having been established separately for each tech-nique, the combination of FLASH-RT and SFRT could therefore represent a winning alliance. In this review, we discuss the state of the art, advantages and current limitations, potential synergies, and where a combination of these two techniques could be implemented today or in the near future.(c) 2022 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 175 (2022) 169-177 LA - English DB - MTMT ER - TY - JOUR AU - Schuler, Emil AU - Acharya, Munjal AU - Montay-Gruel, Pierre AU - Loo, Billy W. Jr Jr AU - Vozenin, Marie-Catherine AU - Maxim, Peter G. TI - Ultra-high dose rate electron beams and the FLASH effect: From preclinical evidence to a new radiotherapy paradigm JF - MEDICAL PHYSICS J2 - MED PHYS VL - 49 PY - 2022 IS - 3 SP - 2082 EP - 2095 PG - 14 SN - 0094-2405 DO - 10.1002/mp.15442 UR - https://m2.mtmt.hu/api/publication/32672567 ID - 32672567 N1 - Funding Agency and Grant Number: Swiss National Fund SNF Synergia [FNS CRS II5_186369]; NIH program projectUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [PO1CA244091]; American Cancer Society (ACS)American Cancer Society [RSG-1714601-CCE]; UCI Institute for Clinical and Translational Sciences [KL2 KL2TR001416]; University Cancer Foundation via the Institutional Research Grant program at the University of Texas MD Anderson Cancer Center, Division of Radiation Oncology; National Cancer Institute of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30 CA016672] Funding text: the Swiss National Fund SNF Synergia, Grant/Award Number: FNS CRS II5_186369; NIH program project, Grant/Award Number: PO1CA244091; the American Cancer Society (ACS) Research Scholar, Grant/Award Number: RSG-1714601-CCE; UCI Institute for Clinical and Translational Sciences, Grant/Award Number: KL2 KL2TR001416; the University Cancer Foundation via the Institutional Research Grant program at the University of Texas MD Anderson Cancer Center, Division of Radiation Oncology; the National Cancer Institute of the National Institutes of Health, Grant/Award Number: P30 CA016672 AB - In their seminal paper from 2014, Fauvadon et al. coined the term FLASH irradiation to describe ultra-high-dose rate irradiation with dose rates greater than 40 Gy/s, which results in delivery times of fractions of a second. The experiments presented in that paper were performed with a high-dose-per-pulse 4.5 MeV electron beam, and the results served as the basis for the modern-day field of FLASH radiation therapy (RT). In this article, we review the studies that have been published after those early experiments, demonstrating the robust effects of FLASH RT on normal tissue sparing in preclinical models. We also outline the various irradiation parameters that have been used. Although the robustness of the biological response has been established, the mechanisms behind the FLASH effect are currently under investigation in a number of laboratories. However, differences in the magnitude of the FLASH effect between experiments in different labs have been reported. Reasons for these differences even within the same animal model are currently unknown, but likely has to do with the marked differences in irradiation parameter settings used. Here, we show that these parameters are often not reported, which complicates large multistudy comparisons. For this reason, we propose a new standard for beam parameter reporting and discuss a systematic path to the clinical translation of FLASH RT. LA - English DB - MTMT ER - TY - JOUR AU - Schwarz, Marco AU - Traneus, Erik AU - Safai, Sairos AU - Kolano, Anna AU - van de Water, Steven TI - Treatment planning for Flash radiotherapy: General aspects and applications to proton beams JF - MEDICAL PHYSICS J2 - MED PHYS VL - 49 PY - 2022 IS - 4 SP - 2861 EP - 2874 PG - 14 SN - 0094-2405 DO - 10.1002/mp.15579 UR - https://m2.mtmt.hu/api/publication/33423788 ID - 33423788 N1 - Cited By :7 Export Date: 11 May 2023 CODEN: MPHYA Correspondence Address: Schwarz, M.; Proton therapy Department, Italy; email: marcosch@uw.edu Chemicals/CAS: proton, 12408-02-5, 12586-59-3; Protons Funding details: Varian Medical Systems Funding text 1: Work by Steven van de Water was funded with a research grant from Varian Medical Systems. We thank Rudi Labarbe (IBA) for the conversations on beam delivery parameters and on planning with the 3D range modulator. AB - The increased radioresistence of healthy tissues when irradiated at very high dose rates (known as the Flash effect) is a radiobiological mechanism that is currently investigated to increase the therapeutic ratio of radiotherapy treatments. To maximize the benefits of the clinical application of Flash, a patient-specific balance between different properties of the dose distribution should be found, that is, Flash needs to be one of the variables considered in treatment planning. We investigated the Flash potential of three proton therapy planning and beam delivery techniques, each on a different anatomical region. Based on a set of beam delivery parameters, on hypotheses on the dose and dose rate thresholds needed for the Flash effect to occur, and on two definitions of Flash dose rate, we generated exemplary illustrations of the capabilities of current proton therapy equipment to generate Flash dose distributions. All techniques investigated could both produce dose distributions comparable with a conventional proton plan and reach the Flash regime, to an extent that was strongly dependent on the dose per fraction and the Flash dose threshold. The beam current, Flash dose rate threshold, and dose rate definition typically had a more moderate effect on the amount of Flash dose in normal tissue. A systematic estimation of the impact of Flash on different patient anatomies and treatment protocols is possible only if Flash-specific treatment planning features become readily available. Planning evaluation tools such as a voxel-based dose delivery time structure, and the inclusion in the optimization cost function of parameters directly associated with Flash (e.g., beam current, spot delivery sequence, and scanning speed), are needed to generate treatment plans that are taking full advantage of the potential benefits of the Flash effect. LA - English DB - MTMT ER - TY - JOUR AU - Singers, Sørensen B. AU - Krzysztof, Sitarz M. AU - Ankjærgaard, C. AU - Johansen, J. AU - Andersen, C.E. AU - Kanouta, E. AU - Overgaard, C. AU - Grau, C. AU - Poulsen, P. TI - In vivo validation and tissue sparing factor for acute damage of pencil beam scanning proton FLASH JF - RADIOTHERAPY AND ONCOLOGY J2 - RADIOTHER ONCOL VL - 167 PY - 2022 SP - 109 EP - 115 PG - 7 SN - 0167-8140 DO - 10.1016/j.radonc.2021.12.022 UR - https://m2.mtmt.hu/api/publication/32672601 ID - 32672601 N1 - Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark DTU Health Tech, Roskilde, Denmark Department of Oncology, Aarhus University Hospital, Aarhus, Denmark Export Date: 14 February 2022 CODEN: RAOND Correspondence Address: Singers Sørensen, B.; Aarhus University Hospital, Boulevard 99 C108, Denmark; email: Bsin@oncology.au.dk LA - English DB - MTMT ER - TY - JOUR AU - Tashiro, Mutsumi AU - Yoshida, Yukari AU - Oike, Takahiro AU - Nakao, Masao AU - Yusa, Ken AU - Hirota, Yuka AU - Ohno, Tatsuya TI - First Human Cell Experiments With FLASH Carbon Ions JF - ANTICANCER RESEARCH J2 - ANTICANCER RES VL - 42 PY - 2022 IS - 5 SP - 2469 EP - 2477 PG - 9 SN - 0250-7005 DO - 10.21873/anticanres.15725 UR - https://m2.mtmt.hu/api/publication/33423777 ID - 33423777 N1 - Gunma University, Heavy Ion Medical Center, Gunma, Japan Department of Radiation Oncology, Gunma University, Graduate School of Medicine, Gunma, Japan Cited By :7 Export Date: 11 May 2023 CODEN: ANTRD Correspondence Address: Tashiro, M.; Gunma University, 3-39-22 Showamachi, Maebashi, Japan; email: tashiro@gunma-u.ac.jp Chemicals/CAS: beta galactosidase; carbon, 7440-44-0; crystal violet, 467-63-0, 548-62-9; Carbon; Ions Funding text 1: We thank Prof. Akihisa Takahashi for generous advice, and Yosuke Kano and Masafumi Oishi at the Accelerator Engineering Corporation for their experimental support. This work was supported by GHMC and carried out as a research project with heavy ions at GHMC. AB - Background/Aim: This study aimed to establish a setup for ultra-high-dose-rate (FLASH) carbon-ion irradiation, and to conduct the first human cell experiments using FLASH carbon ions. Materials and Methods: A system for FLASH carbon-ion irradiation (1-3 Gy at 13 or 50 keV/,um) was developed. The growth and senescence of HFL1 lung fibroblasts were assessed by crystal violet staining assays and senescence associated ??-galactosidase staining, respectively. Survival of HSGc-C5 cancer cells was assessed by clonogenic assays. Results: The dose rates of carbon ions ranged from 96-195 Gy/s, meeting the definition of FLASH. With both 13 and 50 keV/,um beams, no FLASH sparing effect was observed on the growth suppression and senescence of HFL1 cells, nor on the survival of HSGc-C5 cells. Conclusion: We successfully conducted the first human cell experiments with FLASH carbon ions. No FLASH effect was observed under the conditions examined. LA - English DB - MTMT ER - TY - JOUR AU - Titt, U. AU - Yang, M. AU - Wang, X. AU - Iga, K. AU - Fredette, N. AU - Schueler, E. AU - Lin, S.H. AU - Zhu, X.R. AU - Sahoo, N. AU - Koong, A.C. AU - Zhang, X. AU - Mohan, R. TI - Design and validation of a synchrotron proton beam line for FLASH radiotherapy preclinical research experiments JF - MEDICAL PHYSICS J2 - MED PHYS VL - 49 PY - 2022 IS - 1 SP - 497 EP - 509 PG - 13 SN - 0094-2405 DO - 10.1002/mp.15370 UR - https://m2.mtmt.hu/api/publication/32672605 ID - 32672605 N1 - Department of Radiation Physics, M.D. Anderson Cancer Center, University of Texas, Houston, TX, United States Particle Therapy Division, HITACHI America Ltd., Houston, TX, United States Department of Radiation Oncology, M.D. Anderson Cancer Center, University of Texas, Houston, TX, United States Export Date: 14 February 2022 CODEN: MPHYA Correspondence Address: Titt, U.; Department of Radiation Physics, United States; email: utitt@mdanderson.org LA - English DB - MTMT ER - TY - JOUR AU - Togno, M. AU - Nesteruk, K.P. AU - Schäfer, R. AU - Psoroulas, S. AU - Meer, D. AU - Grossmann, M. AU - Christensen, J.B. AU - Yukihara, E.G. AU - Lomax, A.J. AU - Weber, D.C. AU - Safai, S. TI - Ultra-high dose rate dosimetry for pre-clinical experiments with mm-small proton fields JF - PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS J2 - PHYS MEDICA VL - 104 PY - 2022 SP - 101 EP - 111 PG - 11 SN - 1120-1797 DO - 10.1016/j.ejmp.2022.10.019 UR - https://m2.mtmt.hu/api/publication/33810138 ID - 33810138 N1 - Center for Proton Therapy, Paul Scherrer Institut, Villigen, Switzerland Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, United States Department of Radiation Safety and Security, Paul Scherrer Institut, Villigen, Switzerland Department of Physics, ETH Zurich, Zurich, Switzerland Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Switzerland Cited By :2 Export Date: 11 May 2023 CODEN: PHYME Correspondence Address: Togno, M.; Center for Proton Therapy, Switzerland; email: michele.togno@psi.ch Chemicals/CAS: proton, 12408-02-5, 12586-59-3; Protons Tradenames: TM7862, PTW, Germany Manufacturers: PTW, Germany Funding details: Massachusetts General Hospital, MGH Funding details: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNF, 190663 Funding text 1: The authors would like to thank Benno Rohrer and Martina Egloff for the valuable support in collecting the experimental data. K. P. Nesteruk at the time of submission holds a research position at MGH. This study was conducted prior to that, when K. P. Nesteruk was a postdoc researcher at PSI. This work is partially funded by the Swiss National Science Foundation (grant No. 190663). Funding text 2: K. P. Nesteruk at the time of submission holds a research position at MGH. This study was conducted prior to that, when K. P. Nesteruk was a postdoc researcher at PSI. This work is partially funded by the Swiss National Science Foundation (grant No. 190663). AB - Purpose: To characterize an experimental setup for ultra-high dose rate (UHDR) proton irradiations, and to address the challenges of dosimetry in millimetre-small pencil proton beams. Methods: At the PSI Gantry 1, high-energy transmission pencil beams can be delivered to biological samples and detectors up to a maximum local dose rate of ∼9000 Gy/s. In the presented setup, a Faraday cup is used to measure the delivered number of protons up to ultra-high dose rates. The response of transmission ion-chambers, as well as of different field detectors, was characterized over a wide range of dose rates using the Faraday cup as reference. Results: The reproducibility of the delivered proton charge was better than 1 % in the proposed experimental setup. EBT3 films, Al2O3:C optically stimulated luminescence detectors and a PTW microDiamond were used to validate the predicted dose. Transmission ionization chambers showed significant volume ion-recombination (>30 % in the tested conditions) which can be parametrized as a function of the maximum proton current density. Over the considered range, EBT3 films, inorganic scintillator-based screens and the PTW microDiamond were demonstrated to be dose rate independent within ±3 %, ±1.8 % and ±1 %, respectively. Conclusions: Faraday cups are versatile dosimetry instruments that can be used for dose estimation, field detector characterization and on-line dose verification for pre-clinical experiments in UHDR proton pencil beams. Among the tested detectors, the commercial PTW microDiamond was found to be a suitable option to measure real time the dosimetric properties of narrow pencil proton beams for dose rates up to 2.2 kGy/s. © 2022 Associazione Italiana di Fisica Medica e Sanitaria LA - English DB - MTMT ER - TY - JOUR AU - Van Slyke, Alexander L. AU - El Khatib, Mirna AU - Velalopoulou, Anastasia AU - Diffenderfer, Eric AU - Shoniyozov, Khayrullo AU - Kim, Michele M. AU - Karagounis, Ilias V AU - Busch, Theresa M. AU - Vinogradov, Sergei A. AU - Koch, Cameron J. AU - Wiersma, Rodney D. TI - Oxygen Monitoring in Model Solutions and In Vivo in Mice During Proton Irradiation at Conventional and FLASH Dose Rates JF - RADIATION RESEARCH J2 - RADIAT RES VL - 198 PY - 2022 IS - 2 SP - 181 EP - 189 PG - 9 SN - 0033-7587 DO - 10.1667/RADE-21-00232.1 UR - https://m2.mtmt.hu/api/publication/33423770 ID - 33423770 N1 - Department of Radiation Oncology, University of Pennsylvania, Philadelphia, United States Department of Biochemistry and Biophysics, Perelman School of Medicine, Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, United States Cited By :3 Export Date: 11 May 2023 CODEN: RAREA Correspondence Address: Wiersma, R.D.; Department of Biochemistry and Biophysics, United States; email: rodney.wiersma@pennmedicine.upenn.edu Chemicals/CAS: glucose, 50-99-7, 84778-64-3; glutathione, 70-18-8; glycerol, 56-81-5; oxygen, 7782-44-7; proton, 12408-02-5, 12586-59-3; Oxygen; Protons Tradenames: Proteus Plus, IBA, Belgium Manufacturers: IBA, Belgium Funding details: National Institutes of Health, NIH Funding details: Perelman School of Medicine, University of Pennsylvania Funding text 1: Support of the grants P01 CA257904-01A1 (RDW, CJK), HL145092 (MEK), EB027397 and EB028941 (SAV) from the National Institutes of Health, and developmental funds from the Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine is gratefully acknowledged. SAV has partial ownership of Oxygen Enterprises Ltd. which owns the intellectual property for phosphorescent probes technology (US Pat. No. 9,556,213; US, 2017/0137449 A1). All other authors declare no competing interests. AB - FLASH is a high-dose-rate form of radiation therapy that has the reported ability, compared with conventional dose rates, to spare normal tissues while being equipotent in tumor control, thereby increasing the therapeutic ratio. The mechanism underlying this normal tissue sparing effect is currently unknown, however one possibility is radiochemical oxygen depletion (ROD) during dose delivery in tissue at FLASH dose rates. In order to investigate this possibility, we used the phosphorescence quenching method to measure oxygen partial pressure before, during and after proton radiation delivery in model solutions and in normal muscle and sarcoma tumors in mice, at both conventional (Conv) (similar to 0.5 Gy/s) and FLASH (similar to 100 Gy/s) dose rates. Radiation dosimetry was determined by Advanced Markus Chamber and EBT-XL film. For solutions contained in sealed glass vials, phosphorescent probe Oxyphor PtG4 (1 mu M) was dissolved in a buffer (10 mM HEPES) containing glycerol (1 M), glucose (5 mM) and glutathione (5 mM), designed to mimic the reducing and free radical-scavenging nature of the intracellular environment. In vivo oxygen measurements were performed 24 h after injection of PtG4 into the interstitial space of either normal thigh muscle or subcutaneous sarcoma tumors in mice. The "g-value" for ROD is reported in mmHg/Gy, which represents a slight modification of the more standard chemical definition (mu M/Gy). In solutions, proton irradiation at conventional dose rates resulted in a g-value for ROD of up to 0.55 mmHg/Gy, consistent with earlier studies using X or gamma rays. At FLASH dose rates, the g-value for ROD was similar to 25% lower, 0.37 mmHg/Gy. pO(2) levels were stable after each dose delivery. For normal muscle in vivo, oxygen depletion during irradiation was counterbalanced by resupply from the vasculature. This process was fast enough to maintain tissue pO(2) virtually unchanged at Conv dose rates. However, during FLASH irradiation there was a stepwise decrease in pO(2) (g-value similar to 0.28 mmHg/Gy), followed by a rebound to the initial level after similar to 8 s. The g-values were smaller and recovery times longer in tumor tissue when compared to muscle and may be related to the lower initial endogenous pO(2) levels in the former. Considering that the FLASH effect is seen in vivo even at doses as low as 10 Gy, it is difficult to reconcile the amount of protection seen by oxygen depletion alone. However, the phosphorescence probe in our experiments was confined to the extracellular space, and it remains possible that intracellular oxygen depletion was greater than observed herein. In cell-mimicking solutions the oxygen depletion g-vales were indeed significantly higher than observed in vivo. (C) 2022 by Radiation Research Society LA - English DB - MTMT ER - TY - JOUR AU - Villoing, Daphnee AU - Koumeir, Charbel AU - Bongrand, Arthur AU - Guertin, Arnaud AU - Haddad, Ferid AU - Metivier, Vincent AU - Poirier, Freddy AU - Potiron, Vincent AU - Servagent, Noel AU - Supiot, Stephane AU - Delpon, Gregory AU - Chiavassa, Sophie TI - Proton beam dosimetry at ultra-high dose rates (FLASH): Evaluation of GAFchromic (TM) (EBT3, EBT-XD) and OrthoChromic (OC-1) film performances JF - MEDICAL PHYSICS J2 - MED PHYS VL - 49 PY - 2022 IS - 4 SP - 2732 EP - 2745 PG - 14 SN - 0094-2405 DO - 10.1002/mp.15526 UR - https://m2.mtmt.hu/api/publication/33423793 ID - 33423793 N1 - Institut de Cancérologie de l'Ouest, Saint-Herblain, France GIP ARRONAX, Saint-Herblain, France Laboratoire SUBATECH, UMR 6457, CNRS IN2P3, IMT Atlantique, Université de Nantes, Nantes, France Cited By :6 Export Date: 11 May 2023 CODEN: MPHYA Correspondence Address: Chiavassa, S.; Institut de Cancérologie de l'OuestFrance; email: sophie.chiavassa@ico.unicancer.fr Chemicals/CAS: proton, 12408-02-5, 12586-59-3; Protons Funding details: ANR‐11‐EQPX‐0004 Funding details: ANR‐16‐IDEX‐0007 Funding details: ANR‐11‐LABX‐18‐01 Funding details: Labex Iron Funding text 1: This work was partially funded by Equipex ARRONAX‐Plus (ANR‐11‐EQPX‐0004), Labex IRON (ANR‐11‐LABX‐18‐01), ISITE NExT (ANR‐16‐IDEX‐0007), and with financial support from Inserm Cancer. Funding text 2: This work was partially funded by Equipex ARRONAX-Plus (ANR-11-EQPX-0004), Labex IRON (ANR-11-LABX-18-01), ISITE NExT (ANR-16-IDEX-0007), and with financial support from Inserm Cancer. AB - Purpose The ARRONAX cyclotron facility offers the possibility to deliver proton beams from low to ultra-high dose rates (UHDR). As a good control of the dosimetry is a prerequisite of UHDR experimentations, we evaluated in different conditions the usability and the dose rate dependency of several radiochromic films commonly used for dosimetry in radiotherapy. Methods We compared the dose rate dependency of three types of radiochromic films: GAFchromic (TM) EBT3 and GAFchromic (TM) EBT-XD (Ashland Inc., Wayne, NJ, USA), and OrthoChromic OC-1 (OrthoChrome Inc., Hillsborough, NJ, USA), after proton irradiations at various mean dose rates (0.25, 40, 1500, and 7500 Gy/s) and for 10 doses (2-130 Gy). We also evaluated the dose rate dependency of each film considering beam structures, from single pulse to multiple pulses with various frequencies. Results EBT3 and EBT-XD films showed differences of response between conventional (0.25 Gy/s) and UHDR (7500 Gy/s) conditions, above 10 Gy. On the contrary, OC-1 films did not present overall difference of response for doses except below 3 Gy. We observed an increase of the netOD with the mean dose rate for EBT3 and EBT-XD films. OC-1 films did not show any impact of the mean dose rate up to 7500 Gy/s, above 3 Gy. No difference was found based on the beam structure, for all three types of films. Conclusions EBT3 and EBT-XD radiochromic films should be used with caution for the dosimetry of UHDR proton beams over 10 Gy. Their overresponse, which increases with mean dose rate and dose, could lead to non-negligible overestimations of the absolute dose. OC-1 films are dose rate independent up to 7500 Gy/s in proton beams. Films response is not impacted by the beam structure. A broader investigation of the usability of OC-1 films in UHDR conditions should be conducted at intermediate and higher mean dose rates and other beam energies. LA - English DB - MTMT ER - TY - JOUR AU - Vozenin, Marie-Catherine AU - Bourhis, Jean AU - Durante, Marco TI - Towards clinical translation of FLASH radiotherapy JF - NATURE REVIEWS CLINICAL ONCOLOGY J2 - NAT REV CLIN ONCOL VL - 19 PY - 2022 IS - 12 SP - 791 EP - 803 PG - 13 SN - 1759-4774 DO - 10.1038/s41571-022-00697-z UR - https://m2.mtmt.hu/api/publication/33423752 ID - 33423752 N1 - Cited By :5 Export Date: 30 March 2023 Correspondence Address: Durante, M.; GSI Helmholtzzentrum für Schwerionenforschung, Germany; email: m.durante@gsi.de Funding details: GSI Helmholtzzentrum für Schwerionenforschung, GSI Funding text 1: The authors thank L. Volz (GSI) and A. Quarz (GSI and TUDa) for their support in preparing figures, and F. Bochud, J. F. Germond, T. Boehlen, C. Bailat and R. Moeckli for fruitful scientific discussions. AB - The ultimate goal of radiation oncology is to eradicate tumours without toxicity to non-malignant tissues. FLASH radiotherapy, or the delivery of ultra-high dose rates of radiation (>40 Gy/s), emerged as a modality of irradiation that enables tumour control to be maintained while reducing toxicity to surrounding non-malignant tissues. In the past few years, preclinical studies have shown that FLASH radiotherapy can be delivered in very short times and substantially can widen the therapeutic window of radiotherapy. This ultra-fast radiation delivery could reduce toxicity and thus enable dose escalation to enhance antitumour efficacy, with the additional benefits of reducing treatment time and organ motion-related issues, eventually increasing the number of patients who can be treated. At present, FLASH is recognized as one of the most promising breakthroughs in radiation oncology, standing at the crossroads between technology, physics, chemistry and biology; however, several hurdles make its clinical translation difficult, including the need for a better understanding of the biological mechanisms, optimization of parameters and technological challenges. In this Perspective, we provide an overview of the principles underlying FLASH radiotherapy and discuss the challenges along the path towards its clinical application.FLASH radiotherapy involves delivering ultra-high dose rates of radiation, which enables sustained tumour control with reduced toxicity to surrounding tissues. The authors of this Perspective describe the principles underlying FLASH radiotherapy, present the available evidence from preclinical studies testing this modality and discuss the challenges for its application in routine clinical practice. LA - English DB - MTMT ER - TY - JOUR AU - Wei, S. AU - Lin, H. AU - Choi, J.I. AU - Press, R.H. AU - Lazarev, S. AU - Kabarriti, R. AU - Hajj, C. AU - Hasan, S. AU - Chhabra, A.M. AU - Simone, C.B. II AU - Kang, M. TI - FLASH Radiotherapy Using Single-Energy Proton PBS Transmission Beams for Hypofractionation Liver Cancer: Dose and Dose Rate Quantification JF - FRONTIERS IN ONCOLOGY J2 - FRONT ONCOL VL - 11 PY - 2022 SN - 2234-943X DO - 10.3389/fonc.2021.813063 UR - https://m2.mtmt.hu/api/publication/32672603 ID - 32672603 N1 - New York Proton Center, New York, NY, United States Mount Sinai Hospital, New York, NY, United States Montefiore Medical Center, Bronx, NY, United States Memorial Sloan Kettering Cancer Center, New York, NY, United States Export Date: 14 February 2022 Correspondence Address: Kang, M.; New York Proton CenterUnited States; email: mleikang@gmail.com LA - English DB - MTMT ER - TY - JOUR AU - Wei, Shouyi AU - Lin, Haibo AU - Choi, Isabelle AU - Shi, Chengyu AU - Ii, Charles B. Simone AU - Kang, Minglei TI - Advanced pencil beam scanning Bragg peak FLASH-RT delivery technique can enhance lung cancer planning treatment outcomes compared to conventional multiple-energy proton PBS techniques JF - RADIOTHERAPY AND ONCOLOGY J2 - RADIOTHER ONCOL VL - 175 PY - 2022 SP - 238 EP - 247 PG - 10 SN - 0167-8140 DO - 10.1016/j.radonc.2022.08.005 UR - https://m2.mtmt.hu/api/publication/33423757 ID - 33423757 N1 - New York Proton Center, New York, NY 10035, United States City of Hope, Orange County, Irvine, CA 92618, United States Cited By :1 Export Date: 11 May 2023 CODEN: RAOND Correspondence Address: Lin, H.; New York Proton CenterUnited States; email: hlin@nyproton.com Chemicals/CAS: proton, 12408-02-5, 12586-59-3; Protons AB - Purpose: To investigate the dosimetric characteristics between an advanced proton pencil beam scanning (PBS) Bragg peak FLASH technique and conventional PBS planning technique in lung tumors. To evaluate the "FLASHness" of single-field in a multiple-field delivery scheme for a hypofractionation regimen and move a step forward to clinical application.Methods: Single-energy PBS Bragg peak FLASH treatment plans were optimized based on a novel Bragg peak tracking technique to enable Bragg peaks to stop at the distal edge of the target. Inverse treatment planning using multiple-field optimization (MFO) can achieve sufficient FLASH dose rate and intensitymodulated proton therapy (IMPT)-equivalent dosimetric quality. The dose rate of organs-at-risk (OARs) and the target were calculated under FLASH machine parameters. A group of 10 consecutive lung SBRT patients was optimized to 34 Gy/fraction using a standard treatment of PBS technique with multiple energy layers as references to the Bragg peak plans. The dosimetric quality was compared between Bragg peak FLASH and conventional plans based on RTOG0915 dose metrics. FLASH dose rate ratios (V40Gy/s) were calculated as a metric of the FLASH-sparing effect. Results: For higher dose thresholds, the Bragg peak plans achieved greater V40Gy/s FLASH coverage for all major OARs. The V40Gy/s was close to 100% for all OARs when the dose thresholds were > 5 Gy for full plan and single beam evaluations. The less "FLASHness" region was associated with a low dose distribution, mainly occurring in the PBS field penumbra region. The conventional IMPT treatment plans yielded slightly superior target dose uniformity with a D2%(%) of 108.02% versus that of Bragg peak 300 MU plans of 111.81% (p < 0.01) and that of Bragg peak 1200 MU plans of 115.95% (p < 0.01). No significant difference in dose metrics was found between Bragg peak and IMPT treatment plans for the spinal cord, esophagus, heart, or lung-GTV (all p > 0.05).Conclusion: Hypofractionated lung Bragg peak plans can maintain comparable plan quality to conventional PBS while achieving sufficient FLASH dose rate coverage for major OARs for each field under the multiple-field delivery scheme. The novel Bragg peak FLASH technique has the potential to enhance lung cancer planning treatment outcomes compared to standard PBS treatment techniques.(c) 2022 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 175 (2022) 238-247 LA - English DB - MTMT ER - TY - JOUR AU - Yin, Lingshu AU - Zou, Wei AU - Kim, Michele M. AU - Avery, Stephen M. AU - Wiersma, Rodney D. AU - Teo, Boon-Keng K. AU - Dong, Lei AU - Diffenderfer, Eric S. TI - Evaluation of Two-Voltage and Three-Voltage Linear Methods for Deriving Ion Recombination Correction Factors in Proton FLASH Irradiation JF - IEEE TRANSACTIONS ON RADIATION AND PLASMA MEDICAL SCIENCES J2 - IEEE T RADIAT PLASMA VL - 6 PY - 2022 IS - 3 SP - 263 EP - 270 PG - 8 SN - 2469-7311 DO - 10.1109/TRPMS.2021.3078885 UR - https://m2.mtmt.hu/api/publication/33423791 ID - 33423791 N1 - Cited By :5 Export Date: 11 May 2023 Correspondence Address: Yin, L.; Department of Radiation Oncology, United States; email: lingshu.yin@pennmedicine.upenn.edu AB - Ultrahigh dose-rate (FLASH) proton therapy is of great interest due to potential reduced normal tissue toxicities without compromising tumor-killing effect compared to current clinical proton practices. However, the ionization chamber response to proton beams under ultrahigh dose rates (>40 Gy/s) has not been thoroughly investigated. In this study, four different ion chambers (PTW 34045 Advanced Markus, PPC-40, CC-04, and CC-13 from IBA Dosimetry) were irradiated with 230 MeV proton beams at 1.5, 63.7, and 127.6 Gy/s dose rates. Theoretical values of ion recombination correction factor (k(s)) were calculated from saturation curves using Niatel's model. The theoretical k(s) values were compared to the values using the two-voltage (2V) method from standard dosimetry protocols and the three-voltage linear (3VL) method proposed by Rossomme et al. Both parallel plate chambers and CC-04 demonstrated adequate ion collection efficiency at the highest dose rate. For these three chambers, there is no statistically significant difference between theoretical k(s) values and those calculated with 2V and 3VL methods. However, significant ion recombination correction was found in CC-13 (k(s) > 1.50) when dose rate reached 63.7 Gy/s. The assumption of insignificant initial recombination in standard dosimetry protocols also underestimated the ion recombination effect in this scenario. LA - English DB - MTMT ER - TY - JOUR AU - Yu, Kwan Ngok TI - Radiation-Induced Rescue Effect: Insights from Microbeam Experiments JF - BIOLOGY-BASEL J2 - BIOLOGY-BASEL VL - 11 PY - 2022 IS - 11 PG - 29 SN - 2079-7737 DO - 10.3390/biology11111548 UR - https://m2.mtmt.hu/api/publication/33423750 ID - 33423750 N1 - Export Date: 11 May 2023 Correspondence Address: Yu, K.N.; Department of Physics, Hong Kong; email: peter.yu@cityu.edu.hk AB - Simple Summary The present paper introduces a radiobiological phenomenon known as the Radiation-Induced Rescue Effect (RIRE), where the radiobiological effects developed in cells irradiated with ionizing radiations are mitigated by non-irradiated cells. The primary objective of a radiotherapy treatment is to kill cancer cells with ionizing radiation while at the same time sparing the normal cells. However, RIRE was found capable of saving some of the irradiated cancer cells, so the efficacy and outcome of radiotherapy might be undermined. As such, it would be pertinent to have a better understanding of RIRE, including its underlying mechanisms and its relationships with other non-traditional radiobiological phenomena. Microbeam irradiations have some unique features that could help research on RIRE, which are explained. The paper also reviews the insights gained from previous microbeam experiments on RIRE. Some thoughts on future priorities and directions of research on RIRE exploiting unique features of microbeam radiations are presented in the last section. The present paper reviews a non-targeted effect in radiobiology known as the Radiation-Induced Rescue Effect (RIRE) and insights gained from previous microbeam experiments on RIRE. RIRE describes the mitigation of radiobiological effects in targeted irradiated cells after they receive feedback signals from co-cultured non-irradiated bystander cells, or from the medium previously conditioning those co-cultured non-irradiated bystander cells. RIRE has established or has the potential of establishing relationships with other non-traditional new developments in the fields of radiobiology, including Radiation-Induced Bystander Effect (RIBE), Radiation-Induced Field Size Effect (RIFSE) and ultra-high dose rate (FLASH) effect, which are explained. The paper first introduces RIRE, summarizes previous findings, and surveys the mechanisms proposed for observations. Unique opportunities offered by microbeam irradiations for RIRE research and some previous microbeam studies on RIRE are then described. Some thoughts on future priorities and directions of research on RIRE exploiting unique features of microbeam radiations are presented in the last section. LA - English DB - MTMT ER - TY - JOUR AU - Zhang, Guoliang AU - Gao, Wenchao AU - Peng, Hao TI - Design of static and dynamic ridge filters for FLASH-IMPT: A simulation study JF - MEDICAL PHYSICS J2 - MED PHYS VL - 49 PY - 2022 IS - 8 SP - 5387 EP - 5399 PG - 13 SN - 0094-2405 DO - 10.1002/mp.15717 UR - https://m2.mtmt.hu/api/publication/33423775 ID - 33423775 N1 - Cited By :3 Export Date: 11 May 2023 CODEN: MPHYA Correspondence Address: Peng, H.; Department of Medical Physics, China; email: penghao@whu.edu.cn Chemicals/CAS: water, 7732-18-5; Water Funding text 1: We also would like to thank both reviewers and editors for their very insightful comments and constructive suggestions that really helped us to improve the quality of our manuscript. AB - Purpose This paper focused on the design and optimization of ridge filter-based intensity-modulated proton therapy (IMPT), and its potential applications for FLASH. Differing from the standard pencil beam scanning (PBS) mode, no energy/layer switching is required and total treatment time can be shortened. Methods Unique dose-influence matrices were generated as a proton beam traverses through slabs of different thicknesses (i.e., modulation by different layers). To establish the references for comparison, conventional IMPT plans (single field) were created using a large-scale nonlinear solver. The spot weights from the reference IMPT plans were used as inputs for optimizing the design of ridge filters. Two designs were evaluated: model A (static) and model B (dynamic). The ridge filter designs were first verified (by GEANT4 simulation) in a water phantom and then in an H&N case. A direct comparison was made between the GEANT4 simulation results of two models and their respective references, with regard to plan quality, dose-averaged dose rate, and total treatment time. Results In both the water phantom and the H&N case, two models are able to modulate dose distributions with high conformity, showing no significant difference relative to the reference plans. Dose rate-volume histograms suggest that in order to achieve a dose rate of 40 Gy/s over 90% PTV, the beam intensity needs to be 2.5 x 10(11) protons/s for both models. For a fraction dose of 10 Gy, the total treatment time (including both irradiation time and dead time) can be shortened by a factor of 4.9 (model A) and 6.5 (model B), relative to the reference plans. Conclusion Two proposed designs (both static and dynamic) can be used for PBS-IMPT requiring no layer switching. They are promising candidates for FLASH-IMPT capable of reducing treatment time and achieving high dose rates while maintaining dose conformity simultaneously. LA - English DB - MTMT ER - TY - JOUR AU - Zhu, Hongyu AU - Xie, Dehuan AU - Yang, Yiwei AU - Huang, Shaomin AU - Gao, Xingwang AU - Peng, Yinglin AU - Wang, Bin AU - Wang, Jianxin AU - Xiao, Dexin AU - Wu, Dai AU - Li, Changzhi AU - Li, Chenghua AU - Qian, Chao-Nan AU - Deng, Xiaowu TI - Radioprotective effect of X-ray abdominal FLASH irradiation: Adaptation to oxidative damage and inflammatory response may be benefiting factors JF - MEDICAL PHYSICS J2 - MED PHYS VL - 49 PY - 2022 IS - 7 SP - 4812 EP - 4822 PG - 11 SN - 0094-2405 DO - 10.1002/mp.15680 UR - https://m2.mtmt.hu/api/publication/33423783 ID - 33423783 N1 - Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China Institute of Applied Electronics, China Academy of Engineering Physics, Mianyang, China Center of Growth, Metabolism and Aging, Key Laboratory of Biological Resources and Ecological Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China Department of Radiation Oncology, Guangzhou Concord Cancer Center, Guangzhou, China Cited By :6 Export Date: 11 May 2023 CODEN: MPHYA Correspondence Address: Deng, X.; Department of Radiation Oncology, China; email: dengxw@mail.sysu.edu.cn Correspondence Address: Qian, C.-N.; Department of Nasopharyngeal Carcinoma, China; email: qianchn@sysucc.org.cn Correspondence Address: Li, C.; Center of Growth, China; email: lichenghua@scu.edu.cn Chemicals/CAS: diamond, 7782-40-3; hydroethidine, 38483-26-0; isoflurane, 26675-46-7; malonaldehyde, 542-78-9; poly(methyl methacrylate), 39320-98-4, 9008-29-1; superoxide dismutase, 37294-21-6, 9016-01-7, 9054-89-1; Cytokines; Reactive Oxygen Species Tradenames: BC-2800Vet, Mindray, China; Geant4; ImageJ; Infinity, Elekta, Sweden Manufacturers: fankel industrial, China; Mindray, China; Solarbio, China; Olympus, Japan; Elekta, Sweden Funding details: National Natural Science Foundation of China, NSFC, 81872384, 82073220 Funding details: China Academy of Engineering Physics, CAEP Funding details: Tsinghua University, THU Funding details: Sichuan University, SCU Funding details: National Key Research and Development Program of China, NKRDPC, 2017YFC0113200 Funding text 1: The authors would like to thank Zhen Zhou, Lijun Shan, Xuming Shen, Tianhui He, Kui Zhou, Chenglong Lao, Yu Liu, Jie Liu, Longgang Yan, and Peng Li from China Academy of Engineering Physics; Zhen Liu and Long Bai from West China hospital; Shijie Fan and Li Chen from Sichuan University; Ankang Hu from Tsinghua University for their assistance during the FLASH irradiation experiments. Funding text 2: National Key R&D Program of China (2017YFC0113200 to X. Deng.), National Natural Science Foundation of China (No. 82073220 and No. 81872384 to C‐N. Qian., No. 11975218 to D. Wu.). AB - Background Ultrahigh dose-rate irradiation (FLASH-IR) was reported to be efficient in tumor control while reducing normal tissue radiotoxicity. However, the mechanism of such phenomenon is still unclear. Besides, the FLASH experiments using high energy X-ray, the most common modality in clinical radiotherapy, are rarely reported. This study aims to investigate the radiobiological response using 6 MV X-ray FLASH-IR or conventional dose-rate IR (CONV-IR). Methods The superconducting linac of Chengdu THz Free Electron Laser (CTFEL) facility was used for FLASH-IR, a diamond radiation detector and a CeBr3 scintillation detector were used to monitor the time structure and dose rate of FLASH pulses. BALB/c nude mice received whole abdominal 6 MV X-ray FLASH-IR or CONV-IR, the prescribed dose was 15 Gy or 10 Gy and the delivered absolute dose was monitored with EBT3 films. The mice were either euthanized 24 h post-IR to evaluate acute tissue responses or followed up for 6 weeks to observe late-stage responses and survival probability. Complete blood count, histological analyses, and measurement of cytokine expression and redox status were performed. Results The mean dose rate of >150 Gy/s and instantaneous dose rate of >5.5 x 10(5) Gy/s was reached in FLASH-IR at the center of mice body. After 6 weeks' follow-up of mice that received 15 Gy IR, the FLASH group showed faster body weight recovery and higher survival probability than the CONV group. Histological analysis showed that FLASH-IR induced less acute intestinal damage than CONV-IR. Complete blood count and cytokine concentration measurement found that the inflammatory blood cell counts and pro-inflammatory cytokine concentrations were elevated at the acute stage after both FLASH-IR and CONV-IR. However, FLASH irradiated mice had significantly fewer inflammatory blood cells and diminished pro-inflammatory cytokine at the late stage. Moreover, higher reactive oxygen species (ROS) signal intensities but significantly reduced lipid peroxidation were found in the FLASH group than in the CONV group in the acute stage. Conclusions The radioprotective effect of 6 MV X-ray FLASH-IR was observed. The differences in inflammatory responses and redox status between the two groups may be the factors responsible for reduced radiotoxicities following FLASH-IR. Further studies are required to thoroughly evaluate the impact of ROS on FLASH effect. LA - English DB - MTMT ER - TY - JOUR AU - Zou, W. AU - Kim, H. AU - Diffenderfer, E.S. AU - Carlson, D.J. AU - Koch, C.J. AU - Xiao, Y. AU - Teo, B.K. AU - Kim, M.M. AU - Metz, J.M. AU - Fan, Y. AU - Maity, A. AU - Koumenis, C. AU - Busch, T.M. AU - Wiersma, R. AU - Cengel, K.A. AU - Dong, L. TI - A phenomenological model of proton FLASH oxygen depletion effects depending on tissue vasculature and oxygen supply JF - FRONTIERS IN ONCOLOGY J2 - FRONT ONCOL VL - 12 PY - 2022 SN - 2234-943X DO - 10.3389/fonc.2022.1004121 UR - https://m2.mtmt.hu/api/publication/33810140 ID - 33810140 N1 - Cited By :1 Export Date: 11 May 2023 Correspondence Address: Zou, W.; Department of Radiation Oncology, United States; email: wei.zou@pennmedicine.upenn.edu Chemicals/CAS: oxygen, 7782-44-7; proton, 12408-02-5, 12586-59-3 Tradenames: IC-64 Funding details: National Institutes of Health, NIH, 1P01CA257904-01A1 Funding text 1: This work is supported by NIH 1P01CA257904-01A1. AB - Introduction: Radiation-induced oxygen depletion in tissue is assumed as a contributor to the FLASH sparing effects. In this study, we simulated the heterogeneous oxygen depletion in the tissue surrounding the vessels and calculated the proton FLASH effective-dose-modifying factor (FEDMF), which could be used for biology-based treatment planning. Methods: The dose and dose-weighted linear energy transfer (LET) of a small animal proton irradiator was simulated with Monte Carlo simulation. We deployed a parabolic partial differential equation to account for the generalized radiation oxygen depletion, tissue oxygen diffusion, and metabolic processes to investigate oxygen distribution in 1D, 2D, and 3D solution space. Dose and dose rates, particle LET, vasculature spacing, and blood oxygen supplies were considered. Using a similar framework for the hypoxic reduction factor (HRF) developed previously, the FEDMF was derived as the ratio of the cumulative normoxic-equivalent dose (CNED) between CONV and UHDR deliveries. Results: Dynamic equilibrium between oxygen diffusion and tissue metabolism can result in tissue hypoxia. The hypoxic region displayed enhanced radio-resistance and resulted in lower CNED under UHDR deliveries. In 1D solution, comparing 15 Gy proton dose delivered at CONV 0.5 and UHDR 125 Gy/s, 61.5% of the tissue exhibited ≥20% FEDMF at 175 μm vasculature spacing and 18.9 μM boundary condition. This percentage reduced to 34.5% and 0% for 8 and 2 Gy deliveries, respectively. Similar trends were observed in the 3D solution space. The FLASH versus CONV differential effect remained at larger vasculature spacings. A higher FLASH dose rate showed an increased region with ≥20% FEDMF. A higher LET near the proton Bragg peak region did not appear to alter the FLASH effect. Conclusion: We developed 1D, 2D, and 3D oxygen depletion simulation process to obtain the dynamic HRF and derive the proton FEDMF related to the dose delivery parameters and the local tissue vasculature information. The phenomenological model can be used to simulate or predict FLASH effects based on tissue vasculature and oxygen concentration data obtained from other experiments. Copyright © 2022 Zou, Kim, Diffenderfer, Carlson, Koch, Xiao, Teo, Kim, Metz, Fan, Maity, Koumenis, Busch, Wiersma, Cengel and Dong. LA - English DB - MTMT ER - TY - JOUR AU - Christensen, Jeppe Brage AU - Togno, Michele AU - Nesteruk, Konrad Pawel AU - Psoroulas, Serena AU - Meer, David AU - Weber, Damien Charles AU - Lomax, Tony AU - Yukihara, Eduardo G. AU - Safai, Sairos TI - Al2O3:C optically stimulated luminescence dosimeters (OSLDs) for ultra-high dose rate proton dosimetry JF - PHYSICS IN MEDICINE AND BIOLOGY J2 - PHYS MED BIOL VL - 66 PY - 2021 IS - 8 PG - 11 SN - 0031-9155 DO - 10.1088/1361-6560/abe554 UR - https://m2.mtmt.hu/api/publication/32381414 ID - 32381414 N1 - Department of Radiation Safety and Security, Paul Scherrer Institute, Switzerland Center for Proton Therapy, Paul Scherrer Institute, Switzerland Department of Radiation Oncology, University Hospital Zurich, Switzerland Department of Radiation Oncology, University Hospital Bern, Switzerland Department of Physics, ETH Zurich, Switzerland Cited By :3 Export Date: 14 February 2022 CODEN: PHMBA Correspondence Address: Yukihara, E.G.; Department of Radiation Safety and Security, Switzerland; email: eduardo.yukihara@psi.ch AB - The response of Al2O3:C optically stimulated luminescence detectors (OSLDs) was investigated in a 250 MeV pencil proton beam. The OSLD response was mapped for a wide range of average dose rates up to 9000 Gy s(-1), corresponding to a similar to 150 kGy s(-1) instantaneous dose rate in each pulse. Two setups for ultra-high dose rate (FLASH) experiments are presented, which enable OSLDs or biological samples to be irradiated in either water-filled vials or cylinders. The OSLDs were found to be dose rate independent for all dose rates, with an average deviation <1% relative to the nominal dose for average dose rates of (1-1000) Gy s(-1) when irradiated in the two setups. A third setup for irradiations in a 9000 Gy s(-1) pencil beam is presented, where OSLDs are distributed in a 3 x 4 grid. Calculations of the signal averaging of the beam over the OSLDs were in agreement with the measured response at 9000 Gy s(-1). Furthermore, a new method was presented to extract the beam spot size of narrow pencil beams, which is in agreement within a standard deviation with results derived from radiochromic films. The Al2O3:C OSLDs were found applicable to support radiobiological experiments in proton beams at ultra-high dose rates. LA - English DB - MTMT ER - TY - JOUR AU - Darafsheh, Arash AU - Hao, Yao AU - Zhao, Xiandong AU - Zwart, Townsend AU - Wagner, Miles AU - Evans, Tucker AU - Reynoso, Francisco AU - Zhao, Tianyu TI - Spread-out Bragg peak proton FLASH irradiation using a clinical synchrocyclotron: Proof of concept and ion chamber characterization JF - MEDICAL PHYSICS J2 - MED PHYS VL - 48 PY - 2021 IS - 8 SP - 4472 EP - 4484 PG - 13 SN - 0094-2405 DO - 10.1002/mp.15021 UR - https://m2.mtmt.hu/api/publication/32381407 ID - 32381407 N1 - Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, United States Mevion Medical Systems, Littleton, MA, United States Cited By :2 Export Date: 14 February 2022 CODEN: MPHYA Correspondence Address: Darafsheh, A.; Department of Radiation Oncology, United States; email: arash.darafsheh@wustl.edu AB - Purpose The purpose of this work is to (a) demonstrate the feasibility of delivering a spread-out Bragg peak (SOBP) proton beam in ultra-high dose rate (FLASH) using a proton therapy synchrocyclotron as a major step toward realizing an experimental platform for preclinical studies, and (b) evaluate the response of four models of ionization chambers in such a radiation field. Methods A clinical Mevion HYPERSCAN(R) synchrocyclotron was adjusted for ultra-high dose rate proton delivery. Protons with nominal energy of 230 MeV were delivered in pulses with temporal width ranging from 12.5 mu s to 24 mu s spanning from conventional to FLASH dose rates. A boron carbide absorber and a range modulator block were placed in the beam path for range modulation and creating an SOBP dose profile. The radiation field was defined by a brass aperture with 11 mm diameter. Two Faraday cups were used to determine the number of protons per pulse at various dose rates. The dosimetric response of two cylindrical (IBA CC04 and CC13) and two plane-parallel (IBA PPC05 and PTW Advanced Markus(R)) ionization chambers were evaluated. The dose rate was measured using the plane-parallel ionization chambers. The integral depth dose (IDD) was measured with a PTW Bragg Peak(R) ionization chamber. The lateral beam profile was measured with EBT-XD radiochromic film. Monte Carlo simulation was performed in TOPAS as the secondary check for the measurements and as a tool for further optimization of the range modulators' design. Results Faraday cups measurement showed that the maximum protons per pulse is 39.9 pC at 24 mu s pulse width. A good agreement between the measured and simulated IDD and lateral beam profiles was observed. The cylindrical ionization chambers showed very high ion recombination and deemed not suitable for absolute dosimetry at ultra-high dose rates. The average dose rate measured using the PPC05 ionization chamber was 163 Gy/s at the pristine Bragg peak and 126 Gy/s at 1 cm depth for the SOBP beam. The SOBP beam range and modulation were measured 24.4 mm and 19 mm, respectively. The pristine Bragg peak beam had 25.6 mm range. Simulation results showed that the IDD and profile flatness can be improved by the cavity diameter of the range modulator and the number of scanned spots, respectively. Conclusions Feasibility of delivering protons in an SOBP pattern with >100 Gy/s average dose rate using a clinical synchrocyclotron was demonstrated. The dose heterogeneity can be improved through optimization of the range modulator and number of delivered spots. Plane-parallel chambers with smaller gap between electrodes are more suitable for FLASH dosimetry compared to the other ion chambers used in this work. LA - English DB - MTMT ER -