First Human Cell Experiments With FLASH Carbon Ions

Tashiro, Mitsuru; Yoshida, Yukari; Oike, Takahiro; Nakao, Masao; Yusa, K.; Hirota, Yuka; Ohno, Tatsuya

doi:10.21873/anticanres.15725

Cited by 15 publications

(9 citation statements)

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“…A promising modification of C-ion therapy is ultra-high dose rate (FLASH) irradiation, which is expected to reduce radiotoxicity. Pilot experiments using a mouse model of osteosarcoma and human fibroblasts support this assumption [76,77].…”

Section: Carbon Ionsmentioning

confidence: 86%

Particle Therapy: Clinical Applications and Biological Effects

Kiseleva

Гордон

Vishnyakova

et al. 2022

Life

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Particle therapy is a developing area of radiotherapy, mostly involving the use of protons, neutrons and carbon ions for cancer treatment. The reduction of side effects on healthy tissues in the peritumoral area is an important advantage of particle therapy. In this review, we analyze state-of-the-art particle therapy, as compared to conventional photon therapy, to identify clinical benefits and specify the mechanisms of action on tumor cells. Systematization of published data on particle therapy confirms its successful application in a wide range of cancers and reveals a variety of biological effects which manifest at the molecular level and produce the particle therapy-specific molecular signatures. Given the rapid progress in the field, the use of particle therapy holds great promise for the near future.

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Section: Carbon Ionsmentioning

confidence: 86%

Particle Therapy: Clinical Applications and Biological Effects

Kiseleva

Гордон

Vishnyakova

et al. 2022

Life

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“…The SP file basically consists of the position of the beam spots over which the center of the pencil beam is guided over, and the corresponding number of ions represented in the monitor unit, that should be applied to the individual beam positions. The pattern for the uHDR irradiation consists of 7×7 beam spot positions, as shown in Figure 1C, with a grid spacing of 3 mm and a fixed number of 3.125×10 7 ions per beam position. Disposed spots were introduced not to use a rising region of the beam current for creating the field (Figure 1C).…”

Section: Methodsmentioning

confidence: 99%

“…Tinganelli et al showed the FLASH effect on Chinese hamster ovary cells (CHO-K1) with a carbon-ion beam with 7.4 Gy at 70 Gy/s at 13 keV/μm of dose averaged LET in hypoxia (5) and on C3H/He mice osteosarcoma in the hind limb with 18 Gy at 100 Gy/s at about 15 keV/μm (6). However, no FLASH effect was observed in HFL1 and HSGc-C5 cells with 1-3 Gy at 96-195 Gy/s at 13 or 50 keV/μm under aerobic condition (7). The mechanism of the FLASH effect in carbon-ion beam has been postulated (3), including oxygen depletion, radical recombination, in which a high transient concentration of peroxyl radicals results in less oxidation damage to normal tissue, and intertrack effects, in which intertrack recombination for positively charged particle beams determines radiation chemical driven biological consequences of radiation exposure, but is unknown.…”

mentioning

confidence: 92%

Ultra-high Dose-rate Carbon-ion Scanning Beam With a Compact Medical Synchrotron Contributing to Further Development of FLASH Irradiation

et al. 2023

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Background/Aim: The focus of this report is establishing an irradiation arrangement to realize an ultrahigh dose-rate (uHDR; FLASH) of scanned carbon-ion irradiation possible with a compact commonly available medical synchrotron. Materials and Methods: Following adjustments to the operation it became possible to extract ≥1.0×10 9 carbon ions at 208.3 MeV/u (86 mm in range) per 100 ms. The design takes the utmost care to prevent damage to monitors, particularly in the nozzle, achieved by the uHDR beam not passing through this part of the apparatus. Doses were adjusted by extraction times, using a function generator. After one scan by the carbon-ion beam it became possible to create a field within the extraction time. The Advanced Markus chamber (AMC) and Gafchromic film are then able to measure the absolute dose and field size at a plateau depth, with the operating voltage of the chamber at 400 V at the uHDR for the AMC. Results: The beam scanning utilizing this uHDR irradiation could be confirmed at a dose of 6.5±0.08 Gy (±3% homogeneous) at this volume over at least 16×16 mm 2 corresponding to a dose-rate of 92.3 Gy/s (±1.3%). The dose was ca. 0.7, 1.5, 2.9, and 5.4 Gy depending on dose-rate and field size, with the rate of killed cells increasing with the irradiation dose. Conclusion: The compact medical synchrotron achieved FLASH dose-rates of >40 Gy/s at different dose levels and in useful field sizes for research with the apparatus and arrangement developed here.

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“…The experimental results obtained so far were in good accordance with the FLASH studies in which sparsely ionizing radiation was used. The FLASH effect was not observed for carbon ion irradiation in vitro under ambient oxygen concentrations in HFL1 lung fibroblasts and HSGc-C5 salivary gland cancer cells [ 59 ] or in CHO-K1 cells under anoxic and normoxic conditions. However, the protective effect was observed in the CHO-K1 cells at 0.5% and 4% O 2 concentrations [ 58 ].…”

Section: Beam Parameters Necessary To Trigger the Flash Effectmentioning

confidence: 99%

Potential Molecular Mechanisms behind the Ultra-High Dose Rate “FLASH” Effect

Bogaerts

Macaeva

Isebaert

et al. 2022

IJMS

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FLASH radiotherapy, or the delivery of a dose at an ultra-high dose rate (>40 Gy/s), has recently emerged as a promising tool to enhance the therapeutic index in cancer treatment. The remarkable sparing of normal tissues and equivalent tumor control by FLASH irradiation compared to conventional dose rate irradiation—the FLASH effect—has already been demonstrated in several preclinical models and even in a first patient with T-cell cutaneous lymphoma. However, the biological mechanisms responsible for the differential effect produced by FLASH irradiation in normal and cancer cells remain to be elucidated. This is of great importance because a good understanding of the underlying radiobiological mechanisms and characterization of the specific beam parameters is required for a successful clinical translation of FLASH radiotherapy. In this review, we summarize the FLASH investigations performed so far and critically evaluate the current hypotheses explaining the FLASH effect, including oxygen depletion, the production of reactive oxygen species, and an altered immune response. We also propose a new theory that assumes an important role of mitochondria in mediating the normal tissue and tumor response to FLASH dose rates.

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First Human Cell Experiments With FLASH Carbon Ions

Cited by 15 publications

References 0 publications

Particle Therapy: Clinical Applications and Biological Effects

Particle Therapy: Clinical Applications and Biological Effects

Ultra-high Dose-rate Carbon-ion Scanning Beam With a Compact Medical Synchrotron Contributing to Further Development of FLASH Irradiation

Potential Molecular Mechanisms behind the Ultra-High Dose Rate “FLASH” Effect

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