FLASH Radiotherapy: Expectations, Challenges, and Current Knowledge

Borghini, Andrea; Labate, Luca; Piccinini, Simona; Panaino, Costanza Maria Vittoria; Andreassi, Maria Grazia; Gizzi, Leonida Antonio

doi:10.3390/ijms25052546

Cited by 5 publications

(3 citation statements)

References 90 publications

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“…FLASH radiotherapy (FLASH RT) is based on the tissue-sparing effects of ultra-high dose rate (UHDR) radiotherapy. In order to understand the FLASH effect, it is important to know how cells react to DNA damage [41]. FLASH RT is currently being tested as an innovative cancer treatment in clinical research.…”

Section: Consequences Of Ionizing Radiation To the Human Bodymentioning

confidence: 99%

Health Effects of Ionizing Radiation on the Human Body

Talapko,

Katalinić

et al. 2024

Medicina

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Radioactivity is a process in which the nuclei of unstable atoms spontaneously decay, producing other nuclei and releasing energy in the form of ionizing radiation in the form of alpha (α) and beta (β) particles as well as the emission of gamma (γ) electromagnetic waves. People may be exposed to radiation in various forms, as casualties of nuclear accidents, workers in power plants, or while working and using different radiation sources in medicine and health care. Acute radiation syndrome (ARS) occurs in subjects exposed to a very high dose of radiation in a very short period of time. Each form of radiation has a unique pathophysiological effect. Unfortunately, higher organisms—human beings—in the course of evolution have not acquired receptors for the direct “capture” of radiation energy, which is transferred at the level of DNA, cells, tissues, and organs. Radiation in biological systems depends on the amount of absorbed energy and its spatial distribution, particularly depending on the linear energy transfer (LET). Photon radiation with low LET leads to homogeneous energy deposition in the entire tissue volume. On the other hand, radiation with a high LET produces a fast Bragg peak, which generates a low input dose, whereby the penetration depth into the tissue increases with the radiation energy. The consequences are mutations, apoptosis, the development of cancer, and cell death. The most sensitive cells are those that divide intensively—bone marrow cells, digestive tract cells, reproductive cells, and skin cells. The health care system and the public should raise awareness of the consequences of ionizing radiation. Therefore, our aim is to identify the consequences of ARS taking into account radiation damage to the respiratory system, nervous system, hematopoietic system, gastrointestinal tract, and skin.

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Section: Consequences Of Ionizing Radiation To the Human Bodymentioning

confidence: 99%

Health Effects of Ionizing Radiation on the Human Body

Talapko,

Katalinić

et al. 2024

Medicina

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“…Lack of clinical data, uncertainty about tumor metastasis, unclear long-term effects, limited equipment, and questions regarding treatment planning systems must be addressed the successful integration of FLASH-RT into mainstream radiotherapy practices [20,25,106]. The potential benefits of FLASH-RT based on expectations and current knowledge [107] make it a promising avenue for the future of cancer treatment [10]. However, extensive research, clinical trials, and technological advancements are essential to overcome current limitations and ensure its safe and effective application.…”

Section: Future Prospectivementioning

confidence: 99%

Mechanisms of Action in FLASH Radiotherapy: A Comprehensive Review of Physicochemical and Biological Processes on Cancerous and Normal Cells

Chow,

Ruda

2024

Cells

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The advent of FLASH radiotherapy (FLASH-RT) has brought forth a paradigm shift in cancer treatment, showcasing remarkable normal cell sparing effects with ultra-high dose rates (>40 Gy/s). This review delves into the multifaceted mechanisms underpinning the efficacy of FLASH effect, examining both physicochemical and biological hypotheses in cell biophysics. The physicochemical process encompasses oxygen depletion, reactive oxygen species, and free radical recombination. In parallel, the biological process explores the FLASH effect on the immune system and on blood vessels in treatment sites such as the brain, lung, gastrointestinal tract, skin, and subcutaneous tissue. This review investigated the selective targeting of cancer cells and the modulation of the tumor microenvironment through FLASH-RT. Examining these mechanisms, we explore the implications and challenges of integrating FLASH-RT into cancer treatment. The potential to spare normal cells, boost the immune response, and modify the tumor vasculature offers new therapeutic strategies. Despite progress in understanding FLASH-RT, this review highlights knowledge gaps, emphasizing the need for further research to optimize its clinical applications. The synthesis of physicochemical and biological insights serves as a comprehensive resource for cell biology, molecular biology, and biophysics researchers and clinicians navigating the evolution of FLASH-RT in cancer therapy.

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“…The potential differential responses of cancer cells and normal cells to the proposed irradiation setup available in our facility were evaluated by measuring induced double-strand DNA breaks in comparison to X-rays. First step necessary to determine if a certain radiation source and applied protocol has the potential to become one of the elements in the oncologists’ toolbox to be used in the fight against tumours is to evaluate its DNA damage inducing capacity 25 . This step was crucial for demonstrating the quality potential of VHEEs generated by LPA, thus faciliting new opportunities for extensive utilization in clinical studies.…”

Section: Introductionmentioning

confidence: 99%

First in vitro cell co-culture experiments using laser-induced high-energy electron FLASH irradiation for the development of anti-cancer therapeutic strategies

Orobeti,

Sima,

Porosnicu

et al. 2024

Sci Rep

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Radiation delivery at ultrahigh dose rates (UHDRs) has potential for use as a new anticancer therapeutic strategy. The FLASH effect induced by UHDR irradiation has been shown to maintain antitumour efficacy with a reduction in normal tissue toxicity; however, the FLASH effect has been difficult to demonstrate in vitro. The objective to demonstrate the FLASH effect in vitro is challenging, aiming to reveal a differential response between cancer and normal cells to further identify cell molecular mechanisms. New high-intensity petawatt laser-driven accelerators can deliver very high-energy electrons (VHEEs) at dose rates as high as 1013 Gy/s in very short pulses (10–13 s). Here, we present the first in vitro experiments carried out on cancer cells and normal non-transformed cells concurrently exposed to laser-plasma accelerated (LPA) electrons. Specifically, melanoma cancer cells and normal melanocyte co-cultures grown on chamber slides were simultaneously irradiated with LPA electrons. A non-uniform dose distribution on the cell cultures was revealed by Gafchromic films placed behind the chamber slide supporting the cells. In parallel experiments, cell co-cultures were exposed to pulsed X-ray irradiation, which served as positive controls for radiation-induced nuclear DNA double-strand breaks. By measuring the impact on discrete areas of the cell monolayers, the greatest proportion of the damaged DNA-containing nuclei was attained by the LPA electrons at a cumulative dose one order of magnitude lower than the dose obtained by pulsed X-ray irradiation. Interestingly, in certain discrete areas, we observed that LPA electron exposure had a different effect on the DNA damage in healthy normal human epidermal melanocyte (NHEM) cells than in A375 melanoma cells; here, the normal cells were less affected by the LPA exposure than cancer cells. This result is the first in vitro demonstration of a differential response of tumour and normal cells exposed to FLASH irradiation and may contribute to the development of new cell culture strategies to explore fundamental understanding of FLASH-induced cell effect.

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FLASH Radiotherapy: Expectations, Challenges, and Current Knowledge

Cited by 5 publications

References 90 publications

Health Effects of Ionizing Radiation on the Human Body

Health Effects of Ionizing Radiation on the Human Body

Mechanisms of Action in FLASH Radiotherapy: A Comprehensive Review of Physicochemical and Biological Processes on Cancerous and Normal Cells

First in vitro cell co-culture experiments using laser-induced high-energy electron FLASH irradiation for the development of anti-cancer therapeutic strategies

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