FLASH Radiotherapy: History and Future

Lin, Baihan; Gao, Feng; Yang, Yiwei; Wu, Dongxu; Zhang, Yu; Feng, Gang; Dai, Tao; Du, Xiaobo

doi:10.3389/fonc.2021.644400

Cited by 97 publications

(91 citation statements)

References 49 publications

(68 reference statements)

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“…Moreover, the role of the dose-rate would be interesting to study in the context of partial body exposure during RT; for the same dose at a lower dose-rate (e.g., during brachytherapy), irradiation time increases and radiation damage is expected to become more normally distributed amongst cells, resulting in a lower mean dose per leukocyte. A novel promising radiotherapy treatment, FLASH radiotherapy, delivers ionising radiation at ultra-high dose rates (≥40 Gy/s), reducing treatment times and radiation-induced damage to healthy tissues [ 52 , 53 ]. In this type of exposure, only some circulating leukocytes would be exposed, but to a much higher dose.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Dynamics of DNA Damage Responsive Genes in Circulating Leukocytes during Radiotherapy

Cruz-García¹,

Nasser²,

O’Brien³

et al. 2022

Cancers

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External beam radiation therapy leads to cellular activation of the DNA damage response (DDR). DNA double-strand breaks (DSBs) activate the ATM/CHEK2/p53 pathway, inducing the transcription of stress genes. The dynamic nature of this transcriptional response has not been directly observed in vivo in humans. In this study we monitored the messenger RNA transcript abundances of nine DNA damage-responsive genes (CDKN1A, GADD45, CCNG1, FDXR, DDB2, MDM2, PHPT1, SESN1, and PUMA), eight of them regulated by p53 in circulating blood leukocytes at different time points (2, 6–8, 16–18, and 24 h) in cancer patients (lung, neck, brain, and pelvis) undergoing radiotherapy. We discovered that, although the calculated mean physical dose to the blood was very low (0.038–0.169 Gy), an upregulation of Ferredoxin reductase (FDXR) gene transcription was detectable 2 h after exposure and was dose dependent from the lowest irradiated percentage of the body (3.5% whole brain) to the highest, (up to 19.4%, pelvic zone) reaching a peak at 6–8 h. The radiation response of the other genes was not strong enough after such low doses to provide meaningful information. Following multiple fractions, the expression level increased further and was still significantly up-regulated by the end of the treatment. Moreover, we compared FDXR transcriptional responses to ionizing radiation (IR) in vivo with healthy donors’ blood cells exposed ex vivo and found a good correlation in the kinetics of expression from the 8-hours time-point onward, suggesting that a molecular transcriptional regulation mechanism yet to be identified is involved. To conclude, we provided the first in vivo human report of IR-induced gene transcription temporal response of a panel of p53-dependant genes. FDXR was demonstrated to be the most responsive gene, able to reliably inform on the low doses following partial body irradiation of the patients, and providing an expression pattern corresponding to the % of body exposed. An extended study would provide individual biological dosimetry information and may reveal inter-individual variability to predict radiotherapy-associated adverse health outcomes.

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Section: Discussionmentioning

confidence: 99%

Transcriptional Dynamics of DNA Damage Responsive Genes in Circulating Leukocytes during Radiotherapy

Cruz-García¹,

Nasser²,

O’Brien³

et al. 2022

Cancers

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“…There is an unmet need for comparative treatment planning study among different radiotherapy manners for patients to assess the potential benefits and limitations of different treatment modalities ( 11 ). In addition, there have been a number of preclinical studies based on cells and animals showing that ultra-high dose rate (FLASH) irradiation reduces damage to normal tissues while preserving the ability to treat tumors ( 150 ). As traditional therapeutic devices cannot meet the technical and safety requirements of FLASH radiotherapy, there are no publicly reported domestic studies on FLASH radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

Flourish of Proton and Carbon Ion Radiotherapy in China

Jiang

et al. 2022

Front. Oncol.

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Proton and heavy ion therapy offer superior relative biological effectiveness (RBE) in the treatment of deep-seated tumors compared with conventional photon radiotherapy due to its Bragg-peak feature of energy deposition in organs. Many proton and carbon ion therapy centers are active all over the world. At present, five particle radiotherapy institutes have been built and are receiving patient in China, mainly including Wanjie Proton Therapy Center (WPTC), Shanghai Proton Heavy Ion Center (SPHIC), Heavy Ion Cancer Treatment Center (HIMM), Chang Gung Memorial Hospital (CGMH), and Ruijin Hospital affiliated with Jiao Tong University. Many cancer patients have benefited from ion therapy, showing unique advantages over surgery and chemotherapy. By the end of 2020, nearly 8,000 patients had been treated with proton, carbon ion or carbon ion combined with proton therapy. So far, there is no systemic review for proton and carbon ion therapy facility and clinical outcome in China. We reviewed the development of proton and heavy ion therapy, as well as providing the representative clinical data and future directions for particle therapy in China. It has important guiding significance for the design and construction of new particle therapy center and patients’ choice of treatment equipment.

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“…High dose treatments are used in single dose fractions for large brain metastases and other focal lesions such as small peripheral lung tumors. Flash therapy administers higher doses of 10–20 Gy at a higher rate of delivery [ 66 , 67 ]. Therefore, evaluating the effect of higher radiation dose on biomarker release is important to consider for patients receiving radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

Identifying Candidate Biomarkers of Ionizing Radiation in Human Pulmonary Microvascular Lumens Using Microfluidics—A Pilot Study

et al. 2021

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The microvasculature system is critical for the delivery and removal of key nutrients and waste products and is significantly damaged by ionizing radiation. Single-cell capillaries and microvasculature structures are the primary cause of circulatory dysfunction, one that results in morbidities leading to progressive tissue and organ failure and premature death. Identifying tissue-specific biomarkers that are predictive of the extent of tissue and organ damage will aid in developing medical countermeasures for treating individuals exposed to ionizing radiation. In this pilot study, we developed and tested a 17 µL human-derived microvascular microfluidic lumen for identifying candidate biomarkers of ionizing radiation exposure. Through mass-spectrometry-based proteomics, we detected 35 proteins that may be candidate early biomarkers of ionizing radiation exposure. This pilot study demonstrates the feasibility of using humanized microfluidic and organ-on-a-chip systems for biomarker discovery studies. A more elaborate study of sufficient statistical power is needed to identify candidate biomarkers and test medical countermeasures of ionizing radiation.

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FLASH Radiotherapy: History and Future

Cited by 97 publications

References 49 publications

Transcriptional Dynamics of DNA Damage Responsive Genes in Circulating Leukocytes during Radiotherapy

Transcriptional Dynamics of DNA Damage Responsive Genes in Circulating Leukocytes during Radiotherapy

Flourish of Proton and Carbon Ion Radiotherapy in China

Identifying Candidate Biomarkers of Ionizing Radiation in Human Pulmonary Microvascular Lumens Using Microfluidics—A Pilot Study

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