Examining the Occurrence of the FLASH Effect in Animal Models: A Systematic Review and Meta-Analysis of Ultra-High Dose Rate Proton or Carbon Ion Irradiation

Purpose: This systematic review and meta-analysis sought to assess whether ultra-high dose rate (UHDR) ion irradiations can induce the FLASH effect in animal models. Methods: A comprehensive search of the Web of Science, PubMed, and EMBASE databases was conducted from inception until March 20, 2023,...

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Main Authors: Xun Wu MD, Hongtao Luo MD, Qian Wang MD, Tianqi Du MD, Yanliang Chen MD, Mingyu Tan MD, Ruifeng Liu MD, Zhiqiang Liu MR, Shilong Sun MR, Kehu Yang PhD, Jinhui Tian PhD, Qiuning Zhang MD
Format: Article
Language:English
Published: SAGE Publishing 2024-11-01
Series:Technology in Cancer Research & Treatment
Online Access:https://doi.org/10.1177/15330338241289990
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author Xun Wu MD
Hongtao Luo MD
Qian Wang MD
Tianqi Du MD
Yanliang Chen MD
Mingyu Tan MD
Ruifeng Liu MD
Zhiqiang Liu MR
Shilong Sun MR
Kehu Yang PhD
Jinhui Tian PhD
Qiuning Zhang MD
author_facet Xun Wu MD
Hongtao Luo MD
Qian Wang MD
Tianqi Du MD
Yanliang Chen MD
Mingyu Tan MD
Ruifeng Liu MD
Zhiqiang Liu MR
Shilong Sun MR
Kehu Yang PhD
Jinhui Tian PhD
Qiuning Zhang MD
author_sort Xun Wu MD
collection DOAJ
description Purpose: This systematic review and meta-analysis sought to assess whether ultra-high dose rate (UHDR) ion irradiations can induce the FLASH effect in animal models. Methods: A comprehensive search of the Web of Science, PubMed, and EMBASE databases was conducted from inception until March 20, 2023, to identify studies involving irradiated animals subjected to proton or carbon ion beams at varying dose rates. The research content should include various indicators that can reflect the effect and safety of radiation, such as survival, normal tissue toxicity, inflammatory response, tumor volume, etc Results: Compared to conventional dose rate (CONV) ion irradiations, UHDR ion irradiations can significantly improve mouse survival (HR 0.48, 95% CI 0.29 to 0.78, I 2  = 0%) and maintain comparable tumor control. There was no significant impact of different dose rates on the survival of zebrafish embryos (SMD 0.11, 95% CI −0.31 to 0.53, I 2  = 85%). Subgroup analysis showed that radiation dose was an important factor affecting the survival of zebrafish embryos. Achieving normal tissue sparing may require higher radiation dose under UHD.In mouse and zebrafish embryo models, normal tissue sparing did not always occur after UHDR ion irradiations. In addition, only a limited number of cytokines (CXCL1, IL-6, GM-CSF, G-CSF, HMGB1, and TGF-β) and immune cells (microglia and myeloid cells) showed differences at different dose rates. Conclusions: UHDR ion irradiation can achieve FLASH effect, but the reproducibility of normal tissue sparing remains a challenge. Compared to CONV irradiation, UHDR ion irradiations demonstrated equivalent or even superior tumor control.
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spelling doaj-art-63a4ff8d569e4427bcdcfb7aa5e9c3c62025-08-20T02:13:10ZengSAGE PublishingTechnology in Cancer Research & Treatment1533-03382024-11-012310.1177/15330338241289990Examining the Occurrence of the FLASH Effect in Animal Models: A Systematic Review and Meta-Analysis of Ultra-High Dose Rate Proton or Carbon Ion IrradiationXun Wu MD0Hongtao Luo MD1Qian Wang MD2Tianqi Du MD3Yanliang Chen MD4Mingyu Tan MD5Ruifeng Liu MD6Zhiqiang Liu MR7Shilong Sun MR8Kehu Yang PhD9Jinhui Tian PhD10Qiuning Zhang MD11 The First School of Clinical Medicine, , No.1 Donggang West Road, Chengguan District, Lanzhou 730000, People's Republic of China , 509 Nanchang Road, Chengguan District, Lanzhou 730000, People's Republic of China The First School of Clinical Medicine, , No.1 Donggang West Road, Chengguan District, Lanzhou 730000, People's Republic of China The First School of Clinical Medicine, , No.1 Donggang West Road, Chengguan District, Lanzhou 730000, People's Republic of China The First School of Clinical Medicine, , No.1 Donggang West Road, Chengguan District, Lanzhou 730000, People's Republic of China The First School of Clinical Medicine, , No.1 Donggang West Road, Chengguan District, Lanzhou 730000, People's Republic of China , 509 Nanchang Road, Chengguan District, Lanzhou 730000, People's Republic of China , 509 Nanchang Road, Chengguan District, Lanzhou 730000, People's Republic of China , 509 Nanchang Road, Chengguan District, Lanzhou 730000, People's Republic of China Evidence-Based Medicine Center, School of Basic Medical Sciences, , 222 Tianshui South Road, Chengguan District, Lanzhou 730000, People's Republic of China Evidence-Based Medicine Center, School of Basic Medical Sciences, , 222 Tianshui South Road, Chengguan District, Lanzhou 730000, People's Republic of China Graduate School, University of Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing 100000, People's Republic of ChinaPurpose: This systematic review and meta-analysis sought to assess whether ultra-high dose rate (UHDR) ion irradiations can induce the FLASH effect in animal models. Methods: A comprehensive search of the Web of Science, PubMed, and EMBASE databases was conducted from inception until March 20, 2023, to identify studies involving irradiated animals subjected to proton or carbon ion beams at varying dose rates. The research content should include various indicators that can reflect the effect and safety of radiation, such as survival, normal tissue toxicity, inflammatory response, tumor volume, etc Results: Compared to conventional dose rate (CONV) ion irradiations, UHDR ion irradiations can significantly improve mouse survival (HR 0.48, 95% CI 0.29 to 0.78, I 2  = 0%) and maintain comparable tumor control. There was no significant impact of different dose rates on the survival of zebrafish embryos (SMD 0.11, 95% CI −0.31 to 0.53, I 2  = 85%). Subgroup analysis showed that radiation dose was an important factor affecting the survival of zebrafish embryos. Achieving normal tissue sparing may require higher radiation dose under UHD.In mouse and zebrafish embryo models, normal tissue sparing did not always occur after UHDR ion irradiations. In addition, only a limited number of cytokines (CXCL1, IL-6, GM-CSF, G-CSF, HMGB1, and TGF-β) and immune cells (microglia and myeloid cells) showed differences at different dose rates. Conclusions: UHDR ion irradiation can achieve FLASH effect, but the reproducibility of normal tissue sparing remains a challenge. Compared to CONV irradiation, UHDR ion irradiations demonstrated equivalent or even superior tumor control.https://doi.org/10.1177/15330338241289990
spellingShingle Xun Wu MD
Hongtao Luo MD
Qian Wang MD
Tianqi Du MD
Yanliang Chen MD
Mingyu Tan MD
Ruifeng Liu MD
Zhiqiang Liu MR
Shilong Sun MR
Kehu Yang PhD
Jinhui Tian PhD
Qiuning Zhang MD
Examining the Occurrence of the FLASH Effect in Animal Models: A Systematic Review and Meta-Analysis of Ultra-High Dose Rate Proton or Carbon Ion Irradiation
Technology in Cancer Research & Treatment
title Examining the Occurrence of the FLASH Effect in Animal Models: A Systematic Review and Meta-Analysis of Ultra-High Dose Rate Proton or Carbon Ion Irradiation
title_full Examining the Occurrence of the FLASH Effect in Animal Models: A Systematic Review and Meta-Analysis of Ultra-High Dose Rate Proton or Carbon Ion Irradiation
title_fullStr Examining the Occurrence of the FLASH Effect in Animal Models: A Systematic Review and Meta-Analysis of Ultra-High Dose Rate Proton or Carbon Ion Irradiation
title_full_unstemmed Examining the Occurrence of the FLASH Effect in Animal Models: A Systematic Review and Meta-Analysis of Ultra-High Dose Rate Proton or Carbon Ion Irradiation
title_short Examining the Occurrence of the FLASH Effect in Animal Models: A Systematic Review and Meta-Analysis of Ultra-High Dose Rate Proton or Carbon Ion Irradiation
title_sort examining the occurrence of the flash effect in animal models a systematic review and meta analysis of ultra high dose rate proton or carbon ion irradiation
url https://doi.org/10.1177/15330338241289990
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