剂量、剂量率和分割剂量对光子闪光灯照射后小鼠皮肤反应的影响

IF 5.3 1区医学 Q1 ONCOLOGY

Radiotherapy and Oncology Pub Date : 2025-09-06 DOI:10.1016/j.radonc.2025.111125

Kathryn H. Brown , Mihaela Ghita-Pettigrew , Malachy P. McIvor , Mark P. McDowell , Owen McLaughlin , Kevin M. Prise , Daniel Sforza , John W. Wong , Mohammad Rezaee , Stephen J. McMahon , Karl T. Butterworth

{"title":"剂量、剂量率和分割剂量对光子闪光灯照射后小鼠皮肤反应的影响","authors":"Kathryn H. Brown , Mihaela Ghita-Pettigrew , Malachy P. McIvor , Mark P. McDowell , Owen McLaughlin , Kevin M. Prise , Daniel Sforza , John W. Wong , Mohammad Rezaee , Stephen J. McMahon , Karl T. Butterworth","doi":"10.1016/j.radonc.2025.111125","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Preclinical evidence has demonstrated the potential of FLASH radiotherapy (FLASH-RT) to spare normal tissues compared to conventional (CONV) exposures. Most FLASH studies have used ultra-high dose rate (>40 Gy/sec) electrons and protons whilst comparatively few studies have reported photon FLASH responses. Given the widespread use of photons clinically, there is a need to characterise the FLASH effect using photons. In this study, we applied a novel photon FLASH system (FLASH-SARRP, Xstrahl) to investigate the effects of dose, dose rate and split dose on murine skin toxicity.</div></div><div><h3>Methods</h3><div>Skin toxicity was assessed at CONV (3.2 Gy/min) and FLASH (72 Gy/s) dose rates using the SARRP or FLASH-SARRP. CONV responses were investigated at a dose of 20.2 Gy and FLASH responses at doses of 18.1, 21.3 & 25.8 Gy. Comparative studies were conducted using a split dose exposure with an average dose rate of 2.8 Gy/s. Skin toxicity on the hind leg of C57BL/6 mice was visually scored and histopathological analysis performed at 8–12 weeks. Tumour growth delay was also assessed using a melanoma (B16-F10) xenograft model irradiated at FLASH and CONV dose rates.</div></div><div><h3>Results</h3><div>Skin toxicity was delayed for FLASH exposures and tissue analysis showed hyperplasia and significant fibrosis deposition (p < 0.01) in CONV mice compared to FLASH. Tissue recovery was observed for both dose rates from 8 weeks post RT. A dose dependent relationship for FLASH sparing was observed, while a split dose exposure resulted in loss of sparing. FLASH was equally effective for tumour control in comparison to CONV exposures (p = 0.99).</div></div><div><h3>Conclusions</h3><div>These results demonstrate it is feasible to deliver photon FLASH exposures with sparing consistent with observations from previous studies using proton and electron beams. Dose, average dose rate and beam structure are key parameters that modulate radiobiological responses to photon FLASH.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"212 ","pages":"Article 111125"},"PeriodicalIF":5.3000,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Dose, dose rate and split dose impacts murine skin responses following photon FLASH irradiation\",\"authors\":\"Kathryn H. Brown , Mihaela Ghita-Pettigrew , Malachy P. McIvor , Mark P. McDowell , Owen McLaughlin , Kevin M. Prise , Daniel Sforza , John W. Wong , Mohammad Rezaee , Stephen J. McMahon , Karl T. Butterworth\",\"doi\":\"10.1016/j.radonc.2025.111125\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><div>Preclinical evidence has demonstrated the potential of FLASH radiotherapy (FLASH-RT) to spare normal tissues compared to conventional (CONV) exposures. Most FLASH studies have used ultra-high dose rate (>40 Gy/sec) electrons and protons whilst comparatively few studies have reported photon FLASH responses. Given the widespread use of photons clinically, there is a need to characterise the FLASH effect using photons. In this study, we applied a novel photon FLASH system (FLASH-SARRP, Xstrahl) to investigate the effects of dose, dose rate and split dose on murine skin toxicity.</div></div><div><h3>Methods</h3><div>Skin toxicity was assessed at CONV (3.2 Gy/min) and FLASH (72 Gy/s) dose rates using the SARRP or FLASH-SARRP. CONV responses were investigated at a dose of 20.2 Gy and FLASH responses at doses of 18.1, 21.3 & 25.8 Gy. Comparative studies were conducted using a split dose exposure with an average dose rate of 2.8 Gy/s. Skin toxicity on the hind leg of C57BL/6 mice was visually scored and histopathological analysis performed at 8–12 weeks. Tumour growth delay was also assessed using a melanoma (B16-F10) xenograft model irradiated at FLASH and CONV dose rates.</div></div><div><h3>Results</h3><div>Skin toxicity was delayed for FLASH exposures and tissue analysis showed hyperplasia and significant fibrosis deposition (p < 0.01) in CONV mice compared to FLASH. Tissue recovery was observed for both dose rates from 8 weeks post RT. A dose dependent relationship for FLASH sparing was observed, while a split dose exposure resulted in loss of sparing. FLASH was equally effective for tumour control in comparison to CONV exposures (p = 0.99).</div></div><div><h3>Conclusions</h3><div>These results demonstrate it is feasible to deliver photon FLASH exposures with sparing consistent with observations from previous studies using proton and electron beams. Dose, average dose rate and beam structure are key parameters that modulate radiobiological responses to photon FLASH.</div></div>\",\"PeriodicalId\":21041,\"journal\":{\"name\":\"Radiotherapy and Oncology\",\"volume\":\"212 \",\"pages\":\"Article 111125\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2025-09-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Radiotherapy and Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0167814025046298\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Radiotherapy and Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0167814025046298","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

临床前证据表明，与常规（CONV）照射相比，FLASH放疗（FLASH- rt）有可能保护正常组织。大多数FLASH研究使用了超高剂量率（>40 Gy/sec）的电子和质子，而相对较少的研究报道了光子FLASH响应。鉴于光子在临床上的广泛应用，有必要用光子来描述FLASH效应。在本研究中，我们采用一种新型的光子FLASH系统（FLASH- sarrp, Xstrahl）研究了剂量、剂量率和分离剂量对小鼠皮肤毒性的影响。方法采用SARRP或FLASH-SARRP在CONV （3.2 Gy/min）和FLASH （72 Gy/s）剂量率下进行皮肤毒性评价。在20.2 Gy剂量下研究了CONV反应，在18.1、21.3和25.8 Gy剂量下研究了FLASH反应。采用平均剂量率为2.8 Gy/s的分次剂量照射进行了比较研究。8-12周时对C57BL/6小鼠后腿皮肤毒性进行目测评分和组织病理学分析。肿瘤生长延迟也通过在FLASH和CONV剂量率下照射的黑色素瘤（B16-F10）异种移植模型进行评估。结果与FLASH相比，暴露于FLASH的小鼠皮肤毒性延迟，组织分析显示CONV小鼠的增生和显著的纤维化沉积（p < 0.01）。在两种剂量率下，从大鼠放疗后8周开始观察到组织恢复。观察到FLASH保留的剂量依赖关系，而分开剂量暴露导致保留的丧失。与CONV暴露相比，FLASH对肿瘤控制同样有效（p = 0.99）。结论这些结果表明，与先前使用质子和电子束的研究结果一致，提供光子闪光照射是可行的。剂量、平均剂量率和光束结构是调节光子FLASH辐射生物学响应的关键参数。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Dose, dose rate and split dose impacts murine skin responses following photon FLASH irradiation

Introduction

Preclinical evidence has demonstrated the potential of FLASH radiotherapy (FLASH-RT) to spare normal tissues compared to conventional (CONV) exposures. Most FLASH studies have used ultra-high dose rate (>40 Gy/sec) electrons and protons whilst comparatively few studies have reported photon FLASH responses. Given the widespread use of photons clinically, there is a need to characterise the FLASH effect using photons. In this study, we applied a novel photon FLASH system (FLASH-SARRP, Xstrahl) to investigate the effects of dose, dose rate and split dose on murine skin toxicity.

Methods

Skin toxicity was assessed at CONV (3.2 Gy/min) and FLASH (72 Gy/s) dose rates using the SARRP or FLASH-SARRP. CONV responses were investigated at a dose of 20.2 Gy and FLASH responses at doses of 18.1, 21.3 & 25.8 Gy. Comparative studies were conducted using a split dose exposure with an average dose rate of 2.8 Gy/s. Skin toxicity on the hind leg of C57BL/6 mice was visually scored and histopathological analysis performed at 8–12 weeks. Tumour growth delay was also assessed using a melanoma (B16-F10) xenograft model irradiated at FLASH and CONV dose rates.

Results

Skin toxicity was delayed for FLASH exposures and tissue analysis showed hyperplasia and significant fibrosis deposition (p < 0.01) in CONV mice compared to FLASH. Tissue recovery was observed for both dose rates from 8 weeks post RT. A dose dependent relationship for FLASH sparing was observed, while a split dose exposure resulted in loss of sparing. FLASH was equally effective for tumour control in comparison to CONV exposures (p = 0.99).

Conclusions

These results demonstrate it is feasible to deliver photon FLASH exposures with sparing consistent with observations from previous studies using proton and electron beams. Dose, average dose rate and beam structure are key parameters that modulate radiobiological responses to photon FLASH.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Radiotherapy and Oncology 医学-核医学

CiteScore

10.30

自引率

10.50%

发文量

2445

审稿时长

45 days

期刊介绍： Radiotherapy and Oncology publishes papers describing original research as well as review articles. It covers areas of interest relating to radiation oncology. This includes: clinical radiotherapy, combined modality treatment, translational studies, epidemiological outcomes, imaging, dosimetry, and radiation therapy planning, experimental work in radiobiology, chemobiology, hyperthermia and tumour biology, as well as data science in radiation oncology and physics aspects relevant to oncology.Papers on more general aspects of interest to the radiation oncologist including chemotherapy, surgery and immunology are also published.