Abdominal FLASH irradiation reduces radiation-induced gastrointestinal toxicity for the treatment of ovarian cancer in mice

Abstract Radiation therapy is the most effective cytotoxic therapy for localized tumors. However, normal tissue toxicity limits the radiation dose and the curative potential of radiation therapy when treating larger target volumes. In particular, the highly radiosensitive intestine limits the use of...

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Autores principales:	Karen Levy, Suchitra Natarajan, Jinghui Wang, Stephanie Chow, Joshua T. Eggold, Phoebe E. Loo, Rakesh Manjappa, Stavros Melemenidis, Frederick M. Lartey, Emil Schüler, Lawrie Skinner, Marjan Rafat, Ryan Ko, Anna Kim, Duaa H. Al-Rawi, Rie von Eyben, Oliver Dorigo, Kerriann M. Casey, Edward E. Graves, Karl Bush, Amy S. Yu, Albert C. Koong, Peter G. Maxim, Billy W. Loo, Erinn B. Rankin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e19427aedbeb4ad9ab2df08481282096
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spelling	oai:doaj.org-article:e19427aedbeb4ad9ab2df084812820962021-12-02T16:18:04ZAbdominal FLASH irradiation reduces radiation-induced gastrointestinal toxicity for the treatment of ovarian cancer in mice10.1038/s41598-020-78017-72045-2322https://doaj.org/article/e19427aedbeb4ad9ab2df084812820962020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78017-7https://doaj.org/toc/2045-2322Abstract Radiation therapy is the most effective cytotoxic therapy for localized tumors. However, normal tissue toxicity limits the radiation dose and the curative potential of radiation therapy when treating larger target volumes. In particular, the highly radiosensitive intestine limits the use of radiation for patients with intra-abdominal tumors. In metastatic ovarian cancer, total abdominal irradiation (TAI) was used as an effective postsurgical adjuvant therapy in the management of abdominal metastases. However, TAI fell out of favor due to high toxicity of the intestine. Here we utilized an innovative preclinical irradiation platform to compare the safety and efficacy of TAI ultra-high dose rate FLASH irradiation to conventional dose rate (CONV) irradiation in mice. We demonstrate that single high dose TAI-FLASH produced less mortality from gastrointestinal syndrome, spared gut function and epithelial integrity, and spared cell death in crypt base columnar cells compared to TAI-CONV irradiation. Importantly, TAI-FLASH and TAI-CONV irradiation had similar efficacy in reducing tumor burden while improving intestinal function in a preclinical model of ovarian cancer metastasis. These findings suggest that FLASH irradiation may be an effective strategy to enhance the therapeutic index of abdominal radiotherapy, with potential application to metastatic ovarian cancer.Karen LevySuchitra NatarajanJinghui WangStephanie ChowJoshua T. EggoldPhoebe E. LooRakesh ManjappaStavros MelemenidisFrederick M. LarteyEmil SchülerLawrie SkinnerMarjan RafatRyan KoAnna KimDuaa H. Al-RawiRie von EybenOliver DorigoKerriann M. CaseyEdward E. GravesKarl BushAmy S. YuAlbert C. KoongPeter G. MaximBilly W. LooErinn B. RankinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Karen Levy Suchitra Natarajan Jinghui Wang Stephanie Chow Joshua T. Eggold Phoebe E. Loo Rakesh Manjappa Stavros Melemenidis Frederick M. Lartey Emil Schüler Lawrie Skinner Marjan Rafat Ryan Ko Anna Kim Duaa H. Al-Rawi Rie von Eyben Oliver Dorigo Kerriann M. Casey Edward E. Graves Karl Bush Amy S. Yu Albert C. Koong Peter G. Maxim Billy W. Loo Erinn B. Rankin Abdominal FLASH irradiation reduces radiation-induced gastrointestinal toxicity for the treatment of ovarian cancer in mice
description	Abstract Radiation therapy is the most effective cytotoxic therapy for localized tumors. However, normal tissue toxicity limits the radiation dose and the curative potential of radiation therapy when treating larger target volumes. In particular, the highly radiosensitive intestine limits the use of radiation for patients with intra-abdominal tumors. In metastatic ovarian cancer, total abdominal irradiation (TAI) was used as an effective postsurgical adjuvant therapy in the management of abdominal metastases. However, TAI fell out of favor due to high toxicity of the intestine. Here we utilized an innovative preclinical irradiation platform to compare the safety and efficacy of TAI ultra-high dose rate FLASH irradiation to conventional dose rate (CONV) irradiation in mice. We demonstrate that single high dose TAI-FLASH produced less mortality from gastrointestinal syndrome, spared gut function and epithelial integrity, and spared cell death in crypt base columnar cells compared to TAI-CONV irradiation. Importantly, TAI-FLASH and TAI-CONV irradiation had similar efficacy in reducing tumor burden while improving intestinal function in a preclinical model of ovarian cancer metastasis. These findings suggest that FLASH irradiation may be an effective strategy to enhance the therapeutic index of abdominal radiotherapy, with potential application to metastatic ovarian cancer.
format	article
author	Karen Levy Suchitra Natarajan Jinghui Wang Stephanie Chow Joshua T. Eggold Phoebe E. Loo Rakesh Manjappa Stavros Melemenidis Frederick M. Lartey Emil Schüler Lawrie Skinner Marjan Rafat Ryan Ko Anna Kim Duaa H. Al-Rawi Rie von Eyben Oliver Dorigo Kerriann M. Casey Edward E. Graves Karl Bush Amy S. Yu Albert C. Koong Peter G. Maxim Billy W. Loo Erinn B. Rankin
author_facet	Karen Levy Suchitra Natarajan Jinghui Wang Stephanie Chow Joshua T. Eggold Phoebe E. Loo Rakesh Manjappa Stavros Melemenidis Frederick M. Lartey Emil Schüler Lawrie Skinner Marjan Rafat Ryan Ko Anna Kim Duaa H. Al-Rawi Rie von Eyben Oliver Dorigo Kerriann M. Casey Edward E. Graves Karl Bush Amy S. Yu Albert C. Koong Peter G. Maxim Billy W. Loo Erinn B. Rankin
author_sort	Karen Levy
title	Abdominal FLASH irradiation reduces radiation-induced gastrointestinal toxicity for the treatment of ovarian cancer in mice
title_short	Abdominal FLASH irradiation reduces radiation-induced gastrointestinal toxicity for the treatment of ovarian cancer in mice
title_full	Abdominal FLASH irradiation reduces radiation-induced gastrointestinal toxicity for the treatment of ovarian cancer in mice
title_fullStr	Abdominal FLASH irradiation reduces radiation-induced gastrointestinal toxicity for the treatment of ovarian cancer in mice
title_full_unstemmed	Abdominal FLASH irradiation reduces radiation-induced gastrointestinal toxicity for the treatment of ovarian cancer in mice
title_sort	abdominal flash irradiation reduces radiation-induced gastrointestinal toxicity for the treatment of ovarian cancer in mice
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/e19427aedbeb4ad9ab2df08481282096
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Abdominal FLASH irradiation reduces radiation-induced gastrointestinal toxicity for the treatment of ovarian cancer in mice

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