Browsing by Author "Casey, Kerriann M."

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    Abdominal FLASH irradiation reduces radiation-induced gastrointestinal toxicity for the treatment of ovarian cancer in mice
    (Springer Nature, 2020-12-10) Levy, Karen; Natarajan, Suchitra; Wang, Jinghui; Chow, Stephanie; Eggold, Joshua T.; Loo, Phoebe E.; Manjappa, Rakesh; Melemenidis, Stavros; Lartey, Frederick M.; Schüler, Emil; Skinner, Lawrie; Rafat, Marjan; Ko, Ryan; Kim, Anna; Al-Rawi, Duaa H.; von Eyben, Rie; Dorigo, Oliver; Casey, Kerriann M.; Graves, Edward E.; Bush, Karl; Yu, Amy S.; Koong, Albert C.; Maxim, Peter G.; Loo, Billy W., Jr.; Rankin, Erinn B.; Radiation Oncology, School of Medicine
    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.
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    FLASH Irradiation Results in Reduced Severe Skin Toxicity Compared to Conventional-Dose-Rate Irradiation
    (BioOne, 2020-12-01) Soto, Luis A.; Casey, Kerriann M.; Wang, Jinghui; Blaney, Alexandra; Manjappa, Rakesh; Breitkreutz, Dylan; Skinner, Lawrie; Dutt, Suparna; Ko, Ryan B.; Bush, Karl; Yu, Amy S.; Melemenidis, Stavros; Strober, Samuel; Englemann, Edgar; Maxim, Peter G.; Graves, Edward E.; Loo, Billy W., Jr.; Radiation Oncology, School of Medicine
    Radiation therapy, along with surgery and chemotherapy, is one of the main treatments for cancer. While radiotherapy is highly effective in the treatment of localized tumors, its main limitation is its toxicity to normal tissue. Previous preclinical studies have reported that ultra-high dose-rate (FLASH) irradiation results in reduced toxicity to normal tissues while controlling tumor growth to a similar extent relative to conventional-dose-rate (CONV) irradiation. To our knowledge this is the first report of a dose-response study in mice comparing the effect of FLASH irradiation vs. CONV irradiation on skin toxicity. We found that FLASH irradiation results in both a lower incidence and lower severity of skin ulceration than CONV irradiation 8 weeks after single-fraction hemithoracic irradiation at high doses (30 and 40 Gy). Survival was also higher after FLASH hemithoracic irradiation (median survival >180 days at doses of 30 and 40 Gy) compared to CONV irradiation (median survival 100 and 52 days at 30 and 40 Gy, respectively). No ulceration was observed at doses 20 Gy or below in either FLASH or CONV. These results suggest a shifting of the dose-response curve for radiation-induced skin ulceration to the right for FLASH, compared to CONV irradiation, suggesting the potential for an enhanced therapeutic index for radiation therapy of cancer.