{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:42:55Z","timestamp":1785415375464,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,28]]},"group-title":"Cancer Biology","reference-count":37,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["P01CA244091"],"award-info":[{"award-number":["P01CA244091"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Patients with Fanconi anemia (FA) are particularly susceptible to developing squamous cell carcinoma of the head and neck due to impaired DNA repair pathways. However, their hypersensitivity to DNA damaging agents can limit effective treatment with standard radiotherapy due to severe side effects and complications. In pre-clinical models, ultra-rapid FLASH radiotherapy (FLASH) reduces radiation-induced toxicity in normal tissues while maintaining similar tumor control compared to conventional dose rate radiotherapy (CONV). Here, we investigated the safety of FLASH for treatment of the head and neck in a mouse model of FA. 129\/Sv wild-type (WT) and\n                  <jats:italic>Fanca<\/jats:italic>\n                  -deficient (\n                  <jats:italic>Fanca<\/jats:italic>\n                  <jats:sup>-\/-<\/jats:sup>\n                  ) mice received single-dose oral cavity irradiation with electron beam FLASH or CONV to evaluate radiation-induced toxicity in non-tumor-bearing mice.\n                  <jats:italic>Fanca<\/jats:italic>\n                  WT and\n                  <jats:italic>Fanca<\/jats:italic>\n                  <jats:sup>-\/-<\/jats:sup>\n                  mice were irradiated with 25 and 18 Gy, respectively, of FLASH (190 Gy\/sec) or CONV (0.2 Gy\/sec), with tongues harvested at 12 hours (hpi) and 10 days (dpi) post-irradiation. At 10 dpi, FLASH-irradiated tongues in both genetic backgrounds demonstrated reduced ulceration at the dorsal tongue surface compared to CONV-irradiated counterparts. Histopathological analysis of the tongue revealed lower mucositis severity scores with decreased epithelial thinning and ulceration in FLASH-irradiated tongues compared to CONV-irradiated ones. Analysis of \u03b3-H2AX foci formation at 12 hpi demonstrated fewer foci in WT mice treated with FLASH compared to CONV, with a similar trend observed in\n                  <jats:italic>Fanca<\/jats:italic>\n                  <jats:sup>-\/-<\/jats:sup>\n                  mice. These findings suggest a potential normal tissue-sparing effect with FLASH and hold important clinical implications for the treatment of patients with Fanconi anemia and head and neck cancers.\n                <\/jats:p>","DOI":"10.64898\/2026.05.25.727748","type":"posted-content","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:55:14Z","timestamp":1780030514000},"source":"Crossref","is-referenced-by-count":0,"title":["FLASH reduces radiation-induced oral mucositis in a mouse model of Fanconi anemia"],"prefix":"10.64898","author":[{"given":"Phoebe","family":"Loo","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Stanford University School of Medicine, Stanford CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Stanford University School of Medicine, Stanford CA 94305"},{"name":"Department of Comparative Medicine, Stanford University School of Medicine, Stanford CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Stanford University School of Medicine, Stanford CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stavros","family":"Melemenidis","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Stanford University School of Medicine, Stanford CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dixin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Stanford University School of Medicine, Stanford CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Whitmore","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stanford University School of Medicine, Stanford CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Richter","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Stanford University School of Medicine, Stanford CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick M.","family":"Dirbas","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stanford University School of Medicine, Stanford CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerriann M.","family":"Casey","sequence":"additional","affiliation":[{"name":"Department of Comparative Medicine, Stanford University School of Medicine, Stanford CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward E.","family":"Graves","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Stanford University School of Medicine, Stanford CA 94305"},{"name":"Stanford Cancer Institute, Stanford University School of Medicine, Stanford CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Epperly","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Pittsburgh, Pittsburgh PA 15260"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Greenberger","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Pittsburgh, Pittsburgh PA 15260"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Billy W.","family":"Loo","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Stanford University School of Medicine, Stanford CA 94305"},{"name":"Department of Comparative Medicine, Stanford University School of Medicine, Stanford CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2521-0544","authenticated-orcid":false,"given":"Erinn 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