{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:54:04Z","timestamp":1789055644244,"version":"build-2803163510"},"reference-count":30,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Natural Science Foundation Project of Science and Technology Department of Sichuan Province","award":["No. 2025ZNSFSC0787"],"award-info":[{"award-number":["No. 2025ZNSFSC0787"]}]},{"name":"the Chengdu Science and Technology Projects","award":["No. 2024-YF05-02201-SN"],"award-info":[{"award-number":["No. 2024-YF05-02201-SN"]}]},{"name":"Sichuan Science and Technology Program","award":["NO:2024ZDZX0027"],"award-info":[{"award-number":["NO:2024ZDZX0027"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Dose-Response"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>FLASH radiotherapy (FLASH-RT) has been reported to spare skin from acute radiation toxicity. However, systematic quantification is needed to determine the dose and dose-rate thresholds necessary for optimal radioprotection in FLASH radiotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>The hind limbs of male C57BL\/6J mice were irradiated with a single-fraction dose (18-24\u00a0Gy) delivered using either FLASH-RT (ultrahigh dose rate: 250\u00a0Gy\/s) or conventional radiotherapy (CONV-RT: 0.1\u00a0Gy\/s) in the dose optimization experiment. Subsequent studies included a dose-rate optimization trial comparing FLASH-RT (40-400\u00a0Gy\/s) with CONV-RT at 20 Gy; the antitumor efficacy of a single 20\u00a0Gy dose delivered via FLASH-RT (300\u00a0Gy\/s) was compared with that of CONV-RT; and an assessment of the reirradiation response using FLASH-RT (400\u00a0Gy\/s) or CONV-RT at 20\u00a0Gy following a prior hypofractionated CONV-RT regimen (9\u00a0Gy \u00d7 4). Skin injury scores, tumor volume, and body weight were monitored longitudinally for up to 30 days after irradiation or until the experimental endpoint was reached. Tumor weight and lung metastasis nodules were measured at the endpoint.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Dry desquamation, alopecia, moist desquamation, hemorrhage, full-thickness necrosis, and ulceration were observed more frequently in the CONV-RT group than in the FLASH-RT group. Compared with CONV-RT, FLASH-RT resulted in significantly lower acute skin injury scores at doses \u226422\u00a0Gy (18\u00a0Gy, 20\u00a0Gy, 22\u00a0Gy,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001), but this protective effect was absent at doses \u226524\u00a0Gy. Dose-rate optimization (40-400\u00a0Gy\/s) delivering a 20\u00a0Gy dose revealed that acute skin injury scores were significantly reduced only at the higher dose-rates (\u2265300\u00a0Gy\/s, compared with CONV-RT,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001), whereas no significant reduction was observed at the lower dose-rates (\u2264200\u00a0Gy\/s,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2265 0.05). No additional benefit was detected between 300\u00a0Gy\/s and 400\u00a0Gy\/s. Although 250\u00a0Gy\/s provided significant radioprotection compared with CONV-RT (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.01), it was not the minimal rate required for maximal protection, as evidenced by a significantly better outcome at 300\u00a0Gy\/s at 24 days (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.0296). Finally, in B16\/F10 cell-transplanted mouse models, FLASH-RT (300 and 400\u00a0Gy\/s) achieved tumor control equivalent to that of CONV-RT while also reducing lung metastasis nodules and significantly mitigating acute skin toxicity (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001) during reirradiation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this study, a dual-threshold framework was established to guide the clinical implementation of FLASH radiotherapy: a dose ceiling below 24\u00a0Gy to preserve the skin-sparing effect and a dose-rate threshold exceeding 200\u00a0Gy\/s for efficacy, with further optimization achieved at rates above 250\u00a0Gy\/s. These findings provide \u200bguidelines for minimizing radiotherapy-induced acute skin toxicity while maintaining comparable antitumor efficacy, thereby outlining a translatable pathway towards the clinical translation of FLASH-RT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15593258251401947","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T15:10:35Z","timestamp":1764429035000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Towards Clinical Translation: Establishing Optimal Dose and Dose-Rate Parameters for the FLASH Skin-Sparing Effect"],"prefix":"10.1177","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5954-270X","authenticated-orcid":false,"given":"Yufeng","family":"Shen","sequence":"first","affiliation":[{"name":"School of Medicine, University of Electronic Science and Technology of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhou","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyi","family":"Lang","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lintao","family":"Li","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjie","family":"Li","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Electronic Science and Technology of 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