{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T06:02:38Z","timestamp":1774159358371,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute of the National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA266673"],"award-info":[{"award-number":["R01CA266673"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University Cancer Foundation"},{"DOI":"10.13039\/100000054","name":"National Cancer Institute of the National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA016672"],"award-info":[{"award-number":["P30 CA016672"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UTHealth Innovation for Cancer Prevention Research Training Program Pre-doctoral Fellowship","award":["#RP210042"],"award-info":[{"award-number":["#RP210042"]}]},{"name":"Andrew Sabin Family Foundation Fellowship"},{"DOI":"10.13039\/100007313","name":"University of Texas MD Anderson Cancer Center","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007313","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: FLASH radiotherapy (RT) has shown potential to reduce normal tissue toxicity compared with conventional (CONV) RT while maintaining tumor control. FLASH RT is characterized by ultra-high dose rate delivery, commonly using mean dose rates \u2265 40 Gy\/s and sub-second delivery times. Most preclinical studies have used single-fraction regimens, leaving the feasibility and normal tissue impact of clinically relevant fractionation largely unexplored. We evaluated electron FLASH RT given in a standard five-fraction regimen to a porcine skin model, simulating adjuvant treatment workflow for high-risk cutaneous melanoma. Method: Three Yorkshire\u2013Landrace swine received paired five-fraction electron irradiations to dorsolateral skin using either FLASH RT (mean dose rates 175\u2013246 Gy\/s) or CONV RT (8 Gy\/min). Radiation was delivered with a 9-MeV electron beam; field diameters of 4, 7, or 10 cm; and doses of 5 \u00d7 6, 5 \u00d7 7, or 5 \u00d7 8 Gy. Dosimetry was validated with several dosimeters and real-time beam monitoring, confirming dose accuracy within 3%. Skin toxicity was assessed over 22\u201324 weeks using clinical grading, erythema spectrophotometry, and histopathologic evaluation. Results: FLASH RT was well tolerated at 5 \u00d7 6 Gy and 5 \u00d7 7 Gy, with no significant differences in peak radiation dermatitis, erythema index, or histologic damage compared with CONV RT. At 5 \u00d7 8 Gy, both modalities caused unacceptable toxicity, including moist desquamation and necrosis. No volume-dependent effects were observed. Conclusions: Although a FLASH-specific normal tissue sparing effect was not observed, this study demonstrates the technical feasibility and safety of delivering fractionated electron FLASH RT in a large animal model using a clinically relevant workflow. These findings support further investigation of physical beam parameters and biological modifiers, such as tissue oxygenation, and inform the clinical translation of fractionated FLASH RT for cutaneous malignancies.<\/jats:p>","DOI":"10.3390\/cancers18061009","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T10:49:58Z","timestamp":1774003798000},"page":"1009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Initial Evaluation of Feasibility and Cutaneous Toxicity of Electron FLASH Radiotherapy Using a Standard-of-Care Fractionation Scheme in a Porcine Skin Model"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1587-7951","authenticated-orcid":false,"given":"Elise","family":"Konradsson","sequence":"first","affiliation":[{"name":"Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0942-6513","authenticated-orcid":false,"given":"Kevin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7629-7203","authenticated-orcid":false,"given":"Safee","family":"Baig","sequence":"additional","affiliation":[{"name":"Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0947-7388","authenticated-orcid":false,"given":"Susanne Je-Han","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan Hernandez","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brett","family":"Velasquez","sequence":"additional","affiliation":[{"name":"Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4225-6201","authenticated-orcid":false,"given":"Stephanie","family":"Mayor","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayla","family":"Samuel","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Traci","family":"Viscarra","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krystal","family":"Garrow","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3848-5416","authenticated-orcid":false,"given":"Erica J.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Norton","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jody","family":"Swain","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8359-0533","authenticated-orcid":false,"given":"Ziyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert C.","family":"Koong","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4411-0634","authenticated-orcid":false,"given":"Steven H.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emil","family":"Sch\u00fcler","sequence":"additional","affiliation":[{"name":"Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2225-164X","authenticated-orcid":false,"given":"Devarati","family":"Mitra","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/s41571-022-00697-z","article-title":"Towards clinical translation of FLASH radiotherapy","volume":"19","author":"Vozenin","year":"2022","journal-title":"Nat. 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