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Biol."],"published-print":{"date-parts":[[2023,11,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Objective<\/jats:italic>\n                    . The goal of the study was to test the hypothesis that shoot-through FLASH proton beams would lead to lower dose-averaged LET (LET\n                    <jats:sub>D<\/jats:sub>\n                    ) values in critical organs, while providing at least equal normal tissue sparing as clinical proton therapy plans.\n                    <jats:italic>Approach<\/jats:italic>\n                    . For five neurological tumor patients, pencil beam scanning (PBS) shoot-through plans were made, using the maximum energy of 227 MeV and assuming a hypothetical FLASH protective factor (FPF) of 1.5. The effect of different FPF ranging from 1.2 to 1.8 on the clinical goals were also considered. LET\n                    <jats:sub>D<\/jats:sub>\n                    was calculated for the clinical plan and the shoot-through plan, applying a 2 Gy total dose threshold (RayStation 8 A\/9B and 9A-IonRPG). Robust evaluation was performed considering density uncertainty (\u00b13% throughout entire volume).\n                    <jats:italic>Main results.<\/jats:italic>\n                    Clinical plans showed large LET\n                    <jats:sub>D<\/jats:sub>\n                    variations compared to shoot-through plans and the maximum LET\n                    <jats:sub>D<\/jats:sub>\n                    in OAR is 1.2\u20138 times lower for the latter. Although less conformal, shoot-through plans met the same clinical goals as the clinical plans, for FLASH protection factors above 1.4. The FLASH shoot-through plans were more robust to density uncertainties with a maximum OAR D\n                    <jats:sub>2%<\/jats:sub>\n                    increase of 0.6 Gy versus 5.7 Gy in the clinical plans.\n                    <jats:italic>Significance.<\/jats:italic>\n                    Shoot-through proton FLASH beams avoid uncertainties in LET\n                    <jats:sub>D<\/jats:sub>\n                    distributions and proton range, provide adequate target coverage, meet planning constraints and are robust to density variations.\n                  <\/jats:p>","DOI":"10.1088\/1361-6560\/ad0280","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T18:37:49Z","timestamp":1697049469000},"page":"215020","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Shoot-through proton FLASH irradiation lowers linear energy transfer in organs at risk for neurological tumors and is robust against density variations"],"prefix":"10.1088","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5725-1554","authenticated-orcid":false,"given":"Esther","family":"Kneepkens","sequence":"first","affiliation":[{"name":"Maastricht University Medical Centre+"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6428-2762","authenticated-orcid":false,"given":"Cecile","family":"Wolfs","sequence":"additional","affiliation":[{"name":"Maastricht University Medical Centre+"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9720-1666","authenticated-orcid":false,"given":"Roel-Germ","family":"Wanders","sequence":"additional","affiliation":[{"name":"Maastricht University Medical Centre+"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1850-7382","authenticated-orcid":false,"given":"Erik","family":"Traneus","sequence":"additional","affiliation":[{"name":"RaySearch Laboratories AB, SE-103 65, Stockholm,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1917-6279","authenticated-orcid":false,"given":"Danielle","family":"Eekers","sequence":"additional","affiliation":[{"name":"Maastricht University Medical Centre+"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8470-386X","authenticated-orcid":false,"given":"Frank","family":"Verhaegen","sequence":"additional","affiliation":[{"name":"Maastricht University Medical Centre+"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2023,11,2]]},"reference":[{"key":"pmbad0280bib1","doi-asserted-by":"publisher","first-page":"115008","DOI":"10.1088\/1361-6560\/aabb60","type":"journal-article","article-title":"Monte Carlo proton dose calculations using a radiotherapy specific dual-energy CT scanner for tissue segmentation and range assessment","volume":"63","author":"Almeida","year":"2018","journal-title":"Phys. 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