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Med. Biol."],"published-print":{"date-parts":[[2026,5,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Objective.<\/jats:italic>\n                    Proton arc therapy (PAT) has the potential to improve plan conformity while enhancing normal tissue sparing; however, its clinical translation faces practical barriers related to radiobiological uncertainties and delivery inefficiency. This study introduces a novel planning approach, mid-range PAT (MRPAT), designed to enhance delivery efficiency and mitigate range-related uncertainties in PAT.\n                    <jats:italic>Approach.<\/jats:italic>\n                    MRPAT employs a single mid-range energy layer per beam direction, positioning the Bragg peak near the target center (mid-range) plane to confine range uncertainty within the target while reducing dose-averaged linear energy transfer (LET\n                    <jats:sub>d<\/jats:sub>\n                    ) and relative biological effectiveness (RBE) hotspots in adjacent organs at risk (OARs). The feasibility of MRPAT was investigated on an ellipse phantom and three clinical cases (prostate, spine, and head and neck). Physical dose distributions, LET\n                    <jats:sub>d<\/jats:sub>\n                    distributions, RBE-weighted dose distributions, and delivery efficiency were compared with full-range arc employing all possible energy layers (ELs) (full-arc) and intensity-modulated proton therapy (IMPT) plans with two beams.\n                    <jats:italic>Main results.<\/jats:italic>\n                    Compared with IMPT, arc plans provided substantial improvements in entrance dose control and OAR sparing. The MRPAT plan achieved comparable target coverage and OAR sparing compared to the baseline full-arc plan, demonstrating the redundancy of utilizing all possible ELs. MRPAT effectively confined LET\n                    <jats:sub>d<\/jats:sub>\n                    and RBE hotspots to the center of the target, reducing potential biological weighted dose spillage over the surroundings. In terms of delivery efficiency, MRPAT eliminates EL switching within the same control point by using less than 5% of the ELs, requiring only about 20% of the total beam delivery time compared with the full-arc plan.\n                    <jats:italic>Significance.<\/jats:italic>\n                    MRPAT demonstrates a simple, efficient, and high\u2010LET\n                    <jats:sub>d<\/jats:sub>\n                    \/RBE hotspot\u2010containment planning concept that is practical for clinical use and adaptable to future adaptive PAT workflows.\n                  <\/jats:p>","DOI":"10.1088\/1361-6560\/ae674c","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:41:51Z","timestamp":1777596111000},"page":"095031","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mid-range arc therapy for efficient and RBE-robust proton treatment"],"prefix":"10.1088","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0580-6948","authenticated-orcid":true,"given":"Qingying","family":"Wang","sequence":"first","affiliation":[{"name":"The University of Texas Southwestern Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9758-3788","authenticated-orcid":false,"given":"Mingli","family":"Chen","sequence":"additional","affiliation":[{"name":"The University of Texas Southwestern Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9421-2404","authenticated-orcid":false,"given":"Yinheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"The University of Texas Southwestern Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9346-2760","authenticated-orcid":true,"given":"Xingyi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8033-2755","authenticated-orcid":false,"given":"You","family":"Zhang","sequence":"additional","affiliation":[{"name":"The University of Texas Southwestern Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6725-6906","authenticated-orcid":true,"given":"Xuejun","family":"Gu","sequence":"additional","affiliation":[{"name":"Stanford University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3036-7287","authenticated-orcid":true,"given":"Weiguo","family":"Lu","sequence":"additional","affiliation":[{"name":"The University of Texas Southwestern Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"266","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"pmbae674cbib1","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.3109\/0284186X.2010.510640","type":"journal-article","article-title":"Dose- and LET-painting with particle therapy","volume":"49","author":"Bassler","year":"2010","journal-title":"Acta Oncol."},{"key":"pmbae674cbib2","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3109\/0284186X.2013.832835","type":"journal-article","article-title":"LET-painting increases tumour control probability in hypoxic tumours","volume":"53","author":"Bassler","year":"2014","journal-title":"Acta Oncol."},{"key":"pmbae674cbib3","doi-asserted-by":"publisher","DOI":"10.1088\/1361-6560\/ab9455","type":"journal-article","article-title":"Proton monoenergetic arc therapy (PMAT) to enhance LETd within the target","volume":"65","author":"Bertolet","year":"2020","journal-title":"Phys. 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