{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:07:38Z","timestamp":1791378458304,"version":"4.3.2"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["aapm.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medical Physics"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Clinical carbon ion beams offer the potential to overcome hypoxia\u2010induced radioresistance in pancreatic tumors, due to their high dose\u2010averaged Linear Energy Transfer (LETd), as previous studies have linked a minimum LETd within the tumor to improved local control. Current clinical practices at the Heidelberg Ion\u2010Beam Therapy Center (HIT), which use two posterior beams, do not fully exploit the LETd advantage of carbon ions, as the high LETd is primarily focused on the beams\u2019 distal edges. Different LETd\u2010boosting strategies, such as Spot\u2010scanning Hadron Arc (SHArc), could enhance LETd distribution by concentrating high\u2010LETd values in potential hypoxic tumor cores while sparing organs at risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study aims to investigate and verify different LETd\u2010boosting strategies using an anthropomorphic pancreas phantom.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Various LETd\u2010boosting strategies were investigated for a cylindrical and a pancreas\u2010shaped target in an anthropomorphic pancreas phantom. Treatment plans were optimized using single field optimization (SFO) or multi field optimization (MFO), with objective functions based on either physical dose (Phys), relative biological effectiveness\u00a0(RBE)\u2010weighted dose, or a combination of RBE and LETd\u2010based objectives (LETopt). The LETd\u2010boosting planning strategies were optimized with the goal of increasing the minimum LETd in the tumor without compromising its homogeneous dose coverage. Beam configurations investigated included the two\u2010beam in\u2010house clinical standard (2\u2010SFO\n                      <jats:sub>Phys<\/jats:sub>\n                      , 2\u2010SFO\n                      <jats:sub>RBE<\/jats:sub>\n                      and 2\u2010MFO\n                      <jats:sub>RBE\u2010LETopt<\/jats:sub>\n                      ), a three\u2010beam configuration (3\u2010MFO\n                      <jats:sub>RBE<\/jats:sub>\n                      and 3\u2010MFO\n                      <jats:sub>RBE\u2010LETopt<\/jats:sub>\n                      ) and SHArc (SHArc\n                      <jats:sub>Phys<\/jats:sub>\n                      , SHArc\n                      <jats:sub>RBE<\/jats:sub>\n                      and SHArc\n                      <jats:sub>RBE\u2010LETopt<\/jats:sub>\n                      ) using step\u2010and\u2010shoot delivery. The different plans were verified using an anthropomorphic pancreas phantom at HIT and compared to treatment planning system (TPS) predictions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All investigated LETd\u2010boosting strategies altered the LETd distribution while meeting optimization goals and constraints, resulting in varying degrees of LETd enhancement. For the cylindrical volume, the SHArc plan resulted in the highest LETd concentration in the tumor core, with the minimum LETd in the GTV scaling up to 91\u00a0keV\/\u00b5m. For the pancreas\u2010shaped volume, however, the 3\u2010MFO\n                      <jats:sub>RBE\u2010LETopt<\/jats:sub>\n                      achieved a higher minimum LETd in the GTV than SHArc\n                      <jats:sub>RBE<\/jats:sub>\n                      (75.6 and 62.3\u00a0keV\/\u00b5m, respectively). When combining SHArc with LETd optimization, a minimum LETd of 76.3\u00a0keV\/\u00b5m was achieved, suggesting a potential benefit from this combined approach. Most dosimetric verifications showed dose deviations to the TPS within a 5% range, for both beam\u2010per\u2010beam and total dose. LETd\u2010optimized and SHArc plans exhibited slightly higher mean dose deviations (2.0%\u20144.6%) compared to the standard RBE\u2010based plans (&lt;1.5%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrated the feasibility of enhancing LETd in pancreatic tumors using carbon ion arc delivery coupled with LETd optimization. The possibility of delivering these plans was verified through irradiation of an anthropomorphic pancreas phantom, which showed agreement between dose measurements and predictions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mp.17569","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T09:20:24Z","timestamp":1733822424000},"page":"1746-1757","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Investigating LETd optimization strategies in carbon ion radiotherapy for pancreatic cancer: a dosimetric study using an anthropomorphic phantom"],"prefix":"10.1002","volume":"52","author":[{"given":"Filipa","family":"Baltazar","sequence":"first","affiliation":[{"name":"Heidelberg Ion\u2010Beam Therapy Center (HIT) Department of Radiation Oncology  Heidelberg Germany"},{"name":"Clinical Cooperation Unit Radiation Oncology German Cancer Research Center (DKFZ)  Heidelberg 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