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However, there has been limited understanding of how to utilize variables for multi\u2010ion treatment planning such as the selection and arrangement of ion species.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      An in silico study was conducted to explore the feasibility of increasing a minimum LET\n                      <jats:sub>d<\/jats:sub>\n                      , and the optimal selection and arrangement of ion species in multi\u2010ion therapy for increasing LET\n                      <jats:sub>d<\/jats:sub>\n                      in tumors of varying sizes mimicking bone and soft tissue sarcomas (BSTS). Additionally, the robustness of multi\u2010ion therapy against setup and range errors was evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Spherical targets of 500, 1000, and 1500\u2010mL volumes were placed at the center or 80\u00a0mm horizontally displaced from the center of a numerical phantom to simulate BSTS treatments. Treatment plans were made for these targets with two orthogonal fields of carbon\u2010only, oxygen+carbon, and neon+carbon ions with a total dose of 70.4\u00a0Gy (RBE). The treatment parameters were optimized to increase the LET\n                      <jats:sub>d<\/jats:sub>\n                      in the targets while ensuring adequate target dose coverage and dose homogeneity. The plans were evaluated based on the dose covering 95% of the target (\n                      <jats:italic>D<\/jats:italic>\n                      <jats:sub>95%<\/jats:sub>\n                      ), skin dose (\n                      <jats:italic>D<\/jats:italic>\n                      <jats:sub>skin<\/jats:sub>\n                      ), and the minimum LET\n                      <jats:sub>d<\/jats:sub>\n                      excluding the 1\u00a0mL volume with the lowest LET\n                      <jats:sub>d<\/jats:sub>\n                      (\n                      <jats:italic>L<\/jats:italic>\n                      <jats:sub>1mL<\/jats:sub>\n                      ). Multi\u2010ion radiotherapy treatment plans were also developed for 12 patients with BSTS who had previously received carbon\u2010ion radiotherapy.\n                      <jats:italic>D<\/jats:italic>\n                      <jats:sub>95%<\/jats:sub>\n                      and\n                      <jats:italic>L<\/jats:italic>\n                      <jats:sub>1m<\/jats:sub>\n                      of the target, and the dose to organs at risk (OARs) such as the rectum, intestine, and spinal cord were assessed. The robustness of the plans created in the phantom against setup and range errors was evaluated under 2\u00a0mm shifts in six directions combined with 2.5% variation of the stopping power ratio, resulting in 12 scenarios. Differences in the target\n                      <jats:italic>D<\/jats:italic>\n                      <jats:sub>95%<\/jats:sub>\n                      and\n                      <jats:italic>L<\/jats:italic>\n                      <jats:sub>1mL<\/jats:sub>\n                      , and\n                      <jats:italic>D<\/jats:italic>\n                      <jats:sub>skin<\/jats:sub>\n                      in each scenario from those in the nominal plan were evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The target dose coverage was comparable for any ion species combinations regardless of target size and position. The\n                      <jats:italic>L<\/jats:italic>\n                      <jats:sub>1mL<\/jats:sub>\n                      in the target increased by 7\u20139 and 15\u201320\u00a0keV\/\u00b5m with the oxygen+carbon and neon+carbon plans, respectively, compared to the carbon\u2010only plans, while maintaining homogeneity index values below 0.10. Additionally, the skin dose increased by 2.2\u20137.0 and 9.2\u201314.6\u00a0Gy (RBE) for the oxygen+carbon and neon+carbon plans. The\n                      <jats:italic>L<\/jats:italic>\n                      <jats:sub>1mL<\/jats:sub>\n                      was greater than or equal to 40\u00a0keV\/\u00b5m in all phantom targets and most clinical cases for the oxygen+carbon and neon+carbon plans, while meeting the target and OAR dose requirements. In the robustness evaluation, the variations in\n                      <jats:italic>D<\/jats:italic>\n                      <jats:sub>95%<\/jats:sub>\n                      were comparable or smaller in the oxygen+carbon and neon+carbon plans than in the carbon\u2010only plan. The maximum decrease in\n                      <jats:italic>L<\/jats:italic>\n                      <jats:sub>1mL<\/jats:sub>\n                      in the target was 1.5\u00a0keV\/\u00b5m. The maximum increase in\n                      <jats:italic>D<\/jats:italic>\n                      <jats:sub>skin<\/jats:sub>\n                      was 2.4\u00a0Gy (RBE) in the target closest to the skin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The LET\n                      <jats:sub>d<\/jats:sub>\n                      was successfully increased with the oxygen+carbon and neon+carbon ions, while meeting the dose requirements. The multi\u2010ion therapy plans created using the method presented in this study were robust to setup and range errors.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mp.18097","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T07:15:49Z","timestamp":1757488549000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Possibility of increasing linear energy transfer in multi\u2010ion radiotherapy for bone and soft tissue sarcomas"],"prefix":"10.1002","volume":"52","author":[{"given":"Hideyuki","family":"Takei","sequence":"first","affiliation":[{"name":"Department of Accelerator and Medical Physics National Institutes for Quantum Science and Technology (QST)  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiko","family":"Imai","sequence":"additional","affiliation":[{"name":"QST Hospital National Institutes for Quantum 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