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This association suggests to develop an additional physics\u2010detailed layer of modeling that may complement biological modeling and treatment planning. The recently introduced\n                      <jats:italic>cluster dose<\/jats:italic>\n                      may serve as a purely physical quantity bridging the\n                      <jats:italic>Ionization Parameter<\/jats:italic>\n                      () to the macroscopic treatment planning scale.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>In this work, we developed a framework to enable flexible and direct cluster dose optimization using a pencil\u2010beam algorithm, which we validated with condensed history Monte Carlo (MC)\u00a0simulations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cluster dose combines the contributions to  from all particles within a macroscopic volume. Our framework, implemented in the open source planning toolkit matRad, utilizes the particle and energy\u2010dependent  values from an ID database precomputed from MC track strucure (MCTS) simulations. First, we create pencil\u2010beam (PB) kernels, including fluence spectra, from condensed history MC simulations. For a water box phantom and a representative prostate patient, we create treatment plans optimized on dose and cluster dose  coverage and homogeneity for protons, helium and carbon ions. Plans were validated with Geant4\/TOPAS MC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our framework provided accurate, practical cluster dose calculation and planning. PB algorithms achieve typical accuracy for cluster dose calculation comparable to dose calculation. Recalculation with TOPAS on the box phantom yielded 3D gamma passing rates (GPRs) greater than . For the prostate patient, GPRs exceeded . Both used the  criterion with a threshold of  of the maximum dose. Using cluster dose  optimization, homogeneous cluster dose target coverage was achieved in all plans. A constant cluster dose prescription across all ion species shows the expected decrease in required absorbed dose for heavier\u00a0ions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We demonstrate that fast, direct cluster dose calculation and optimization is feasible using MC validated planning with PB algorithms. Cluster dose prescription and optimization results in the expected cluster dose coverage and physical dose levels depending on the respective primary\u00a0ion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mp.70579","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:47:08Z","timestamp":1784699228000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An ion treatment planning framework for inclusion of nanodosimetric ionization detail through cluster dose"],"prefix":"10.1002","volume":"53","author":[{"given":"Simona","family":"Facchiano","sequence":"first","affiliation":[{"name":"Department of Medical Physics in Radiation Oncology German Cancer Research Center (DKFZ) Heidelberg Germany"},{"name":"National Center for Radiation Research in Oncology (NCRO) Heidelberg Institute for Radiation Oncology (HIRO) Heidelberg Germany"},{"name":"Faculty of Physics and Astronomy Heidelberg University Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of California San Francisco (UCSF) San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remo","family":"Cristoforetti","sequence":"additional","affiliation":[{"name":"Department of Medical Physics in Radiation Oncology German Cancer Research Center (DKFZ) Heidelberg Germany"},{"name":"National Center for Radiation Research in Oncology (NCRO) Heidelberg Institute for Radiation Oncology (HIRO) Heidelberg Germany"},{"name":"Faculty of Physics and Astronomy Heidelberg University Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"D\u2010Kondo","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of California San Francisco (UCSF) San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"J\u00e4kel","sequence":"additional","affiliation":[{"name":"Department of Medical Physics in Radiation Oncology German Cancer Research Center (DKFZ) Heidelberg Germany"},{"name":"National Center for Radiation Research in Oncology (NCRO) Heidelberg Institute for Radiation Oncology (HIRO) Heidelberg Germany"},{"name":"Department of Radiation Oncology Heidelberg Ion Beam Therapy Center (HIT) University Hospital Heidelberg (UKHD) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Faddegon","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of California San Francisco (UCSF) San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Wahl","sequence":"additional","affiliation":[{"name":"Department of Medical Physics in Radiation Oncology German Cancer Research Center (DKFZ) Heidelberg Germany"},{"name":"National Center for Radiation Research in Oncology (NCRO) Heidelberg Institute for Radiation Oncology (HIRO) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/59\/22\/R419"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1667\/RR13795.1"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2016.02.029"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0924-4212(96)84885-7"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004110050055"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2010.05.014"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2307\/3579114"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1667\/RR0536.1"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/60\/8\/3271"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2016.05.031"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2010.10.027"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2013.05.013"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2016.08.038"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mp.13347"},{"key":"e_1_2_8_16_1","unstructured":"PszonaS.A track ion counter. 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