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While external beam therapy with accelerated ions allows for a reduced dose to surrounding healthy organs, its biological effectiveness can be markedly higher than that of conventional x\u2010rays and should be considered during treatment planning. Current biophysical models possess limitations in computing in vivo normal tissue complication probability (NTCP) curves for clinically relevant ion beams.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study introduces and validates a novel computational framework capable of predicting NTCP curves for serial organs following ion exposures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The proposed framework integrates the linear\u2010quadratic model, the critical volume NTCP model, a novel two\u2010stage fitting process of fractionated photon NTCP data, histological data, and the Mayo Clinic Florida Microdosimetric Kinetic Model (MCF MKM) of relative biological effectiveness. The model was applied to predict the NTCP for the spinal cord myelopathy of rats exposed at different depths along the spread\u2010out Bragg peaks (SOBPs) of protons, helium, carbon, and oxygen ions. Radiation transport simulations were conducted to assess the microdosimetric pattern of energy deposition at the subcellular scale.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The two\u2010stage photon fitting process yielded a \u03b1\n                      <jats:sub>photons<\/jats:sub>\n                      \/\u03b2\n                      <jats:sub>photons<\/jats:sub>\n                      ratio of 2.3\u00a0\u00b1\u00a00.6\u00a0Gy and NTCP model parameters for calculations considering either endothelial or glial cells as the primary targets for the spinal cord myelopathy. Without using any ion data for calibration, the predicted NTCP showed an overall good agreement with the corresponding animal data. The model successfully reproduced the experimentally observed trends in the NTCP dependence with respect to fractionation, ion type, and exposure position along the SOBPs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The model's ability to predict the NTCP curves for ion exposures, based solely on photon in vivo data, provides mechanistic insights and can guide preclinical investigations into the biological effects of different ions and fractionation schemes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mp.70200","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T02:01:28Z","timestamp":1767924088000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Myelopathy in rats after exposure to clinically relevant ions: A predictive NTCP modeling framework"],"prefix":"10.1002","volume":"53","author":[{"given":"Alessio","family":"Parisi","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology Mayo Clinic  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith M.","family":"Furutani","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Mayo Clinic  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris J.","family":"Beltran","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Mayo Clinic  Jacksonville Florida 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