{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T01:42:19Z","timestamp":1787103739778,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T00:00:00Z","timestamp":1575417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["aapm.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medical Physics"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      The enhanced relative biological effectiveness (RBE) at the end of the proton range might increase the risk of radiation\u2010induced toxicities. This is of special concern for intracranial treatments where several critical organs at risk (OARs) surround the tumor. In the light of this, a retrospective analysis of dose\u2010averaged linear energy transfer (LET\n                      <jats:sub>d<\/jats:sub>\n                      ) and RBE\u2010weighted dose (D\n                      <jats:sub>RBE<\/jats:sub>\n                      ) distributions was conducted for three clinical cases with suspected treatment\u2010related toxicities following intracranial proton therapy. Alternative treatment strategies aiming to reduce toxicity risks are also presented.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The clinical single\u2010field optimized (SFO) plans were recalculated for 81 error scenarios with a Monte Carlo dose engine. The fractionation D\n                      <jats:sub>RBE<\/jats:sub>\n                      was 1.8\u00a0Gy (RBE) in 28 or 30 fractions assuming a constant RBE of 1.1. Two LET\n                      <jats:sub>d<\/jats:sub>\n                      \u2010 and \u03b1\/\u03b2\u2010dependent variable RBE models were used for evaluation, including a sensitivity analysis of the \u03b1\/\u03b2 parameter. Resulting distributions of D\n                      <jats:sub>RBE<\/jats:sub>\n                      and LET\n                      <jats:sub>d<\/jats:sub>\n                      were analyzed together with normal tissue complication probabilities (NTCPs). Subsequently, four multi\u2010field optimized (MFO) plans, with an additional beam and\/or objectives penalizing protons stopping in OARs, were created to investigate the potential reduction of LET\n                      <jats:sub>d<\/jats:sub>\n                      , D\n                      <jats:sub>RBE<\/jats:sub>\n                      , and NTCP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The two variable RBE models agreed well and predicted average RBE values around 1.3 in the toxicity volumes, resulting in an increased near\u2010maximum D\n                      <jats:sub>RBE<\/jats:sub>\n                      of 7\u201311\u00a0Gy (RBE) compared to RBE\u00a0=\u00a01.1 in the nominal scenario. The corresponding NTCP estimates increased from 0.8%, 0.0%, and 3.7% (RBE\u00a0=\u00a01.1) to 15.5%, 1.8%, and 45.7% (Wedenberg RBE model) for the three patients, respectively. The MFO plans generally allowed for LET\n                      <jats:sub>d<\/jats:sub>\n                      , D\n                      <jats:sub>RBE<\/jats:sub>\n                      , and NTCP reductions in OARs, without compromising the target dose. Compared to the clinical SFO plans, the maximum reduction in the near\u2010maximum LET\n                      <jats:sub>d<\/jats:sub>\n                      was 56%, 63%, and 72% in the OAR exhibiting the toxicity for the three patients, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Although a direct causality between RBE and toxicity cannot be established here, high LET\n                      <jats:sub>d<\/jats:sub>\n                      and D\n                      <jats:sub>RBE<\/jats:sub>\n                      correlated spatially with the observed toxicities, whereas setup and range uncertainties had a minor impact. Individual factors, which might affect the patient\u2010specific radiosensitivity, were however not included in these calculations. The MFO plans using both an additional beam and proton track\u2010end objectives allowed the largest reductions in LET\n                      <jats:sub>d<\/jats:sub>\n                      , D\n                      <jats:sub>RBE<\/jats:sub>\n                      , and NTCP, and might be future tools for similar cases.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mp.13911","type":"journal-article","created":{"date-parts":[[2019,11,9]],"date-time":"2019-11-09T06:10:36Z","timestamp":1573279836000},"page":"342-351","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Spatial correlation of linear energy transfer and relative biological effectiveness with suspected treatment\u2010related toxicities following proton therapy for intracranial tumors"],"prefix":"10.1002","volume":"47","author":[{"given":"Jakob","family":"\u00d6d\u00e9n","sequence":"first","affiliation":[{"name":"Department 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