{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T03:39:27Z","timestamp":1771472367954,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["aapm.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medical Physics"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>The primary objective of our study was to perform a quantitative robustness analysis of the dose\u2010averaged linear energy transfer (LET<jats:sub>d<\/jats:sub>) and related RBE\u2010weighted dose in robustly optimized (in terms of the range and set up uncertainties) pencil beam scanning (PBS) proton lung cancer plans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we utilized the 4DCT dataset of six anonymized lung patients. PBS lung plans were generated using a robust optimization technique (range uncertainty: \u00b13.5% and setup errors: \u00b15\u00a0mm) on the CTV for a total dose of 5000 cGy (RBE) in five fractions using the RBE of 1.1. For each patient, the LET<jats:sub>d<\/jats:sub> distributions were calculated for the nominal plan and three groups. <jats:italic>Group 1<\/jats:italic>: two plan robustness scenarios for range uncertainties of \u00b13.5%; <jats:italic>Group 2<\/jats:italic>: twelve plan robustness scenarios (range uncertainty (\u00b13.5%) in conjunction with setup errors (\u00b15\u00a0mm)); and <jats:italic>Group 3<\/jats:italic>: ten different breathing phases of the 4DCT dataset. The RBE\u2010weighted dose to the OARs was evaluated for all robustness scenarios and breathing phases. The variation (\u2206) in the mean LET<jats:sub>d<\/jats:sub> and mean RBE\u2010weighted dose from each group was recorded.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mean LET<jats:sub>d<\/jats:sub> in the CTV of nominal PBS lung plans among six patients ranged from 2.2 to 2.6\u00a0keV\/\u00b5m. On average, for the combined range and setup uncertainties, the \u2206 in the mean LET<jats:sub>d<\/jats:sub> among 12 scenarios of all six patients was 0.6\u00a0keV\/\u00b5m, which is slightly higher than when only the range uncertainties were considered (0.4\u00a0keV\/\u00b5m). The \u2206 in the mean LET<jats:sub>d<\/jats:sub> in a patient was \u22641.7\u00a0keV\/\u00b5m in the heart and \u22641.2\u00a0keV\/\u00b5m in the esophagus and total lung. The \u2206 in the mean RBE\u2010weighted dose in a patient was up to 79 cGy for the total lung, 165 cGy for the heart, and 258 cGy for the esophagus. For ten breathing phases, the \u2206 in the mean LET<jats:sub>d<\/jats:sub> in a patient was \u22640.3\u00a0keV\/\u00b5m in the CTV, \u22640.5\u00a0keV\/\u00b5m in the heart, \u22640.4\u00a0keV\/\u00b5m in the esophagus, and \u22640.7\u00a0keV\/\u00b5m in the total lung.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The addition of setup errors to the range uncertainties resulted in slightly less homogeneous LET<jats:sub>d<\/jats:sub> distributions. The variations in the mean LET<jats:sub>d<\/jats:sub> among the ten breathing phases were slightly larger in the total lung than in the heart and esophagus. The combination of setup and range uncertainties had a greater impact than the effect of breathing phases on the variations in the mean RBE\u2010weighted dose to the OARs. Overall, the LET<jats:sub>d<\/jats:sub> distributions in the CTV were less sensitive than those in the OARs to setup errors, range uncertainties, and breathing phases for robustly optimized (in terms of range and setup uncertainities) PBS proton lung cancer plans.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mp.15569","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T09:05:09Z","timestamp":1645607109000},"page":"3444-3456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Quantitative analysis of dose\u2010averaged linear energy transfer (LET<sub>d<\/sub>) robustness in pencil beam scanning proton lung plans"],"prefix":"10.1002","volume":"49","author":[{"given":"Suresh","family":"Rana","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology Lynn Cancer Institute Boca Raton Regional Hospital Baptist Health South Florida  Boca Raton Florida USA"},{"name":"Department of 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