{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T05:38:25Z","timestamp":1792993105510,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["22DX1900200"],"award-info":[{"award-number":["22DX1900200"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aapm.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medical Physics"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The thyroid gland lies adjacent to the supraclavicular target and is highly radiosensitive, placing patients at risk for radiation\u2010induced hypothyroidism (RIHT). While RIHT incidence and predictive models have been well described after photon\u2010based irradiation, evidence in the proton therapy setting remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To evaluate the incidence of RIHT in breast cancer patients undergoing proton\u2010based supraclavicular nodal irradiation and to develop proton\u2010specific normal tissue complication probability (NTCP) models incorporating dose\u2010volume, dose\u2010averaged linear energy transfer (LETd)\u2010volume, and dose\u2013LETd\u2013volume histogram (DLVH) metrics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 113 breast cancer patients treated with proton supraclavicular irradiation were retrospectively analyzed. Dose\u2010volume, LETd\u2010volume, and DLVH metrics were extracted for the thyroid gland and individual thyroid lobes. After exclusion of non\u2010informative variables, univariable logistic regression models were developed for all retained candidate predictors. Internal validation and model selection were performed using 1000 bootstrap resamples, and the final bootstrap\u2010selected predictor was defined as the variable with the highest selection frequency. Model performance was assessed using apparent and optimism\u2010corrected area under the receiver operating characteristic curve (AUC). Biological dose metrics were additionally generated using six published LET\u2010dependent relative biological effectiveness (RBE) models and compared with the fixed\u2010RBE model using paired DeLong tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seventeen patients (15.0%) developed RIHT after a median follow\u2010up of 25 months (range, 9\u201380 months). Under the fixed\u2010RBE framework, the final bootstrap\u2010selected predictors were complementary DLVH metrics: CD10L2 (cc), denoting the absolute volume not simultaneously receiving dose \u2265\u00a010\u00a0Gy(RBE) and LETd \u2265\u00a02\u00a0keV\/\u00b5m, CD35L3 (cc), and CD5L4 (cc) for the thyroid gland, ipsilateral lobe, and contralateral lobe, respectively. The corresponding apparent AUCs were 0.794, 0.763, and 0.817, with optimism\u2010corrected AUCs of 0.738, 0.708, and 0.766, respectively. Among the LET\u2010dependent RBE models, the Wedenberg model based on contralateral lobe CD10L4 (cc) yielded the numerically highest optimism\u2010corrected AUC of 0.772. Although LET\u2010dependent RBE models showed slightly higher apparent AUCs than the fixed\u2010RBE model in some analyses, paired DeLong tests did not demonstrate statistically significant differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>RIHT is a clinically relevant toxicity after proton\u2010based supraclavicular irradiation. Under the fixed\u2010RBE framework, the optimal cutoff values for the final bootstrap\u2010selected complementary DLVH predictors were 5.6\u00a0cc for thyroid gland CD10L2 (cc), 2.9\u00a0cc for ipsilateral lobe CD35L3(cc), and 4.3\u00a0cc for contralateral lobe CD5L4 (cc). Complementary DLVH metrics may be informative for RIHT risk prediction and support thyroid\u2010aware optimization strategies in proton treatment planning, pending further validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mp.70703","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:25:08Z","timestamp":1792038308000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prediction of radiation\u2010induced hypothyroidism after proton\u2010based supraclavicular nodal irradiation in breast cancer"],"prefix":"10.1002","volume":"53","author":[{"given":"Jiayao","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Medical Physics Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital  Shanghai China"},{"name":"Shanghai Key Laboratory of Radiation Oncology  Shanghai China"},{"name":"Shanghai Engineering Research Center of Proton and 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