{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:22:46Z","timestamp":1787314966872,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","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":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Radiation\u2010induced lymphopenia (RIL) is a frequent complication in head and neck cancer (HNC) patients undergoing radiotherapy (RT), and its severity is associated with poorer survival outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This work aims to develop a patient\u2010specific modeling method to simulate lymphocyte kinetics during and after RT and evaluate the lymphocyte\u2010sparing effects across different RT treatment regimens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A cohort of 17 HNC patients receiving unilateral irradiation with protons or photons were included in this study. The dose to circulating lymphocytes was calculated using the HEDOS model, considering lymph nodes on the irradiated side, the esophagus, auto\u2010segmented bilateral carotid arteries and jugular veins, skeletal muscle, fat, skin, compact bone, spongy bone, red marrow, and other skeleton. A patient\u2010specific model was developed to simulate lymphocyte kinetics that account for radiation\u2010induced damage to both circulating lymphocytes and lymph nodes. The weekly absolute lymphocyte counts (ALC) before, during and after RT, were assembled to estimate the patient\u2010specific parameters. Four different RT treatment regimens\u2014conventional fractionation, hypofractionation, stereotactic body radiotherapy (SBRT), and FLASH\u2014were evaluated to compare their lymphocyte\u2010sparing effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients treated with protons had 17.1% less grade 3 and 4 RIL compared to photons. The mean dose to circulating lymphocytes was 1.28\u00a0\u00b1\u00a00.37 Gy(RBE) for proton therapy and 3.12\u00a0\u00b1\u00a00.75 Gy for photon therapy. The patient\u2010specific model captured three distinct patterns of ALC kinetics: plateau phase, normal recovery, and incomplete recovery, with a mean squared error (MSE) of 0.024\u00a0\u00b1\u00a00.025 (mean\u00a0\u00b1\u00a0SD) between the simulated and observed ALC values. On average, 42.72% of circulating lymphocytes received more than 0.1 Gy(RBE) in proton FLASH, significantly less than the 81.94% in photon FLASH. Hypofractionated RT, SBRT, and FLASH were 6.5%, 20.2%, and 29.9%, respectively, higher than conventional RT in term of ALC levels 3 months post\u2010RT. At 1 year post\u2010RT, most patients achieved at least 70% recovery of baseline ALC for all treatment regimens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A patient\u2010specific method has been developed for modeling lymphocyte dynamics over the course of RT and the subsequent follow\u2010up period for HNC patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mp.17829","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T21:00:21Z","timestamp":1744664421000},"page":"3583-3594","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Patient\u2010specific modeling of radiation\u2010induced lymphopenia for head and neck cancer"],"prefix":"10.1002","volume":"52","author":[{"given":"Jiaxin","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Modern Physics Chinese Academy of Sciences  Lanzhou China"},{"name":"University of Chinese Academy of Sciences  Beijing China"},{"name":"Department of Radiation Oncology University of Kansas Medical Center  Kansas City USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Mali","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of Kansas Medical Center  Kansas City USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory N.","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of Kansas Medical Center  Kansas City USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Lominska","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of Kansas Medical Center  Kansas City 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