{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T16:42:01Z","timestamp":1789058521752,"version":"build-2803163510"},"reference-count":75,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1C1C1005930"],"award-info":[{"award-number":["2021R1C1C1005930"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aapm.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Applied Clin Med Phys"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In cancer radiotherapy, radiation\u2010induced lymphopenia (RIL) has been reported to be correlated with adverse clinical outcomes such as reduced locoregional control (LRC), distant\u2010metastasis\u2010free survival (DMFS), and overall survival (OS) in various treatment sites. Frameworks to simulate the radiation dose to circulating blood have been developed in response, and simulated blood dose values have been reported to be correlated with severe RIL and\/or adverse clinical outcomes. However, validations with different patient datasets or expansions to additional treatment sites, as well as the identification of particularly relevant blood dose metrics and blood compartments to allow for their inclusion during radiotherapy treatment planning, remain lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study aims to investigate a potential correlation between simulated blood dose values and adverse clinical outcomes in 215 patients with head\u2010and\u2010neck squamous cell carcinoma (HNSCC), 180 patients with glioblastoma (GBM), and 490 patients with non\u2010small\u2010cell lung cancer (NSCLC), and to identify particularly relevant blood dose metrics and blood compartments to allow for their inclusion during radiotherapy treatment planning and thereby enable the optimization of the estimated dose delivered to circulating blood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      For all 885 patients, TotalSegmentator was used to automatically delineate additional organs\u2010at\u2010risk (OARs), blood vessels, and tissues which were not already manually delineated for radiotherapy treatment planning. Subsequently, the dynamic HEDOS model, which considers temporal aspects such as blood flow dynamics and treatment delivery time, was used to simulate the radiation dose delivered to circulate blood during radiotherapy. Static blood dose models consisting of the mean dose to the union of all HEDOS blood compartments (\n                      <jats:italic>D<\/jats:italic>\n                      <jats:sub>static,HEDOS<\/jats:sub>\n                      ) and the integral body dose (\n                      <jats:italic>D<\/jats:italic>\n                      <jats:sub>static,body<\/jats:sub>\n                      ) were also investigated to verify whether a simplified blood dose model equally exhibited any correlations with adverse clinical outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During multivariable Cox regression analysis, the blood dose estimates from the dynamic blood dose model exhibited a statistically significant (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) correlation with DMFS and OS in the HNSCC and NSCLC datasets as well as with LRC in the HNSCC dataset.\n                      <jats:italic>D<\/jats:italic>\n                      <jats:sub>static,body<\/jats:sub>\n                      and\n                      <jats:italic>D<\/jats:italic>\n                      <jats:sub>static,HEDOS<\/jats:sub>\n                      only exhibited a statistically significant correlation with OS in the GBM and NSCLC datasets. Within a dataset, different dynamic blood dose metrics generally consistently exhibited correlations with the same clinical outcomes. Large arteries and veins were found to be a particularly relevant blood compartment within the HNSCC dataset, while the dose to the healthy portion of the brain and the dose to the heart and lungs were found to exhibit particularly strong correlations with dynamic blood dose estimates in the GBM and NSCLC datasets, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The dynamic blood dose model exhibited a statistically significant correlation with adverse clinical outcomes in five out of seven cases, compared to just two cases for the static blood dose models. Consideration of temporal aspects such as blood flow dynamics and treatment delivery time was therefore essential to some of the observed correlations. For each treatment site, particularly relevant blood compartments were identified, allowing for their inclusion during radiotherapy treatment planning as part of future studies which aim to reduce the estimated dose to circulating blood.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acm2.70341","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T08:50:43Z","timestamp":1766998243000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dynamic blood dose estimates in radiotherapy and correlations with adverse clinical outcomes in brain, head\u2010and\u2010neck, and lung cancer patients"],"prefix":"10.1002","volume":"27","author":[{"given":"Sebastian","family":"Tattenberg","sequence":"first","affiliation":[{"name":"School of Natural Sciences Laurentian University  Sudbury Ontario Canada"},{"name":"Life Sciences Division TRIUMF  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungwook","family":"Shin","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Hoehr","sequence":"additional","affiliation":[{"name":"Life Sciences Division TRIUMF  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanfeng","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Beaumont Health  Royal Oak Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan L.","family":"Deraniyagala","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Beaumont Health  Royal Oak Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0172-0646","authenticated-orcid":false,"given":"Wonmo","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering College of Medicine The Catholic University of Korea  Seoul South Korea"},{"name":"Department of Medical Sciences Graduate School of The Catholic University of Korea  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.adro.2018.08.014"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201011\u20100774"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060\u2010015\u20102037\u20101"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/07357907.2013.767342"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2014.04.025"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/07357907.2012.700987"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/COC.0b013e3182940ff9"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00066\u2010019\u201001462\u20105"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.adro.2020.03.021"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoto.2019.0034"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2017.11.028"},{"issue":"7","key":"e_1_2_9_13_1","first-page":"3541","article-title":"Prognostic value of severe lymphopenia during pelvic concurrent chemoradiotherapy in cervical cancer","volume":"36","author":"Cho O","year":"2016","journal-title":"Anticancer Res"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1088\/1361\u20106560\/ad3c8d"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2019.12.023"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611977"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201015\u20101412"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.27564"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/07357907.2012.762780"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13014\u2010018\u20100952\u2010y"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2019.11.014"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2020.02.015"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1088\/1361\u20106560\/ab6c41"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1088\/1361\u20106560\/ac16ea"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1088\/1361\u20106560\/ad02d6"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.768956"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2023.11.060"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2024.110603"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2019.05.064"},{"key":"e_1_2_9_30_1","unstructured":"GrossbergA ElhalawaniH MohamedA et\u00a0al.Anderson Cancer Center Head and Neck Quantitative Imaging Working Group. HNSCC Version 4. The Cancer Imaging Archive.2020. doi:10.7937\/k9\/tcia.2020.a8sh\u20107363"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2018.173"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2017.77"},{"key":"e_1_2_9_33_1","unstructured":"ZolotovaSV GolanovAV ProninIN et\u00a0al.Burdenko's Glioblastoma Progression Dataset (Burdenko\u2010GBM\u2010Progression) (Version 1) [Data set]. The Cancer Imaging Archive.2023. doi:10.7937\/E1QP\u2010D183"},{"key":"e_1_2_9_34_1","unstructured":"BradleyJ ForsterK Data from NSCLC\u2010Cetuximab. The Cancer Imaging Archive.2018. doi:10.7937\/TCIA.2018.jze75u7v"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.3969"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(14)71207\u20100"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10278\u2010013\u20109622\u20107"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1148\/ryai.230024"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0146\u20106453(03)00002\u20102"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.4103\/jmp.JMP_18_17"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1088\/0031\u20109155\/61\/8\/3208"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0895\u20104356(96)00025\u2010x"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1201500"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.23535"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2019.08.047"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13014\u2010019\u20101287\u2010z"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtocrr.2022.100391"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001648\u2010199001000\u201000010"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1209\u20101135"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE\u201020\u20101375"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7992"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2019.11.017"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdab153"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2023.109934"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00066\u2010021\u201001855\u20105"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2020.07.026"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2007.08.009"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2308511120"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1970.01340260018003"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2024.110390"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2003.12.024"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2009.04.005"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2014.10.009"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13014\u2010020\u201001503\u20109"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13014\u2010020\u201001677\u20102"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1700640403"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230600867727"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124507"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2018.08.008"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0360\u20103016(03)00664\u20103"},{"issue":"3","key":"e_1_2_9_71_1","first-page":"110","article-title":"Immune defects in breast cancer patients after radiotherapy","volume":"6","author":"Standish LJ","year":"2008","journal-title":"J Soc Integr Oncol"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2018.1496881"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1088\/0031\u20109155\/61\/8\/3208"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1088\/0031\u20109155\/61\/11\/4048"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2019.08.047"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtocrr.2022.100391"}],"container-title":["Journal of Applied Clinical Medical Physics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aapm.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acm2.70341","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aapm.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acm2.70341","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aapm.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acm2.70341","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T13:09:44Z","timestamp":1771333784000},"score":1,"resource":{"primary":{"URL":"https:\/\/aapm.onlinelibrary.wiley.com\/doi\/10.1002\/acm2.70341"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,29]]},"references-count":75,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/acm2.70341"],"URL":"https:\/\/doi.org\/10.1002\/acm2.70341","archive":["Portico"],"relation":{},"ISSN":["1526-9914","1526-9914"],"issn-type":[{"value":"1526-9914","type":"print"},{"value":"1526-9914","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,29]]},"assertion":[{"value":"2025-05-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70341"}}