{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T12:38:46Z","timestamp":1782131926636,"version":"3.54.5"},"reference-count":57,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001732","name":"Danish National Research Foundation (DNRF)","doi-asserted-by":"publisher","award":["126"],"award-info":[{"award-number":["126"]}],"id":[{"id":"10.13039\/501100001732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001732","name":"Danish National Research Foundation (DNRF)","doi-asserted-by":"publisher","award":["A20676"],"award-info":[{"award-number":["A20676"]}],"id":[{"id":"10.13039\/501100001732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008363","name":"Danish Cancer Society","doi-asserted-by":"publisher","award":["126"],"award-info":[{"award-number":["126"]}],"id":[{"id":"10.13039\/100008363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008363","name":"Danish Cancer Society","doi-asserted-by":"publisher","award":["A20676"],"award-info":[{"award-number":["A20676"]}],"id":[{"id":"10.13039\/100008363","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: No reliable noninvasive biomarkers are available to predict RT-induced cardiotoxicity. Because the pericardial sac is a fast responder to cardiac injury, we investigated whether RT-induced radiographic pericardial changes might serve as early imaging biomarkers for late cardiotoxicity. Methods: We performed a retrospective study of 476 patients (210 males, 266 females; median age, 69 years; median follow-up, 26.7 months) treated with chemo-RT for small cell and non-small cell lung cancers at one single institution from 2009 to 2020. The heart and its 4 mm outmost layer (representing the pericardial sac) were contoured on standard-of-care baseline CTs. Six-month post-RT follow-up CTs were deformably registered on the baseline CTs. Data were harmonized for the effect of contrast. We labeled voxels as Fat, Fluid, Heme, Fibrous, and Calcification using Hounsfield units (HUs). We studied pericardial HU-change histograms as well as volume change and voxel-based mass change in each tissue composition. Results: Pericardial HU-change histograms had skewed distributions with a mean that was significantly correlated with mean pericardial dose. Voxels within Fluid, Heme, and Fibrous had mass changes consistent with the dose. In Kaplan\u2013Meier curves, Fibrous and Heme volume changes (translating into thickening and effusion), Fat mass change, mean doses to heart and pericardium, history of cardiac disease, and being male were significantly associated with shorter survival, whereas thickening and effusion were significantly associated with shorter time to a post-RT cardiovascular disease diagnosis. Conclusions: Pericardium composition distribution has dose-dependent changes detectable on standard-of-care CTs at around 6 months post-RT and may serve as surrogate markers for clinically relevant cardiotoxicity. The findings should be validated with additional research.<\/jats:p>","DOI":"10.3390\/cancers17162635","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T07:45:31Z","timestamp":1755071131000},"page":"2635","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CT-Based Pericardial Composition Change as an Imaging Biomarker for Radiation-Induced Cardiotoxicity"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7341-5862","authenticated-orcid":false,"given":"Arezoo","family":"Modiri","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan R.","family":"Vogelius","sequence":"additional","affiliation":[{"name":"Department of Oncology, Rigshospitalet, 2100 Copenhagen, Denmark"},{"name":"Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia Terrones","family":"Campos","sequence":"additional","affiliation":[{"name":"Department of Oncology, Rigshospitalet, 2100 Copenhagen, Denmark"},{"name":"Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2347-6637","authenticated-orcid":false,"given":"Denis","family":"Kutnar","sequence":"additional","affiliation":[{"name":"Department of Oncology, Rigshospitalet, 2100 Copenhagen, Denmark"},{"name":"Department of Computer Science, University of Copenhagen, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6028-459X","authenticated-orcid":false,"given":"Jean","family":"Jeudy","sequence":"additional","affiliation":[{"name":"Diagnostic Radiology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9266-8662","authenticated-orcid":false,"given":"Mette","family":"Pohl","sequence":"additional","affiliation":[{"name":"Department of Oncology, Rigshospitalet, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timm-Michael L.","family":"Dickfeld","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, University of Maryland Medical Center, Baltimore; MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soren M.","family":"Bentzen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Sawant","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Oncology, Rigshospitalet, 2100 Copenhagen, Denmark"},{"name":"Department of Computer Science, University of Copenhagen, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e013754","DOI":"10.1161\/JAHA.119.013754","article-title":"Reverse Cardio-Oncology: Cancer Development in Patients With Cardiovascular Disease","volume":"9","author":"Aboumsallem","year":"2020","journal-title":"J. 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