{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:48:52Z","timestamp":1792043332765,"version":"4.4.0"},"reference-count":37,"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:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"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\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1260578"],"award-info":[{"award-number":["1260578"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020884","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["ICN2021_004"],"award-info":[{"award-number":["ICN2021_004"]}],"id":[{"id":"10.13039\/501100020884","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":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Most evidence on post\u2010radiotherapy cardiotoxicity (CDT) derives from Global North cohorts, and the relative contribution of baseline clinical risk versus cardiac dosimetry remains poorly characterized in Latin American\u00a0populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To examine, in a Chilean breast cancer cohort, whether baseline clinical risk factors or cardiac dose\u2010volume metrics better predict post\u2010RT cardiac events, using supervised and unsupervised\u00a0learning.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Retrospective cohort of 42 breast cancer patients treated with thoracic radiotherapy (RT, median heart dose 2.6\u00a0Gy; median follow\u2010up 84.4\u00a0months). CDT was defined per CTCAE\u00a0v5.0 ( Grade\u00a01), excluding Grade\u00a01 events coded under the non\u2010specific term\n                      <jats:italic>\u201cCardiac disorders \u2013 Other, specify\u201d<\/jats:italic>\n                      , which on review were incidental imaging findings. Dose\u2010volume histogram (DVH) parameters from seven cardiac substructures were extracted. Firth penalized logistic regression was used for prediction, principal component analysis (PCA) and kernel PCA for exploratory clustering, and bootstrap 0.632+ for optimism correction. The 2023 American Heart Association (AHA) PREVENT score was evaluated post\u00a0hoc.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ten patients (23.8%) developed CDT and 16 (38.1%) experienced cardiovascular events. No DVH differences were found between CDT+ and CDT\u2212 groups across any cardiac structure (all ), although the design is powered only for large effects. By contrast, IMRT delivered significantly higher cardiac doses than 3D\u2010CRT across multiple substructures, without a differential CDT rate. Pre\u2010existing cardiovascular disease was the strongest predictor (crude OR\u00a0=\u00a06.50, ; adjusted OR\u00a0=\u00a02.08, 95%\u00a0CI 1.03\u20134.16, ). The median time to the first CTCAE\u2010graded event was 48.4\u00a0months. The clinical\u2010only model reached an area under the curve (AUC) of 0.783 versus 0.604 for dosimetry alone; the combined model corrected to 0.649 (95% CI 0.204\u20130.933). The AHA PREVENT score showed no significant risk gradient (trend ) but was markedly less susceptible to overfitting than DVH\u2010only models (optimism 0.089 vs. 0.194).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this low\u2010cardiac\u2010dose cohort, baseline clinical variables outperformed cardiac dose\u2010volume metrics in predicting post\u2010RT cardiac events, although the design was not powered to exclude a dose\u2010effect relationship at these exposures. Registry\u2010based baseline risk assessment is therefore the more robust starting point in this setting, and IMRT breast RT planning warrants multi\u2010substructure cardiac dosimetry\u00a0monitoring.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acm2.70862","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:31:29Z","timestamp":1792042289000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Machine learning predictors of post\u2010radiotherapy cardiotoxicity in a Latin American breast cancer cohort: Clinical risk factors outperform cardiac dosimetry"],"prefix":"10.1002","volume":"27","author":[{"given":"V\u00edctor","family":"Aguirre\u2010Bravo","sequence":"first","affiliation":[{"name":"Radiation Safety UC CHRISTUS Santiago Chile"},{"name":"Institute of Physics Pontificia Universidad Cat\u00f3lica de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"El Far","sequence":"additional","affiliation":[{"name":"Radiotherapy UC CHRISTUS Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Herrera Ruiz","sequence":"additional","affiliation":[{"name":"Radiation Safety UC CHRISTUS Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"G\u00e1lvez Santelices","sequence":"additional","affiliation":[{"name":"Radiation Safety UC CHRISTUS Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Munoz\u2010Schuffenegger","sequence":"additional","affiliation":[{"name":"Radiotherapy UC CHRISTUS Santiago Chile"},{"name":"Department of Hematology\u2010Oncology School of Medicine Pontificia Universidad Cat\u00f3lica de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1s","family":"Merino","sequence":"additional","affiliation":[{"name":"Radiotherapy UC CHRISTUS Santiago Chile"},{"name":"Department of Hematology\u2010Oncology School of Medicine Pontificia Universidad Cat\u00f3lica de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Diez Domingo","sequence":"additional","affiliation":[{"name":"Department of Physiology Universitat de Val\u00e8ncia Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo E.","family":"Andia","sequence":"additional","affiliation":[{"name":"Department of Radiology School of Medicine Pontificia Universidad Cat\u00f3lica de Chile Santiago Chile"},{"name":"Millennium Institute for Intelligent Healthcare Engineering (iHEALTH) Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"World Cancer Research Fund.Global cancer incidence: both sexes;2026. Available from:https:\/\/www.wcrf.org\/preventing\u2010cancer\/cancer\u2010statistics\/worldwide\u2010cancer\u2010data\/#global\u2010cancer\u2010incidence\u2010both\u2010sexes"},{"key":"e_1_2_12_3_1","unstructured":"Ministerio de Salud Gobierno de Chile.Plan Nacional de C\u00e1ncer 2018\u20102028.Ministerio de Salud Gobierno de Chile;2018."},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw211"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.70.5400"},{"key":"e_1_2_12_6_1","doi-asserted-by":"crossref","unstructured":"GagliardiG ConstineLS MoiseenkoV et\u00a0al.Radiation dose\u2010volume effects in the heart.Int J Radiat Oncol Biol Phys.2010;76(3 SUPPL). doi:10.1016\/j.ijrobp.2009.04.093","DOI":"10.1016\/j.ijrobp.2009.04.093"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2009.09.064"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/clc.22631"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rpor.2019.12.008"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209825"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.69.8480"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/acm2.14614"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1557382"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001191"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3332\/ecancer.2025.2014"},{"key":"e_1_2_12_16_1","doi-asserted-by":"crossref","DOI":"10.1093\/acprof:oso\/9780199392285.001.0001","volume-title":"Textbook of Global Health","author":"Birn AE","year":"2017"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccao.2024.02.009"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010021\u201008823\u20103"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2017.01.008"},{"key":"e_1_2_12_20_1","unstructured":"National Cancer Institute.Common terminology criteria for adverse events (CTCAE) version 5.0. U.S. Department of Health and Human Services National Institutes of Health National Cancer Institute;2017. Available from:https:\/\/ctep.cancer.gov\/protocolDevelopment\/electronic_applications\/ctc.htm"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2014.07.012"},{"issue":"6","key":"e_1_2_12_22_1","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1093\/aje\/kwk052","article-title":"Relaxing the rule of ten events per variable in logistic and Cox regression","volume":"165","author":"Vittinghoff E","year":"2007","journal-title":"Am J Epidemiol"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.067626"},{"issue":"2065","key":"e_1_2_12_24_1","doi-asserted-by":"crossref","DOI":"10.1098\/rsta.2015.0202","article-title":"Principal component analysis: a review and recent developments","volume":"374","author":"Jolliffe IT","year":"2016","journal-title":"Philos Trans R Soc A"},{"key":"e_1_2_12_25_1","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-0716-1418-1","volume-title":"An Introduction to Statistical Learning with Applications in R","author":"James G","year":"2021"},{"issue":"336","key":"e_1_2_12_26_1","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1080\/01621459.1971.10482356","article-title":"Objective criteria for the evaluation of clustering methods","volume":"66","author":"Rand WM","year":"1971","journal-title":"J Am Stat Assoc"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0377\u20100427(87)90125\u20107"},{"issue":"1","key":"e_1_2_12_28_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/biomet\/80.1.27","article-title":"Bias reduction of maximum likelihood estimates","volume":"80","author":"Firth D","year":"1993","journal-title":"Biometrika"},{"issue":"16","key":"e_1_2_12_29_1","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1002\/sim.1047","article-title":"A solution to the problem of separation in logistic regression","volume":"21","author":"Heinze G","year":"2002","journal-title":"Stat Med"},{"issue":"438","key":"e_1_2_12_30_1","first-page":"548","article-title":"Improvements on cross\u2010validation: the .632+ bootstrap method","volume":"92","author":"Efron B","year":"1997","journal-title":"J Am Stat Assoc"},{"issue":"1","key":"e_1_2_12_31_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1175\/1520-0493(1950)078<0001:VOFEIT>2.0.CO;2","article-title":"Verification of forecasts expressed in terms of probability","volume":"78","author":"Brier GW","year":"1950","journal-title":"Mon Weather Rev"},{"issue":"10","key":"e_1_2_12_32_1","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1080\/03610928008827941","article-title":"Goodness of fit tests for the multiple logistic regression model","volume":"9","author":"Hosmer DW","year":"1980","journal-title":"Commun Stat Theory Methods"},{"issue":"6","key":"e_1_2_12_33_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1177\/0272989X06295361","article-title":"Decision curve analysis: a novel method for evaluating prediction models","volume":"26","author":"Vickers AJ","year":"2006","journal-title":"Med Decis Making"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7992"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.breast.2025.104581"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1613773"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.038285"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac244"}],"container-title":["Journal of Applied Clinical Medical Physics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aapm.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acm2.70862","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aapm.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acm2.70862","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aapm.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acm2.70862","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:31:33Z","timestamp":1792042293000},"score":1,"resource":{"primary":{"URL":"https:\/\/aapm.onlinelibrary.wiley.com\/doi\/10.1002\/acm2.70862"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":37,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/acm2.70862"],"URL":"https:\/\/doi.org\/10.1002\/acm2.70862","archive":["Portico"],"relation":{},"ISSN":["1526-9914","1526-9914"],"issn-type":[{"value":"1526-9914","type":"print"},{"value":"1526-9914","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-06-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70862"}}