Baseline atrial volume indices and major adverse cardiac events following thoracic radiotherapy

IntroductionPatients receiving thoracic radiotherapy (RT) have an increased risk of major adverse cardiac events (MACE) posttreatment. We utilized machine learning (ML) to discover novel predictors of MACE and validated them on an external cohort.MethodsThis multi-institutional retrospective study i...

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Main Authors: Edmund M. Qiao, John He, Katrina D. Silos, Jordan O. Gasho, Patrick Belen, Danielle S. Bitterman, Elizabeth McKenzie, Jennifer Steers, Christian Guthier, Anju Nohria, Michael T. Lu, Hugo J. W. L. Aerts, Andriana P. Nikolova, Raymond H. Mak, Katelyn M. Atkins
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Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Cardiovascular Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2025.1560922/full
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author Edmund M. Qiao
John He
Katrina D. Silos
Jordan O. Gasho
Patrick Belen
Danielle S. Bitterman
Danielle S. Bitterman
Elizabeth McKenzie
Jennifer Steers
Christian Guthier
Anju Nohria
Michael T. Lu
Hugo J. W. L. Aerts
Hugo J. W. L. Aerts
Hugo J. W. L. Aerts
Andriana P. Nikolova
Raymond H. Mak
Raymond H. Mak
Katelyn M. Atkins
Katelyn M. Atkins
author_facet Edmund M. Qiao
John He
Katrina D. Silos
Jordan O. Gasho
Patrick Belen
Danielle S. Bitterman
Danielle S. Bitterman
Elizabeth McKenzie
Jennifer Steers
Christian Guthier
Anju Nohria
Michael T. Lu
Hugo J. W. L. Aerts
Hugo J. W. L. Aerts
Hugo J. W. L. Aerts
Andriana P. Nikolova
Raymond H. Mak
Raymond H. Mak
Katelyn M. Atkins
Katelyn M. Atkins
author_sort Edmund M. Qiao
collection DOAJ
description IntroductionPatients receiving thoracic radiotherapy (RT) have an increased risk of major adverse cardiac events (MACE) posttreatment. We utilized machine learning (ML) to discover novel predictors of MACE and validated them on an external cohort.MethodsThis multi-institutional retrospective study included 984 patients [n = 803 non-small cell lung cancer (NSCLC), n = 181 breast cancer] treated with radiotherapy. Extreme gradient boosting was utilized to discover novel clinical, dosimetric, and anatomical features (CT-based cardiac substructure segmentations) associated with MACE in a cohort of locally advanced NSCLC patients. Fine–Gray regression was performed with non-cardiac death as a competing risk. External validation was performed utilizing independent cohorts of NSCLC or breast cancer patients.ResultsIn the discovery dataset (n = 701), 70 patients experienced MACE. ML modeling (training AUC, 0.68; testing AUC, 0.71) identified right and left atrial volume indices (RAVI and LAVI, respectively) as top predictors. After adjusting for baseline cardiovascular risk and known radiotherapy predictive factors, RAVI was associated with an increased risk of MACE [subdistribution hazard ratio (sHR) 1.02/unit, 95% confidence interval (CI): 1.00–1.04; p = 0.03]. In the validation cohorts (n = 102 NSCLC; n = 181 breast cancer), RAVI was associated with an increased risk of MACE (NSCLC: sHR 1.05, 95% CI: 1.001–1.106, p = 0.04; breast cancer: sHR 1.06, 95% CI: 1.01–1.11, p = 0.03). Similar findings were found for LAVI.DiscussionML modeling identified right and left atrial enlargement as novel radiographic predictors for increased risk of MACE following chest radiotherapy, which was validated in independent breast and lung cancer datasets. Given that echocardiography studies have demonstrated the prognostic utility of atrial volume indices across cardiovascular risk groups, these findings warrant further study to identify additional strategies for upfront cardiovascular risk profiling.
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spelling doaj-art-d9b885e2f69140bf8d0edddd9cf740e12025-08-20T03:25:59ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2025-06-011210.3389/fcvm.2025.15609221560922Baseline atrial volume indices and major adverse cardiac events following thoracic radiotherapyEdmund M. Qiao0John He1Katrina D. Silos2Jordan O. Gasho3Patrick Belen4Danielle S. Bitterman5Danielle S. Bitterman6Elizabeth McKenzie7Jennifer Steers8Christian Guthier9Anju Nohria10Michael T. Lu11Hugo J. W. L. Aerts12Hugo J. W. L. Aerts13Hugo J. W. L. Aerts14Andriana P. Nikolova15Raymond H. Mak16Raymond H. Mak17Katelyn M. Atkins18Katelyn M. Atkins19Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, United StatesDepartment of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, United StatesDepartment of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDepartment of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDepartment of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDepartment of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, United StatesArtificial Intelligence in Medicine (AIM) Program, Mass General Brigham and Harvard Medical School, Boston, MA, United StatesDepartment of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDepartment of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDepartment of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, United StatesDepartment of Cardiovascular Medicine, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, United StatesDepartment of Radiology, Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesDepartment of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, United StatesArtificial Intelligence in Medicine (AIM) Program, Mass General Brigham and Harvard Medical School, Boston, MA, United StatesRadiology and Nuclear Medicine, GROW & CARIM Maastricht University, Maastricht, NetherlandsDepartment of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDepartment of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, United StatesArtificial Intelligence in Medicine (AIM) Program, Mass General Brigham and Harvard Medical School, Boston, MA, United StatesDepartment of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDepartment of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesIntroductionPatients receiving thoracic radiotherapy (RT) have an increased risk of major adverse cardiac events (MACE) posttreatment. We utilized machine learning (ML) to discover novel predictors of MACE and validated them on an external cohort.MethodsThis multi-institutional retrospective study included 984 patients [n = 803 non-small cell lung cancer (NSCLC), n = 181 breast cancer] treated with radiotherapy. Extreme gradient boosting was utilized to discover novel clinical, dosimetric, and anatomical features (CT-based cardiac substructure segmentations) associated with MACE in a cohort of locally advanced NSCLC patients. Fine–Gray regression was performed with non-cardiac death as a competing risk. External validation was performed utilizing independent cohorts of NSCLC or breast cancer patients.ResultsIn the discovery dataset (n = 701), 70 patients experienced MACE. ML modeling (training AUC, 0.68; testing AUC, 0.71) identified right and left atrial volume indices (RAVI and LAVI, respectively) as top predictors. After adjusting for baseline cardiovascular risk and known radiotherapy predictive factors, RAVI was associated with an increased risk of MACE [subdistribution hazard ratio (sHR) 1.02/unit, 95% confidence interval (CI): 1.00–1.04; p = 0.03]. In the validation cohorts (n = 102 NSCLC; n = 181 breast cancer), RAVI was associated with an increased risk of MACE (NSCLC: sHR 1.05, 95% CI: 1.001–1.106, p = 0.04; breast cancer: sHR 1.06, 95% CI: 1.01–1.11, p = 0.03). Similar findings were found for LAVI.DiscussionML modeling identified right and left atrial enlargement as novel radiographic predictors for increased risk of MACE following chest radiotherapy, which was validated in independent breast and lung cancer datasets. Given that echocardiography studies have demonstrated the prognostic utility of atrial volume indices across cardiovascular risk groups, these findings warrant further study to identify additional strategies for upfront cardiovascular risk profiling.https://www.frontiersin.org/articles/10.3389/fcvm.2025.1560922/fulloncologyradiotherapylungbreastmajor adverse cardiac eventsatrial volume
spellingShingle Edmund M. Qiao
John He
Katrina D. Silos
Jordan O. Gasho
Patrick Belen
Danielle S. Bitterman
Danielle S. Bitterman
Elizabeth McKenzie
Jennifer Steers
Christian Guthier
Anju Nohria
Michael T. Lu
Hugo J. W. L. Aerts
Hugo J. W. L. Aerts
Hugo J. W. L. Aerts
Andriana P. Nikolova
Raymond H. Mak
Raymond H. Mak
Katelyn M. Atkins
Katelyn M. Atkins
Baseline atrial volume indices and major adverse cardiac events following thoracic radiotherapy
Frontiers in Cardiovascular Medicine
oncology
radiotherapy
lung
breast
major adverse cardiac events
atrial volume
title Baseline atrial volume indices and major adverse cardiac events following thoracic radiotherapy
title_full Baseline atrial volume indices and major adverse cardiac events following thoracic radiotherapy
title_fullStr Baseline atrial volume indices and major adverse cardiac events following thoracic radiotherapy
title_full_unstemmed Baseline atrial volume indices and major adverse cardiac events following thoracic radiotherapy
title_short Baseline atrial volume indices and major adverse cardiac events following thoracic radiotherapy
title_sort baseline atrial volume indices and major adverse cardiac events following thoracic radiotherapy
topic oncology
radiotherapy
lung
breast
major adverse cardiac events
atrial volume
url https://www.frontiersin.org/articles/10.3389/fcvm.2025.1560922/full
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