Prediction for cardiac and pulmonary toxicity in a multicentric cohort of advanced stage NSCLC patients using sub-regions of the heart

Purpose: Follow-up investigations in locally advanced stage non-small cell lung cancer (NSCLC) patients treated with radiochemotherapy (RCHT) regularly focus around lung toxicity. However, Cardiac Adverse Events (CAE) can occur much earlier in patients than originally anticipated with serious reperc...

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Main Authors: Albrecht Weiß, Steffen Löck, Ting Xu, Zhongxing Liao, Miguel Garrett Fernandes, René Monshouwer, Johan Bussink, Esther G.C. Troost
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Clinical and Translational Radiation Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405630825000424
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author Albrecht Weiß
Steffen Löck
Ting Xu
Zhongxing Liao
Miguel Garrett Fernandes
René Monshouwer
Johan Bussink
Esther G.C. Troost
author_facet Albrecht Weiß
Steffen Löck
Ting Xu
Zhongxing Liao
Miguel Garrett Fernandes
René Monshouwer
Johan Bussink
Esther G.C. Troost
author_sort Albrecht Weiß
collection DOAJ
description Purpose: Follow-up investigations in locally advanced stage non-small cell lung cancer (NSCLC) patients treated with radiochemotherapy (RCHT) regularly focus around lung toxicity. However, Cardiac Adverse Events (CAE) can occur much earlier in patients than originally anticipated with serious repercussions for patient quality-of-life and survival.Therefore, here we investigated spatial dependencies of dose within the heart and their correlation with toxicity, with dosimetric parameters of sub-regions of the heart at the focus of this analysis.Additionally, we aimed to explore the connection between cardiac toxicity and pulmonary toxicity. Methods: Patient treatment plans with dosimetric data for the lungs and the heart, as well as toxicity data for 502 NSCLC patients treated with either passively scattered proton therapy (PSPT), intensity modulated radiation therapy (IMRT), three-dimensional conformal radiation therapy (3DCRT) or volumetric arc therapy (VMAT) with or without chemotherapy was retrospectively retrieved from prospective clinical studies of three international centers. Cardiac toxicity data was not available for all patients. Data was randomly split into a training set (336) and validation set (166). Statistical analyses were performed using binomial logistic regression. Results: In univariate modeling, the Mean Lung Dose (MLD) significantly predicted CAE grade ≥ 3 in the training-set (pMLD = 0.02, AUCtrain = 0.69), which was confirmed in validation (AUCval, = 0.77). No suitable candidates for the construction of multivariate models could be identified. Parameters of the heart and its subregions did not significantly predict CAE grade ≥ 3 in the investigated cohorts. No parameters were found to significantly predict CAE grade ≥ 2 or RP. Finally, no spatial dependency was found in the investigated toxicity data. Conclusion: The pulmonary dosimetric parameter MLD successfully predicted CAE grade ≥ 3 in a cohort treated with either photons or protons. Cardiac dosimetric parameters as well as spatial parameters did not perform similarly. No parameters were found to significantly predict RP in the investigated cohorts.
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spelling doaj-art-567cd4dea1a64f85bf597f5f4d4de31f2025-08-20T03:30:51ZengElsevierClinical and Translational Radiation Oncology2405-63082025-07-015310095210.1016/j.ctro.2025.100952Prediction for cardiac and pulmonary toxicity in a multicentric cohort of advanced stage NSCLC patients using sub-regions of the heartAlbrecht Weiß0Steffen Löck1Ting Xu2Zhongxing Liao3Miguel Garrett Fernandes4René Monshouwer5Johan Bussink6Esther G.C. Troost7German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany; OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, GermanyGerman Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany; OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyDepartment of Thoracic Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Thoracic Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Radiation Oncology, Radboud Institute for Health Sciences, Radboud University, Medical Center, Nijmegen, the Netherlands; Department of Medical Physics and Biomedical Engineering, University College London, London, United KingdomDepartment of Radiation Oncology, Radboud Institute for Health Sciences, Radboud University, Medical Center, Nijmegen, the NetherlandsDepartment of Radiation Oncology, Radboud Institute for Health Sciences, Radboud University, Medical Center, Nijmegen, the NetherlandsGerman Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany; OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology-OncoRay, Dresden, Germany; Corresponding author at: OncoRay – National Center for Radiation Research in Oncology, Fetscherstr. 74, PF 41, 01307 Dresden, Germany.Purpose: Follow-up investigations in locally advanced stage non-small cell lung cancer (NSCLC) patients treated with radiochemotherapy (RCHT) regularly focus around lung toxicity. However, Cardiac Adverse Events (CAE) can occur much earlier in patients than originally anticipated with serious repercussions for patient quality-of-life and survival.Therefore, here we investigated spatial dependencies of dose within the heart and their correlation with toxicity, with dosimetric parameters of sub-regions of the heart at the focus of this analysis.Additionally, we aimed to explore the connection between cardiac toxicity and pulmonary toxicity. Methods: Patient treatment plans with dosimetric data for the lungs and the heart, as well as toxicity data for 502 NSCLC patients treated with either passively scattered proton therapy (PSPT), intensity modulated radiation therapy (IMRT), three-dimensional conformal radiation therapy (3DCRT) or volumetric arc therapy (VMAT) with or without chemotherapy was retrospectively retrieved from prospective clinical studies of three international centers. Cardiac toxicity data was not available for all patients. Data was randomly split into a training set (336) and validation set (166). Statistical analyses were performed using binomial logistic regression. Results: In univariate modeling, the Mean Lung Dose (MLD) significantly predicted CAE grade ≥ 3 in the training-set (pMLD = 0.02, AUCtrain = 0.69), which was confirmed in validation (AUCval, = 0.77). No suitable candidates for the construction of multivariate models could be identified. Parameters of the heart and its subregions did not significantly predict CAE grade ≥ 3 in the investigated cohorts. No parameters were found to significantly predict CAE grade ≥ 2 or RP. Finally, no spatial dependency was found in the investigated toxicity data. Conclusion: The pulmonary dosimetric parameter MLD successfully predicted CAE grade ≥ 3 in a cohort treated with either photons or protons. Cardiac dosimetric parameters as well as spatial parameters did not perform similarly. No parameters were found to significantly predict RP in the investigated cohorts.http://www.sciencedirect.com/science/article/pii/S2405630825000424NTCPNSCLCCardio-oncologyCardiac adverse eventsPulmonary toxicity
spellingShingle Albrecht Weiß
Steffen Löck
Ting Xu
Zhongxing Liao
Miguel Garrett Fernandes
René Monshouwer
Johan Bussink
Esther G.C. Troost
Prediction for cardiac and pulmonary toxicity in a multicentric cohort of advanced stage NSCLC patients using sub-regions of the heart
Clinical and Translational Radiation Oncology
NTCP
NSCLC
Cardio-oncology
Cardiac adverse events
Pulmonary toxicity
title Prediction for cardiac and pulmonary toxicity in a multicentric cohort of advanced stage NSCLC patients using sub-regions of the heart
title_full Prediction for cardiac and pulmonary toxicity in a multicentric cohort of advanced stage NSCLC patients using sub-regions of the heart
title_fullStr Prediction for cardiac and pulmonary toxicity in a multicentric cohort of advanced stage NSCLC patients using sub-regions of the heart
title_full_unstemmed Prediction for cardiac and pulmonary toxicity in a multicentric cohort of advanced stage NSCLC patients using sub-regions of the heart
title_short Prediction for cardiac and pulmonary toxicity in a multicentric cohort of advanced stage NSCLC patients using sub-regions of the heart
title_sort prediction for cardiac and pulmonary toxicity in a multicentric cohort of advanced stage nsclc patients using sub regions of the heart
topic NTCP
NSCLC
Cardio-oncology
Cardiac adverse events
Pulmonary toxicity
url http://www.sciencedirect.com/science/article/pii/S2405630825000424
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