+1 Recommend
1 collections

      To submit your manuscript, please click here

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Early Detection of Cardiovascular Changes After Radiotherapy for Breast Cancer: Protocol for a European Multicenter Prospective Cohort Study (MEDIRAD EARLY HEART Study)

      , MSc 1 , , MD, PhD 2 , , MD, PhD 2 , , MSc 2 , , MD, PhD 3 , , MD, PhD 4 , 5 , 6 , , MD 4 , , MD, PhD 7 , , MD, PhD 8 , , MD, PhD 9 , , PhD 10 , , PhD 11 , , PhD 12 , , MD, PhD 13 , 14 , , MD, PhD 15 , , PhD 16 , 17 , 18 , , PhD 1 ,
      (Reviewer), (Reviewer)
      JMIR Research Protocols
      JMIR Publications
      biomarkers, breast cancer, cardiotoxicity, cardiac diagnostic imaging, radiotherapy, radiation dosimetry

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.



          Breast cancer is the most common cancer among women, and radiotherapy plays a major role in its treatment. However, breast cancer radiotherapy can lead to incidental irradiation of the heart, resulting in an increased risk for a variety of heart diseases arising many years after radiotherapy. Therefore, identifying breast cancer patients at the highest risk for radiation-induced cardiac complications is crucial for developing strategies for primary and secondary prevention, which may contribute to healthy aging. There is still a need for precise knowledge on the relationship between radiation dose to specific cardiac structures and early subclinical cardiac changes and their occurrence over time that could finally lead to cardiac complications.


          The MEDIRAD EARLY HEART study aims to identify and validate new cardiac imaging and circulating biomarkers of radiation-induced cardiovascular changes arising within first 2 years of breast cancer radiotherapy and to develop risk models integrating these biomarkers combined with precise dose metrics of cardiac structures based on three-dimensional dosimetry.


          The EARLY HEART study is a multicenter, prospective cohort study in which 250 women treated for breast cancer and followed for 2 years after radiotherapy will be included. Women treated with radiotherapy without chemotherapy for a unilateral breast cancer and aged 40-75 years meet the inclusion criteria. Baseline and follow-up data include cardiac measurements based on two-dimensional speckle-tracking echocardiography, computed tomography coronary angiography, cardiac magnetic resonance imaging, and a wide panel of circulating biomarkers of cardiac injury. The absorbed dose will be evaluated globally for the heart and different substructures. Furthermore, the dose-response relationship will allow modeling the radiation-induced occurrence and evolution of subclinical cardiac lesions and biomarkers to develop prediction models.


          This study details the protocol of the MEDIRAD EARLY HEART study and presents the main limits and advantages of this international project. The inclusion of patients began in 2017. Preliminary results are expected to be published in 2019, and complete analysis should be published in 2021.


          The MEDIRAD EARLY HEART study will allow identifying the main cardiac imaging and blood-based determinants of radiation-induced cardiac injuries to better propose primary and secondary preventive measures in order to contribute to enhanced patient care and quality of life.

          Trial Registration

          ClinicalTrials.gov NCT03297346; https://clinicaltrials.gov/ct2/show/NCT03297346 (Archived by WebCite at http://www.webcitation.org/72KS7MIUU)

          Registered Report Identifier


          Related collections

          Most cited references37

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Validation and Modification of a Prediction Model for Acute Cardiac Events in Patients With Breast Cancer Treated With Radiotherapy Based on Three-Dimensional Dose Distributions to Cardiac Substructures

          Purpose A relationship between mean heart dose (MHD) and acute coronary event (ACE) rate was reported in a study of patients with breast cancer (BC). The main objective of our cohort study was to validate this relationship and investigate if other dose-distribution parameters are better predictors for ACEs than MHD. Patients and Methods The cohort consisted of 910 consecutive female patients with BC treated with radiotherapy (RT) after breast-conserving surgery. The primary end point was cumulative incidence of ACEs within 9 years of follow-up. Both MHD and various dose-distribution parameters of the cardiac substructures were collected from three-dimensional computed tomography planning data. Results The median MHD was 2.37 Gy (range, 0.51 to 15.25 Gy). The median follow-up time was 7.6 years (range, 0.1 to 10.1 years), during which 30 patients experienced an ACE. The cumulative incidence of ACE increased by 16.5% per Gy (95% CI, 0.6 to 35.0; P = .042). Analysis showed that the volume of the left ventricle receiving 5 Gy (LV-V5) was the most important prognostic dose-volume parameter. The most optimal multivariable normal tissue complication probability model for ACEs consisted of LV-V5, age, and weighted ACE risk score per patient (c-statistic, 0.83; 95% CI, 0.75 to 0.91). Conclusion A significant dose-effect relationship was found for ACEs within 9 years after RT. Using MHD, the relative increase per Gy was similar to that reported in the previous study. In addition, LV-V5 seemed to be a better predictor for ACEs than MHD. This study confirms the importance of reducing exposure of the heart to radiation to avoid excess risk of ACEs after radiotherapy for BC.
            • Record: found
            • Abstract: found
            • Article: not found

            Diagnostic and prognostic impact of six circulating microRNAs in acute coronary syndrome.

            Circulating microRNAs may have diagnostic potential in acute coronary syndrome (ACS). Previous studies, however, were based on low patient numbers and could not assess the relation of microRNAs to clinical characteristics and their potential prognostic value. We thus assessed the diagnostic and prognostic value of cardiomyocyte-enriched microRNAs in the context of clinical variables and a sensitive myonecrosis biomarker in a larger ACS cohort. MiR-1, miR-133a, miR-133b, miR-208a, miR-208b, and miR-499 concentrations were measured by quantitative reverse transcription PCR in plasma samples obtained on admission from 444 patients with ACS. High-sensitivity troponin T (hsTnT) was measured by immunoassay. Patients were followed for 6 months regarding all-cause mortality. In a multiple linear regression analysis that included clinical variables and hsTnT, miR-1, miR-133a, miR-133b, and miR-208b were independently associated with hsTnT levels (all P<0.001). Patients with myocardial infarction presented with higher levels of miR-1, miR-133a, and miR-208b compared with patients with unstable angina. However, all six investigated microRNAs showed a large overlap between patients with unstable angina or myocardial infarction. MiR-133a and miR-208b levels were significantly associated with the risk of death in univariate and age- and gender-adjusted analyses. Both microRNAs lost their independent association with outcome upon further adjustment for hsTnT. The present study tempers speculations about the potential usefulness of cardiomyocyte-enriched microRNAs as diagnostic or prognostic markers in ACS. Copyright © 2011 Elsevier Ltd. All rights reserved.
              • Record: found
              • Abstract: found
              • Article: not found

              Risk of cardiac death after adjuvant radiotherapy for breast cancer.

              Women with breast cancer who are treated with adjuvant radiation have a decreased risk of local recurrence but an increased risk of mortality from ischemic heart disease. Patients with left-sided breast tumors receive a higher dose of radiation to the heart than patients with right-sided tumors. Because radiation techniques have improved over time, we investigated whether the risk of death from ischemic heart disease after adjuvant breast radiotherapy decreased over time. We used the 12-registry 1973-2000 dataset from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Women (n = 27,283) treated with adjuvant radiation for breast cancer diagnosed in 1973-1989 were included in the study. Ischemic heart disease mortality was calculated at 15 years and compared for women diagnosed during 1973-1979, 1980-1984, and 1985-1989. Cox proportional hazards models were used to calculate the hazard of death from ischemic heart disease for women diagnosed 1973-1988 and censored at 12 years. All statistical tests were two-sided. There were no differences in age, race/ethnicity, disease stage, or follow-up time between the 13 998 women with left-sided and 13 285 with right-sided cancer. For women diagnosed in 1973-1979, there was a statistically significant difference in 15-year mortality from ischemic heart disease between patients with left-sided (13.1%, 95% confidence interval [CI] = 11.6 to 14.6) and those with right-sided (10.2%, 95% CI = 8.9 to 11.5) breast cancer (P = .02); no such difference was found for women diagnosed in 1980-1984 (9.4%, [95% CI = 8.1 to 10.6] versus 8.7% [95% CI = 7.4 to 10.0], respectively, P = .64) or 1985-1989 (5.8% [95% CI = 4.8 to 6.8] versus 5.2% [95% CI = 4.4 to 5.9], respectively, P = .98). In the Cox model, the hazard ratio [HR] for ischemic heart disease mortality for women with left-sided versus women with right-sided disease was 1.50 (95% CI = 1.19 to 1.87) in 1979. With each succeeding year after 1979, the hazard of death from ischemic heart disease for women with left-sided versus those with right-sided disease declined by 6% (HR = 0.94, 95% CI = 0.91 to 0.98). Risk of death from ischemic heart disease associated with radiation for breast cancer has substantially decreased over time.

                Author and article information

                JMIR Res Protoc
                JMIR Res Protoc
                JMIR Research Protocols
                JMIR Publications (Toronto, Canada )
                October 2018
                01 October 2018
                : 7
                : 10
                : e178
                [1 ] Pôle Santé-Environnement (PSE-SANTE), Service de recherche sur les effets biologiques et sanitaires des rayonnements ionisants (SESANE) Laboratoire d'épidémiologie des rayonnements ionisants (LEPID) Institut de Radioprotection et de Sûreté Nucléaire (IRSN) Fontenay-aux-Roses France
                [2 ] Department of Radiation Oncology University Medical Center Groningen University of Groningen Groningen Netherlands
                [3 ] Center for Medical Imaging, Department of Radiology University Medical Center Groningen University of Groningen Groningen Netherlands
                [4 ] Department of Radiation Oncology Technische Universität München (TUM) München Germany
                [5 ] Department of Radiation Sciences (DRS) Institute of Innovative Radiotherapy (iRT) Helmholtz Zentrum München (HMGU) München Germany
                [6 ] Deutsches Konsortium für Translationale Krebsforschung (DKTK) Partner Site Munich München Germany
                [7 ] Department of Radiation Oncology Institut Català d'Oncologia Girona Spain
                [8 ] Department of Radiation Oncology Institut Català d'Oncologia L’Hospitalet del Llobregat Spain
                [9 ] Department of Cardiology Centro Cardiovascular da Universidade de Lisboa Lisbon Portugal
                [10 ] Laboratory of Angiogenesis Centro Cardiovascular da Universidade de Lisboa Lisbon Portugal
                [11 ] Pôle Santé-Environnement (PSE-SANTE) Institut de Radioprotection et de Sûreté Nucléaire (IRSN) Fontenay-aux-Roses France
                [12 ] Pôle Santé-Environnement (PSE-SANTE), Service de recherche sur les effets biologiques et sanitaires des rayonnements ionisants (SESANE) Institut de Radioprotection et de Sûreté Nucléaire (IRSN) Fontenay-aux-Roses France
                [13 ] Department of Cardiology B and Epidemiology University Hospital Toulouse France
                [14 ] Unite Mixte de Recherche (UMR) 1027 The Institut national de la santé et de la recherche médicale (INSERM) Toulouse France
                [15 ] Department of Radiology Hôpital Européen Georges Pompidou Paris Descartes University Paris France
                [16 ] Institute for Global Health (ISGlobal) Radiation Programme Barcelona Biomedical Research Park (PRBB) Barcelona Spain
                [17 ] Pompeu Fabra University (UPF) Barcelona Spain
                [18 ] Consorcio Centro de Investigación Biomédica en Red Epidemiologia y Salud Pública (CIBERESP) Madrid Spain
                Author notes
                Corresponding Author: Sophie Jacob sophie.jacob@ 123456irsn.fr
                Author information
                ©Valentin Walker, Anne Crijns, Johannes Langendijk, Daan Spoor, Rozemarijn Vliegenthart, Stephanie E Combs, Michael Mayinger, Arantxa Eraso, Ferran Guedea, Manuela Fiuza, Susana Constantino, Radia Tamarat, Dominique Laurier, Jean Ferrières, Elie Mousseaux, Elisabeth Cardis, Sophie Jacob. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 01.10.2018.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on http://www.researchprotocols.org.as well as this copyright and license information must be included.

                : 22 January 2018
                : 22 February 2018
                : 30 March 2018
                : 17 April 2018

                biomarkers,breast cancer,cardiotoxicity,cardiac diagnostic imaging,radiotherapy,radiation dosimetry


                Comment on this article