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CompletedNCT03297346EARLY-HEARTUpdated Nov 7, 2023

Early Detection of Cardiovascular Changes After Radiotherapy for Breast Cancer

An interventional study of Cardiac imaging and circulating biomarkers in Breast Cancer Female, sponsored by Institut de Radioprotection et de Surete Nucleaire. Completed at 5 sites in 5 countries. Open to female participants aged 40 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-11-07.

Sponsored by Institut de Radioprotection et de Surete Nucleaire · Not applicable, Interventional, and Prevention

Phase
Not applicable
Study type
Interventional
Enrollment
250
Allocation
Not applicable
Ages
40 Years to 75 Years
Sex
Female
01

Study summary

Breast cancer (BC) radiotherapy leads to coincidental radiation of the heart, resulting in increased risk of a variety of heart diseases. Identifying BC patients with the highest risk of radiation-induced cardiac complications is crucial for developing strategies for primary and secondary prevention. Little has been done on the relationship between dose distribution to different anatomical cardiac structures during radiotherapy and early cardiovascular changes that may lead to cardiac complications.

In the framework of the European project MEDIRAD, the EARLY-HEART multicenter prospective cohort was launched in August 2017, involving 5 investigating centers from France, Netherlands, Germany, Spain and Portugal. With 250 BC patients prospectively followed for 2 years, the main objective is to identify and validate the most important cardiac imaging (echocardiography, computed tomography coronary angiography, cardiac magnetic resonance imaging) and circulating biomarkers of radiation-induced cardiovascular changes arising in the first 2 years after BC radiotherapy.

Read the detailed description

EARLY-HEART is a multicentre prospective cohort study that will include 250 female primary breast cancer cases aged 40-75 years treated with postoperative radiotherapy (RT) alone after breast-conserving surgery using modern planning-CT based RT technologies and followed for 2 years after RT in one of the 5 participating hospitals. In addition to the standard follow-up, patients will need to give repeated blood samples and will undergo repeated cardiac imaging:

  • Functional and anatomical cardiac imaging biomarkers will be based on automated 2D-speckle-tracking echocardiography (ECHO-ST); Computed Tomography Coronary Angiography (CT) and cardiac magnetic resonance imaging (MRI).
  • Circulating biomarkers (BLOOD) will be based on a panel of multiple classical or novel blood-based biomarkers.

Imaging and circulating biomarkers measurements will be assessed at baseline before RT (ECHO, CT, MRI, BLOOD); at the end of RT (BLOOD); 6 months after RT (ECHO, MRI, BLOOD) and 24 months after RT (ECHO, CT, MRI, BLOOD).

Changes in functional and anatomical cardiac imaging and circulating biomarkers between unexposed status before RT and exposed status after RT at different time points will be first analysed to evaluate the effects of RT on the heart.

All relevant DICOM-data (including planning-CT scans and the ECHO, MRI and CT) will be centralized to the MEDIRAD-ENACT database managed by University of Groningen for automated segmentation of all cardiac substructures (including coronary arteries) to ensure uniformity of the segmentation procedure between centres. The RT planning CTs will be used to generate dose volume histograms and 3D dose maps of the heart and cardiac substructures in order to correlate the localization of any cardiovascular change with the anatomical dose distribution.

In the presence of a cardiac outcome, a multimetric Normal Tissue Complication Probability (NTCP) individual risk model will be constructed and an integrative clinical-biologic risk score will be developed for individual risk prediction.

02

Conditions studied

  • Breast Cancer Female

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Keywords

  • radiotherapy
  • cardiovascular changes
  • cardiac imaging
  • circulating biomarkers
  • dosimetry
03

Who can participate

Ages eligible
40 Years to 75 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

Inclusion criteria

  • Female unilateral breast cancer patients
  • Treated with primary breast conserving surgery for stage I-III invasive adenocarcinoma of the breast or ductal carcinoma in situ (DCIS)
  • Age between 40-75 years at time of start radiotherapy
  • World Health Organisation (WHO) performance status 0-1
  • Planned for radiotherapy alone to the breast with or without the lymph node areas
  • Radiotherapy based on planning-CT scan using either three dimensional conformal radiation therapy (3D-CRT), Intensity-modulated radiotherapy (IMRT), or Volumetric Arc Therapy (VMAT/RapidArc)
  • Written Informed consent

Exclusion criteria

Exclusion Criteria:

  • Male breast cancer patients
  • Neoadjuvant or adjuvant chemotherapy
  • M1 disease (metastatic breast cancer)
  • Medical history of coronary artery disease and/or myocardial infarction and/or atrial fibrillation
  • Previous thoracic or mediastinal radiation
  • Contraindications to injection of iodinated contrast such as allergy or renal failure
  • Pregnancy or lactation
  • Atrial fibrillation detected during electrocardiogram before radiotherapy
  • Abnormal echocardiography before radiotherapy defined as: Left Ventricular Ejection Fraction\<50%; longitudinal strain ≤ -16%; longitudinal strain rate \<-1%, and/or abnormal wall motion
  • Presence of myocardial infarction detected during MRI before radiotherapy
  • CT or MRI results before radiotherapy requiring revascularisation
04

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
250 participants (actual)

Study arms

  • Other
    Breast cancer patients treated with RT

    Cardiac imaging and circulating biomarkers measurements to evaluate: * myocardial dysfunction and deformation (ECHO-ST) * coronary artery lesions and coronary artery calcium score (CT) * myocardium including tissue abnormalities, cardiac morphology and function (MRI) * blood-based biomarkers of cardiovascular changes (BLOOD)

    Other: Cardiac imaging and circulating biomarkers

Interventions

  • OtherCardiac imaging and circulating biomarkers

    Automated 2D-speckle-tracking echocardiography (ECHO-ST); Computed tomography coronary angiography (CT); Cardiac magnetic resonance imaging (MRI); Blood samples for circulating biomarkers measurements (BLOOD)

05

What researchers measure

Primary outcomes

  1. Number of patients with decreased myocardial function assessed by echocardiography

    Number of patients with an increased of at least 2.5% in the Global Longitudinal Strain (GLS) between baseline and 2 years after radiotherapy

    Time frame: 2 years after radiotherapy (baseline measurements performed before radiotherapy)

Secondary outcomes

  1. Changes in myocardial function measurements assessed by echocardiography

    Increase of the segmental strain measurements (unit of measures:%)

    Time frame: 6 months and 2 years after radiotherapy (baseline measurements performed before radiotherapy)

  2. Anatomical changes in coronary arteries assessed by cardiac CT

    Increase of the number of coronary segments containing any plaque or increase of the calcium score

    Time frame: 2 years after radiotherapy (baseline measurements performed before radiotherapy)

  3. Myocardial tissue abnormalities assessed by cardiac MRI

    Increase of the native mean myocardial T1 mapping value

    Time frame: 6 months and 2 years after radiotherapy (baseline measurements performed before radiotherapy)

  4. Changes in circulating biomarkers measurements

    Significant increase or decrease in the following biomarkers: classical biomarkers of cardiac injury (C-reactive protein, Troponin I, Troponin T, B-type natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-Pro BNP), beta2-Microglobulin, Galectin 3); Inflammatory cytokines; biomarkers of endothelial activation and dysfunction; Microparticles; MicroRNAs; circulating DNA methylation

    Time frame: at the end of radiotherapy (through radiotherapy completion, an average of 5 weeks after starting date of radiotherapy), 6 months and 2 years after radiotherapy (baseline measurements performed before radiotherapy)

06

Study locations

5 sites
  • IRSN - Clinique Pasteur
    Toulouse, France
  • Klinikum rechts der Isar der Technischen Universität München
    Munich, Germany
  • Academisch Ziekenhuis Groningen
    Groningen, Netherlands
  • Associação para Investigação e Desenvolvimento da Faculdade de Medicina
    Lisbon, Portugal
  • Institut Català d'Oncologia
    Girona, Spain
07

References and documents

Publications

  • Locquet M, Spoor D, Crijns A, van der Harst P, Eraso A, Guedea F, Fiuza M, Santos SCR, Combs S, Borm K, Mousseaux E, Gencer U, Frija G, Cardis E, Langendijk H, Jacob S. Subclinical Left Ventricular Dysfunction Detected by Speckle-Tracking Echocardiography in Breast Cancer Patients Treated With Radiation Therapy: A Six-Month Follow-Up Analysis (MEDIRAD EARLY-HEART study). Front Oncol. 2022 Jun 28;12:883679. doi: 10.3389/fonc.2022.883679. eCollection 2022. PubMed 35837099 ↗
  • Walker V, Crijns A, Langendijk J, Spoor D, Vliegenthart R, Combs SE, Mayinger M, Eraso A, Guedea F, Fiuza M, Constantino S, Tamarat R, Laurier D, Ferrieres J, Mousseaux E, Cardis E, Jacob S. Early Detection of Cardiovascular Changes After Radiotherapy for Breast Cancer: Protocol for a European Multicenter Prospective Cohort Study (MEDIRAD EARLY HEART Study). JMIR Res Protoc. 2018 Oct 1;7(10):e178. doi: 10.2196/resprot.9906. PubMed 30274965 ↗

Study documents

  • Protocol, analysis plan and consent form · Jul 5, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03297346
Lead sponsor
Institut de Radioprotection et de Surete Nucleaire
Collaborators
Academisch Ziekenhuis Groningen, Technical University of Munich, Institut Català d'Oncologia, Hospital de Santa Maria, Portugal, University of Paris 5 - Rene Descartes
Responsible party
Sophie JACOB (PhD, Institut de Radioprotection et de Surete Nucleaire) — Principal investigator
First posted
Sep 29, 2017
Start date
Sep 1, 2017
Primary completion
Oct 1, 2020
Completion
May 31, 2021
Last update
Nov 7, 2023

Study contacts

Sophie Jacob, PhD
study chair · Institut de Radioprotection et de Sûreté Nucléaire

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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