Early Detection of Cardiovascular Changes After Radiotherapy for Breast Cancer
Condition: Breast Cancer Female
MeSH terms: Breast Neoplasms
Study type: Interventional

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.
    

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.
    

Intervention name(s): Cardiac imaging and circulating biomarkers
Intervention type(s): Other
Intervention description(s): Automated 2D-speckle-tracking echocardiography (ECHO-ST); Computed tomography coronary angiography (CT); Cardiac magnetic resonance imaging (MRI); Blood samples for circulating biomarkers measurements (BLOOD)
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: radiotherapy; cardiovascular changes; cardiac imaging; circulating biomarkers; dosimetry