Early Detection of Cardiovascular Changes After Radiotherapy for Breast Cancer

NCT03297346 | Completed

• 1 other identifier: MEDIRAD EARLY-HEART_1.2
• Study Type: interventional
• Target: 250
• Locations: 5 countries
• Sites: 5

Brief 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.

Conditions

Breast Cancer Female

Keywords

radiotherapy; cardiovascular changes; cardiac imaging; circulating biomarkers; dosimetry

Outcome Measures

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

  2 years after radiotherapy (baseline measurements performed before radiotherapy)

Secondary Outcomes (4)

• Changes in myocardial function measurements assessed by echocardiography

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

• Anatomical changes in coronary arteries assessed by cardiac CT

  2 years after radiotherapy (baseline measurements performed before radiotherapy)

• Myocardial tissue abnormalities assessed by cardiac MRI

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

• Changes in circulating biomarkers measurements

  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)

Study Arms (1)

Breast cancer patients treated with RT

OTHER

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

Cardiac imaging and circulating biomarkers OTHER

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

Breast cancer patients treated with RT

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institut de Radioprotection et de Surete Nucleaire: lead
• Academisch Ziekenhuis Groningen: collaborator
• Technical University of Munich: collaborator
• Institut Català d'Oncologia: collaborator
• Hospital de Santa Maria, Portugal: collaborator
• University of Paris 5 - Rene Descartes: collaborator

Study Sites (5)

IRSN - Clinique Pasteur

Toulouse, France

Location

Klinikum rechts der Isar der Technischen Universität München

Munich, Germany

Location

Academisch Ziekenhuis Groningen

Groningen, Netherlands

Location

Associação para Investigação e Desenvolvimento da Faculdade de Medicina

Lisbon, Portugal

Location

Institut Català d'Oncologia

Girona, Spain

Location

Related Publications (2)

• 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.

  PMID: 35837099 DERIVED

• 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.

  PMID: 30274965 DERIVED

Study Officials

• Sophie Jacob, PhD

  Institut de Radioprotection et de Sûreté Nucléaire

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: September 21, 2017
• First Posted: September 29, 2017
• Study Start: September 1, 2017
• Primary Completion: October 1, 2020
• Study Completion: May 31, 2021
• Last Updated: November 7, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); NL (1); PT (1); ES (1); FR (1)