Early Detection of Imaging-derived Subclinical Cardiac Injuries

Cardiovascular Diseases Clinical Trial

— EMIRA  

Official title:

Early Detection of Imaging-derived Subclinical Cardiac Injuries After Radiotherapy and Chemotherapy for Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03575650
• Other study ID #: 2018-06
• Status: Recruiting
• Start date: January 24, 2019
• Est. completion date: September 2, 2024

Study information

• Verified date: February 2024
• Source: University Medical Center Groningen
• Contact: Anne Crijns, MD, PhD
• Phone: +31503616161
• Email: a.p.g.crijns[@]umcg.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Breast cancer (BC) radiotherapy leads to incidental cardiac irradiation, resulting in an increased risk of various major cardiac events (MCEs). In addition, recent studies indicate that for the treatment of BC, the addition of chemotherapy further enhances the risk of MCEs. Information regarding morphological and functional early subclinical cardiac injuries (ESCIs) induced by chemotherapy and radiotherapy that develop into MCEs is largely lacking in scientific literature. This information is essential towards the development of primary and secondary preventive strategies. The EMIRA prospective cohort has as main objective to identify morphological and functional ESCIs in BC patients treated with adjuvant radiotherapy and chemotherapy.

Description:

EMIRA is a single centre prospective observational cohort study performed in the UMCG. The study includes breast cancer patients that underwent primary surgery, either by mastectomy or breast conserving surgery, who are treated with adjuvant radiotherapy and chemotherapy as part of routine clinical care. The patient follow up time continues for 2 years after radiotherapy to identify early subclinical cardiac injuries (ESCIs), using repeat echocardiography (cECHO), cardiac MRI (cMRI) scans and cardiac CT (cCT) scans. The images are acquired prior to chemotherapy and/or radiotherapy (depending on the sequence of adjuvant treatment), and at 6 and 24 months after radiotherapy The first primary aim of this project is to detect ESCIs that are considered risk factors for clinically apparent major cardiac events in breast cancer patients treated with radiotherapy and chemotherapy. The second is to use this information to develop prediction models describing the relationship between the radiation dose to cardiac substructures and ESCIs. In detail, the investigators aim to: 1. identify longitudinal morphological and functional ESCIs using echocardiography, cardiac MRI and cardiac CT before and after BC treatment; 2. determine the relationship between 3D-dose distributions to cardiac substructures and ESCI; 3. establish the effect of chemotherapy on the dose-effect relationship between radiation dose and ESCI.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 148
• Est. completion date: September 2, 2024
• Est. primary completion date: September 2, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Female unilateral BC patients

2. Primary breast conserving surgery or mastectomy for stage I-III invasive adenocarcinoma of the breast or ductal carcinoma in situ (DCIS)

3. Age between 40-70 years at time of chemotherapy/radiotherapy

4. WHO performance status 0-1

5. Planned radiotherapy to the breast/chest wall with or without the lymph node areas

6. Radiotherapy based on planning CT-scan, using either 3D CRT, (partial) IMRT or (partial) VMAT/RapidArc with or without deep inspiration breath-hold

7. Adjuvant systemic chemotherapy (before or after radiotherapy)

8. Written informed consent

Exclusion Criteria:

1. Male BC patients

2. M1 disease (metastatic BC)

3. Previous thoracic or mediastinal radiation

4. Neo-adjuvant chemotherapy not allowed

5. Targeted HER2 therapy not allowed

6. Medical history of coronary artery disease and/or myocardial infarction and/or atrial fibrillation

7. Contraindications to injection of iodinated contrast such as allergy or renal failure

8. Pregnancy or lactation

9. Atrial fibrillation detected during electrocardiogram before chemotherapy/radiotherapy

10. Abnormal echocardiography before chemotherapy/radiotherapy defined as: LVEF <50%, longitudinal strain <-16%, longitudinal strain rate <-1%, and/or abnormal wall motion

11. Presence of myocardial infarction detected during cMRI before chemotherapy/radiotherapy

12. cMRI or cCT results before chemotherapy/radiotherapy requiring revascularisation

Related Conditions & MeSH terms

• Cardiovascular Diseases

Intervention

Other:
• Cardiac imaging modalities
Repeat cardiac echocardiographies, MRI-scans and CT-scans for early subclinical biomarker assessments in breast cancer patients treated with chemotherapy and radiotherapy

Locations

Country	Name	City	State
Netherlands	UMCG	Groningen

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Groningen	Utrecht University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Left Ventricle Global Longitudinal Strain (LV-GLS) assessed by echocardiography	Increasement in left ventricle Global Longitudinal Strain (GLS) of at least 5%	6 and 24 months after radiotherapy with reference to baseline
Secondary	Changes in myocardial function assessed by echocardiography	Increasement of segmental strain measurements (unit of measures:%)	6 and 24 after completion of radiotherapy with reference to baseline
Secondary	Anatomical changes in coronary arteries by cardiac CT	Increase in the number of coronary segments containing any plaque/stenosis, or increase in calcium score	6 and 24 after completion of radiotherapy with reference to baseline
Secondary	Myocardial tissue abnormalities assessed by cardiac MRI	Increase of the native mean myocardial T1 mapping value assessed by cardiac MRI	6 and 24 after completion of radiotherapy with reference to baseline