Early Detection of Imaging-derived Subclinical Cardiac Injuries

NCT ID: NCT03575650

Last Updated: 2024-02-28

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 148 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-01-24
• Study Completion Date: 2024-09-02

Brief 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.

Detailed 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.

Conditions

Cardiovascular Diseases

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Cardiac imaging modalities

Repeat echocardiography (cECHO), cardiac MRI (cMRI) scans and cardiac CT (cCT) scans will be performed to evaluate myocardial dysfunction and deformation; myocardium inclusing tissue abnormalities, cardiac morphology and function and; coronary artery lesions and coronary artery calcium score.

Cardiac imaging modalities

Intervention Type: OTHER

Repeat cardiac echocardiographies, MRI-scans and CT-scans for early subclinical biomarker assessments in breast cancer patients treated with chemotherapy and radiotherapy

Interventions

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

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Utrecht University

OTHER

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hans Langendijk, Prof.Dr

Role: STUDY_CHAIR

UMCG

Locations

UMCG

Groningen, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Anne Crijns, MD, PhD

Role: CONTACT

a.p.g.crijns@umcg.nl

+31503616161

Facility Contacts

Anne Crijns, MD PhD

Role: primary

a.p.g.crijns@umcg.nl

+31-652724432

Other Identifiers

2018-06

Identifier Type: -

Identifier Source: org_study_id