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BreAst Cancer and Cardiotoxicity Induced by RAdioTherapy: the BACCARAT Study

Not Applicable
Completed
Conditions
Breast Cancer
Cardiac Toxicity
Interventions
Other: Subclinical cardiac lesions and biomarkers
Registration Number
NCT02605512
Lead Sponsor
Sophie JACOB
Brief Summary

Breast radiotherapy RT used until the 1990s was clearly responsible for increased mortality due to long term cardiac complications. Since the 2000s, improvements have appeared in dose distributions to organ at risks such as heart, but now, little is known on the risk of potential cardiac impairment in this population, in particular for chemotherapy naive patients. Based on the state that clinically detectable cardiotoxicity is generally preceded by subclinical cardiac dysfunctions, the aim of the BACCARAT study (BreAst Cancer and Cardiotoxicity induced by RAdioTherapy) is to evaluate whether adjuvant 3DCRT induces cardiac toxicity that could be detected in the first two years after treatment based on a global approach with repeated analysis of subclinical functional and anatomical cardiac lesions in myocardial and coronary levels and circulating biomarkers.

Detailed Description

BACCARAT study consists in a monocentric prospective cohort study that will finally include 120 women treated with adjuvant RT for breast cancer in the Clinique Pasteur in Toulouse, and followed for 2 years after RT.

Women aged 50 to 70 years, treated for breast cancer and for whom adjuvant 3DCRT is indicated, without chemotherapy are eligible for the study.

Baseline and follow-up include measures of functional myocardial dysfunction based on 2D-speckle tracking echocardiography, anatomical coronary lesions based on Coronary computed tomography angiography, and a wide panel of circulating biomarkers. Absorbed doses is evaluated for whole heart and for each different parts of heart, in particular coronary arteries.

Analysis on occurrence and evolutions of subclinical cardiac lesions and biomarkers will be performed and completed with dose-response relations with absorbed doses of different heart segments.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
118
Inclusion Criteria
  • Age between 50 and 70 years
  • Women surgically treated for left or right breast cancer and for whom adjuvant treatment is radiotherapy with irradiation of the breast or chest wall irradiation and possibly ganglion chains,
  • Adjuvant radiotherapy with 3DCRT performed in Clinique Pasteur Toulouse
  • WHO performance status ECOG - Eastern Cooperative Oncology Group (index normally used to describe the patient's condition) = 0 or 1
  • Being volunteer to participate in the study and have signed the consent form
Exclusion Criteria
  • Indication of adjuvant chemotherapy
  • Clinically or radiologically detectable metastasis
  • Personal history of coronary artery disease or myocardial disease
  • Personal history of breast cancer or other cancer requiring radiotherapy to the thorax
  • Patient with controlled infection or severe disease and / or non-hazardous to their participation in the study
  • Contraindications to injection of iodinated contrast (for CCTA): pregnancy, renal failure, allergy.
  • Pregnancy, lactation
  • Abnormal echocardiography before radiotherapy:
  • LVEF <50%
  • Longitudinal strain> - 16%
  • Longitudinal strain rate <1% / s
  • Abnormal wall motion
  • CCTA before radiotherapy showing that therapeutic management is required (coronary-artery calcium (CAC) score>600)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Breast cancer patients with 3DCRTSubclinical cardiac lesions and biomarkersMeasures of subclinical functional and anatomical cardiac lesions and circulating biomarkers 'Subclinical cardiac lesions and biomarkers'
Primary Outcome Measures
NameTimeMethod
Number of patients with decreased myocardial function assessed by echocardiography2 years after 3DCRT (baseline measures performed before radiotherapy)

Number of patients with a decrease in the mean strain or strain rate measured from the echocardiography of the order of 5% between the measurement before RT and 24 months after RT

Number of patients with increased coronary plaques assessed by CT coronary angiography2 years after 3DCRT (baseline measures performed before radiotherapy)

Number of patients with an increase of the average index of coronary plaques measured from the CT coronary angiography in the order of 15% between the measurements before RT and 24 months after RT

Secondary Outcome Measures
NameTimeMethod
Decrease in the strain or strain rate6 months after 3DCRTand 2 years after 3DCRT (baseline measures performed before radiotherapy)
Correlation between the absorbed radiation dose by the whole heart and different structures of the heart and measurements of strain and strain rate and indices of coronary plaques2 years
Modification in series of circulating biomarkers of cardiac lesions5 weeks after initiation of 3DCRT (corresponding to the end of 3DCRT sessions), 6 months after 3DCRTand 2 years after 3DCRT (baseline measures performed before radiotherapy)

Classical biomarkers of cardiac injury: C-reactive protein, Troponin I, B-type natriuretic peptide (NT-Pro BNP), beta2-Microglobulin, Galectin 3 / Inflammatory cytokines: Interleukin 6, Interleukin 8, Interleukin 18, TNF-α / Endothelial activation and dysfunction: sVCAM,-1 , s-ICAM-1, E-selectin, P-selectin , vWF, PAI-1, Fibrinogen , Thrombomodulin, TGF-β1 / Microparticles: CD14, CD31, CD41, CD3, CD235a / microRNAs : miR-1, miR-133, miR-208, miR-499, miR-126, miR-130, miR-145, miR-181, miR-150, miR-155, miR-223, miR-17, miR-18, miR-22, miR-34, miR-92, miR-140, miR-182, miR-199, miR-423, miR-590

Trial Locations

Locations (1)

Clinique Pasteur

🇫🇷

Toulouse, France

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