Clinical trial NCT02605512: BreAst Cancer and Cardiotoxicity Induced by RAdioTherapy: the BACCARAT Study
Official title: Early Detection and Prediction of Cardiotoxicity in Radiotherapy-treated Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Cardiac Toxicity
Keywords: Radiotherapy
Echocardiography
Strain strain rate
Coronary computed tomography angiography
Segments of coronary arteries
Subclinical functional and anatomical cardiac lesions
Biomarkers
Heart dosimetry
Lead sponsor: Institut de Radioprotection et de Surete Nucleaire
Sponsor class: OTHER_GOV
Collaborators: name: Institut de Radioprotection et de Surete Nucleaire
name: Clinique Pasteur
name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2015-11-16
Enrollment: 118
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of patients with decreased myocardial function assessed by echocardiography
timeFrame: 2 years after 3DCRT (baseline measures performed before radiotherapy)
measure: Number of patients with increased coronary plaques assessed by CT coronary angiography
timeFrame: 2 years after 3DCRT (baseline measures performed before radiotherapy)
Secondary outcomes:
measure: Decrease in the strain or strain rate
timeFrame: 6 months after 3DCRTand 2 years after 3DCRT (baseline measures performed before radiotherapy)
measure: Modification in series of circulating biomarkers of cardiac lesions
timeFrame: 5 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)
measure: 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 plaques
timeFrame: 2 years
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Clinique Pasteur
Study officials:
affiliation: Clinique Pasteur Toulouse
name: Atul Pathak, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Walker V, Lairez O, Fondard O, Jimenez G, Camilleri J, Panh L, Broggio D, Bernier MO, Laurier D, Ferrieres J, Jacob S. Myocardial deformation after radiotherapy: a layer-specific and territorial longitudinal strain analysis in a cohort of left-sided breast cancer patients (BACCARAT study). Radiat Oncol. 2020 Aug 20;15(1):201. doi: 10.1186/s13014-020-01635-y.
citation: Walker V, Lairez O, Fondard O, Pathak A, Pinel B, Chevelle C, Franck D, Jimenez G, Camilleri J, Panh L, Broggio D, Derreumaux S, Bernier MO, Laurier D, Ferrieres J, Jacob S. Early detection of subclinical left ventricular dysfunction after breast cancer radiation therapy using speckle-tracking echocardiography: association between cardiac exposure and longitudinal strain reduction (BACCARAT study). Radiat Oncol. 2019 Nov 14;14(1):204. doi: 10.1186/s13014-019-1408-8.
citation: Jacob S, Camilleri J, Derreumaux S, Walker V, Lairez O, Lapeyre M, Bruguiere E, Pathak A, Bernier MO, Laurier D, Ferrieres J, Gallocher O, Latorzeff I, Pinel B, Franck D, Chevelle C, Jimenez G, Broggio D. Is mean heart dose a relevant surrogate parameter of left ventricle and coronary arteries exposure during breast cancer radiotherapy: a dosimetric evaluation based on individually-determined radiation dose (BACCARAT study). Radiat Oncol. 2019 Feb 7;14(1):29. doi: 10.1186/s13014-019-1234-z.
citation: Jacob S, Pathak A, Franck D, Latorzeff I, Jimenez G, Fondard O, Lapeyre M, Colombier D, Bruguiere E, Lairez O, Fontenel B, Milliat F, Tamarat R, Broggio D, Derreumaux S, Ducassou M, Ferrieres J, Laurier D, Benderitter M, Bernier MO. Early detection and prediction of cardiotoxicity after radiation therapy for breast cancer: the BACCARAT prospective cohort study. Radiat Oncol. 2016 Apr 7;11:54. doi: 10.1186/s13014-016-0627-5.