title: Early detection and prediction of cardiotoxicity after radiation therapy for breast cancer: the BACCARAT prospective cohort study.
abstract: BACKGROUND
  Radiotherapy (RT) for breast cancer presents a benefit in terms of reducing local recurrence and deaths resulting from breast cancer but it can lead to secondary effects due to the presence of neighboring cardiac normal tissues within the irradiation field. Breast RT has been shown to be associated with long-term increased risk of heart failure, coronary artery disease, myocardial infarction and finally cardiovascular death more than 10 years after RT. However, there is still a lack of knowledge for early cardiotoxicity induced by breast RT that can appear long before the onset of clinically significant cardiac events. Based on a 2-year follow-up prospective cohort of patients treated with breast RT, the BACCARAT (BreAst Cancer and CArdiotoxicity Induced by RAdioTherapy) study aims to enhance knowledge on detection and prediction of early subclinical cardiac dysfunction and lesions induced by breast RT and on biological mechanisms potentially involved, based on functional and anatomical cardiac imaging combined with simultaneous assessment of multiple circulating biomarkers and accurate heart dosimetry.
  
  
  METHODS
  BACCARAT study consists in a monocentric prospective cohort study that will finally include 120 women treated with adjuvant 3D CRT for breast cancer, and followed for 2 years after RT. Women aged 50 to 70 years, treated for breast cancer and for whom adjuvant 3D CRT is indicated, without chemotherapy are eligible for the study. Baseline (before RT) and follow-up data include measurements of functional myocardial dysfunction including strain and strain rate based on 2D-speckle tracking echocardiography, anatomical coronary lesions including description of plaques in segments of coronary arteries based on Coronary computed tomography angiography, and a wide panel of circulating biomarkers. The absorbed dose is evaluated for the whole heart and its substructures, in particular the coronary arteries. Analysis on occurrence and evolution of subclinical cardiac lesions and biomarkers will be performed and completed with dose-response relationship. Multivariate model of normal tissue complication probability (NTCP) will also be proposed.
  
  
  CONCLUSIONS
  Tools and results developed in the BACCARAT study should allow improving prediction and prevention of potential lesions to cardiac normal tissues surrounding tumors and ultimately enhance patients' care and quality of life.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT02605512.
authors.affiliation: Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-HOM, SRBE, LEPID, Fontenay-aux-Roses, France. sophie.jacob@irsn.fr.
authors.forename: Sophie
authors.initials: S
authors.lastname: Jacob
authors.affiliation: Clinique Pasteur, Unité d'Hypertension artérielle, facteurs de risque et insuffisance cardiaque, Toulouse, France.
authors.forename: Atul
authors.initials: A
authors.lastname: Pathak
authors.affiliation: Clinique Pasteur, Radiothérapie (Oncorad), Toulouse, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Franck
authors.affiliation: Clinique Pasteur, Radiothérapie (Oncorad), Toulouse, France.
authors.forename: Igor
authors.initials: I
authors.lastname: Latorzeff
authors.affiliation: Clinique Pasteur, Radiothérapie (Oncorad), Toulouse, France.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Jimenez
authors.affiliation: Clinique Pasteur, Cardiologie générale et interventionnelle, Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Fondard
authors.affiliation: Clinique Pasteur, Radiologie, Toulouse, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Lapeyre
authors.affiliation: Clinique Pasteur, Radiologie, Toulouse, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Colombier
authors.affiliation: Clinique Pasteur, Radiologie, Toulouse, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Bruguiere
authors.affiliation: University Hospital Rangueil, Cardiologie B, Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lairez
authors.affiliation: Clinique Pasteur, Laboratoire d'analyse, Toulouse, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Fontenel
authors.affiliation: Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-HOM, SRBE, L3R, Fontenay-aux-Roses, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Milliat
authors.affiliation: Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-HOM, SRBE, LR2I, Fontenay-aux-Roses, France.
authors.forename: Radia
authors.initials: R
authors.lastname: Tamarat
authors.affiliation: Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-HOM/SDI/LEDI, Fontenay-aux-Roses, France.
authors.forename: David
authors.initials: D
authors.lastname: Broggio
authors.affiliation: Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-HOM, SER, UEM, Fontenay-aux-Roses, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Derreumaux
authors.affiliation: Clinique Pasteur, Radiothérapie (Oncorad), Toulouse, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Ducassou
authors.affiliation: INSERM, University Paul Sabatier, UMR1027, Epidemiology of cardiovascular diseases, Toulouse, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Ferrières
authors.affiliation: Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-HOM, SRBE, LEPID, Fontenay-aux-Roses, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Laurier
authors.affiliation: Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-HOM, SRBE, Fontenay-aux-Roses, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
authors.affiliation: Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-HOM, SRBE, LEPID, Fontenay-aux-Roses, France.
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Bernier
mesh_terms: D000368:Aged; D015415:Biomarkers; D001943:Breast Neoplasms / Q000150:complications* / Q000532:radiotherapy*; D066126:Cardiotoxicity / Q000175:diagnosis*; D003331:Coronary Vessels / Q000528:radiation effects; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000528:radiation effects; D006331:Heart Diseases / Q000209:etiology*; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D010641:Phenotype; D011446:Prospective Studies; D011788:Quality of Life; D011874:Radiometry; D011878:Radiotherapy / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers
keywords: Biomarkers; Breast cancer; Cardiac toxicity; Functional and anatomical cardiac imaging; Heart dosimetry; Radiotherapy