Early detection and prediction of cardiotoxicity after radiation therapy for breast cancer: the BACCARAT prospective cohort study.

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/DESIGN: 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. DISCUSSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02605512.

Diagnostic performance of complete lower limb venous ultrasound in patients with clinically suspected acute pulmonary embolism.

A limited ultrasound (US) confined to the popliteal and femoral veins is usually performed to detect deep vein thrombosis (DVT) in patients with clinically suspected acute pulmonary embolism (PE). Our objective was to assess the diagnostic accuracy of complete lower limb US examining both the proximal and distal veins in this setting. In this prospective study, 210 consecutive patients were included. Complete US was performed by independent operators and compared blindly with a reference strategy combining clinical probability, ventilation perfusion scan and pulmonary angiography to a three-month clinical follow-up. Simultaneously, VIDAS D-dimer (DD) assay and helical computed tomography (HCT) of the lungs were assessed independently and blindly. PE was present in 74 patients (35%). Complete US detected DVT in 91 patients (43%), proximal in 51 and distal in 40. Sensitivity and specificity with a 0.95 confidence interval were respectively 0.93 [0.85 - 0.97] and 0.84 [0.77 - 0.89]. Limited US detected DVT in only 46 patients (22%). Sensitivity and specificity were respectively 0.55 [0.44 - 0.66] and 0.96 [0.92 - 0.98]. For DD they were 0.92 [0.83 - 0.96] and 0.24 [0.17 - 0.32] and for HCT 0.84 [0.73 - 0.90] and 0.87 [0.80 - 0.92]. Complete lower limb US has higher sensitivity and capacity to exclude PE than limited US, but a slightly lower specificity. Complete US results also compared favourably with those of HCT and DD. The utility of including this method in diagnostic strategies for PE needs to be assessed in cost-effectiveness analysis and in outcome studies.