Cardiac Magnetic Resonance Imaging in Early Detection and Therapy Monitoring of Myocardial Cardiotoxicity under Chemotherapy

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Breast cancer is the leading cancer in women with a 5-year survival of 90%. However, survival is significantly reduced in patients (15-20%) with an additional overexpression of HER2 /neu receptors (5-year survival rate 80%). Treatment in these patients relies on a combination of Anthracyclines and Trastuzumab (monoclonal antibody) with an increased risk of cardiotoxicity related to the combination therapy.Monitoring of the left ventricular (LV) function during/after therapy is of outmost impartance in these patients in order to identify dysfunction early on and to allow for therapy modification avoiding possible longtime cardiac damage (e.g. heart failure). Currently, monitoring is performed by radionuclide ventriculography (MUGA) and echocardiography (Echo); however, both methods focus on global functional parameters and do not investigate direct changes of the myocardium.Cardiac MRI not only allows for accurate assessment of ventricular function but also non-invasive tissue diagnosis to detect early changes such as edema or fibrosis. Beside current techniques, new quantitative methods such as cardiac relaxometry (T1 / T2 mapping) are at the forefront of investigations. Furthermore, MRI is superior to Echo in assessment of regional myocardial function/deformation (Strain) due to its high reproducibility.The value of these quantitative approaches in the early detection of cardiotoxicity under Anthracyclines / Trastuzumab therapy to avoid possible long-term effects is the focus of projects outlines in this application.For this reason the applicant plans a one year stay at the Department of Medical Imaging of the University Health Network / Peter Munk Cardiac Center at the University of Toronto (Canada). One of the largest and comprehensive studies on the subject of cardiotoxicity and MRI, the EMBRACE-MRI (clincialtrial.gov: NCT02306538) study is currently conducted as this center. The study population included 150 patients with an HER2 / neu+ tumor under Anthracyclines / Trastuzumab therapy; beside many different laboratory parameters close interval Echo and MRI examinations are performed (-1,3,6,9,15,24 months after the start of therapy).The work plan contains the evaluation/analysis of these MRI examinations with regard to late gadolinium enhancement (LGE), Strain, T1 / T2 mapping and ECV (Extracellular Volume Fraction) in the prediction of cardiotoxicity.This study provides a comprehensive insight into the problem of cardiotoxicity; and based on the results, it is anticipated to establish quantitative imaging biomarkers for early detection of cardiotoxicity.The resulting expertise in the planning / conduction of various cardio-oncology projects would also further strengthen the interdisciplinary expertise of the cancer center at University of Cologne and the Institute for Diagnostic and Interventional Radiology.