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  • br Introduction br Modern treatment strategies have improved


    1. Introduction
    Modern treatment strategies have improved short- and long-term relapse-free survival in cancer patients [1]. Many patients with childhood- or adult-onset cancer are cured or live for ten years or longer [2]. Consequently, increasing numbers of adverse cardiovascular events in cancer survivors indicate that success in cancer care comes at a price [3].
    Early stage cancers are surgically treated. Patients with advanced or metastatic cancers often require multiple modalities, including radio-therapy, cytotoxic chemotherapy, molecularly targeted inhibitors and Pentostatin targeting signal transduction pathways and immune check-points. The more advanced the cancer, the more potentially cardiotoxic therapy is used. These treatments also impact the cardiovascular sys-tem, and such impact may become clinically evident even years after completion of therapy [4,5]. Quality of life in cancer survivors may be limited by cardiotoxic complications, and many patients die not from
    Corresponding author at: University Hospital Essen, West German Heart and Vascular Center, Department for Cardiology and Vascular Medicine, Hufelandstr. 55, 45147 Essen, Germany.
    E-mail address: [email protected] (T. Rassaf).
    cancer recurrence, but from cardiovascular disease. Treatment-related cardiovascular events have been covered and reported in cancer trials. However, the spectrum of cardiotoxicity for the large number of novel cancer medicines that have been introduced in the past decade is not well defined, and this is particularly true for long-term sequelae [6]. The growing concern over cancer therapy-associated cardiotoxicity has opened the new field of cardio-oncology. A multidisciplinary ap-proach involving cardiologists, oncologists, radiologists and nuclear medicine physicians will provide individualized risk assessment, pre-vention and early detection of toxicities and optimized care.
    Cardio-oncology aims to provide comprehensive care for cancer pa-tients with or at risk for cardiovascular disease. Today, definitions of cardiotoxicity related to cancer therapy and its epidemiology remain in-complete [4,7], guidelines are pending, and there is little evidence from randomized, controlled clinical trials [3]. Uncertainty exists as to which patients should be referred to a cardio-oncology unit for screening and specific disease-related treatments. Treatment recommendations are mainly based on established guidelines for cardiovascular diseases that were not tailored to the need of cancer patients, or from consensus recommendations in oncology practice guidelines.
    In the present review, we outline cardiotoxic effects of clinically rel-evant classes of cancer therapies. We further propose criteria for
    selection of patients to be referred to a cardiologist or cardio-oncology unit. We discuss strategies for the diagnosis of treatment-related ad-verse cardiovascular effects in cancer patients. We consider limitations of current prevention and treatment regimens for treatment-related cardiovascular disease and highlight the need for specific trials in cancer patients. Finally, we propose rational algorithms for the prevention and treatment of adverse cardiovascular effects, particularly with novel can-cer therapies.
    2. Assessment before cancer therapy – preexisting risk factors and cardiovascular disease
    Globally, cardiovascular and malignant disease are the most com-mon causes of death with N65% of deaths attributed to either condition in developed countries. However, there is little awareness that these two pathologies are connected at multiple levels. Both heart disease and cancer share several common risk factors (hypertension, dyslipid-emia, diabetes mellitus, obesity, smoking, age and sex), and risk reduc-tion strategies result in positive outcomes for both diseases. Good cardiovascular health also supports cancer therapy and reduces adverse cancer therapy-related cardiovascular events, while preexisting cardio-vascular risk factors come with increased cardiotoxicities [8–13]. Finally, clinically evident cardiovascular disease may require a prelimi-nary diagnostic work-up or even preclude patients from specific cancer treatments [8]. Cardiovascular risk factors predispose to cardiotoxicity from cancer therapy, particularly from therapies associated with left ventricular dysfunction and heart failure (e.g. anthracyclines). The risk to develop signs of cardiotoxicity is increased in older patients (N60 years) and further increased in the presence of at least two of the following risk factors: hypertension, dyslipidemia, diabetes mellitus, obesity, smoking [8–13]. The individual risk profile must be particularly considered for patients scheduled for ‘high risk’ cancer therapies (Sup-plementary Table 1, e.g. anthracycline therapy). Not every patient will benefit from a strict regulation of these risk factors before, during and after therapy. Cardio-oncology is probably less relevant for patients with poor prognosis or frailty. On the other hand, large numbers of e.g. younger breast cancer patients will likely profit from risk factor monitoring. All risks should therefore be managed according to current AHA/ESC guidelines in patients with good prognosis [3,8,14,15].