Articles for this Review were found through searches of PubMed and Embase by use of the terms ācardiovascular toxicityā, ācardiotoxicityā, ācancer treatmentā, āchemotherapyā, ābiochemicalā, āendothelial damageā, āgenetic variationsā, āelectrocardiographyā, āechocardiographyā, āMultiple Gated Acquisition Scanā, āMagnetic Resonance Imagingā, āPositron Emission Tomographyā, and āSingle Photon Emission Tomographyā. Trials with highest quality study design were selected. Only studies of
ReviewCardiovascular toxicity caused by cancer treatment: strategies for early detection
Introduction
Methods for detection and treatment of different types of cancer have developed impressively in the past 20 years. Life-expectancy for patients with cancer is steadily improving, with an age-adjusted 10-year survival of 70% for breast cancer, 80% for Hodgkin's disease, and 90% for testicular cancer.1 Around 3 million patients are diagnosed with cancer in Europe each year, which means there is a large group at risk of treatment-related complications.2 Long-term complications include development of second malignancies and cardiovascular disease, but up to now, the incidence and extent of these complications in adults are largely unknown. By contrast, studies of childhood cancer survivors have produced many more data on long-term complications of treatment.3
In trials of adjuvant anthracycline-based treatment for breast cancer, 5-year incidence of chronic heart failure is between 0% and 3Ā·2%, depending on the combination regimen and cumulative dose of anthracycline.4 However, long-term follow up of cardiovascular morbidity and mortality is not available. A large meta-analysis of the Early Breast Cancer Trialists' Collaborative Group, in which 42ā000 patients with breast cancer participated in 78 randomised trials, found that patients treated with radiotherapy had a high rate of non-breast cancer mortality, mainly from heart-disease (rate ratio 1Ā·12). This high rate of heart disease was observed during the first 5 years after treatment and continued for up to 15 years.5 However, data are partly based on outdated radiation-techniques in use from 1976 until 1995.
10 years ago, we reviewed methods for detection of anthracycline-induced cardiotoxicity.6 Improvements have since resulted in more sensitive monitoring strategies (Figure 1, Figure 2). Changes in cancer treatment have introduced both, more as well as less, potentially cardiotoxic regimens, through the increased use of anthracyclines, platinum compounds, radiation therapy, and introduction of monoclonal antibodies such as trastuzumab and bevacizumab.
Although monitoring guidelines exist for several potentially cardiotoxic treatments, little data are available to formulate evidence-based screening and follow-up recommendations for treatment-induced cardiotoxicity. In 2007, the American Society of Clinical Oncology (ASCO) Survivorship Expert Panel clearly stated the need for such recommendations.7
In this Review, we give an update of the methods available for early detection of cardiac damage caused by cancer treatment. Each method is assigned a level of evidence backing up its applicability, according to the system used by the Oxford Centre of Evidence Based Medicine (panel 1).8 Level 1a evidence is viewed as definite and level 5 as weak. Most studies reviewed in this paper were not designed to assess the sensitivity of monitoring strategies as a primary goal, which implies that level of evidence is based on indirect evidence or retrospective data.
Section snippets
Detection of treatment-induced cardiotoxicity
Cardiac function is monitored during a potentially cardiotoxic cancer treatment to identify patients who are susceptible to this toxicity as early as possible and prevent morbidity and mortality. Efforts to prevent further complications include intensified monitoring, initiation of preventive measures, or changes to cancer treatments. Detection of possible toxicity should not result in holding back an essential treatment, which would compromise effectiveness.
Mitani and colleagues9 did a
LVEF
Measurement of LVEF with multiple gated acquisition (MUGA) scintigraphy and echocardiography,12 gives an assessment of systolic cardiac function and is the most common method of monitoring cardiac function during cancer treatment. However, LVEF can underestimate actual cardiac damage13 because of the compensatory reserve of the myocardium that enables adequate ventricular output even in the presence of dysfunctional myocytes. With left ventricular dysfunction, deterioration of diastolic cardiac
Methods for assessment of cardiovascular function
Strategies for early detection of potential cardiovascular damage from cancer treatment will be addressed. Advantages, disadvantages, and level of evidence behind each strategy are summarised in panel 2.
Conclusion
The identification of patients who are at an increased risk of cardiovascular damage caused by cancer treatment can be achieved by detection of early changes in cardiovascular function and estimation of a baseline risk of late morbidity (figure 3).16, 17, 18, 19 Current guidelines and monitoring strategies for detection of cardiovascular toxicity caused by cancer treatment are mostly derived from medium-level evidenceātrue even for MUGA scintigraphy (panel 2).
LVEF is the most widely used
Search strategy and selection criteria
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