Chemotherapy-Associated Cardiotoxicity: How Often Does it Really Occur and How Can it Be Prevented?

Magnetic nanoparticles in general, and iron oxide nanoparticles in particular, have been studied extensively during the past 20 years for numerous biomedical applications. The main applications of these nanoparticles are in magnetic resonance imaging (MRI), magnetic targeting, gene and drug delivery, magnetic hyperthermia for tumor treatment, and manipulation of the immune system by macrophage polarization for cancer treatment. Recently, considerable attention has been paid to magnetic particle imaging (MPI) because of its better sensitivity compared to MRI. In recent years, MRI and MPI have been combined as a dual or multimodal imaging method to enhance the signal in the brain for the early detection and treatment of brain pathologies. Because magnetic and iron oxide nanoparticles are so diverse and can be used in multiple applications such as imaging or therapy, they have attractive features for brain delivery. However, the greatest limitations for the use of MRI/MPI for imaging and treatment are in brain delivery, with one of these limitations being the brain-blood barrier (BBB). This review addresses the current status, chemical compositions, advantages and disadvantages, toxicity and most importantly the future directions for the delivery of iron oxide based substances across the blood-brain barrier for targeting, imaging and therapy of primary and metastatic tumors of the brain.

Preclinical studies have reported that a single treadmill session performed 24 h prior to doxorubicin provides cardio-protection. We aimed to characterize the acute change in cardiac function following an initial doxorubicin treatment in humans and determine whether an exercise session performed 24 h prior to treatment changes this response.

Breast cancer patients were randomized to either 30 min of vigorous-intensity exercise 24 h prior to the first doxorubicin treatment (n = 13), or no vigorous exercise for 72 h prior to treatment (control, n = 11). Echocardiographically-derived left ventricular volumes, longitudinal strain, twist, E/A ratio, and circulating NT-proBNP, a marker of later cardiotoxicity, were measured before and 24–48 h after the treatment.

Following treatment in the control group, NT-proBNP, end-diastolic and stroke volumes, cardiac output, E/A ratio, strain, diastolic strain rate, twist, and untwist velocity significantly increased (all p ≤ 0.01). Whereas systemic vascular resistance (p < 0.01) decreased, and ejection fraction (p = 0.02) and systolic strain rate (p < 0.01) increased in the exercise group only. Relative to control, the exercise group had a significantly lower NT-proBNP (p < 0.01) and a 46% risk reduction of exceeding the cut-point used to exclude acute heart failure.

The first doxorubicin treatment is associated with acutely increased NT-proBNP, echocardiographic parameters of myocardial relaxation, left ventricular volume overload, and changes in longitudinal strain and twist opposite in direction to documented longer-term changes. An exercise session performed 24 h prior to treatment attenuated NT-proBNP release and increased systolic function. Future investigations should verify these findings in a larger cohort and across multiple courses of doxorubicin.

Cardiovascular toxicity is one of the most feared complications of cancer treatment. Recent advances in oncologic therapies have resulted in improved cancer outcomes but also a new set of cardiovascular adverse effects. Common toxicities include left ventricular dysfunction/heart failure, hypertension, and myocardial ischemia. Accurate risk stratification allows avoidance of potentially harmful treatments in those patients at greatest risk while maintaining the ability to deliver high doses of effective therapies to the lower-risk population. Cardiac investigations, including echocardiography, nuclear imaging, magnetic resonance imaging, biomarker measurement, blood pressure monitoring, electrocardiography, stress testing, and invasive angiography, can help to risk-stratify selected patients. In this review, common complications are discussed in terms of the factors used to identify patients with elevated risk, the monitoring strategies available, and selected interventions that have been used to modify outcomes in patients identified as being at high risk for cardiac complications of cancer treatment.

Due to advances in prevention, early detection and treatment, early breast cancer mortality has decreased by nearly 40% during the last four decades. Yet, the risk of cardiovascular disease (CVD) mortality is significantly elevated following a breast cancer diagnosis, and it is a leading cause of death in this population. This review will discuss the most recent evidence for risks, pathology, mechanisms, and prevention of CVD morbidity and mortality in women with breast cancer. This evidence will be synthesized into a new model ‘the compounding risk and protection model.’ This model proposes that the balance between risk factors (i.e., older age, pre-existing traditional CVD risk factors and shared biologic pathways for CVD and cancer such as inflammation, as well as treatment-related and lifestyle toxicity) and potential protection factors (i.e., lifelong non-smoking, regular physical activity, a healthy diet rich in fruits and vegetables, and management of body weight and stress, heart failure therapy) determine the individual risk of CVD morbidity and mortality after diagnosis of early breast cancer.