Patients diagnosed with cancer between the ages of 15–39 years, the adolescent and young adult (AYA) population, are an understudied group given their historically poor participation in clinical trials.(1) It is further recognized that the incidence of different types of cancer, as well as the biology of site-specific cancers in the AYA population differs from those of children and of older adults.(2, 3)
Recent data from the Surveillance, Epidemiology, and End Results (SEER) program noted improved cancer survival rates in the AYA population, with almost 80% surviving more than 5 years after their cancer diagnosis.(4) Despite advances in cancer therapeutics that have contributed to the improving survival rates, survivors remain at increased risk of morbidity and mortality from non-cancer causes, attributed to prior therapies received. Cardiovascular disease (CVD) has emerged as a leading cause of nonrelapse-related mortality among cancer survivors, with more recent reports suggesting that the AYA population are at significant risk.(5–8) Cardiovascular toxicity (CT), including but not limited to hypertension, arrhythmias, and cardiomyopathy, have been associated with a variety of chemotherapeutic agents, with anthracycline therapy demonstrating the most clear association.(9)
The cardiotoxic effects of anthracycline are at least partially mediated by topoisomerase-II\(\beta\) in cardiomyocytes, resulting in DNA double-strand breaks, defective mitochondrial biogenesis, and reactive oxygen species formation.(10) Over the long-term, these cardiotoxic effects can lead to left ventricular dysfunction and, in the most severe cases, congestive heart failure. High cumulative doses remain the best predictor of eventual cardiac dysfunction,(9) and CT can take several decades before obvious symptomatic changes develop.
Newer, more targeted therapies have emerged for the treatment of cancer, specifically vascular endothelial growth factor (VEGF) inhibitors. VEGF is secreted by tumors and plays a critical role in angiogenesis via the VEGF signaling pathway.(11) VEGF inhibitors have demonstrated promising anti-tumor activity given their ability to target the tumor itself and avoid more systemic toxicity to the patient. Given the role of VEGF in the survival and proliferation of endothelial and vascular smooth muscle cells, adverse cardiovascular effects have been noted acutely with the use of VEGF inhibitors, including hypertension, thrombosis, and cardiomyopathy.(12) However, to date there have been no reports evaluating CT following completion of treatment.
As the cancer incidence rate continues to increase in the AYA population, there is a need to continue to improve or maintain disease-control rates while limiting long-term side effects. Furthermore, given that known CVD risk factors, such as tobacco use, diabetes, and hyperlipidemia, are more prevalent in the AYA than the pediatric population, it is vital to understand the interplay between the patient’s own CV risk factors, their cancer therapy, and their risk for future CV disease.
Therefore, we conducted a retrospective study using clinical data obtained from the electronic medical record (EMR) in an attempt to gain insight into the burden of CTs in an AYA cancer population who received VEGF therapy, comparing these patients to patients exposed to anthracycline therapy, an agent known for its long-term toxicity to the heart.