Late Cardiotoxicity in Aging Adult Survivors of Childhood Cancer

Abstract

The survival rate for childhood cancer is steadily improving, and the current estimate for the prevalence of childhood cancer survivors in the United States is 420,000. With this encouraging trend and the aging of this population, there is an ever-increasing responsibility to identify adult survivors of childhood cancer with adverse health outcomes related to cancer treatment across the span of their lives. To accomplish this, large cohort studies have been developed to follow survivors longitudinally. Compared to siblings, survivors have a higher cumulative incidence of morbidity and mortality, and this gap in incidence only widens with age. One of the most significant late toxicities in survivors is late onset cardiotoxicity, largely due to anthracycline and chest-directed radiation exposure. Survivors also have an increased prevalence of traditional cardiovascular risk factors as they age, which potentiates the risk for major cardiac events. Prevention is essential. Minimizing anthracycline dose exposure in pediatric cancer patients is a primary method of cardioprotection. Dexrazoxane and enalapril have also been studied as primary (pre-exposure) and secondary (post-exposure) cardioprotecant agents, respectively. Additionally, the Children's Oncology Group has published exposure-driven, risk-based screening guidelines for long-term follow-up, which may be a cost-effective way to identify subclinical cardiac disease before progression to clinical presentation. Ongoing research is needed to determine the most effective diagnostic modality for screening (e.g. echocardiography), and the most effective intervention strategies to improve long-term outcomes.

Keywords: Anthracycline; cardiomyopathy; cardioprotection; intervention; screening.

Figure 1. Cumulative incidence of grade 3 to 5 conditions in childhood cancer survivors

Cumulative incidence of selected grade 3 to 5 conditions by organ system. (A) New malignancy, (B) Cardiac, (C) hearing, (D) vision, (E) respiratory, and (F) renal.

Figure 2. Prevalence of cardiovascular risk factors in childhood cancer survivors with increasing age

Prevalence of cardiovascular risk factors—(A) hypertension, (B), dyslipidemia, (C), diabetes, (D) obesity, and (E) multiple cardiac risk factors—with increasing age.

Figure 3. Age-specific cumulative incidence of the four major cardiac events by therapeutic exposure in childhood cancer survivors, compared with siblings

Age-specific cumulative incidence of the four major cardiac events—(A) coronary artery disease, (B) valvular disease, (C) arrhythmia, and (D) heart failure—by therapeutic exposure (survivors) compared with siblings. RT, chest-directed radiotherapy.