Managing Chemotherapy-Related Cardiotoxicity in Survivors of Childhood Cancers

Abstract

In the US, children diagnosed with cancer are living longer, but not without consequences from the same drugs that cured their cancer. In these patients, cardiovascular disease is the leading cause of non-cancer-related morbidity and mortality. Although this review focuses on anthracycline-related cardiomyopathy in childhood cancer survivors, the global lifetime risk of other cardiovascular diseases such as atherosclerosis, arrhythmias and intracardiac conduction abnormalities, hypertension, and stroke also are increased. Besides anthracyclines, newer molecularly targeted agents, such as vascular endothelial growth factor receptor and tyrosine kinase inhibitors, also have been associated with acute hypertension, cardiomyopathy, increased risk of ischemic cardiac events and arrhythmias, and are summarized here. This review also covers other risk factors for chemotherapy-related cardiotoxicity (including both modifiable and non-modifiable factors), monitoring strategies (including both blood and imaging-based biomarkers) during and following cancer treatment, and discusses the management of cardiotoxicity (including prevention strategies such as cardioprotection by use of dexrazoxane).

Survivor care for pediatric cancer survivors

“…Cardiovascular complications after exposure to anthracyclines or cardiac irradiation are a leading cause of morbidity and mortality in CCSs [5,13,17]. When adult CCSs were clinically evaluated using systematic medical evaluations for the detection of cardiac dysfunction, 2.6% were diagnosed with cardiomyopathy before and 5.7% after the survivor care visit, and 6.2% were diagnosed with heart valve disorders before and 53.1% after their survivor care visit.…”

Circulating microRNAs: Potential Markers of Cardiotoxicity in Children and Young Adults Treated With Anthracycline Chemotherapy

“…The estimated prevalence of cardiomyopathy in 50‐year‐old survivors of childhood cancer exposed to cardiotoxic chemotherapy or radiation is 21% . Once AC‐induced cardiomyopathy develops, it is commonly progressive, with no definitive treatment other than implantation of a left ventricular assist device and/or heart transplantation . Currently, methods to detect subclinical cardiac injury early in the course of progressive cardiotoxicity are lacking.…”

Dexrazoxane for reducing anthracycline-related cardiotoxicity in children with cancer: An update of the evidence

“…a 15 dexrazoxane full references: 1, [16][17][18]22,31,40,43,50,60,70,78,82,83,89 b 10 dexrazoxane abstract references: 19,35,45,51,52,59,[71][72][73]79 A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 5 Several long-term studies have focused on the late effects of cancer treatment including anthracycline therapy. Childhood cancer survivors have a significantly higher risk of premature death than that of the general population, and a wide range of health problems that can reduce their overall well-being and quality of life [1,3,5,[11][12][13][14].…”

“…Cumulative doses of anthracycline of 300 mg/m 2 or higher increase the risk of cardiomyopathy, valve disorders, and conduction abnormalities over that of unexposed survivors; radiotherapy is an added risk factor [18][19][20]. Heart damage resulting from anthracycline chemotherapy is a serious problem because it reduces quality of life and can lead to premature death.…”

“…etoposide), female sex, cardiovascular history, previous cytotoxic therapy, concomitant mediastinal or cranial radiotherapy, younger age at diagnosis, longer follow-up, trisomy 21, and AfricanAmerican race [17]. The correlation between high cumulative doses of anthracyclines and cardiotoxicity is well established, but lower doses can also be cardiotoxic, with no safe dose established [18]. This was clearly shown in a study specifically designed to evaluate the effects of low-dose anthracyclines (≤100 mg/m 2 ) on LV function in 91 children after a mean of 9.8 years from diagnosis, as a significant proportion demonstrated subclinical abnormalities [25].…”