Cardiac Outcomes in Adult Survivors of Childhood Cancer Exposed to Cardiotoxic Therapy

Abstract

Background Studies of cardiac disease among adult survivors of childhood cancer have generally relied upon self-reported or registry-based data. Objective Systematically assess cardiac outcomes among childhood cancer survivors Design Cross-sectional Setting St. Jude Children's Research Hospital Patients 1,853 adult survivors of childhood cancer, ≥18 years old, and ≥10 years from treatment with cardiotoxic therapy for childhood cancer. Measurements History/physical examination, fasting metabolic and lipid panels, echocardiogram, electrocardiogram (ECG), 6-minute walk test (6MWT) all collected at baseline evaluation. Results Half (52.3%) of the survivors were male, median age 8.0 years (range: 0-24) at cancer diagnosis, 31.0 years (18-60) at evaluation. Cardiomyopathy was present in 7.4% (newly identified at the time of evaluation in 4.7%), coronary artery disease (CAD) in 3.8% (newly identified in 2.2%), valvular regurgitation/stenosis in 28.0% (newly identified in 24.8%), and conduction/rhythm abnormalities in 4.6% (newly identified in 1.4%). Nearly all (99.7%) were asymptomatic. The prevalences of cardiac conditions increased with age at evaluation, ranging from 3-24% among those 30-39 years to 10-37% among those ≥40 years. On multivariable analysis, anthracycline exposure ≥250 mg/m2 increased the odds of cardiomyopathy (odds ratio [OR] 2.7, 95% CI 1.1-6.9) compared to anthracycline unexposed survivors. Radiation to the heart increased the odds of cardiomyopathy (OR 1.9 95% CI 1.1-3.7) compared to radiation unexposed survivors. Radiation >1500 cGy with any anthracycline exposure conferred the greatest odds for valve findings. Limitations 61% participation rate of survivors exposed to cardiotoxic therapies, which were limited to anthracyclines and cardiac-directed radiation. A comparison group and longitudinal assessments are not available. Conclusions Cardiovascular screening identified considerable subclinical disease among adult survivors of childhood cancer. Funding Cancer Center Support Grant (CA21765), U01 CA195547 1, American Lebanese Syrian Associated Charities

Obesity and Metabolic Syndrome Among Adult Survivors of Childhood Leukemia

“…The high prevalence of obesity, the metabolic syndrome and other constellations of cardiovascular disease risk factors among ALL survivors is particularly concerning given their increased risk for both GHD and adverse cardiovascular outcomes [4, 53, 54]. Although previous treatment exposures are a fixed risk factor in the long-term follow-up setting, individual components of the metabolic syndrome are potentially modifiable, representing an area where targeted surveillance and secondary prevention strategies are needed.…”

Out of the frying pan and into the fire: damage-associated molecular patterns and cardiovascular toxicity following cancer therapy

“…36 The elevated risk of developing cardiovascular disease could be confounded by pre-existing genetic, lifestyle, age, endocrine, and environmental factors unique to each cancer patient (Figure 1). However, these factors, as well as traditional cardiovascular disease risk factors (obesity, dyslipidemia, insulin resistance, and tobacco use), 4,5 do not fully account for the increased incidence of cancer therapy-induced cardiovascular toxicity. 18 The main cancer therapies reported to induce cardiovascular dysfunction and disease are radiation, vascular endothelial growth factor (VEGF) inhibitors, which encompass tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib, as well as monoclonal antibodies bevacizumab and ramucirumab, human epidermal growth factor receptor type 2 (HER2) monoclonal antibody trastuzumab, and chemotherapeutic agents such as anthracyclines, platinum-based antineoplastic drugs, microtubule inhibitors, and antimetabolites.…”

“…Interestingly, several studies have demonstrated a poor correlation between traditional cardiovascular risk factors such as obesity, dyslipidemia, insulin resistance, and tobacco use, with the onset of cardiovascular disease in cancer survivors, 4,5 suggesting an alternative mechanism for systemic cardiovascular toxicity. One such mechanism could be inappropriate immune system activation, which has an active role in both cancer and cardiovascular disease.…”

Reproductive Health as a Marker of Subsequent Cardiovascular Disease

“…In a recent cross-sectional cohort study of survivor outcomes, 7.4% of males and females had cardiomyopathy and 3.8% had coronary artery disease. 10 These risks are associated with anthracyclin drugs, specifically doxorubicin, and radiation therapy to the pleural region. As gonadal damage can also occur from these treatments, dissecting the contribution of endocrine dysfunction to disease progression is an important challenge for future research relevant to this patient population.…”