Andrea S. Hinkle

Anthracycline-induced cardiotoxicity in children and young adults

a Department of Pediatrics, Di6ision of Pediatric Cardiology, Children’s Hospital at Strong, Uni6ersity of Rochester Medical Center, 601 Elmwood A6enue, Box 631, Rochester, NY 14642, USA b Department of Pediatrics, Di6ision of Cardiology, Children’s Hospital Medical Center, Cincinnati, OH, USA c Department of Pediatrics, Di6ision of Pediatric Oncology/Hematology, Children’s Hospital at Strong, Uni6ersity of Rochester Medical Center, 601 Elmwood A6enue, Rochester, NY 14642, USA

Physical Inactivity in Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Report from the Childhood Cancer Survivor Study

Purpose: To determine if adult survivors of childhood acute lymphoblastic leukemia (ALL) are less active (and more inactive) than the general population and to identify modifying factors. Patients and Methods: Physical activity was assessed by self-report in 2,648 adult survivors of the Childhood Cancer Survivor Study. Participants in the Behavioral Risk Factor Surveillance System (BRFSS) survey administered through the Centers for Disease Control and Prevention (CDC) were used as a comparison group. Results: Survivors had a mean age of 28.7 years (range, 18.0-44.0 years) and were a mean of 23.1 years from their cancer diagnosis (range, 16.0-33.8 years). In multivariate models, ALL survivors were more likely to not meet CDC recommendations for physical activity [odds ratio (OR), 1.44; 95% confidence interval (95% CI), 1.32-1.57] and more likely to be inactive (OR, 1.74; 95% CI, 1.56-1.94) in comparison with the BRFSS general population. Survivors treated with >20-Gy cranial radiotherapy were at particular risk. Compared with BRFSS participants and adjusted for age, race, and ethnicity, survivors were more likely to not meet CDC recommendations (females: OR, 2.07, 95% CI, 1.67-2.56; males: OR, 1.43, 95% CI, 1.16-1.76) and more likely to be inactive (females: OR, 1.86; 95% CI, 1.50-2.31; males: OR, 1.84; 95% CI, 1.45-2.32). Conclusions: Long-term survivors of childhood ALL are less likely to meet physical activity recommendations and more likely to report no leisure-time physical activity in the past month. This level of inactivity likely further increases their risk of cardiovascular disease, osteoporosis, and all-cause mortality. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1356–63)

Cardiovascular Status of Childhood Cancer Survivors Exposed and Unexposed to Cardiotoxic Therapy

PURPOSE To determine whether cardiovascular abnormalities in childhood cancer survivors are restricted to patients exposed to cardiotoxic anthracyclines and cardiac irradiation and how risk factors for atherosclerotic disease and systemic inflammation contribute to global cardiovascular status. METHODS We assessed echocardiographic characteristics and atherosclerotic disease risk in 201 survivors of childhood cancer with and without exposure to cardiotoxic treatments at a median of 11 years after diagnosis (range, 3 to 32 years) and in 76 sibling controls. RESULTS The 156 exposed survivors had below normal left ventricular (LV) mass, wall thickness, contractility, and fractional shortening and above normal LV afterload. The 45 unexposed survivors also had below normal LV mass overall, and females had below normal LV wall thickness. Exposed and unexposed survivors, compared with siblings, had higher levels of N-terminal pro-brain natriuretic peptide (81.7 and 69.0 pg/mL, respectively, v 39.4 pg/mL), higher mean fasting serum levels of non-high-density lipoprotein cholesterol (126.5 and 121.1 mg/dL, respectively, v 109.8 mg/dL), higher insulin levels (10.4 and 10.5 μU/mL, respectively, v 8.2 μU/mL), and higher levels of high-sensitivity C-reactive protein (2.7 and 3.1 mg/L, respectively, v 0.9 mg/L; P < .001 for all comparisons). Age-adjusted, predicted-to-ideal 30-year risk of myocardial infarction, stroke, or coronary death was also higher for exposed and unexposed survivors compared with siblings (2.16 and 2.12, respectively, v 1.70; P < .01 for both comparisons). CONCLUSION Childhood cancer survivors not receiving cardiotoxic treatments nevertheless have cardiovascular abnormalities, systemic inflammation, and an increased risk of atherosclerotic disease. Survivorship guidelines should address cardiovascular concerns, including the risk of atherosclerotic disease and systemic inflammation, in exposed and unexposed survivors.

Characteristics and Determinants of Adiposity in Pediatric Cancer Survivors

Background: Adiposity and the diseases associated with it, including cardiovascular disease, are emerging long-term complications of pediatric cancer survivors. Direct evaluations of adiposity and comparisons to contemporary controls that can differentiate recent trends in obesity from cancer-related treatments and sequelae are limited. Methods: We evaluated demographic, treatment, lifestyle, and endocrine factors at the time of dual-energy X-ray absorptiometry testing in 170 non-Hispanic white survivors and 71 sibling controls, and compared three measures of adiposity [body mass index (BMI), total body fat, and trunk fat]. For the survivors alone, we determined factors independently associated with BMI and body fat. Results: Survivors were at 12 years since diagnosis; 58% had leukemia or lymphoma. BMI did not differ between groups. Among males, body fat was greater in survivors than in controls (25.8% versus 20.7%; P = 0.007), as was trunk fat (26.7% versus 21.3%; P = 0.008). Total or trunk fat did not differ among females. Cholesterol, triglycerides, low-density lipoprotein cholesterol, and television viewing hours were higher among male survivors than in controls. Independent factors associated with higher BMI and total and trunk fat included any cranial radiation and television viewing hours, whereas prior treatment with cyclophosphamide was associated with lower BMI and body fat measures. Conclusions: Compared with siblings, male survivors have greater body fat and metabolic risks. Cranial irradiation and television hours are important risk factors for adiposity in pediatric cancer survivors. Impact: Pediatric cancer survivors should be carefully monitored for cardiovascular risk factors and sedentary lifestyles. Cancer Epidemiol Biomarkers Prev; 19(8); 2013–22. ©2010 AACR.

Exercise capacity in long-term survivors of pediatric cancer: An analysis from the cardiac risk factors in childhood cancer survivors study†

Childhood cancer survivors may have premature symptomatic cardiovascular and non‐cardiovascular diseases that contribute to reduced capacity for physical activity. Studies of exercise capacity and identification of risk factors for reduced capacity in survivors are limited.

Dietary Quality, Caloric Intake, and Adiposity of Childhood Cancer Survivors and Their Siblings: An Analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study

Childhood cancer survivors are at increased risk of cardiovascular disease, in part because of adiposity. Whether survivors have healthy diets and whether dietary quality is associated with adiposity among survivors are not known. Survivors and siblings from the Cardiac Risk Factors in Childhood Cancer Survivors Study completed 3-day food records that were used to estimate daily caloric intake relative to recommended and dietary quality using the Healthy Eating Index-2005 (HEI). Medical records were reviewed for cancer therapies. Body composition was measured by dual-energy x-ray absorptiometry. Of 91 childhood cancer survivors and 30 sibling controls, there were no marked differences in mean daily caloric intakes (98% vs. 100% of recommended) or HEI total scores (55.5 vs. 53.3), respectively, with both groups scoring worst for the consumption of dark green vegetables and whole grains. Survivors exposed to cranial irradiation had lower total HEI scores (−6.4, P = 0.01). Among survivors, better dietary quality, as reflected by the total HEI score, was associated with decreasing percent body fat (β = −0.19, P = 0.04). Survivors consume diets similar to their siblings although these diets are only moderately adherent to current guidelines. Decreased dietary quality is associated with higher body fat and receipt of cranial irradiation in survivors.

Aggregating traditional cardiovascular disease risk factors to assess the cardiometabolic health of childhood cancer survivors: an analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study.

BACKGROUND Childhood cancer survivors are at increased risk of cardiovascular disease (CVD), which may be associated with traditional CVD risk factors. We used CVD risk aggregation instruments to describe survivor cardiometabolic health and compared their results with sibling controls. METHODS Traditional CVD risk factors measured in 110 survivors and 31 sibling controls between 15 and 39 years old were aggregated using Pathobiological Determinants of Atherosclerosis in Youth (PDAY) scores and the Framingham Risk Calculator (FRC) and expressed as ratios. The PDAY odds ratio represents the increased odds of currently having an advanced coronary artery lesion, and the FRC risk ratio represents the increased risk of having a myocardial infarction, stroke, or coronary death in the next 30 years. Ratios are relative to an individual of similar age and sex without CVD risk factors. RESULTS The median PDAY odds ratio for survivors was 2.2 (interquartile range 1.3-3.3), with 17% >4. The median FRC risk ratio was 1.7 (interquartile range 1.0-2.0), with 12% >4. Survivors and siblings had similar mean PDAY odds ratios (2.33 vs 2.29, P = .86) and FRC risk ratios (1.72 vs 1.53, P = .24). Cancer type and treatments were not associated with cardiometabolic health. There was a suggested association for physical inactivity with PDAY odds ratios (r = 0.17, P = .10) and FRC risk ratios (r = 0.19, P = .12). CONCLUSIONS Cardiometabolic health is poor in childhood cancer survivors but not different than that of their siblings, highlighting the importance of managing traditional CVD risk factors and considering novel exposures in survivors.

ROHHADNET syndrome presenting as major behavioral changes in a 5-year-old obese girl.

Behavioral issues are a frequent problem in the pediatric population. Often, these are evaluated and considered to be psychiatric in origin. We report on a pediatric patient who presented with severe behavioral disturbance and developed organic symptoms including hypoventilation and dysautonomia and who was ultimately diagnosed with ROHHADNET syndrome, a syndrome of rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation associated with a neuroendocrine tumor. Autopsy findings revealed novel findings of the syndrome, including hypothalamic encephalitis.

Subclinical thyroid disease after radiation therapy detected by radionuclide scanning

Results: Seven patients (21.6%) had abnormal scans, and the percentage was higher among children (25%) and females (25%) compared to adults (16.7%) and males (16.7%), respectively. Two of 34 patients (5.9%) were discovered to have a thyroid cancer; histopathologies were papillary and follicular carcinoma. Conclusion: In this population of clinically normal cancer survivors who had been irradiated to the cervical region, subclinical thyroid disease, of potential clinical significance, was detected by 99m Tc TcO4 2 in about 20%. Children may be more commonly affected. Although the cost effectiveness of screening will require a larger sample number, we propose a surveillance schema for this patient population.

Cardiotoxicity related to cancer therapy

Abstract Because of recent advances in treatment of childhood cancer, there are increasing numbers of children who have survived cancer. Their future lives are complicated by late sequelae of the disease and treatment. Cardiovascular late effects are usually correlated with cardiotoxic treatment. Other late effects, however, affect organ systems which may have an impact on a patients cardiovascular status. Of particular interest are the cardiovascular effects of thyroid dysfunction (either hypothyroidism or hyperthyroidism), growth hormone deficiency, obesity, ovarian failure, pulmonary disease and renal dysfunction. In addition, psychosocial issues, such as risk-taking behavior and neurocognitive abnormalities requiring pharmacotherapy, present further cardiovascular concerns. This review discusses some of the more common non-cardiac sequelae of treatment of childhood cancer which may effect cardiac function. Knowledge of these late effects and their cardiac impact is essential as we attempt to lessen associated morbidity and mortality.