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 (ß = -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.

Cranial irradiation as an additional risk factor for anthracycline cardiotoxicity in childhood cancer survivors: an analysis from the cardiac risk factors in childhood cancer survivors study.

Anthracycline-treated childhood cancer survivors experience cardiac damage that results in decreased left ventricular (LV) mass, leading to increased LV wall stress, which underlies their greater risk of cardiomyopathy. Many of these survivors also are at risk of growth hormone (GH) abnormalities from cranial irradiation exposure, although it is unknown whether such exposure is associated with cardiotoxicity. Echocardiograms and insulin-like growth factor-1 (IGF-1), a marker of GH, were measured in 130 anthracycline-treated childhood cancer survivors, 59 of whom had been exposed to cranial irradiation, a mean 10 years after their cancer diagnosis. Echocardiographic parameters and IGF-1 were standardized relative to age or body surface area using data from sibling control subjects and expressed as the percentage difference from normal values. The results showed that after adjustment for other risk factors, survivors exposed to cranial irradiation had an additional 12 % decrease in LV mass compared with unexposed survivors (P < 0.01) and an additional 3.6 % decrease in LV dimension (P = 0.03). Survivors exposed to cranial irradiation also had a 30.8 % decrease in IGF-1 relative to normal values, which was greater than the 10.5 % decrease in unexposed survivors (P < 0.01). The above findings led us to conclude that in anthracycline-treated childhood cancer survivors a mean 10 years after their diagnosis, those with cranial irradiation exposure had significantly greater decreases in LV mass and dimension. Because cranial irradiation also was associated with decreased IGF-1, it is possible that GH deficiencies mediated this effect, suggesting that GH replacement therapy may help to prevent the development of cardiotoxicity.

Exercise capacity in long-term survivors of pediatric cancer: an analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study.

BACKGROUND: 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. PROCEDURE: We assessed maximal myocardial oxygen consumption (V(O(2)max), a measure of exercise capacity) in survivors at least 4 years after cancer diagnosis and sibling controls. We evaluated associations between V(O(2)max) and age, sex, treatments, cardiac structure and function, biomarkers, endocrine function, and physical activity. RESULTS: Of 72 survivors (mean age, 22 years; range, 8.0-40 years) and 32 siblings (mean age, 20.2 years; range, 8-46 years), about half were male. Mean time since diagnosis was 13.4 years (range, 4.5-31.6 years). In age- and sibling-pair adjusted analyses, V(O(2)max) was lower in survivors than siblings (males, 28.53 vs. 30.90 ml/kg/minute, P = 0.08; females, 19.81 vs. 23.40 ml/kg/minute, P = 0.03). In males, older age (P = 0.01), higher percent body fat (P < 0.001) and high or low left ventricular (LV) mass Z-scores (P = 0.03) predicted lower V(O(2)max). In females, older age (P < 0.001), methotrexate exposure (P = 0.01), and higher, but normal, LV load-dependent contractility (P = 0.02) predicted lower V(O(2)max). CONCLUSIONS: Fitness for most survivors and controls was poor and generally lower in survivors, particularly females. Older age, higher body fat, methotrexate exposure, and extremes of LV mass/function were associated with lower V(O(2)max) in survivors. Because physical activity can improve nutritional and cardiac conditions, survivors should be encouraged to exercise regularly with close monitoring.

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.

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.

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.

A clinic-based, comprehensive care model for studying late effects in long-term survivors of pediatric illnesses.

OBJECTIVE: Long-term survivors of several childhood illnesses are at risk for multiple late effects of their illness or therapy, and children with documented toxic exposures may also experience long-term health consequences. Clinical studies of these effects are difficult to conduct. The Cardiovascular Status in Childhood Cancer Survivors Study is an established study that highlights the ability to perform comprehensive clinical investigations when patients are cared for in a formal, long-term follow-up clinic. This clinic model facilitates long-term retention and recruitment of patients, allowing comprehensive clinical studies of late effects of illness or exposures, in this case, of cardiovascular complications of cancer treatment during childhood. METHODS: The study is funded through the National Institute of Health Office of Cancer Survivorship. Participants are recruited from the Long-Term Survivors Clinic at the University of Rochester. The clinic provides care for all survivors of childhood cancer in the region. The Long-Term Survivors Clinic provides medical care and psychosocial and educational support to patients and facilitates coordination of care. Patients remain in close contact with clinic staff for extended periods. RESULTS: We recruited a representative sample of this long-term survivor population, with a wide range of ages, diagnoses, and time since diagnosis. Longitudinal collection of detailed clinical data will enable us to conduct cohort studies of late effects as well as case-control studies of toxic exposures. CONCLUSIONS: The success of this study shows the advantages of formal programs for continued care of patients with chronic illnesses or treatment or toxic exposures. The Long-Term Survivors Clinic provides an excellent model for clinical care and research that is applicable to multiple pediatric and young adult populations.