[Show abstract][Hide abstract] ABSTRACT: Background: Childhood cancer survivors (CCS) are more insulin resistant (IR) and have higher levels of several cardiovascular (CV) risk factors even while still children. This study examines specific treatment exposures associated with CV risk factors and IR. Methods: CCS age 9-18 years at study entry and in remission >5 years from diagnosis (n=319) and 208 sibling controls were recruited into this cross-sectional study that included physiologic assessment of IR (hyperinsulinemic euglycemic clamp) and assessment of CV risk factors.. Regression and recursive tree modeling were used to ascertain treatment combinations associated with IR and CV risk. Results: Mean current age of CCS was 14.5yr, 54% were male (siblings 13.6yr, 54% male). Diagnoses included leukemia (35%), brain tumors (36%), solid tumors (33%) or lymphoma (6%). Among CCS, analysis of individual chemotherapy agents failed to find associations with CV risk factors or IR. Compared to siblings, IR was significantly higher in CCS who received platinum plus cranial radiation (CRT, 92% brain tumors) and in those who received steroids but no platinum (majority leukemia). IR did not differ between CCS who received surgery alone vs. siblings. Within survivor comparisons failed to elucidate treatment combinations that increased IR compared to those who received surgery only. Conclusions: Exposure to platinum, CRT or steroids is associated with IR and CV risk factors and should be taken into consideration in the development of screening recommendations for CV risk. Impact: Earlier identification of CCS who may benefit from targeted prevention efforts may reduce their future risk of CV disease.
[Show abstract][Hide abstract] ABSTRACT: To determine the prevalence and severity of bone deficits in a cohort of childhood cancer survivors (CCS) compared to a healthy sibling control group, and the modifiable factors associated with bone deficits in CCS.
Cross-sectional study of bone health in 319 CCS and 208 healthy sibling controls. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). Generalized estimating equations were used to compare measures between CCS and controls. Among CCS, multivariable logistic regression was used to evaluate odds ratios for BMD Z-score ≤ -1.
All subjects were younger than 18 years of age. Average time since treatment was 10.1 years (range 4.3 - 17.8 years). CCS were 3.3 times more likely to have whole body BMD Z-score ≤ -1 than controls (95% CI: 1.4-7.8; p = 0.007) and 1.7 times more likely to have lumbar spine BMD Z-score ≤ -1 than controls (95% CI: 1.0-2.7; p = 0.03). Among CCS, hypogonadism, lower lean body mass, higher daily television/computer screen time, lower physical activity, and higher inflammatory marker IL-6, increased the odds of having a BMD Z-score ≤ -1.
CCS, less than 18 years of age, have bone deficits compared to a healthy control group. Sedentary lifestyle and inflammation may play a role in bone deficits in CCS. Counseling CCS and their caretakers on decreasing television/computer screen time and increasing activity may improve bone health.
[Show abstract][Hide abstract] ABSTRACT: Increased cardiovascular (CV) risk has been reported in adults who are childhood cancer survivors (CCS). We sought to determine the emergence of CV risk factors in CCS while still children.
CCS in remission ≥5 years from cancer diagnosis (n=319, age=14.5 years) and their siblings (control subjects, n=208, age=13.6 years) participated in this cross-sectional study of CV risk, which included physiologic assessment of insulin sensitivity/resistance (hyperinsulinemic euglycemic clamp). Adjusted comparisons between CCS major diagnoses (leukemia [n=110], central nervous system tumors [n=82], solid tumors [n=127]) and control subjects were performed with linear regression for CV risk factors and insulin sensitivity.
Despite no significant differences in weight and body mass index, CCS had greater adiposity (waist [73.1 versus 71.1 cm, P=.02]; percent fat [28.1 versus 25.9%, P=.007]), lower lean body mass (38.4 versus 39.9 kg, P=.01) than control subjects. After adjustment for adiposity, CCS had higher total cholesterol level (154.7 versus 148.3 mg/dL, P=.004), low-density lipoprotein cholesterol level (89.4 versus 83.7 mg/dL, P=.002), and triglyceride level (91.8 versus 84 mg/dL, P=.03) and were less insulin sensitive (insulin stimulated glucose uptake, measure of insulin resistance, adjusted for lean body mass 12.1 versus 13.4 mg/kg/min, P=.002) than control subjects.
CCS have greater CV risk than healthy children. Because CV risk factors track from childhood to adulthood, early development of altered body composition and decreased insulin sensitivity in CCS may contribute significantly to their risk of early CV morbidity and mortality.
The Journal of pediatrics 09/2011; 160(3):494-9. DOI:10.1016/j.jpeds.2011.08.018 · 3.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An association has been reported between neuroblastoma and congenital heart disease, frequently bicuspid aortic valve [Holzer and Franklin. Arch Dis Child 2002;87:61-64; George et al. J Pediatr 2004;144:444-448; Friedman et al. Pediatr Cardiol 1998;19:480-481; Monte et al. Am J Pediatr Hematol Oncol 1985;7:109-116]. To evaluate this in a large patient group with neuroblastoma, we examined echocardiograms of patients with neuroblastoma from 1987 to January 2007 to determine if there was a higher incidence of bicuspid aortic valves compared to the general population without neuroblastoma. We found that only 0.7% of neuroblastoma patients had the congenital heart defect of bicuspid aortic valves compared with 1-2% in the general population [Braverman et al. Curr Prob Cardiol 2005;30:470-522]. Our data show that neuroblastoma is not associated with bicuspid aortic valves.
[Show abstract][Hide abstract] ABSTRACT: Current theory suggests that neurocognitive late effects of treatments for childhood cancer such as difficulties with attention, processing speed and visual-motor ability are the result of white matter damage. Neuroimaging studies have produced a variety of white matter findings. However, although white matter is thought to be differentially affected, previous studies have not demonstrated a discrepancy between white and gray matter function. The present study included 36 children treated for childhood leukemia with hematopoietic stem cell transplant (HCT). Their performance on neurocognitive measures traditionally thought to measure white matter was compared to performance on measures thought to measure gray matter function. Composite white and gray matter standard scores were created based on neuropsychological measures that individuals with known white or gray matter damage perform poorly. As predicted, composite white matter scores (mean = 98.1) were significantly lower (t = 2.26, p = 0.03) than composite gray matter scores (mean = 102.5). Additionally, as gray matter performance increased, the difference between gray and white matter scores increased (R = 0.353, p = 0.035). Overall, the results of this study support the current theory that white matter damage is responsible for the more subtle neurocognitive late effects resulting from treatment for childhood leukemia.
Neuropsychiatric Disease and Treatment 03/2008; 4(1):283-8. · 1.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hematopoeitic cell transplantation (HCT) in childhood has been associated with late complications including endocrine, neurocognitive, and cardiopulmonary abnormalities. Little is known about the complications of transplantation in infants.
Eligible subjects underwent HCT for acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) at less than 3 years of age. Seventeen out of 33 eligible patients were evaluated, transplanted between 1981-2000. Eleven patients had AML, 11 were female. Preparative regimen included total body irradiation (TBI) for eleven. Age at HCT ranged from 0.58 to 2.97 years, and survival 3.25 to 22.33 years. Patients underwent physical and laboratory evaluation, dual-energy X-ray absorptiometry (DXA) scan, bone age X-ray, neuropsychological, and quality of life (QOL) evaluation.
Identified abnormalities included: growth hormone deficiency (59%), hypothyroidism (35%), osteochondromas (24%), decreased bone mineral density (24%), and dyslipidemias (59%). Two patients developed a second malignancy. Neuropsychological testing revealed average intelligence quotient (IQ) with attention deficits and other weaknesses for most patients. There were no overall differences between QOL in these children when compared to population norms.
Of the survivors evaluated, typical late effects seen after radiation exposure are common, yet most subjects were doing well without major ongoing medical issues. Dyslipidemias affect more than half of patients and may be associated with metabolic syndrome, placing patients at increased risk for early cardiovascular disease. Even in this group of patients where the majority was exposed to TBI at a very young age, most are functioning at an average or above-average level.
[Show abstract][Hide abstract] ABSTRACT: Nonmelanoma skin cancer (NMSC) has become the most common type of cancer in many populations throughout the world. Ultraviolet and ionizing radiation are known risk factors. Because NMSCs are rarely lethal and most cancer registries do not routinely report data regarding these cancers, they have received little attention in studies evaluating long-term effects of cancer therapy. This article reports on the occurrence of secondary NMSC as a long-term effect of cancer therapy in survivors of childhood cancer.
The Childhood Cancer Survivor Study (CCSS) is a cohort study of 5-year survivors of childhood and adolescent cancer from 25 participating institutions in North America. NMSC patients were defined by a history of basal cell or squamous cell carcinoma of the skin after primary malignancy treatment. Demographic and treatment data were collected and analyzed.
Among the 13,132 eligible CCSS participants, 213 have reported NMSC; 99 patients (46%) have had multiple occurrences. Median age of occurrence was 31 years (range, 7 to 46 years). Location of NMSC included head and neck (43%), back (24%), chest (22%), abdomen and pelvis (5%), extremity (3%), and unknown (4%). Ninety percent of patients had previously received radiation therapy (RT); 90% of tumors occurred within the RT field. RT was associated with a 6.3-fold increase in risk (95% CI, 3.5- to 11.3-fold).
Long-term survivors of childhood and adolescent cancer who were treated with RT are at highest risk for developing NMSC. Educational efforts need to be directed to this population to facilitate early diagnosis of NMSC and reduction in sun exposure.