Endothelial dysfunction in adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10564-10564
Author(s):  
Daniel A. Mulrooney ◽  
Kirsten K. Ness ◽  
Sujuan Huang ◽  
Aimee Santucci ◽  
Robert P. Hebbel ◽  
...  

10564 Background: Endothelial dysfunction, as an indicator of vascular disease in childhood cancer survivors (CCS) has not been widely studied. Methods: Markers of vascular inflammation (high sensitivity C-reactive protein [hsCRP]), hemostasis (fibrinogen), activation (endothelial cell expression of vascular cell adhesion molecule [VCAM-1]) and functional testing (large/small artery elasticity [L/SAE], pulse wave velocity [PWV]) were assessed in 200 CCS, ≥10 years from diagnosis, and 192 age/gender matched healthy controls. Exclusion criteria included: inflammatory processes, use of anti-inflammatory or cardiovascular medications, or pregnancy. Differences were assessed by adjusted multivariable linear regression. Results: CCS (53% male) of leukemia/lymphoma (59%), central nervous system tumors (6%), sarcomas (11.5%), embryonal tumors (22.5%), and other (1%) had a mean age at diagnosis 7.3 years (SD ±5.7). CCS and controls did not differ in current age (mean 34.1 ±9.2 vs. 33.5 years ±9.8), body mass index, smoking, mean systolic (124 mm Hg ±11.7 vs. 123 ±11.9) or diastolic blood pressure (73 ±9.5 vs. 71 ±9.5). Fasting low- (110 mg/dl ±31 vs. 102 ±30) and high-density (52 ±16 vs. 56 ±18) cholesterol levels differed between survivors and controls (p<0.01). Endothelial expression of VCAM-1 and PWV were statistically significantly increased in CCS; arterial elasticity was significantly reduced (table). Therapeutic exposures (anthracyclines and radiation) were not significantly associated with endothelial dysfunction. Conclusions: Childhood cancer survivors have greater endothelial dysfunction, a sign of atherosclerosis, and preventive measures should be investigated. [Table: see text]

2020 ◽  
Author(s):  
Vincent Pluimakers ◽  
Marta Fiocco ◽  
Jenneke van Atteveld ◽  
Monique Hobbelink ◽  
Dorine Bresters ◽  
...  

BACKGROUND Potential late effects of treatment for childhood cancer include adiposity, insulin resistance, dyslipidemia and hypertension. These risk factors cluster together as metabolic syndrome (MetS) and increase the risk for development of diabetes mellitus and cardio- and cerebrovascular disease. Knowledge on risk factors, timely diagnosis and preventive strategies is of importance to prevent cardio- and cerebrovascular complications and improve quality of life. Currently, no studies in national cohorts on prevalence and determinants of MetS in childhood cancer survivors including biomarkers and genetic predisposition are available. OBJECTIVE The objectives of the Dutch LATER METS study are to assess 1) the prevalence and risk factors of MetS and its separate components, and 2) the potential value of additional biomarkers, in the national cohort of adult long-term survivors of childhood cancer. METHODS This is a cross-sectional study, based on recruitment of all survivors treated in the Netherlands between 1963 and 2002. MetS will be classified according to the definitions of the National Cholesterol Education Program (NCEP-ATP III) as well as the Joint Interim Statement (JIS), and compared to reference data. Dual-energy X-ray absorptiometry (DXA) scans were performed to assess body composition in more detail. The effect of patient characteristics, previous treatment, and genetic variation on the risk of MetS will be assessed. The diagnostic and predictive value of novel biomarkers will be tested. RESULTS Patient accrual started in 2016 and lasted until April 2020. A total of 2380 survivors has participated, in seven pediatric oncology hospitals. From July 2020, biomarker testing, SNP analysis and data analysis will be performed. CONCLUSIONS The Dutch LATER METS study will provide knowledge on clinical and genetic determinants of MetS, and the diagnostic value of biomarkers, in childhood cancer survivors. The results of this study will be used to optimize surveillance guidelines for MetS in survivors, based on enhanced risk stratification and screening strategies. This will improve diagnosis of MetS, and prevent complications. CLINICALTRIAL Registered at toetsingonline.nl, NL32117.018.10


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10057-10057
Author(s):  
Kirsten K. Ness ◽  
Robyn Partin, MS ◽  
Carrie R. Howell ◽  
Kevin R. Krull ◽  
Tara M. Brinkman ◽  
...  

10057 Background: Childhood cancer survivors are at risk for premature aging; over 8% (ages18-60 years) meet Fried Frailty Criteria (≥3 of low lean muscle mass, muscle weakness, slow walking speed, exhaustion, low energy expenditure). Longitudinal changes and new onset frailty has not been studied. Methods: Childhood cancer survivors (N = 1501, 51.5% male, 14.9% black, median age at diagnosis 7 [0-22] years), were evaluated clinically to ascertain frailty at baseline (median age 30 [18-45] years) and five years later. Risk factors for incident frailty and impact of baseline frailty on mortality were evaluated in proportional hazard models. Results: Frailty increased from 6.0% (95% CI 4.1-8.9) to 11.7% (95% CI 6.7-12.2) overall, and for all diagnoses (Table). Risk factors for new onset frailty among those not frail at baseline were amputation (HR 5.1, 95% CI 1.1-14.4), anthracyclines (HR 1.2, 95% CI 1.1-1.4 per 100 mg/m2), and carboplatin (HR 1.3, 95% CI 1.1-1.5 per 2000 mg/m2). Severe, disabling or life threatening chronic conditions (HR 1.2, 95% CI 1.1-1.4 per organ system) and inactivity (HR 2.0, 95% CI 1.2-3.2) also predicted new onset frailty. Sixty-nine participants died from baseline to follow-up. Accounting for age, sex and chronic conditions, baseline frailty was associated with a 2.9 (95% CI 1.6-5.2) increased hazard of death. Conclusions: Prevalent frailty nearly doubled in five years and was associated with increased risk for death. Given that previous treatment exposures cannot be altered, interventions to remediate chronic disease and promote activity may impact function and longevity for childhood cancer survivors. [Table: see text]


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Echo L. Warner ◽  
Mark Fluchel ◽  
Jennifer Wright ◽  
Carol Sweeney ◽  
Kenneth M. Boucher ◽  
...  

Background.Population-based studies are needed to estimate the prevalence of underweight or overweight/obese childhood cancer survivors.Procedure.Adult survivors (diagnosed ≤20 years) were identified from the linked Utah Cancer Registry and Utah Population Database. We included survivors currently aged ≥20 years and ≥5 years from diagnosis(N=1060), and a comparison cohort selected on birth year and sex(N=5410). BMI was calculated from driver license data available from 2000 to 2010. Multivariable generalized linear regression models were used to calculate prevalence relative risks (RR) and 95% confidence intervals (95% CI) of BMI outcomes for survivors and the comparison cohort.Results.Average time since diagnosis was 18.5 years(SD=7.8), and mean age at BMI for both groups was 30.5 (survivorsSD=7.7, comparisonSD=8.0). Considering all diagnoses, survivors were not at higher risk for being underweight or overweight/obese than the comparison. Male central nervous system tumor survivors were overweight (RR=1.12, 95% CI 1.01–1.23) more often than the comparison. Female survivors, who were diagnosed at age 10 and under, had a 10% higher risk of being obese than survivors diagnosed at ages 16–20(P<0.05).Conclusion.While certain groups of childhood cancer survivors are at risk for being overweight/obese, in general they do not differ from population estimates.


2009 ◽  
Vol 19 (9) ◽  
pp. 982-990 ◽  
Author(s):  
Jacqueline Casillas ◽  
Katherine L. Kahn ◽  
Michelle Doose ◽  
Wendy Landier ◽  
Smita Bhatia ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10062-10062
Author(s):  
Carmen L Wilson ◽  
Wendy M. Leisenring ◽  
Kevin C. Oeffinger ◽  
Paul C. Nathan ◽  
Karen Wasilewski-Masker ◽  
...  

10062 Background: Childhood cancer survivors are at increased risk of developing obesity-related diseases, yet many survivors do not meet established guidelines for physical activity. We aimed to identify demographic and health-related predictors of declining physical activity among participants in the Childhood Cancer Survivor Study (CCSS). Methods: Analyses included 6617 >5 year childhood cancer survivors diagnosed between 1970-86 who completed the CCSS 2003 and 2007 follow-up questionnaires, and1992 siblings. Participants were classified as active if they reported engaging in any physical activity other than their regular job duties in the prior month. Generalized linear models using a log-link and Poisson distribution were used to compare participants whose physical activity levels fell from active to inactive over the study interval to those who remained active or whose activity levels improved. In addition to analyses comparing survivors to siblings, selected demographic factors and chronic conditions (CTCAE v4.0 Grade 3 and 4) were evaluated as risk factors in an analysis among survivors alone. Risk ratios (RR) with 95% confidence intervals (CI) are reported. Results: The median age at last follow-up among survivors and siblings was 36 (range: 21-58) and 38 (range: 21-62) years, respectively. Approximately 14% of survivors and 9% of siblings reported declines in physical activity across the study interval (p<0.01). Factors that predicted declining levels of physical activity included BMI≥30kg/m2 (RR=1.4, 95% CI=1.3-1.7, p<0.01), BMI<18.5kg/m2 (RR=1.4, 95% CI=1.0-1.8, p=0.03), not completing high school (RR=1.7, 95% CI=1.2-2.2, p<0.01), and black race (RR=1.6, 95% CI=1.2-2.1, p<0.01). In a model limited to survivors, declining levels of physical activity were more likely among survivors who reported the presence of Grade 3 or 4 neurological (RR=1.5, 95% CI=1.2-1.8, p<0.01) or cardiac conditions (RR=1.5, 95% CI=1.3-1.9, p<0.01). Conclusions: Childhood cancer survivors are at increased risk of becoming inactive over time compared to siblings. Interventions targeting survivors at highest risk of decline are required to reduce the risk of chronic diseases associated with an inactive lifestyle.


2006 ◽  
Vol 16 (1) ◽  
pp. 26-37 ◽  
Author(s):  
Judith A. Punyko ◽  
James G. Gurney ◽  
K. Scott Baker ◽  
Robert J. Hayashi ◽  
Melissa M. Hudson ◽  
...  

Life ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 45
Author(s):  
Marco Crocco ◽  
Giuseppe d’Annunzio ◽  
Alberto La Valle ◽  
Gianluca Piccolo ◽  
Decimo Silvio Chiarenza ◽  
...  

Assessment of endothelial dysfunction in cancer survivors may have a role in the early identification of non-communicable diseases and cardiovascular late effects. Oncological therapies may impair endothelial function. Therefore, in patients such as childhood cancer survivors who could benefit from early cardioprotective pharmacological interventions, it is essential to monitor endothelial function, even if the optimal methodology for investigating the multifaceted aspects of endothelial dysfunction is still under debate. Biochemical markers, as well as invasive and non-invasive tools with and without pharmacological stimuli have been studied. Human clinical studies that have examined lifestyle or cancer treatment protocols have yielded evidence showing the involvement of lipid and lipoprotein levels, glycemic control, blood pressure, adiposity, inflammation, and oxidative stress markers on the state of endothelial health and its role as an early indicator of cardiometabolic risk. However, with regards to pharmacological interventions, cautious interpretation of the result attained whilst monitoring the endothelial function is warranted due to methodological limitations and substantial heterogeneity of the results reported in the published studies. In this narrative review, an overview of evidence from human clinical trials examining the effects of cancer therapies on endothelial disease is provided together with a discussion of endothelial function assessment using the different non-invasive techniques available for researchers and clinicians, in recent years.


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