Welcome to SIOP 2022 Interactive Programme
The Congress will officially run on CET time zone (Central European Time, Barcelona)
- Jurgen Lemiere (Belgium)
PREDIABETES, PROGRESSION TO DIABETES, AND RISK FOR LATE CARDIOVASCULAR EVENTS AND RENAL COMPLICATIONS AMONG ADULT SURVIVORS OF CHILDHOOD CANCER IN THE ST. JUDE LIFETIME COHORT
- Stephanie B. Dixon (United States of America)
Abstract
Background and Aims
Prediabetes is a potentially reversible precursor to diabetes and subsequent increased risk for cardiovascular events; however, little is known about prediabetes in childhood cancer survivors.
Methods
Prevalence of prediabetes (fasting glucose 100-125 mg/dL or HbA1c 5.7-6.4%) and diabetes were assessed in 3529 5+ year survivors, ≥18 years old (median 30, range 18-65 years) and compared to 450 community controls stratified by age (10 year groups) and adjusted for race, sex, and BMI. Among survivors with available follow-up, Cox proportional hazards regression estimated risk for progression from prediabetes to diabetes and risk of future cardiovascular events and renal complications reported as hazard ratio (HR) with 95% confidence intervals (CI).
Results
The prevalence of prediabetes overall was 29.2% (95% CI 27.7-30.7) and of diabetes 6.5% (5.7-7.3). In each age strata, survivors had significantly higher prevalence of prediabetes and diabetes than controls (p<0.001; e.g, among those aged 30-39 35.0% of survivors vs. 14.3% of controls had prediabetes). Among 695 survivors with prediabetes, 68 (10%; median follow-up 5.1 years) progressed to diabetes. After adjustment for age, sex, race and body composition, risk of progression to diabetes was increased by treatment including pancreatic radiation ≥10 Gy (HR 2.7 [95% CI 1.1-6.8]) or total body irradiation (4.4 [1.5-13.1]). Compared to survivors with normal glucose control, independent of demographic characteristics and relevant treatment exposures, those with prediabetes were at increased risk of future myocardial infarction (HR 2.4 [95% CI 1.2-4.8]) and chronic kidney disease (3.6 [1.6-8.0]) while those with diabetes were also at increased risk for future cardiomyopathy (3.8 [1.4-10.5]) or stroke (3.4 [1.3-8.9]).
Conclusions
Nearly one-third of young adult survivors of childhood cancer have prediabetes which increases risk for future cardiovascular events and renal complications independent of cancer treatment. Future interventions should target prediabetes as a modifiable risk factor to prevent progression to diabetes and subsequent morbidity.
INFORMATICS TOOLS TO IMPLEMENT LATE CARDIOVASCULAR RISK PREDICTION MODELING FOR POPULATION HEALTH MANAGEMENT OF HIGH-RISK CHILDHOOD CANCER SURVIVORS
- David Noyd (United States of America)
Abstract
Background and Aims
Marked improvements in outcomes for children with cancer and robust cohort studies with longitudinal follow-up inform evidence-based guidelines for survivors at risk for late cardiomyopathy. Clinical informatics tools to integrate data from multiple sources have the potential to catalyze population health management.
Methods
Two institutional cohorts used distinct approaches to implement previously validated late cardiovascular risk prediction modeling from the Childhood Cancer Survivor Study (CCSS) for cardiomyopathy. The Oklahoma Childhood Cancer Survivor cohort was constructed from an institutional cancer registry of survivors diagnosed between 2005 and 2014 (n=382). Data elements (cumulative anthracycline, cumulative chest-directed radiotherapy, alkylator, and platinum exposures) were extracted from Passport for Care (PFC). The Duke Childhood Cancer Survivor Cohort integrated cancer registry and electronic health record data, using standard query language, to automatically extract chemotherapy exposures. Risk groups were compared to the Children’s Oncology Group (COG) Long-Term Follow-up Guidelines.
Results
In Oklahoma, of 481 survivors documented in PFC, 29%, 56%, and 15% were classified as low, moderate, high risk for cardiomyopathy, respectively, based on the CCSS late cardiomyopathy risk calculator. At Duke (n=737), 64%, 31%, and 6% were classified as low, moderate, and high risk, respectively. Concordance was modest for high (Kappa = 0.42 and 0.53 for the Oklahoma and Duke cohorts, respectively) and moderate risk groups (Kappa = 0.46 and 0.46) and good for the low risk group (Kappa = 0.77 and 0.70) compared to COG risk groups.
Conclusions
Clinical informatics tools represent a feasible approach to leverage discrete data elements regarding key treatment exposures from PFC to successfully implement previously validated late cardiovascular risk prediction models on a population health level. Alternative strategies to automatically extract data elements from the EHR in the Duke cohort support interoperability to catalyze broader impact.
MODIFIABLE RISK FACTORS (MRFS) AND LATE MORTALITY IN THE ST. JUDE LIFETIME COHORT STUDY (SJLIFE)
- Matthew J. Ehrhardt (United States of America)
Abstract
Background and Aims
The contribution of MRFs toward late mortality among childhood cancer survivors is unknown.
Methods
We characterized mortality among 9,602 ≥5-year survivors of childhood cancer diagnosed (1962-2012) and treated at St. Jude Children’s Research Hospital. Treatments were abstracted from medical records and cause of death obtained from the National Death Index, supplemented by record review. For a subgroup who participated SJLIFE (n=4,321), baseline clinical study assessments identified traditional (hypertension, diabetes, underweight/obesity) and potentially MRFs (bone mineral deficiency, hypogonadism, hypothyroidism, adrenal insufficiency) and a healthy lifestyle index [composite score, 0 (unhealthy) to 4 (healthy) of smoking, alcohol intake, body mass index, physical activity, available for 3,694 adult survivors only]. Standardized mortality ratios (SMRs) were estimated for 5-year survivors using age-sex-race/ethnicity-specific US-population mortality rates. Associations between MRFs/lifestyle and post-baseline mortality were assessed using piecewise exponential models, adjusting for attained age, sex, race, age at diagnosis, income, employment, and insurance status.
Results
SMRs were increased for all-cause (7.4, 95%CI:7.0-7.8), health-related (7.2, 95%CI:6.7-7.8), and external (1.7, 95%CI:1.4-1.9) causes of death. Among adult SJLIFE participants, MRFs (vs. none) were associated with increased risk of post-baseline all-cause mortality [any one MRF (RR=1.8, 95% confidence interval [CI]: 1.1-3.0); any two (RR=3.8, 95%CI:2.3-6.4); any three (RR=4.2, 95%CI:2.3-7.6); and ≥ four (RR=3.8, 95%CI:1.8-8.2)], health-related mortality [any one (RR=2.3, 95%CI: 1.2-4.3); any two (RR=4.9, 95%CI:2.6-9.3); any three (RR=6.3, 95%CI:3.2-12.7); ≥ four (RR=3.7, 95%CI:1.4-9.5)], and subsequent neoplasm-related mortality, a subtype of health-related mortality [any one (RR=4.3, 95%CI:1.4-12.9); any two (RR=8.2, 95%CI:2.7-25.0); any three (RR=11.1, 95%CI:3.3-37.3); and ≥ four (RR=7.0, 95%CI:1.6-29.5)]. Among individual risk factors, only hypertension (RR=1.8, 95%CI:1.3-2.7, p=0.001) and healthy lifestyle index of 0 vs. 4 (RR=3.6, 95%CI:1.0-12.4, p=0.043) were associated with an increased risk of post-baseline all-cause mortality.
Conclusions
MRFs and unhealthy lifestyle are associated with increased risk of all-cause and health-related mortality in adult survivors of childhood cancer.
PREVALENCE AND RISK FACTORS OF UNHEALTHY LIFESTYLE BEHAVIORS AMONG SURVIVORS OF CHILDHOOD CANCER IN THE NETHERLANDS
- Eline Bouwman (Netherlands)
Abstract
Background and Aims
Childhood cancer survivors (CCSs) are at an increased risk for the development of chronic health conditions. These late effects can be exacerbated by unhealthy lifestyle behaviors. This study aims to investigate the prevalence of unhealthy lifestyle behaviors in Dutch CCSs compared to their siblings. In addition, we aimed to assess the risk factors for unhealthy lifestyle behaviors in Dutch CCSs.
Methods
We included 2677 CCSs (i.e. 5-year survivors of all childhood malignancies diagnosed between 1963 and 2001; current age ≥18 years) and 992 sibling controls of the Dutch Childhood Cancer Survivor Study LATER cohort part 1. Questionnaire data was collected on alcohol consumption, drug use, smoking, BMI, and physical activity levels. Multivariable logistic regression analyses were done to compare the prevalence of each unhealthy behavior between CCSs and their siblings, adjusted for confounding (sociodemographic factors, comorbidities, limb amputation), and to examine risk factors for unhealthy lifestyle behaviors within CCSs.
Results
Prevalence rates of daily alcohol consumption (CCSs: 28.8%, siblings: 30.6%), daily smoking (CCSs: 14.9%; siblings: 15.0%), any drug use in the past year (CCSs: 13.3%; siblings: 12.9%), and BMI ≥25 (CCSs: 36.2%; siblings: 36.1%) did not statistically differ between CCSs and siblings. However, CCSs more often failed to meet the national guidelines for physical activity than their siblings (CCSs: 27.0%; siblings: 18.5%; adjusted OR 1.45, 95% CI = 1.19-1.76). Within CCSs, male sex, age ≥45 years, a low and middle educational level, marital status, presence of ≥1 comorbidities, and limb amputation were all associated with an unhealthy lifestyle.
Conclusions
This study shows high prevalence rates of overweight and physical inactivity in CCSs. This illustrates the need for dietary and physical activity interventions personalized to CCSs. The findings will also help healthcare professionals to identify CCSs at risk for unhealthy lifestyle behaviors, and thus those who will benefit the most from lifestyle interventions.
NEUROCOGNITIVE IMPAIRMENT AND FUNCTIONAL INDEPENDENCE IN ADULT SURVIVORS OF CHILDHOOD MEDULLOBLASTOMA: A REPORT FROM THE CHILDHOOD CANCER SURVIVOR STUDY (CCSS)
- Chiara Papini (United States of America)
Abstract
Background and Aims
Survivors of childhood medulloblastoma are at risk of developing chronic health conditions (CHCs) and neurocognitive late effects secondary to their tumor and intensive multimodal therapies. The contribution of these morbidities to attainment of functional independence in adulthood has not previously been examined.
Methods
505 adult survivors of medulloblastoma (58% male, median [min-max] 7 [0-20] years at diagnosis, 29 [18-46] years at evaluation) completed the CCSS Neurocognitive Questionnaire (impairment: scores> 90th %ile of siblings). Treatment exposures were categorized as surgery + craniospinal irradiation (CSI)<30Gy (± chemotherapy); surgery + CSI≥30Gy (no chemotherapy); or surgery + CSI≥30Gy + chemotherapy. Self-reported CHCs were graded using NCI’s CTCAE v4.3. Latent class analysis utilized five indicators (employment, marital status, independent living, driver’s license, assistance with routine/personal care needs) to identify mutually exclusive groups of functional independence. Multivariable modified Poisson regressions examined relative risk (RR) of neurocognitive impairment between the groups, adjusting for sex, race, age at diagnosis, and age at assessment. Path analysis examined the impact of treatment on functional independence, mediated by Grade 2-4 CHCs and/or neurocognitive impairment.
Results
Three latent groups of survivors varying in functional independence were identified: independent (37%), moderately independent (non-independent living and unmarried; 21%), and non-independent (42%). Survivors with impaired task efficiency (RR=1.83, 95% CI, 1.37-2.45), organization (RR=1.33, 95% CI, 1.09-1.61), and emotional regulation (RR=1.26, 95% CI, 1.03-1.55) were at elevated risk for being non-independent compared to independent. Path analysis revealed no direct or indirect paths from treatment exposures to non-independence through neurocognitive impairment and/or CHCs. There were, however, significant direct paths from impaired organization (β=0.23, p=0.013) and stroke/seizure (β=0.47, p<0.001) to non-independence.
Conclusions
Neurocognitive impairment and neurologic sequelae in medulloblastoma survivors contribute to reduced independence in adulthood, irrespective of past treatment exposures. Functional rehabilitation efforts following seizures/strokes and interventions for neurocognitive deficits may promote attainment of independence in long-term survivors of medulloblastoma.
NEUROCOGNITIVE FUNCTION AND HEALTH-RELATED QUALITY OF LIFE IN A NATIONWIDE COHORT OF LONG-TERM SURVIVORS OF CHILDHOOD BRAIN TUMOR
- Anne Sophie Lind Helligsoe (Denmark)
Abstract
Background and Aims
Survivors of childhood brain tumor are at high risk of late effects, but limited data exists regarding their neurocognitive function and associations with quality of life and symptom burden. Our aim was to examine neurocognitive function in childhood brain tumor survivors and associations with quality of life and symptom burden.
Methods
Five-year survivors of brain tumor over the age of 15 were identified in the Danish Childhood Cancer Registry (n = 423). Eligible and consenting participants completed neuropsychological tests and questionnaires assessing quality of life, insomnia, fatigue, anxiety and depression. Survivors treated with radiation (n = 59) were statistically compared with survivors not treated with radiation (n = 102). Correlations of neurocognitive function with quality of life and symptom burden were performed.
Results
In total, 170 survivors participated (40.2% participation rate). Sixty-six percent of the survivors who completed neuropsychological tests (n = 161) exhibited overall neurocognitive impairment. Neurocognitive outcomes for survivors treated with surgery were below normative expectations. Survivors treated with radiation, especially whole-brain irradiation, exhibited poorer neurocognitive outcomes than survivors not treated with radiation. Furthermore, a number of survivors experienced significant fatigue (40%), anxiety (23%), insomnia (13%), and/or depression (6%). Survivors treated with radiation reported lower quality of life and higher symptom burden scores than survivors not treated with radiation; particularly in physical functioning, social functioning with symptoms of fatigue. Neurocognitive impairment was not associated with quality of life or symptom burden.
Conclusions
In this study, a majority of the childhood brain tumor survivors experienced neurocognitive impairment, reduced quality of life, and high symptom burden. Although not associated with each other, it is apparent that childhood brain tumor survivors experience not only neurocognitive dysfunction, but may also experience quality of life impairments and significant symptom burden.