Diabetes risk in childhood cancer survivors: A population-based study.

10558 Background: Cure rates for childhood cancer have improved significantly over the last three decades. Diabetes has emerged as a delayed side-effect of treatment for childhood cancer. Methodologic limitations may have led to underestimation of the risk for diabetes in previous studies. Understanding the extent of diabetes risk and identifying risk factors for diabetes is imperative for improving screening and prevention strategies in this population. Methods: We used the Ontario population-based cancer registry and administrative health databases to evaluate the risk of diabetes in adult survivors of childhood cancer. Diabetes was measured using a validated algorithm. Survivors were compared to age and sex-matched controls from the general population using a multivariable, cause-specific hazard regression model where death and development of another cancer was treated as a competing risk. Results: We identified 10,438 1-year survivors of childhood cancer diagnosed prior to age 21 years between January 1st, 1990 and December 31st, 2010. Mean age at cancer diagnosis was 10.7 years (standard deviation [SD] 6.8) and the mean follow up was 11.2 years (SD 6.9). In multivariable models adjusted for rurality and income status, cancer survivors had a 55% increased rate of developing diabetes compared to matched controls (HR 1.55, 95% CI 1.31-1.83). Individuals treated for cancer between age 6-10 years (HR 4.01, 2.33-6.91) had the highest increased rate for diabetes among age categories. Leukemia (HR 2.39, 1.74-3.27) and lymphoma (HR 1.61, 1.12-2.31) was also associated with an increased risk for diabetes compared to the general population. Conclusions: Our study provides evidence of an increased risk for diabetes in adult survivors of childhood cancer. The increased risk is highest among those treated at younger ages, and after treatment for leukemia and lymphoma. Future research is warranted to identify optimal ways for diabetes screening and prevention in this population. Given the burden of cardiovascular disease in survivors, identifying and treating diabetes early may help improve overall morbidity and mortality.

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Premature Physiologic Aging as a Paradigm for Understanding Increased Risk of Adverse Health Across the Lifespan of Survivors of Childhood Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2017.76.7467 ◽

2018 ◽

Vol 36 (21) ◽

pp. 2206-2215 ◽

Cited By ~ 23

Author(s):

Kirsten K. Ness ◽

James L. Kirkland ◽

Maria Monica Gramatges ◽

Zhaoming Wang ◽

Mondira Kundu ◽

...

Keyword(s):

General Population ◽

Childhood Cancer ◽

First Generation ◽

Clinical Care ◽

Adult Survivors ◽

Premature Aging ◽

Cancer Therapies ◽

Increased Risk ◽

Improvement In Survival ◽

Survivors Of Childhood Cancer

The improvement in survival of childhood cancer observed across the past 50 years has resulted in a growing acknowledgment that simply extending the lifespan of survivors is not enough. It is incumbent on both the cancer research and the clinical care communities to also improve the health span of survivors. It is well established that aging adult survivors of childhood cancer are at increased risk of chronic health conditions, relative to the general population. However, as the first generation of survivors age into their 50s and 60s, it has become increasingly evident that this population is also at risk of early onset of physiologic aging. Geriatric measures have uncovered evidence of reduced strength and speed and increased fatigue, all components of frailty, among survivors with a median age of 33 years, which is similar to adults older than 65 years of age in the general population. Furthermore, frailty in survivors independently increased the risk of morbidity and mortality. Although there has been a paucity of research investigating the underlying biologic mechanisms for advanced physiologic age in survivors, results from geriatric populations suggest five biologically plausible mechanisms that may be potentiated by exposure to cancer therapies: increased cellular senescence, reduced telomere length, epigenetic modifications, somatic mutations, and mitochondrial DNA infidelity. There is now a critical need for research to elucidate the biologic mechanisms of premature aging in survivors of childhood cancer. This research could pave the way for new frontiers in the prevention of these life-changing outcomes.

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Relation between platelet coagulant and vascular function, sex-specific analysis in adult survivors of childhood cancer compared to a population-based sample

Scientific Reports ◽

10.1038/s41598-019-56626-1 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Marina Panova-Noeva ◽

Bianca Wagner ◽

Markus Nagler ◽

Natalie Arnold ◽

Jürgen H. Prochaska ◽

...

Keyword(s):

Arterial Hypertension ◽

Cancer Survivors ◽

Childhood Cancer ◽

Vascular Function ◽

Adult Survivors ◽

Population Based ◽

Peak Height ◽

Stiffness Index ◽

Increased Risk ◽

Female Cancer Survivors

AbstractFemale sex is a risk factor for long-term adverse outcome in cancer survivors, however very little is known for the underlying pathophysiological mechanisms rendering the increased risk. This study investigated sex-specifically the relation between thrombin generation (TG) with and without presence of platelets and vascular function in 200 adult survivors of a childhood cancer compared to 335 population-based control individuals. TG lag time, peak height and endogenous thrombin potential (ETP) measured in presence and absence of platelets were correlated to reflection index (RI) and stiffness index (SI). A sex-specific correlation analysis showed a negative relation in female survivors for platelet-dependent peak height and/or ETP and RI only. An age adjusted linear regression model confirmed the negative association between RI and platelet-dependent ETP (beta estimate: −6.85, 95% confidence interval: −12.19,−1.51) in females. Adjustment for cardiovascular risk factors resulted in loss of the association, whereby arterial hypertension and obesity showed the largest effects on the observed association. No other relevant associations were found in male and female cancer survivors and all population-based controls. This study demonstrates a link between platelet coagulant and vascular function of resistance vessels, found in female cancer survivors, potentially mediated by the presence of arterial hypertension and obesity.

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Dietary Intake and Diet Quality of Adult Survivors of Childhood Cancer and the General Population: Results from the SCCSS-Nutrition Study

Nutrients ◽

10.3390/nu13061767 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1767

Author(s):

Fabiën N. Belle ◽

Angeline Chatelan ◽

Rahel Kasteler ◽

Luzius Mader ◽

Idris Guessous ◽

...

Keyword(s):

General Population ◽

Dietary Intake ◽

Childhood Cancer ◽

Diet Quality ◽

Saturated Fat ◽

Adult Survivors ◽

Childhood Cancer Survivors ◽

Population Based ◽

Healthy Eating Index ◽

Increased Risk

Childhood cancer survivors (CCSs) are at increased risk of developing chronic health conditions. This may potentially be reduced by a balanced diet. We aimed to compare dietary intake and diet quality using the Alternative Healthy Eating Index (AHEI) of adult CCSs and the general Swiss population. A food frequency questionnaire (FFQ) was completed by CCSs with a median age of 34 (IQR: 29–40) years. We compared dietary intake of 775 CCSs to two population-based cohorts who completed the same FFQ: 1276 CoLaus and 2529 Bus Santé study participants. CCSs consumed particular inadequate amounts of fiber and excessive amounts of sodium and saturated fat. Dietary intake was similar in CCSs and the general population. The mean AHEI was low with 49.8 in CCSs (men: 47.7, women: 51.9), 52.3 in CoLaus (men: 50.2, women: 54.0), and 53.7 in Bus Santé (men: 51.8, women: 54.4) out of a maximum score of 110. The AHEI scores for fish, fruit, vegetables, and alcohol were worse in CCSs than in the general population, whereas the score for sugar-sweetened beverages was better (all p < 0.001). Diet quality at follow-up did not differ between clinical characteristics of CCSs. Long-term CCSs and the general population have poor dietary intake and quality in Switzerland, which suggests similar population-based interventions for everyone.

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Perceived Health among Adolescent and Young Adult Survivors of Childhood Cancer

Current Oncology ◽

10.3390/curroncol28010080 ◽

2021 ◽

Vol 28 (1) ◽

pp. 825-836

Author(s):

Morgan Young-Speirs ◽

Caitlin Forbes ◽

Michaela Patton ◽

K. Brooke Russell ◽

Mehak Stokoe ◽

...

Keyword(s):

Childhood Cancer ◽

Health Resources ◽

Adult Survivors ◽

Perceived Health ◽

Good Health ◽

Adolescent And Young Adult ◽

Control Group ◽

Increased Risk ◽

Patient Reported ◽

Survivors Of Childhood Cancer

Survivors of childhood cancer (SCCs) are at increased risk of late effects, which are cancer- and treatment-related side-effects that are experienced months to years post-treatment and encapsulate a range of physical, cognitive and emotional problems including secondary malignancies. Perceived health can serve as an indicator of overall health. This study aims to (1) understand how a patient reported outcome (PRO) of perceived health of SCCs compares to controls who have not had a cancer diagnosis and (2) examine the relationships between perceived health and demographic and clinical variables, and health behavior. A total of 209 SCCs (n = 113 (54.10%) males; median age at diagnosis = 6.50 years; median time off treatment = 11.10 years; mean age at study = 19.00 years) were included. SCCs completed annual assessments as part of Long-Term Survivor Clinic appointments, including a question on perceived health answered on a five-point Likert scale. Data were collected retrospectively from medical charts. Perceived health of SCCs was compared to a control group (n = 836) using data from the 2014 Canadian Community Health Survey. Most SCCs (67%) reported excellent or very good health. The mean perceived health of SCCs (2.15 ± 0.91) was not statistically different from population controls (2.10 ± 0.87). Pain (B = 0.35; p < 0.001), physical activity (B = −0.39; p = 0.013) and concerns related to health resources (B = 0.59; p = 0.002) were significant predictors of perceived health. Factors shown to influence SCCs’ perceived health may inform interventions. Exploration into how SCCs develop their conception of health may be warranted.

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Genetic and treatment risks for diabetes mellitus (DM) in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS) and St. Jude Lifetime (SJLIFE) cohorts.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.10014 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 10014-10014

Author(s):

Melissa A. Richard ◽

Sogol Mostoufi-Moab ◽

Nisha Rathore ◽

Austin L. Brown ◽

Stephen J. Chanock ◽

...

Keyword(s):

Risk Factors ◽

Cancer Survivors ◽

Cancer Treatment ◽

Childhood Cancer ◽

Regulatory Region ◽

Childhood Cancer Survivors ◽

Population Based ◽

European Ancestry ◽

Radiation Group ◽

Increased Risk

10014 Background: Childhood cancer survivors face increased risk for DM, a polygenic trait also attributable to cancer treatment exposures, particularly abdominal radiation. We aimed to characterize the role of genetic and treatment risk factors for DM among two large cohorts of childhood cancer survivors. Methods: We performed a nested case-control genome-wide association study for DM managed with oral medications in the original CCSS cohort (diagnosed 1970-1986). Logistic regression was conducted in the total sample (N = 5083) and stratified by 1) European ancestry (EA) and 2) abdominal radiation. Replication of suggestive variants (P < 1×10-7) using Fisher’s exact test was performed in independent cohorts: i) CCSS expansion diagnosed 1987-1999 (N = 2588) and ii) SJLIFE diagnosed 1962-2012 (N = 2182). To evaluate the effect of cancer treatment on the background genetic predisposition to DM, we estimated standardized effect sizes (Z’) among EA survivors in each abdominal radiation group for 398 index variants from the largest population-based EA DM study. Radiation group Z’ estimates were compared using linear regression. Results: In the original CCSS cohort we identified nine variants associated with DM and provide further support for four linked variants in the ERCC6L2 locus. Among all survivors, the rs55849673-A allele was associated with increased odds for DM among survivors in the original CCSS cohort (minor allele frequency [MAF]-cases = 0.055; MAF-controls = 0.024; adjusted odds ratio [aOR] = 2.9, 95% CI: 2.0-4.2, P = 3.7×10-8). Allele frequencies were consistent in the CCSS expansion (MAF-cases = 0.075; MAF-controls = 0.028; P = 0.07) and SJLIFE (MAF-cases = 0.036; MAF-controls = 0.027; P = 0.5). Additionally, rs55849673-A estimates were consistent among EA survivors and stronger among survivors not treated with abdominal radiation (MAF-cases = 0.052; MAF-controls = 0.021; aOR = 3.6, P = 1.6×10-6). Notably, in the CCSS expansion all rs55849673-A EA carriers who developed DM did not receive abdominal radiation (MAF-cases = 0.1; MAF-controls = 0.026; P = 0.04). More broadly, the Z’ of population-based DM index variants were 78% lower in survivors treated with abdominal radiation than survivors not treated with abdominal radiation (beta = 0.22; P = 0.01), indicating the background genetic risk for DM may be altered by treatment. Conclusions: We provide evidence for a novel locus of DM in childhood cancer survivors. This locus is a regulatory region associated with expression of ERCC6L2, a gene implicated in an East Asian population-based DM study. Taken together, our findings support the overwhelming effect of abdominal radiation on DM risk in childhood cancer survivors, relative to other risk factors, and provide insight on a genetic locus that may be useful for DM risk prediction in the context of cancer treatment.

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Prevalence of mental distress among adult survivors of childhood cancer in Germany—Compared to the general population

Cancer Medicine ◽

10.1002/cam4.1936 ◽

2019 ◽

Vol 8 (4) ◽

pp. 1865-1874 ◽

Cited By ~ 9

Author(s):

Juliane Burghardt ◽

Eva Klein ◽

Elmar Brähler ◽

Mareike Ernst ◽

Astrid Schneider ◽

...

Keyword(s):

General Population ◽

Childhood Cancer ◽

Mental Distress ◽

Adult Survivors ◽

Survivors Of Childhood Cancer

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The attainment of life goals by adult survivors of childhood cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.9536 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 9536-9536

Author(s):

D. B. Crom ◽

S. Lensing ◽

S. Rai ◽

M. Snider ◽

M. M. Hudson

Keyword(s):

At Risk ◽

Radiation Therapy ◽

Health Insurance ◽

General Population ◽

Childhood Cancer ◽

Hematological Malignancy ◽

Adult Survivors ◽

Life Goals ◽

Full Time ◽

Survivors Of Childhood Cancer

9536 Background: Adult survivors of childhood cancer are at risk for disease- and therapy-related morbidity, which can adversely affect marriage and employment status, ability to obtain health insurance and access to care. Our aim was to identify factors associated with survivors’ ability to achieve these goals. Methods: We surveyed 1,437 survivors of different types of childhood cancer who were >18 years of age and >10 years from diagnosis. We compared our cohort's data to normative data in the Medical Expenditure Panel Survey and the Current Population Surveys of the U.S. Census Bureau. Survivors were categorized into 3 groups (hematological malignancy, solid tumors, or central nervous system tumors) and whether they had received radiation therapy. Results: The majority of respondents (response rate 65%) were survivors of hematological malignancies (71%), white (91%), and working full-time (62%); (43%) were married. When compared to age- and gender-adjusted national averages, only survivors of hematological malignancy who received radiation therapy were significantly less likely to be married than the general population (44% vs. 52%). Full-time employment among survivors was lower than national norms, except for survivors of hematological malignancy who had not received radiation therapy. The prevalence of having any health insurance, especially public insurance, was higher in all diagnostic groups than in the general population. Difficulty obtaining care was reported by 11% of all survivors; 12% reported not receiving needed health care. Additionally, 26.9% reported having been denied insurance. Current unemployment and lack of insurance were significantly associated with difficulty in obtaining care (p=0.049 and p<0.001, respectively). CNS tumor survivors reported greater difficulty in obtaining needed care (p=0.030). Current employment and solid tumor diagnosis were associated with lower rates of denial of insurance (p=0.018 and p=0.003, respectively). Conclusion: Subgroups of adult childhood cancer survivors are at risk of problems with attaining life goals, including access to care. This has serious implications given the known long-term secondary medical complications in this at- risk population. No significant financial relationships to disclose.

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Mental healthcare use and severe psychiatric diagnoses in adult survivors of childhood cancer: A population-based study using health services data.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.10565 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 10565-10565

Author(s):

Sumit Gupta ◽

Alex Nachman ◽

Paul Kurdyak ◽

Rinku Sutradhar ◽

Jason D Pole ◽

...

Keyword(s):

Mental Health ◽

Health Services ◽

Health Outcomes ◽

Childhood Cancer ◽

Mental Healthcare ◽

Childhood Cancer Survivors ◽

Population Based ◽

Increased Risk ◽

Health Event ◽

Survivors Of Childhood Cancer

10565 Background: Though physical late effects in childhood cancer survivors are well documented, their risk for adverse mental health outcomes is less clear; existing evidence is contradictory. Health services data offer an objective method for measuring population-based mental health outcomes. Methods: Using a provincial registry with detailed patient, disease, treatment, and outcome data, we assembled a cohort of all five-year survivors of childhood cancer diagnosed before age 18 years and treated in an Ontario pediatric cancer centre between 1987-2008. Patients were linked to population-based healthcare data capturing inpatient, outpatient, and emergency department (ED) visits. The primary outcome was the rate of mental healthcare visits (primary care, psychiatrist, ED or hospital). Secondary outcomes included the time to a severe mental health event (ED visit, hospitalization, or suicide) both overall and by psychiatric diagnostic categories. Outcomes were compared between survivors and matched controls using recurrent event and survival analyses, and predictors of adverse outcomes modeled. Results: When compared to 20,269 controls, 4,117 survivors had a significantly higher rate of mental health visits [47.1 vs. 36.1 visits/100 person years; adjusted relative rate (RR) 1.3, 95% confidence interval (CI) 1.2-1.5]. Higher rates of visits were associated with female gender (RR 1.4, CI 1.1-1.7; p = 0.008) and adolescent age at diagnosis (RR 2.0, CI 1.3-3.0; p = 0.004). Cancer type, treatment intensity or treatments targeting the central nervous system were not significant predictors. The hazard of a severe mental health event did not differ between survivors and controls. Though rare in both groups, survivors were at increased risk of a severe event due to a psychotic disorder (HR 1.8, CI 1.1-2.8; p < 0.05). Conclusions: Childhood cancer survivors experience higher rates of mental health visits than the general population, but are no more likely to experience a severe mental health event. Their risk is not attributable to a specific diagnosis or aspect of treatment. An increased risk of severe psychotic disorders requires confirmation in other cohorts.

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