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Insulin and glucose homeostasis in childhood cancer survivors treated with abdominal radiation: A pilot study.

ABSTRACT: BACKGROUND:Childhood cancer survivors exposed to abdominal radiation (abdRT) are at increased risk for both insulin-dependent and non-insulin-dependent diabetes. We sought to clarify the pathophysiology of diabetes after abdRT by performing dynamic studies of insulin and glucose and testing for type 1 diabetes-associated autoantibodies. PROCEDURE:Cross-sectional analysis of 2-year childhood cancer survivors treated with abdRT at age ?21 years who underwent oral glucose tolerance testing and assessment of diabetes-related autoantibodies from December 2014 to September 2016. Prevalence of insulin/glucose derangements, indices of insulin sensitivity/secretion (homeostatic model assessment of insulin resistance [HOMA-IR], whole-body insulin sensitivity, insulinogenic index), autoantibody positivity, and treatment/demographic factors associated with adverse metabolic outcomes were assessed. RESULTS:Among 40 participants previously exposed to abdRT (57.5% male; median age at cancer diagnosis, 3.3 years [range, 0.5-20.1]; median age at study 14.3 years [range, 8.3-49.8]; none with obesity), 9 (22.5%) had glucose derangements (n = 4 with impaired fasting glucose [?100 mg/dL]; n = 4 with impaired glucose tolerance [2-hour glucose 140-199 mg/dL]; n = 1 with previously unrecognized diabetes [2-hour glucose ?200 mg/dL]). Three of the four individuals with impaired fasting glucose also had insulin resistance, as measured by HOMA-IR; an additional four subjects with normal glucose tolerance were insulin resistant. The subject with diabetes had normal HOMA-IR. No participant had absolute insulinopenia or >1 positive diabetes-related autoantibody. CONCLUSIONS:This study suggests that radiation-induced damage to the insulin-producing ?-cells is an unlikely explanation for the early derangements in glucose metabolism observed after abdRT. Research into alternative pathways leading to diabetes after abdRT is needed.

SUBMITTER: Friedman DN

PROVIDER: S-EPMC6150783 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Insulin and glucose homeostasis in childhood cancer survivors treated with abdominal radiation: A pilot study.

Friedman Danielle Novetsky DN Hilden Patrick P Moskowitz Chaya S CS Wolden Suzanne L SL Tonorezos Emily S ES Antal Zoltan Z Carlow Dean D Modak Shakeel S Cheung Nai-Kong NK Oeffinger Kevin C KC Sklar Charles A CA

Pediatric blood & cancer 20180715 11

<h4>Background</h4>Childhood cancer survivors exposed to abdominal radiation (abdRT) are at increased risk for both insulin-dependent and non-insulin-dependent diabetes. We sought to clarify the pathophysiology of diabetes after abdRT by performing dynamic studies of insulin and glucose and testing for type 1 diabetes-associated autoantibodies.<h4>Procedure</h4>Cross-sectional analysis of 2-year childhood cancer survivors treated with abdRT at age ≤21 years who underwent oral glucose tolerance t ...[more]

PMID: 30009519

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Project description:BackgroundSurveillance with annual mammography and breast magnetic resonance imaging (MRI) is recommended for female survivors of childhood cancer treated with chest radiation, yet benefits, harms, and costs are uncertain.ObjectiveTo compare the benefits, harms, and cost-effectiveness of breast cancer screening strategies in childhood cancer survivors.DesignCollaborative simulation modeling using 2 Cancer Intervention and Surveillance Modeling Network breast cancer models.Data sourcesChildhood Cancer Survivor Study and published data.Target populationWomen aged 20 years with a history of chest radiotherapy.Time horizonLifetime.PerspectivePayer.InterventionAnnual MRI with or without mammography, starting at age 25, 30, or 35 years.Outcome measuresBreast cancer deaths averted, false-positive screening results, benign biopsy results, and incremental cost-effectiveness ratios (ICERs).Results of base-case analysisLifetime breast cancer mortality risk without screening was 10% to 11% across models. Compared with no screening, starting at age 25 years, annual mammography with MRI averted the most deaths (56% to 71%) and annual MRI (without mammography) averted 56% to 62%. Both strategies had the most screening tests, false-positive screening results, and benign biopsy results. For an ICER threshold of less than $100 000 per quality-adjusted life-year gained, screening beginning at age 30 years was preferred.Results of sensitivity analysisAssuming lower screening performance, the benefit of adding mammography to MRI increased in both models, although the conclusions about preferred starting age remained unchanged.LimitationElevated breast cancer risk was based on survivors diagnosed with childhood cancer between 1970 and 1986.ConclusionEarly initiation (at ages 25 to 30 years) of annual breast cancer screening with MRI, with or without mammography, might reduce breast cancer mortality by half or more in survivors of childhood cancer.Primary funding sourceAmerican Cancer Society and National Institutes of Health.

Project description:Background:Improved cancer survival in patients treated with thoracic ionizing radiation (XRT) has resulted in unanticipated surge of aortic stenosis. Transcatheter aortic valve replacement (TAVR) has revolutionized the management of severe aortic stenosis. However, long-term clinical outcomes in radiation-exposed cohorts undergoing TAVR are unknown. We compared the all-cause mortality and major adverse cardiac events (MACE) in patients with prior chest XRT (C-XRT) undergoing TAVR. Methods:This is an observational cohort study in subjects who underwent TAVR for symptomatic severe aortic stenosis from 2012 to 2017 in a tertiary care referral center. We examined the all-cause mortality and MACE using cox proportional hazard analysis to identify the clinical predictors of survival in the cohort of patients who had a history of prior C-XRT for malignancy. Results:Of the 610 patients who underwent TAVR for symptomatic severe aortic stenosis, 75 had prior C-XRT. The majority of C-XRT patients had prior breast cancer (44%) followed by Hodgkin's lymphoma (31%), with the median time from XRT to TAVR of 19.0 years. During a mean follow up of 17.1 months after TAVR, all-cause mortality was 17%. Those with prior C-XRT had higher all-cause mortality (XRT: 29%; non-XRT:15%, p<0.01) and MACE (XRT: 57%; non-XRT: 27%, p<0.001) after TAVR. Patients with prior XRT had a higher incidence of atrial fibrillation (XRT: 48 %; non-XRT: 2.4%, p<0.01) and high-grade heart block (XRT: 20%; non-XRT: 9.1%, p=0.007) requiring pacemaker implant after TAVR. On multivariate cox proportional hazard analysis, prior XRT (HR: 2.07, p=0.003), poor renal function (HR: 1.29, p<0.001) and post-operative anemia requiring transfusion (HR: 1.16, p:0.001) were the strongest predictors of reduced survival. Conclusions:Cancer survivors with prior C- XRT have higher incidence of all-cause mortality and MACE after TAVR. Careful patient selection and follow-up strategies are needed to improve outcomes.

Dataset Information

Insulin and glucose homeostasis in childhood cancer survivors treated with abdominal radiation: A pilot study.

Publications

Insulin and glucose homeostasis in childhood cancer survivors treated with abdominal radiation: A pilot study.

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