Diabetes Risk Following Treatment for Childhood and Young Adult Cancer Diabetes in Childhood Cancer Survivors

<p dir="ltr">Objective: Diabetes is a potential late consequence of childhood and young-adult cancer (CYAC) treatment. Causative treatments associated with diabetes have been identified in retrospective cohort studies but have not been validated in population-based cohorts. Our aim was to define the extent of diabetes risk and explore contributory factors for its development in survivors of CYAC in the United Kingdom.</p><p dir="ltr">Research Design and Methods: Cancer registration data (n=4,238) was linked to electronic-healthcare databases to identify cases of diabetes through clinical coding or HbA1c. Total effect of pre-specified treatment exposures on diabetes risk was estimated using flexible parametric modelling and standardized cause-specific cumulative incidence functions (CIF).</p><p dir="ltr">Results: After median follow up of 14.4 years, 163 (3.8%) individuals were identified with diabetes. Total body irradiation (TBI) increases diabetes risk over time, with a 40-year CIF reaching 21.0% (95% CI: 13.8-31.9) compared to 8.4% (6.1-11.5) without TBI. Survivors treated with corticosteroids had a 7.7% increased risk at 40-years post-cancer-diagnosis. Hematopoietic stem-cell transplant (HSCT) survivors had markedly higher risk, with a 40-year CIF of 19.6% (13.4-28.6) versus 8.2% (6.0-11.3) for non-HSCT patients. Among allogeneic HSCT patients, the 40-year CIF of diabetes was 25.7% (17.4-38.0), compared to 7.9% (3.3-19.1) in autologous transplant patients.</p><p dir="ltr">Conclusions: This evaluation of a hospital-based cohort of CYAC identifies their increased long-term risk of developing diabetes and how this varies temporally according to treatment modalities. Notable contrasts in risk by treatment were detected as early as 10-years post cancer-diagnosis. Findings should inform the development of risk-stratified evidence-based screening.</p>