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