Purpose: Wilms tumor (WT) survivors face increased mortality due to late effects, including cardiovascular-related disease. Cardiovascular risk factors include adiposity, insulin resistance, dyslipidemia, and hypertension, clustered as metabolic syndrome (MetS). We assessed the prevalence and determinants of MetS in the first registered Dutch national cohort of survivors of WT.
Method: This cross-sectional 1:3 age and sex-matched case-control study investigated WT survivors treated between 1963-2002, recruited as part of the DCCSS-LATER-2 study (2016-2020). MetS prevalence was assessed using existing classification criteria. Controls included adults from a Dutch reference cohort without a history of cancer (Lifelines). Multivariable logistic regression models, adjusted for age and sex, were used to investigate the association between the presence of MetS (components) and abdominal radiotherapy. 2D-reconstruction of the radiotherapy beams was used to estimate dose to pancreas, liver, renal vessels, contralateral kidney, and abdominal fat.
Results: In total, 265/491 survivors of WT participated (median age: 33.9 years; median follow-up: 29.8 years). MetS prevalence was 18.8% in survivors and 7.3% in matched controls (OR:95%CI) (2.94:1.92-4.49). Survivors showed higher triglycerides (2.39:1.65-3.49), fasting glucose levels (1.67:1.03-2.70), and lower HDL-cholesterol (2.79:2.00-3.91). Univariable analysis identified abdominal radiotherapy to be the most important determinant associated with increased risk for MetS (2.42:1.2404.75). Multivariable analysis identified a significant increased risk of high fasting glucose levels (3.14:1.14-9.56) in abdominal irradiated survivors. A median radiotherapy dose between 10-20 Gy on the abdominal fat, liver, pancreas or kidney +/- vessels results in a 5% risk of developing one or more components of MetS, while the risk further increases up to 25% with doses between 20-30 Gy.
Conclusion: WT survivors, particularly those treated with abdominal radiotherapy >20 Gy, have an increased risk of developing MetS.