Purpose: Augmented survival of childhood nephroblastoma and neuroblastoma has increased long-term side effects such as metabolic syndrome (MetS). Risk stratification is difficult after abdominal radiation because waist circumference underestimates adiposity. We aimed to develop a strategy for determining MetS in irradiated survivors using an integrated biomarker profile and vascular ultrasonography. Methods: The NCEP-ATPIII MetS-components, 14 additional serum biomarkers and 9 vascular measurements were assessed in a single-centre cohort of childhood nephroblastoma (n = 67) and neuroblastoma (n = 36) survivors and controls (n = 61). Multivariable regression models were used to study treatment effects. Principal component analysis (PCA) was used to study all biomarkers in a combined analysis, to identify patterns and correlations. Results: After 27.5 years of follow-up, MetS occurred more often in survivors (14%) than controls (3%). Abdominal radiotherapy and nephrectomy, to a lesser extent, were associated with MetS and separate components and with several biomarker abnormalities. PCA of biomarkers revealed a pattern on PC1 from favourable lipid markers (HDL-cholesterol, adiponectin) towards unfavourable markers (triglycerides, LDL-cholesterol, apoB, uric acid). Abdominal radiotherapy was associated with the unfavourable biomarker profile (β = 1.45, P = 0.001). Vascular measurements were not of added diagnostic value. Conclusions: Long-term childhood nephro- and neuroblastoma survivors frequently develop MetS. Additional assessment of biomarkers identified in PCA – adiponectin, LDL, apoB, and uric acid – may be used especially in abdominally irradiated survivors, to classify MetS as alternative for waist circumference. Vascular ultrasonography was not of added value.

Additional Metadata
Keywords childhood cancer survivor, metabolic syndrome, nephroblastoma, neuroblastoma, principal component analysis, biomarker
Persistent URL dx.doi.org/10.1530/ec-20-0144, hdl.handle.net/1765/130579
Journal Endocrine Connections
Pluimakers, V.G., van Waas, M, Looman, C.W.N., de Maat, M.P.M, de Jonge, R., Delhanty, P.J.D, … Neggers, S.J.C.M.M. (2020). Metabolic syndrome detection with biomarkers in childhood cancer survivors. Endocrine Connections, 9(7), 676–686. doi:10.1530/ec-20-0144