Metabolic syndrome detection with biomarkers in childhood cancer survivors

Purpose: Augmented childhood nephroblastoma and neuroblastoma survival has increased long-term side effects 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, apo-B, uric acid). Abdominal radiotherapy was associated with the unfavourable biomarker profile (ß=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, apo-B, 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.