The challenge of defining “ultra-high-risk” neuroblastoma

Given the biological and clinical heterogeneity of neuroblastoma, risk stratification is vital to determining appropriate treatment. Historically, most patients with high-risk neuroblastoma (HR-NBL) have been treated uniformly without further stratification. Attempts have been made to identify factors that can be used to risk stratify these patients and to characterize an “ultra-high-risk” (UHR) subpopulation with particularly poor outcome. However, among published data, there is a lack of consensus in the definition of the UHR population and heterogeneity in the endpoints and statistical methods used. This review summarizes our current understanding of stratification of HR-NBL and discusses the complex issues in defining UHR neuroblastoma.