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

Abstract

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.

A nomogram of clinical and biologic factors to predict survival in children newly diagnosed with high‐risk neuroblastoma: An International Neuroblastoma Risk Group project

“…Multiple attempts to develop stratification within the high‐risk group have been reported, and the term “ultra‐high‐risk” has been loosely applied to this group 8,9 . To date, none of these ultra‐high‐risk definitions have been applied to assigning treatment at the time of diagnosis.…”

Nomogram for predicting overall survival in children with neuroblastoma based on SEER database

“…Multimodal therapy currently seems an effective treatment for NB, which includes operation, chemotherapy, radiotherapy and immunotherapy [ 4 5 6 7 8 ]. Generally, children with low-risk NB have a good prognosis and seldom need intensified therapy [ 9 10 11 ], while patients with high-risk NB are diagnosed with obvious tumor progression, showing a bad prognosis, with the long-term survival rate being 50% [ 12 13 ].…”

Bufalin exerts antitumor effects in neuroblastoma via the induction of reactive oxygen species‑mediated apoptosis by targeting the electron transport chain

“…Regardless of MYCN amplification status, bufalin exhibited consistent antitumor activity, indicating that the antitumor activity of bufalin was MYCN-independent. The Children's Oncology Group stratifies the patients into low risk, medium risk and high-risk group based on a number of variables, including age, MYCN status, pathology, DNA polyploid and differentiation status; the status of MYCN is an important factor for assessing clinical malignant behavior, and is strongly associated with poor prognosis, even with intensive chemotherapy regimens ( 5 , 7 ). Indeed, MYCN amplification is an important in patients with high-risk neuroblastoma ( 46 ).…”

“…Neoadjuvant chemotherapy therefore becomes the first choice to create an opportunity for further surgery; however, a number of patients with neuroblastoma exhibit a minimal response to current chemotherapy treatments ( 6 ). The prognosis for high-risk neuroblastoma is poor (5-year survival rate, <35%) and has not markedly improved over the past few decades ( 7 ). In fact, the drugs currently used in clinical settings for treating neuroblastoma, such as cisplatin and cyclophosphamide, were developed in the middle of the previous century, and none of them were specifically approved for pediatric patients with neuroblastoma.…”