Sequential Combination of Unfavorable Histology, Followed by Clinical Stage M, Defines High-Risk Neuroblastoma: A Report from the Children’s Oncology Group

Abstract Purpose: Historically, neuroblastoma risk stratification has been performed with clinical stage as the starting point and successively adding other prognostic factors thereafter. This study takes an alternative approach to define risk groups of patients with neuroblastoma by starting with the International Neuroblastoma Pathology Classification (INPC). Experimental Design: The cohort of patients with neuroblastoma previously used for developing the Children’s Oncology Group–Revised Neuroblastoma Risk Classification (RNRC) system was reanalyzed by survival tree regression analysis, starting with the INPC distinguishing favorable-histology and unfavorable-histology categories. The resultant two branches were further divided first by the International Neuroblastoma Risk Group Staging System and successively by other prognostic factors. Results: This new stratification system, the INPC-Risk Grouping (INPC-RG), is simpler than the RNRC system, eliminating unnecessary decision trees, and distinguishes four risk groups (groups I–IV). Using only INPC (unfavorable histology) and International Neuroblastoma Risk Group Staging System (stage M), INPC-RG defines patients with highly aggressive group IV tumors, whose 5-year event-free survival was worse than that of the RNRC high-risk group. Additionally, it identifies group III patients whose 5-year event-free survival spanned 50% to 80%, which was not identified by the RNRC. Conclusions: The benefits of using this new INPC-RG system are fourfold: (1) it allows for the rapid identification of group IV patients, (2) it lays the foundation for further refinement of group III, (3) it can stratify patients when the amount of tumor tissue is limited, and (4) it allows patients in resource-limited areas to be appropriately stratified, potentially improving the worldwide treatment of patients with neuroblastoma.