A revised Children's Oncology Group (COG) neuroblastoma risk classification system: Report from the COG biology study ANBL00B1.

Abstract

10012 Background: The COG risk classification system previously used the International Neuroblastoma Staging System (INSS). The pre-treatment INRG staging system (INRGSS) has been adopted internationally, requiring integration of INRGSS with known prognostic biological and clinical characteristics to evaluate outcomes and assess whether this incorporation will require revision to the established COG risk classifier. Methods: 4,037 newly diagnosed neuroblastoma patients were enrolled on COG ANBL00B1 between 2006-2014. Staging per the INSS and INRGSS was determined. Tumor biological and histologic features, including MYCN status [amplified (A) versus not amplified (NA)], ploidy, histology, and segmental chromosome aberrations (SCA) including 1p and 11q LOH, were assessed centrally. Survival analyses were performed to identify independent prognostic factors and to calculate event-free and overall survival (EFS, OS) for combinations of variables used to determine risk group assignments according to COG and INRG classification templates. Results: Using the original COG risk classifier 1,309 low (LR), 992 intermediate (IR) and 1,736 high-risk (HR) patients were identified with 5-year EFS of 91.4±2.1%, 84.3±2.9%, 45.2±3.1%, and OS of 98.1±1.0%, 94.0±1.9%, 54.1±3.0%, respectively. Outcomes based on combinations of clinical and biological prognostic factors were determined and compared for subsets of patients according to the COG (version1) and INRG risk classification systems to develop a revised COG risk classifier that incorporates the INRGSS (version 2, subset shown in table). Conclusions: Use of INRGSS requires a revision to the COG risk classifier. By combining INRGSS and presence of SCA together with age, MYCN status, ploidy, and histology to determine outcome of patients treated with modern era therapies, we developed a revised risk classification system to inform therapy and COG clinical trial eligibility. Clinical trial information: NCT00904241. [Table: see text]