Characterization of neuroblastic tumors as developmental cancers with survival determined by histology, age, and location.

Abstract

10046 Background: Mortality associated with peripheral neuroblastic tumors (pNT), comprising neuroblastoma (NB) and ganglioneuroblastoma (GNB), varies with some tumors spontaneously regressing and others showing poor response to therapy, indicating different biologic mechanisms. We aimed to determine how epidemiologic constructs inform the underlying biology of pNT. Methods: Using the Surveillance Epidemiology and End Results (SEER 18) population-based registry, we identified 3,540 pNT (3,003 NB and 537 GNB) in patients from 1973-2009. Differences in histology (NB vs. GNB), gender, age (<18 months, 18 months-4 years, 5-14 years, or ≥15 years), race (white, black, or other), location of primary tumor (adrenal, abdominal, chest, head/neck, pelvic, or other), and stage (locoregional vs. metastatic) were evaluated with chi-squared tests using SAS 9.3. Kaplan Meier curves with log-rank tests as well as univariate and multivariate Cox proportional hazard regression methods were employed to determine the influence of these factors on survival. Results: NB occurred more frequently in infants (50%), arose in the adrenals (45%), and were metastatic at diagnosis (57%), while GNB more often affected children 18 months-4 years (48%, p <0.001), occurred in the chest (31%, p <0.001), and were locoregional (78%, p <0.001). The 5-year overall survival (OS) rate in NB was 59% compared to 80% in GNB (p <0.001). In NB, the 5-year OS rate was 81% in infants <18 months and 21-39% in the older groups (p <0.001); however, in GNB, the 5-year OS was 40% in subjects >15 years and 81-93% in the younger groups (p <0.001). In multivariate analysis of pNT, neuroblastoma, age >18 months, adrenal site of primary tumor, and metastatic disease were independent poor prognostic factors. Chest (HR 0.27 [0.21-0.35]), head/neck (HR 0.34 [0.20-0.52]), and pelvic (HR 0.35 [0.24-0.52]) tumors had the most improved survival compared to adrenal primaries. Conclusions: Although pNT are often evaluated together, NB and GNB represent two significantly distinct diseases. For each, survival is strongly determined by age, primary tumor location, and stage. These differences may stem from unique developmental mechanisms underlying tumorigenesis.