10007 Background: Patients with metastatic neuroblastoma confined to distant lymph nodes (4N) were identified as a subgroup with superior outcomes to those with metastases to other sites. Over the past two decades, outcomes for high-risk neuroblastoma have improved from increasingly effective and intense therapy, while intermediate-risk patients have maintained excellent outcomes with biology and response-based therapy. We aimed to determine if 4N patients remained a favorable subgroup with contemporary therapy. Methods: Patients with International Neuroblastoma Staging System (INSS) stage 4 disease in the International Neuroblastoma Risk Group Data Commons diagnosed between 1990-2020 were evaluated. Those with metastases only to the distant lymph nodes were defined as 4N. All other patients were defined as non-4N. Treatment eras included: 1999 and prior, 2000-2009, 2010 and later which correspond to standardization of multimodal therapy, stem cell transplant, and anti-GD2 immunotherapy for high-risk patients. Differences between 4N and non-4N patients were assessed with chi-square, Wilcoxon rank sum, and t-tests. Five-year Kaplan-Meier estimates of survival with 95% confidence intervals and multivariable Cox proportional hazards modeling were used to evaluate event-free (EFS) and overall (OS) survival. Results: The analytic cohort included 107 4N and 5976 non-4N patients. There were no clinical differences between 4N and non-4N patients apart from unfavorable histology (74.2% 4N versus 60.1% non-4N; p=0.02). 5-year EFS and OS were higher for 4N compared to non-4N patients (p=0.001 and 0.001, respectively). Though survival estimates for 4N were higher in each era, the difference was not statistically significant for patients diagnosed from 2000-2009 nor 2010 and beyond; (1999 and prior: EFS 58.7% (40.9-72.7%) versus 31.8% (29.7-33.9%) p=0.001; OS, 66.2% (48.1-79.3%) versus 37.9% (35.7-40.1%) p=0.002, 2000-2009: EFS, 47.9% (34.0-60.5%) versus 36% (34.1-37.9%) p=0.179; OS, 55.4% (40.7-67.8%) versus 45.1% (43.1-47.1%) p=0.122, and 2010 and later: EFS, 63.6% (29.7-84.5%) versus 42.8% (39.9-45.6%) p=0.178; OS, 71.6% (35.0-89.9%) versus 52.3% (49.2-55.3%) p=0.207. Log-rank calculations may have been underpowered in part due to small sample sizes (n=39, 56, and 12) of each 4N subgroup, respectively. 4N patients had superior EFS (HR=0.48; p=0.0004) and OS (HR=0.49; p=0.0009) in a model which included age, MYCN -amplification status, treatment era, ferritin, and LDH. A sensitivity analysis using only high-risk patients age >18 months yielded similar results. Conclusions: Patients with stage 4N neuroblastoma are a rare subgroup which appears to continue to have favorable outcomes with contemporary therapy. Additional studies to identify opportunities to reduce therapy intensity for this subgroup are warranted.
Mitchell et al. (Wed,) studied this question.