# Characterization of Clinical Outcomes for Patients with Relapsed High-Risk Neuroblastoma After Autologous Stem Cell Transplant and External Beam Radiotherapy

## TL;DR

This study examines outcomes for high-risk neuroblastoma patients who relapse after standard treatments, finding poor survival rates and identifying longer time to relapse as a positive predictor.

## Contribution

The study provides new insights into clinical outcomes and prognostic factors for relapsed high-risk neuroblastoma patients following standard therapies.

## Key findings

- Patients with local recurrences had higher rates of MYCN amplification compared to those with distant relapses.
- A time to interval relapse of ≥ 2 years was significantly associated with improved overall survival.
- Overall survival remained poor with a median of less than 2 years after relapse, regardless of relapse pattern.

## Abstract

Despite intensive multimodal treatment, patients with high-risk neuroblastoma (HR-NBL) remain at risk of relapse with an overall survival of approximately 50%. There is little data regarding outcomes for patients with relapsed HR-NBL, thus we sought to better characterize outcomes in a multi-institutional cohort of 84 patients with HR-NBL who relapsed after receiving the current standard of care, including autologous stem cell transplantation and external beam radiotherapy, stratified by patterns of first relapse. Patients with local recurrences with or without distant relapses had higher rates of MYCN amplification. For the entire cohort, overall survival remained poor after relapse with a median of <2 years with no difference when stratifying by patterns of first relapse. Multivariable analysis found that a time to interval relapse ≥ 2 years was a significant predictor of improved survival. Future studies are needed to validate these findings and identify additional prognostic clinical or molecular factors.

Background: Limited data inform the outcomes of patients with high-risk neuroblastoma (HR-NBL) who relapse after high-dose chemotherapy, autologous stem cell transplantation (ASCT), and external beam radiotherapy (EBRT). Methods: This is a multi-institutional retrospective study of 84 patients with HR-NBL diagnosed between 1997–2021 with a first recurrence after definitive upfront treatment, including ≥1 ASCT and EBRT. Site(s) of first relapse were defined with relation to a patient’s primary tumor location. Progression-free survival (PFS) and overall survival (OS) outcomes were analyzed using Kaplan–Meier curves and log-rank tests. Cox proportional hazard models were used for univariate and multivariable analyses. Results: Twenty-four patients had local recurrences with or without distant relapses (LR) and 60 had distant relapses only. The LR cohort had higher rates of MYCN amplification (70% vs. 36%, p = 0.016). At relapse, the LR cohort had lower rates of additional radiotherapy (32% vs. 61%, p = 0.029) and higher rates of additional surgery (29% vs. 5%, p = 0.005), with similar rates of chemotherapy for both cohorts. With a median follow-up after first relapse of 1.53 years (range: 0.03–15.82), there were no significant differences in interval PFS and OS between the cohorts. After controlling for age at diagnosis and pattern of recurrence, time to interval relapse ≥ 2 years was a significant predictor of improved OS (HR: 0.50, 95% CI: 0.29–0.85, p = 0.011). Conclusions: Patients with relapsed HR-NBL have poor outcomes with median OS < 2 years. Time to relapse was a significant predictor of OS.