Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Apr 14;29(8):1546-1556.
doi: 10.1158/1078-0432.CCR-22-3032.

Impact of Genomic and Clinical Factors on Outcome of Children ≥18 Months of Age with Stage 3 Neuroblastoma with Unfavorable Histology and without MYCN Amplification: A Children's Oncology Group (COG) Report

Navin Pinto  1 , Arlene Naranjo  2 , Xiangming Ding  3 , Fan F Zhang  4 , Emily Hibbitts  2 , Rebekah Kennedy  3 , Rachelle Tibbetts  3 , Shannon Wong-Michalak  3 , David W Craig  3 , Zarko Manojlovic  3 , Michael D Hogarty  5 , Susan Kreissman  6 , Rochelle Bagatell  5 , Meredith S Irwin  7 , Julie R Park #  1 , Shahab Asgharzadeh #  3
Affiliations

Impact of Genomic and Clinical Factors on Outcome of Children ≥18 Months of Age with Stage 3 Neuroblastoma with Unfavorable Histology and without MYCN Amplification: A Children's Oncology Group (COG) Report

Navin Pinto et al. Clin Cancer Res. .

Abstract

Purpose: Patients ≥18 months of age with International Neuroblastoma Staging System (INSS) stage 3 unfavorable histology (UH), MYCN-nonamplified (MYCN-NA) tumors have favorable survival rates compared with other high-risk neuroblastoma populations. The impact of select clinical and biological factors on overall survival (OS) and event-free survival (EFS) were evaluated.

Experimental design: Patients enrolled on Children's Oncology Group (COG) A3973 (n = 34), ANBL0532 (n = 27), and/or biology protocol ANBL00B1 (n = 72) were analyzed. Tumors with available DNA (n = 65) and RNA (n = 42) were subjected to whole-exome sequencing (WES) and RNA sequencing. WES analyses and gene expression profiling were evaluated for their impact on survival. Multivariate analyses of EFS/OS using significant factors from univariate analyses were performed.

Results: 5-year EFS/OS for patients treated with high-risk therapy on A3973 and ANBL0532 were 73.0% ± 8.1%/87.9% ± 5.9% and 61.4% ± 10.2%/73.0% ± 9.2%, respectively (P = 0.1286 and P = 0.2180). In the A3973/ANBL0532 cohort, patients with less than partial response (PR; n = 5) at end-induction had poor outcomes (5-year EFS/OS: 0%/20.0% ± 17.9%. Univariate analyses of WES data revealed that subjects whose tumors had chromosome 1p or 11q loss/LOH and chromosome 5 or 9 segmental chromosomal aberrations had inferior EFS compared with those with tumors without these aberrations. Multivariate analysis revealed that 11q loss/LOH was an independent predictor of inferior OS [HR, 3.116 (95% confidence interval, 1.034-9.389), P = 0.0435].

Conclusions: Patients ≥18 months of age at diagnosis who had tumors with UH and MYCN-NA INSS stage 3 neuroblastoma assigned to high-risk therapy had an 81.6% ± 5.3% 5-year OS. Less than PR to induction therapy and chromosome 11q loss/LOH are independent predictors of inferior outcome and identify patients who should be eligible for future high-risk clinical trials.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Statement: The authors have no significant conflicts of interest to declare

Figures

Figure 1.
Figure 1.. Clinical Outcomes and Impact of Clinical Features on Outcome.
(A) EFS and (B) OS of all patients and by trial cohort. (C) EFS and (D) OS by end-induction response. (E) EFS and (F) OS by receipt of dinutuximab.
Fig 2.
Fig 2.. Summary Heatmap of Clinical and Biological Factors Evaluated Stratified by EFS.
Figure 3.
Figure 3.. Impact of 11q SCAs on Outcome.
(A) EFS and (B) OS by chromosome 11q status
Figure 4.
Figure 4.. Impact of SCA count on EFS.
EFS by number of segmental chromosomal aberrations.
Figure 5.
Figure 5.. RNA Sequencing Data.
(A) Top 50 differentially expressed genes by NMF Cluster (B) Top differentially expressed hallmark pathways by NMF cluster (C) EFS by NMF cluster (D) OS by NMF cluster
See this image and copyright information in PMC

References

    1. Cohn SL, Tweddle DA. MYCN amplification remains prognostically strong 20 years after its “clinical debut”. Eur J Cancer. 2004;40(18):2639–42. - PubMed
    1. Evans AE, D’Angio GJ. Age at diagnosis and prognosis in children with neuroblastoma. J Clin Oncol. 2005;23(27):6443–4. - PubMed
    1. Park JR, Eggert A, Caron H. Neuroblastoma: biology, prognosis, and treatment. Hematol Oncol Clin North Am. 2010;24(1):65–86. - PubMed
    1. Pinto NR, Applebaum MA, Volchenboum SL, Matthay KK, London WB, Ambros PF, et al. Advances in Risk Classification and Treatment Strategies for Neuroblastoma. J Clin Oncol. 2015;33(27):3008–17. - PMC - PubMed
    1. Sano H, Bonadio J, Gerbing RB, London WB, Matthay KK, Lukens JN, et al. International neuroblastoma pathology classification adds independent prognostic information beyond the prognostic contribution of age. Eur J Cancer. 2006;42(8):1113–9. - PubMed

Publication types

Substances