Log in

Multivariate analysis of risk factors for patients with stage 4 neuroblastoma who were older than 18 months at diagnosis: a report from a single institute in Shanghai, China

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

This retrospective study evaluated the long-term outcomes and prognostic indicators of patients with stage 4 neuroblastoma who were older than 18 months at diagnosis. The medical records of 118 such children who were treated at Shanghai Children’s Medical Center, China, from June 1998–December 2013 were reviewed. Event-free survival (EFS) and overall survival (OS) were analyzed by log-rank tests. Of the 118 patients, 14 improving patients did not complete treatment because of parental decisions, and 1 patient died during surgery. Of the 103 patients who completed the comprehensive protocols, 60 (58.3%) achieved very good partial remission (VGPR), 26 (25.2%) achieved partial remission (PR) after four courses of chemotherapy, and 17 (16.5%) progressed during treatment. The response to induction (including VGPR + PR) was 83.5%. After a median follow-up of 105 months (range 36–160 months), the 5- and 10-year OS were 21 and 18%, and the EFS was 19 and 13%, respectively. EFS was significantly better for patients with normal levels of urinary vanillylmandelic acid (VMA) at diagnosis, who had complete resection of the primary tumor, who were minimal residual disease- (MRD-) negative in their bone marrow after four courses of chemotherapy, and who achieved VGPR at the end of treatment (P < 0.05). The prognosis remains poor for patients with stage 4 neuroblastoma who are older than 18 months at diagnosis. Elevated VMA level, incomplete tumor resection, persistent MRD in bone marrow, and poor curative effect are associated with worse prognosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Cai JY, Tang YJ, Jiang LM, Pan C, Chen J, Tang JY (2007) Prognostic influence of minimal residual disease detected by flow cytometry and peripheral blood stem cell transplantation by CD34+ selection in childhood advanced neuroblastoma. Pediatr Blood Cancer 49:952–957

    Article  PubMed  Google Scholar 

  • Cai JY, Pan C, Tang YJ, Chen J, Ye QD, Zhou M, Xue H, Tang JY (2012) Minimal residual disease is a prognostic marker for neuroblastoma with bone marrow infiltration. Am J Clin Oncol 35:275–278

    Article  PubMed  Google Scholar 

  • Chambon F, Tchirkov A, Pereira B, Rochette E, Deméocq F, Kanold J (2013) Molecular assessment of minimal residual disease in PBSC harvests provides prognostic information in neuroblastoma. Pediatr Blood Cancer 60(9):109–112

    Article  Google Scholar 

  • Cohn SL, Pearson AD, London WB, Monclair T, Ambros PF, Brodeur GM, Faldum A, Hero B, Iehara T, Machin D, Mosseri V, Simon T, Garaventa A, Castel V, Matthay KK; INRG Task Force (2009) The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol 27:289–297

    Article  PubMed  PubMed Central  Google Scholar 

  • Corrias MV, Haupt R, Carlini B, Parodi S, Rivabella L, Garaventa A, Pistoia V, Dallorso S (2006) Peripheral blood stem cell tumor cell contamination and survival of neuroblastoma patients. Clin Cancer Res 12(19):5680–5685

    Article  CAS  PubMed  Google Scholar 

  • Kushner BH, Ostrovnaya I, Cheung IY, Kuk D, Modak S, Kramer K, Roberts SS, Basu EM, Yataghene K, Cheung NK (2016) Lack of survival advantage with autologous stem-cell transplantation in high-risk neuroblastoma consolidated by anti-GD2 immunotherapy and isotretinoin. Oncotarget 7(4):4155–4166

    PubMed  Google Scholar 

  • Maris JM (2010) Recent advances in neuroblastoma. N Engl J Med 362:2202–2211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matthay KK, Reynolds CP, Seeger RC, Shimada H, Adkins ES, Haas-Kogan D, Gerbing RB, London WB, Villablanca JG (2009) Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a Children’s Oncology Group study. J Clin Oncol 27:1007–1013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matthay KK, George RE, Yu AL (2012) Promising therapeutic targets in neuroblastoma. Clin Cancer Res 18:2740–2753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Richards MW, Burgess SG, Poon E, Carstensen A, Eilers M, Chesler L, Bayliss R (2016) Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors. Proc Natl Acad Sci USA 113(48):13726-13731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saletta F, Wadham C, Ziegler DS, Marshall GM, Haber M, McCowage G, Norris MD, Byrne JA (2014) Molecular profiling of childhood cancer: biomarkers and novel therapies. BBA Clin 1:59–77

    Article  PubMed  PubMed Central  Google Scholar 

  • Seeger RC, Reynolds CP, Gallego R, Stram DO, Gerbing RB, Matthay KK (2000) Quantitative tumor cell content of bone marrow and blood as a predictor of outcome in stage IV neuroblastoma: a Children’s Cancer Group Study. J Clin Oncol 18:4067–4076

    Article  CAS  PubMed  Google Scholar 

  • Shen H, Tang Y, Dong A, Li H, Shen D, Yang S, Tang H, Gu W, Shu Q (2014) Staging and monitoring of childhood rhabdomyosarcoma with flow cytometry. Oncol Lett 7: 970–976

    PubMed  PubMed Central  Google Scholar 

  • Simon T, Hero B, Bongartz R, Schmidt M, Müller RP, Berthold F (2006) Intensified external-beam radiation therapy improves the outcome of stage 4 neuroblastoma in children >1 year with residual local disease. Strahlenther Onkol 182:389–394

    Article  PubMed  Google Scholar 

  • Suganuma R, Wang LL, Sano H, Naranjo A, London WB, Seeger RC, Hogarty MD, Gastier-Foster JM, Look AT, Park JR, Maris JM, Cohn SL, Amann G, Beiske K, Cullinane CJ, d’Amore ES, Gambini C, Jarzembowski JA, Joshi VV, Navarro S, Peuchmaur M, Shimada H (2013) Peripheral neuroblastic tumors with genotype-phenotype discordance: a report from the Children’s Oncology Group and the International Neuroblastoma Pathology Committee. Pediatr Blood Cancer 60(3):363–370

    Article  PubMed  Google Scholar 

  • Yanik GA, Parisi MT, Shulkin BL, Naranjo A, Kreissman SG, London WB, Villablanca JG, Maris JM, Park JR, Cohn SL, McGrady P, Matthay KK (2013) Semiquantitative mIBG scoring as a prognostic indicator in patients with Stage 4 neuroblastoma: a Report from the Children’s Oncology Group. J Nucl Med 54:541–548

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to **gyan Tang.

Ethics declarations

Conflict of interest

Author Jiaoyang Cai, Ci Pan, Yan**g Tang, **g Chen, Min Zhou, Benshang Li, Huiliang Xue, Shuhong Shen, Yi** Gao, AnAn Zhang, and **gyan Tang declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cai, J., Pan, C., Tang, Y. et al. Multivariate analysis of risk factors for patients with stage 4 neuroblastoma who were older than 18 months at diagnosis: a report from a single institute in Shanghai, China. J Cancer Res Clin Oncol 143, 1327–1335 (2017). https://doi.org/10.1007/s00432-017-2379-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-017-2379-5

Keywords

Navigation