DOI: 10.1007/s00259-017-3829-7Pages: 292-305

Validation of the mIBG skeletal SIOPEN scoring method in two independent high-risk neuroblastoma populations: the SIOPEN/HR-NBL1 and COG-A3973 trials

1. Children’s Cancer Research Institute

2. Medical University, Department of Paediatrics

3. Ghent University, Radiology and Nuclear Medicine

4. Fondazione IRCCS Istituto Nazionale dei Tumori, Nuclear Medicine Division

5. Guy’s and St Thomas’ NHS Foundation Trust

6. Schneider Children’s Medical Center of Israel

7. Oscar Lambret Center, Department of Nuclear Medicine Lille

8. Children’s Memorial Health Institute

9. Motol University Hospital

10. Great Ormond Street Hospital for Children NHS Foundation Trust

11. University of Michigan Medical Center

12. University of Florida, Children’s Oncology Group Statistics and Data Center

13. University of Washington School of Medicine/ Seattle Children’s Hospital, Department of Radiology

14. St. Jude Children’s Research Hospital, Department of Diagnostic Imaging

15. BC Children’s Hospital, Department of Radiology

16. Cincinnati Children’s Hospital Medical Center, Department of Radiology

17. University of California San Francisco School of Medicine, Department of Pediatrics

18. University of Washington School of Medicine/ Seattle Children’s Hospital, Department of Pediatrics

19. Duke University Medical Center, Department of Pediatrics

20. Université Paris-Sud, Pediatric and Adolescent Oncology, Gustave Roussy Institute

21. Clinique de La Source, Institute of Radiology

Correspondence to:
Ruth Ladenstein
Tel: +43(1)40470-4750




Validation of the prognostic value of the SIOPEN mIBG skeletal scoring system in two independent stage 4, mIBG avid, high-risk neuroblastoma populations.


The semi-quantitative SIOPEN score evaluates skeletal meta-iodobenzylguanidine (mIBG) uptake on a 0–6 scale in 12 anatomical regions. Evaluable mIBG scans from 216 COG-A3973 and 341 SIOPEN/HR-NBL1 trial patients were reviewed pre- and post-induction chemotherapy. The prognostic value of skeletal scores for 5-year event free survival (5 yr.-EFS) was tested in the source and validation cohorts. At diagnosis, both cohorts showed a gradual non-linear increase in risk with cumulative scores. Several approaches were explored to test the relationship between score and EFS. Ultimately, a cutoff score of ≤3 was the most useful predictor across trials. A SIOPEN score ≤ 3 pre-induction was found in 15% SIOPEN patients and in 22% of COG patients and increased post-induction to 60% in SIOPEN patients and to 73% in COG patients. Baseline 5 yr.-EFS rates in the SIOPEN/HR-NBL1 cohort for scores ≤3 were 47% ± 7% versus 26% ± 3% for higher scores at diagnosis (p < 0.007) and 36% ± 4% versus 14% ± 4% (p < 0.001) for scores obtained post-induction. The COG-A3973 showed 5 yr.-EFS rates for scores ≤3 of 51% ± 7% versus 34% ± 4% for higher scores (p < 0.001) at diagnosis and 43% ± 5% versus 16% ± 6% (p = 0.004) for post-induction scores. Hazard ratios (HR) significantly favoured patients with scores ≤3 after adjustment for age and MYCN-amplification. Optimal outcomes were recorded in patients who achieved complete skeletal response.


Validation in two independent cohorts confirms the prognostic value of the SIOPEN skeletal score. In particular, patients with an absolute SIOPEN score > 3 after induction have very poor outcomes and should be considered for alternative therapeutic strategies.

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  • Accepted: Sep 3, 2017
  • Online: Sep 23, 2017

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