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

Journal Article (Clinical Trial;Journal Article)

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

Full Text

Duke Authors

Cited Authors

  • Ladenstein, R; Lambert, B; Pötschger, U; Castellani, M-R; Lewington, V; Bar-Sever, Z; Oudoux, A; Śliwińska, A; Taborska, K; Biassoni, L; Yanik, GA; Naranjo, A; Parisi, MT; Shulkin, BL; Nadel, H; Gelfand, MJ; Matthay, KK; Park, JR; Kreissman, SG; Valteau-Couanet, D; Boubaker, A

Published Date

  • February 2018

Published In

Volume / Issue

  • 45 / 2

Start / End Page

  • 292 - 305

PubMed ID

  • 28940046

Pubmed Central ID

  • PMC5747549

Electronic International Standard Serial Number (EISSN)

  • 1619-7089

Digital Object Identifier (DOI)

  • 10.1007/s00259-017-3829-7


  • eng

Conference Location

  • Germany