Individualized risk assessment in neuroblastoma: does the tumoral metabolic activity on 123I-MIBG SPECT predict the outcome?

  • Julian M. M. Rogasch
  • Patrick Hundsdoerfer
  • Christian Furth
  • Florian Wedel
  • Frank Hofheinz
  • Paul-Christian Krüger
  • Holger Lode
  • Winfried Brenner
  • Angelika Eggert
  • Holger Amthauer
  • Imke Schatka
Original Article

Abstract

Purpose

Risk-adapted treatment in children with neuroblastoma (NB) is based on clinical and genetic factors. This study evaluated the metabolic tumour volume (MTV) and its asphericity (ASP) in pretherapeutic 123I-MIBG SPECT for individualized image-based prediction of outcome.

Methods

This retrospective study included 23 children (11 girls, 12 boys; median age 1.8 years, range 0.3–6.8 years) with newly diagnosed NB consecutively examined with pretherapeutic 123I-MIBG SPECT. Primary tumour MTV and ASP were defined using semiautomatic thresholds. Cox regression analysis, receiver operating characteristic analysis (cut-off determination) and Kaplan-Meier analysis with the log-rank test for event-free survival (EFS) were performed for ASP, MTV, laboratory parameters (including urinary homovanillic acid-to-creatinine ratio, HVA/C), and clinical (age, stage) and genetic factors. Predictive accuracy of the optimal multifactorial model was determined in terms of Harrell’s C and likelihood ratio χ2.

Results

Median follow-up was 36 months (range 7–107 months; eight patients showed disease progression/relapse, four patients died). The only significant predictors of EFS in the univariate Cox regression analysis were ASP (p = 0.029; hazard ratio, HR, 1.032 for a one unit increase), MTV (p = 0.038; HR 1.012) and MYCN amplification status (p = 0.047; HR 4.67). The mean EFS in patients with high ASP (>32.0%) and low ASP were 21 and 88 months, respectively (p = 0.013), and in those with high MTV (>46.7 ml) and low MTV were 22 and 87 months, respectively (p = 0.023). A combined risk model of either high ASP and high HVA/C or high MTV and high HVA/C best predicted EFS.

Conclusions

In this exploratory study, pretherapeutic image-derived and laboratory markers of tumoral metabolic activity in NB (ASP, MTV, urinary HVA/C) allowed the identification of children with a high and low risk of progression/relapse under current therapy.

Keywords

Neuroblastoma Prognosis 123I-MIBG Asphericity Metabolic tumour volume 

Supplementary material

259_2017_3786_Fig5_ESM.gif (55 kb)
ESM 1

ROC curves for ASP, MTV and HVA/C regarding the occurrence of an event (GIF 54 kb)

259_2017_3786_MOESM1_ESM.tif (23.3 mb)
High resolution image (TIFF 23828 kb)

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Julian M. M. Rogasch
    • 1
  • Patrick Hundsdoerfer
    • 2
    • 3
  • Christian Furth
    • 1
  • Florian Wedel
    • 1
  • Frank Hofheinz
    • 4
  • Paul-Christian Krüger
    • 5
  • Holger Lode
    • 6
  • Winfried Brenner
    • 1
  • Angelika Eggert
    • 2
  • Holger Amthauer
    • 1
  • Imke Schatka
    • 1
  1. 1.Department of Nuclear MedicineCharité - Universitätsmedizin BerlinBerlinGermany
  2. 2.Department of Pediatric Oncology/HematologyCharité - Universitätsmedizin BerlinBerlinGermany
  3. 3.Berlin Institute of Health (BIH)BerlinGermany
  4. 4.PET CenterHelmholtz Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer ResearchDresdenGermany
  5. 5.Institute for Diagnostic Radiology and NeuroradiologyUniversity Medicine GreifswaldGreifswaldGermany
  6. 6.Department of Pediatric Oncology and HematologyUniversity Medicine GreifswaldGreifswaldGermany

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