DOI: 10.1007/s00259-017-3786-1Pages: 2203-2212

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

1. Charité - Universitätsmedizin Berlin, Department of Nuclear Medicine

2. Charité - Universitätsmedizin Berlin, Department of Pediatric Oncology/Hematology

3. Berlin Institute of Health (BIH)

4. Helmholtz Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, PET Center

5. University Medicine Greifswald, Institute for Diagnostic Radiology and Neuroradiology

6. University Medicine Greifswald, Department of Pediatric Oncology and Hematology

Correspondence to:
Julian M. M. Rogasch
Tel: +49 (0) 30/450-627106
Email: julian.rogasch@charite.de

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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.

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  • Accepted: Jul 19, 2017
  • Online: Aug 14, 2017

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