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

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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 χ 2.

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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Acknowledgments

The authors thank Dr. Ingo Steffen for his advice on statistical methodology and Mr. René Höhne for his support in obtaining patient data.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Julian M. M. Rogasch, Christian Furth, Florian Wedel, Winfried Brenner, Holger Amthauer & Imke Schatka

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

    Patrick Hundsdoerfer & Angelika Eggert

  3. Berlin Institute of Health (BIH), 10178, Berlin, Germany

    Patrick Hundsdoerfer

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

    Frank Hofheinz

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

    Paul-Christian Krüger

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

    Holger Lode

Authors
  1. Julian M. M. Rogasch
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  2. Patrick Hundsdoerfer
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  3. Christian Furth
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  4. Florian Wedel
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  10. Holger Amthauer
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Corresponding author

Correspondence to Julian M. M. Rogasch.

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Conflicts of interest

None.

Ethical approval

All procedures were in accordance with the ethical standards of the respective institutional ethics commissions (vote, EA2/150/16; MV05/11) and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

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

Electronic supplementary material

ESM 1

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

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Rogasch, J.M.M., Hundsdoerfer, P., Furth, C. et al. Individualized risk assessment in neuroblastoma: does the tumoral metabolic activity on 123I-MIBG SPECT predict the outcome?. Eur J Nucl Med Mol Imaging 44, 2203–2212 (2017). https://doi.org/10.1007/s00259-017-3786-1

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  • DOI: https://doi.org/10.1007/s00259-017-3786-1

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