Oral Presentation Advances in Neuroblastoma Research Congress 2016

Diagnostic FDG and FDOPA positron emission tomography scans distinguish the genomic type and treatment outcome of neuroblastoma (#59)

Yen-Lin Liu 1 2 , Meng Yao Lu 3 , Hsiu-Hao Chang 3 , Ching-Chu Lu 4 , Dong-Tsamn Lin 3 , Shiann-Tarng Jou 3 , Yung-Li Yang 3 , Ya-Ling Lee 5 , Shiu-Feng Huang 6 , Yung-Ming Jeng 7 , Hsinyu Lee 8 , James S. Miser 9 , Kai-Hsin Lin 3 , Yung-Feng Liao 10 , Wen-Ming Hsu 11 , Kai-Yuan Tzen 4
  1. Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan
  2. PhD Program in Translational Medicine, National Taiwan University and Academia Sinica, Taipei, Taiwan
  3. Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
  4. Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan
  5. Nursing, National Taiwan University College of Medicine, Taipei, Taiwan
  6. Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan
  7. Pathology, National Taiwan University Hospital, Taipei, Taiwan
  8. Life Science, National Taiwan University, Taipei, Taiwan
  9. College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
  10. Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
  11. Pediatric Surgery, National Taiwan University Hospital, Taipei, Taiwan

Neuroblastoma (NB) is a heterogeneous childhood cancer that requires multiple imaging modalities for accurate staging and surveillances. The aim of this study is to investigate the utility of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) and 18F-fluoro-dihydroxyphenylalanine (FDOPA) in determining the prognosis of NB. During 2007–2014, NB patients undergoing paired FDG and FDOPA PET scans at diagnosis were evaluated for the maximum standardized uptake value (SUVmax) of FDG or FDOPA by the primary tumor, which values were correlated with clinical features, genomic types, treatment outcomes, and imaging-related gene expression. Among 42 NB patients (28 boys and 14 girls; median age, 2.0 years) who were eligible for analysis, patients with older age, advanced stages, or MYCN amplification showed higher FDG and lower FDOPA SUVmax (all P < 0.02). Receiver operating characteristics analysis identified FDG SUVmax ≥ 3.31 and FDOPA SUVmax < 4.12 as an ultra-high-risk feature (PET-UHR) that distinguished the most unfavorable genomic types, i.e. segmental chromosomal alterations and/or MYCN amplification, at a sensitivity of 81.3% (54.4%–96.0%) and a specificity of 93.3% (68.1%–99.8%). Considering with age, stage, MYCN status, and anatomical image-defined risk factor, PET-UHR was an independent predictor of inferior event-free survival (multivariate hazard ratio, 4.9 [1.9–30.1]; P = 0.012). Meanwhile, the ratio between FDG and FDOPA SUVmax (G:D) correlated positively with hexokinase 2 (HK2; Spearman's ρ = 0.86, P < 0.0001) and negatively with dopa decarboxylase (DDC; Spearman's ρ = -0.58, P = 0.02) gene expression levels, which might suggest higher glycolytic activity and less catecholaminergic differentiation in NB tumors taking up higher FDG and lower FDOPA. In conclusion, the intensity of FDG and FDOPA uptake on diagnostic PET scans may predict the tumor behavior and complement the current risk stratification systems of NB.