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

Abstract

Neuroblastoma (NB) is a heterogeneous childhood cancer that requires multiple imaging modalities for accurate staging and surveillances. This study aims 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, forty-two NB patients (male:female, 28:14; median age, 2.0 years) undergoing paired FDG and FDOPA PET scans at diagnosis were evaluated for the maximum standardized uptake value (SUV_max) of FDG or FDOPA by the primary tumor. Patients with older age, advanced stages, or MYCN amplification showed higher FDG and lower FDOPA SUV_max (all P < 0.02). Receiver operating characteristics analysis identified FDG SUV_max≥ 3.31 and FDOPA SUV_max < 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 SUV_max (G:D) correlated positively with HK2 (Spearman’s ρ = 0.86, P < 0.0001) and negatively with DDC (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.