The prognostic value of (18)F-FDG PET/CT intra-tumoural metabolic heterogeneity in pretreatment neuroblastoma patients

BACKGROUND: Neuroblastoma (NB) is the most common tumour in children younger than 5 years old and notable for highly heterogeneous. Our aim was to quantify the intra-tumoural metabolic heterogeneity of primary tumour lesions by using (18)F-FDG PET/CT and evaluate the prognostic value of intra-tumoural metabolic heterogeneity in NB patients. METHODS: We retrospectively enrolled 38 pretreatment NB patients in our study. (18)F-FDG PET/CT images were reviewed and analyzed using 3D slicer software. The semi-quantitative metabolic parameters of primary tumour were measured, including the maximum standard uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG). The areas under the curve of cumulative SUV-volume histogram index (AUC-CSH index) was used to quantify intra-tumoural metabolic heterogeneity. The median follow-up was 21.3 months (range 3.6 - 33.4 months). The outcome endpoint was event-free survival (EFS), including progression-free survival and overall survival. Survival analysis was performed using Cox regression models and Kaplan Meier survival plots. RESULTS: In all 38 newly diagnosed NB patients, 2 patients died, and 17 patients experienced a relapse. The AUC-CSH(total) (r=0.630, P<0.001) showed moderate correlation with the AUC-CSH(40%). In univariate analysis, chromosome 11q deletion (P=0.033), Children's Oncology Group (COG) risk grouping (P=0.009), bone marrow involvement (BMI, P=0.015), and AUC-CSH(total) (P=0.007) were associated with EFS. The AUC-CSH(total) (P=0.036) and BMI (P=0.045) remained significant in multivariate analysis. The Kaplan Meier survival analyses demonstrated that patients with higher intra-tumoural metabolic heterogeneity and BMI had worse outcomes (log-rank P=0.002). CONCLUSION: The intra-tumoural metabolic heterogeneity of primary lesions in NB was an independent prognostic factor for EFS. The combined predictive effect of intra-tumoural metabolic heterogeneity and BMI provided prognostic survival information in NB patients.