¹⁸F-FDG Avidity and Correlation with Histopathologic and Cytogenetic Prognostic Factors in Neuroblastoma

Objectives: ¹⁸F-Fluorodeoxyglucose (FDG) avidity has clinical significance in initial staging. High accumulation of FDG is associated with unfavorable prognosis, but correlation with other prognostic factors is not well understood. There has been a study about FDG uptake discrepancy between favorable and unfavorable histology, defined by International Neuroblastoma Pathology Classification (INPC). However, in the recent International Neuroblastoma Risk Group (INRG) risk classification criteria, additional genetic factors such as MYCN gene amplification, 11q aberrancy and DNA ploidy have been implemented. The objective of this study is to determine correlation of FDG avidity with histopathologic and cytogenetic prognostic factors in neuroblastoma. Methods: 112 patients diagnosed and pathologically confirmed of neuroblastoma who underwent FDG PET/CT scan as initial staging before any treatments from 2009 to 2017 at a single medical center were enrolled and retrospectively evaluated. FDG avidity of primary neuroblastoma lesion was measured using maximum standardized uptake value (SUV_max). Pathology was divided into neuroblastoma and ganglioneuroblastoma, further classified into subtypes according to differentiation. Mitosis-karyorrhexis index (MKI), presence of MYCN amplification, 1p del, 11q del, and 17q gain were also reviewed and analyzed in accordance with FDG avidity. Statistical analyses were performed using independent t-test with p-value of less than 0.05 considered significant. Results: FDG avidity measured by SUV_max was higher in lesions with poor pathologic and genetic prognostic factors of neuroblastoma. Neuroblastoma (n=88) showed higher glucose metabolism than ganglioneuroblastoma (n=24) (p=0.002). Group with poorly differentiated and undifferentiated neuroblastoma (n=61) showed higher glucose metabolism than the group with well differentiated neuroblastoma (n=25) (p=0.003). Presence of MYCN gene amplification, which is known to be the strongest prognostic factor, showed higher FDG avidity in neuroblastoma (p=0.022). Presence of any chromosomal aberrancy among 1p del, 11q del and 17q gain showed higher FDG avidity compared to triple negative genetic profiles regardless of MYCN amplification status (p=0.036). Neuroblastoma group with high (>4%) MKI showed higher FDG uptake than the group with intermediate (2-4%) and low (<2%) MKI (p=0.039). Conclusions: FDG avidity showed positive correlation with poor histopathologic and cytogenetic prognostic factors in neuroblastoma. With INRG staging using image-defined risk factors (IDRFs) which can be obtained from the PET/CT scan, predicting prognosis based on INRG system can be achieved solely from pretreatment FDG PET/CT. FDG uptake measurement can be useful alternative to pathologic and genetic profiles especially when biopsy cannot be performed or complex histopathological evaluation cannot be fully evaluated.