Potential Prognostic Value of FDG PET/CT–derived Intratumoral Metabolic Heterogeneity in Neuroblastoma

Take-Away Points

• ■ Major Focus: To assess the prognostic value of intratumoral metabolic heterogeneity via fluorine 18 fluorodeoxyglucose (¹⁸F-FDG) PET/CT in patients with neuroblastoma.

• ■ Key Result: In pretreatment patients with neuroblastoma, intratumoral metabolic heterogeneity, as determined by baseline ¹⁸F-FDG PET/CT, was an independent predictor of event-free survival, and patients with greater heterogeneity and bone marrow involvement had worse outcomes.

• ■ Impact: Use of semiquantitative tumor heterogeneity measurements at baseline ¹⁸F-FDG PET/CT may improve prediction of event-free survival in patients with neuroblastoma.

Patients with neuroblastoma have varying clinical presentations, treatment responses, and outcomes, from complete regression to multidrug resistant disease. Studies suggest that intratumoral heterogeneity is linked to treatment failure, and metabolic heterogeneity at ¹⁸F-FDG PET/CT may correlate with treatment failure and greater likelihood of metastatic cancers. Thorough assessments of tumor heterogeneity can assist in tailoring treatment decisions and prognoses.

In this retrospective study, Liu et al evaluated the prognostic value of ¹⁸F-FDG PET/CT–derived intratumoral metabolic heterogeneity in 38 pediatric patients with histopathologically proven neuroblastoma. Patients underwent baseline ¹⁸F-FDG PET/CT imaging before treatment, and the authors documented presence of bone marrow involvement. The primary tumor was manually segmented by two nuclear medicine physicians. In addition to traditional parameters such as peak standardized uptake value, total lesion glycolysis (TLG), and metabolic tumor volume (MTV), the authors used a measure to assess intratumoral metabolic heterogeneity, namely the areas under the curve of cumulative SUV-volume histogram index (AUC-CSH index). This index represents the percent tumor volume greater than the percentage of maximum standard uptake value (SUVmax), with lower AUC-CSH index values corresponding to greater tumor heterogeneity.

Comparing the two methods of calculating this index (AUC-CSH_40%, based on 40% SUVmax-threshold; and AUC-CSH_total, based on manual segmentation of primary tumor), AUC-CSH_total better represented intratumoral metabolic heterogeneity in patients. While traditional parameters such as MTV and TLG did not show significant association with event-free survival, Kaplan-Meier survival analysis demonstrated that the group with AUC-CSH_total ≤ 0.49 and bone marrow involvement had significantly worse outcomes with shorter event-free survival. In addition to bone marrow involvement, metabolic heterogeneity (as measured by the AUC-CSH_total index) served as an independent prognostic factor for event-free survival.

This semiquantitative measure derived from ¹⁸F-FDG PET/CT may help predict survival and prognosis in neuroblastoma. Large prospective studies must be performed to validate these findings.

Highlighted Article

• Liu J, Si Y, Zhou Z, et al. The prognostic value of ¹⁸F-FDG PET/CT intra-tumoural metabolic heterogeneity in pretreatment neuroblastoma patients. Cancer Imaging 2022;22:32. doi: https://doi.org/10.1186/s40644-022-00472-4