Prognostic significance of dynamic 18F-FET PET in newly diagnosed astrocytic high-grade glioma

Abstract

Despite advances in diagnosis and the use of different therapeutic regimens in astrocytic high-grade glioma (HGG), the prognosis for patients remains grim. Additional pretherapeutic information is needed to tailor management. To gain additional prognostic information at primary diagnosis, we investigated the value of dynamic O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET.

Methods: We retrospectively evaluated 121 patients who had a primary diagnosis of astrocytic HGG (51 World Health Organization [WHO] grade III; 70 WHO IV) and underwent dynamic (18)F-FET PET before histopathologic assessment. We assessed static parameters (maximal and mean tumoral standardized uptake value corrected for mean background activity in the contralateral hemisphere [SUV(max)/BG and SUV(mean)/BG, respectively], biologic tumor volume) and dynamic time-activity curves, including minimal time to peak (TTP(min)). The prognostic influence of PET parameters and other clinical parameters on progression-free and overall survival was evaluated using uni- and multivariate Cox regression and Kaplan-Meier survival estimates.

Results: In the group overall, median progression-free survival and overall survival were 12.2 and 21.9 mo. SUV(max)/BG, SUV(mean)/BG, and biologic tumor volume were significantly higher in WHO IV than in WHO III gliomas; median TTP(min) was 12.5 min in both groups. On univariate analysis, the factors age, WHO grade, O6-methylguanine-DNA methyltransferase promoter methylation status, contrast enhancement, initial treatment, and TTP(min) showed prognostic significance, with WHO grade, O6-methylguanine-DNA methyltransferase status, age, and TTP(min) remaining significant in the multivariate analysis. WHO grade and TTP(min) reached a similar fit for the prognostic evaluation. The prognosis of WHO III astrocytoma with an early TTP(min) of 12.5 min or less did not differ significantly from that of glioblastoma.

Conclusion: Early TTP(min) is associated with worse outcome in patients with newly diagnosed astrocytic HGG. In the preoperative setting, TTP(min) can be a valuable noninvasive prognostic marker with comparable significance to WHO grade. Additionally, TTP(min) can help identify highly aggressive WHO III astrocytoma tumors and may help in adjusting standard treatment toward an individualized, risk-adapted therapy regime.

Keywords: 18F-FET PET; high-grade glioma; kinetic analysis; prognostic value.