Biological tumor volume in 18FET-PET before radiochemotherapy correlates with survival in GBM

Abstract

Objective: The aim of this prospective longitudinal study was to identify static and dynamic O-(2- [18F]fluoroethyl)-L-tyrosine PET (18FET-PET)-derived imaging biomarkers in patients with glioblastoma (GBM). Methods: Seventy-nine patients with newly diagnosed GBM were included; 42 patients underwent stereotactic biopsy (unresectable tumors) and 37 patients microsurgical tumor resection. All patients were scheduled to receive radiotherapy plus concomitant and adjuvant temozolomide (RCx/TMZ). 18FET-PET evaluation using static and dynamic analysis was done before biopsy/ resection, after resection, 4 to 6 weeks following RCx, and after 3 cycles of TMZ. Endpoints were survival and progression-free-survival. Prognostic factors were obtained from proportional hazards models. Results: Biological tumor volume before RCx (BTVpreRCx) was the most important 18FET-PET- derived imaging biomarker and was independent of MGMT promoter methylation and clinical prognostic factors: patients with smaller BTVpreRCx had significantly longer progression-free and overall survival (OS). 18FET time-activity curves (TACs) before treatment and their changes after RCx were also related to outcome; patients with initially increasing TACs experienced longer OS. Conclusion: BTVpreRCx and TAC represent important 18FET-PET-derived imaging biomarkers in GBM. Increasing TACs are associated with prolonged OS. The BTVpreRCx is a strong prognostic factor for progression-free survival and OS independent of the mode of surgery. Our data furthermore suggest that patients harboring resectable GBM might benefit from maximal PETguided tumor resection.