F-FET PET prior to recurrent high-grade glioma re-irradiation-additional prognostic value of dynamic time-to-peak analysis and early static summation images?

Most high-grade gliomas (HGG) recur after initial multimodal therapy and re-irradiation (Re-RT) has been shown to be a valuable re-treatment option in selected patients. We evaluated the prognostic value of dynamic time-to-peak analysis and early static summation images in O-(2-F-fluoroethyl)-l-tyrosine (F-FET) PET for patients treated with Re-RT ± concomitant bevacizumab. We retrospectively analyzed 72 patients suffering from recurrent HGG with F-FET PET prior to Re-RT. PET analysis revealed the maximal tumor-to-background-ratio (TBR), the biological tumor volume, the number of PET-foci and pattern of time-activity-curves (TACs; increasing vs. decreasing). Furthermore, the novel PET parameters early TBR (at 5-15 min post-injection) and minimal time-to-peak (TTP) were evaluated. Additional analysis was performed for gender, age, KPS, O6-methylguanine-DNA methyltransferase methylation status, isocitrate dehydrogenase 1 mutational status, WHO grade and concomitant bevacizumab therapy. The influence of PET and clinical parameters on post-recurrence survival (PRS) was investigated. Shorter TTP was related to shorter PRS after Re-RT with 6 months for TTP < 12.5 min, 7 months for TTP 12.5-25 min and 11 months for TTP >25 min (p = 0.027). TTP had a significant impact on PRS both on univariate (p = 0.027; continuous) and multivariate analysis (p = 0.011; continuous). Other factors significantly related to PRS on multivariate analysis were increasing vs. decreasing TACs (p = 0.008) and Karnofsky Performance Score (p = 0.015; <70 vs. ≥70). Early TBR as well as the other conventional PET parameters were not significantly related to PRS on univariate analysis. Dynamic F-FET PET with TTP provides a high prognostic value for recurrent HGG prior to Re-RT, whereas early TBR does not. Dynamic F-FET PET using TTP might help to personalize Re-RT treatment regimens in future through voxelwise TTP analysis for dose painting purposes and PET-guided dose escalation.