title: 18F-FET PET prior to recurrent high-grade glioma re-irradiation-additional prognostic value of dynamic time-to-peak analysis and early static summation images?
abstract: 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-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) PET for patients treated with Re-RT ± concomitant bevacizumab. We retrospectively analyzed 72 patients suffering from recurrent HGG with18F-FET PET prior to Re-RT. PET analysis revealed the maximal tumor-to-background-ratio (TBRmax), 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 TBRmax(at 5-15 min post-injection) and minimal time-to-peak (TTPmin) 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 TTPminwas related to shorter PRS after Re-RT with 6 months for TTPmin< 12.5 min, 7 months for TTPmin12.5-25 min and 11 months for TTPmin>25 min (p = 0.027). TTPminhad 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 TBRmaxas well as the other conventional PET parameters were not significantly related to PRS on univariate analysis. Dynamic18F-FET PET with TTPminprovides a high prognostic value for recurrent HGG prior to Re-RT, whereas early TBRmaxdoes not. Dynamic18F-FET PET using TTPminmight help to personalize Re-RT treatment regimens in future through voxelwise TTPminanalysis for dose painting purposes and PET-guided dose escalation.
authors.affiliation: Department of Radiation Oncology, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.|German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Fleischmann
authors.affiliation: Department of Nuclear Medicine, LMU Munich, Munich, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Unterrainer
authors.affiliation: Department of Nuclear Medicine, LMU Munich, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
authors.affiliation: Department of Radiation Oncology, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.|German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Belka
authors.affiliation: Department of Nuclear Medicine, LMU Munich, Munich, Germany.
authors.forename: Nathalie L
authors.initials: NL
authors.lastname: Albert
authors.affiliation: Department of Radiation Oncology, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany. maximilian.niyazi@med.uni-muenchen.de.|German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. maximilian.niyazi@med.uni-muenchen.de.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Niyazi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D006801:Humans; D017567:Karnofsky Performance Status; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging / Q000532:radiotherapy; D017711:Nonlinear Dynamics; D049268:Positron-Emission Tomography; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D000069475:Re-Irradiation / Q000379:methods*; D016019:Survival Analysis; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000074322:Antineoplastic Agents, Immunological; C117289:O-(2-fluoroethyl)tyrosine; D019275:Radiopharmaceuticals; D000068258:Bevacizumab; D014443:Tyrosine
keywords: 18F-FET PET; High-grade glioma; Kinetic analysis; Prognostic value; Re-irradiation