title: Dynamic 18F-FET PET in suspected WHO grade II gliomas defines distinct biological subgroups with different clinical courses.
abstract: In suspected grade II gliomas, three distinct patterns of time-activity curves (TAC) on O-(2-[(18)F]fluoroethyl)-1-tyrosine ((18)F-FET) positron emission tomography (PET) have been delineated (i) increasing TAC homogeneously throughout the tumor, and decreasing TAC, (ii) either homogeneously throughout the tumor or (iii) only focally within otherwise increasing TAC patterns. Increasing TAC was associated with low-grade histology and decreasing TAC with high-grade histology. This prospective study analyzed whether these patterns correlate with distinct biological tumor subtypes and differential outcome. (18)F-FET PET-guided biopsies were used for stepwise histopathological evaluation. Molecular-genetic evaluation included O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation, isocitrate dehydrogenase (IDH1/2) mutational and 1p/19q codeletion status. Progression-free survival (PFS) was estimated with the Kaplan-Meier method. Prognostic factors were obtained from multivariate regression models. 98 adult patients were included. Homogeneous increasing, focal decreasing and homogeneous decreasing TAC were seen in 51, 19 and 28 patients. The corresponding 1-year (2-years) PFS were 92% (85%), 89% (51%) and 50% (28%; p = 0.002). IDH1/2 mutations were more frequent in tumors with homogeneous increasing (90%) and focal decreasing (79%) TAC, but were rare in those exhibiting homogeneous decreasing TAC (25%; p < 0.001). Overall, TAC patterns, IDH1/2 mutational and 1p/19q codeletion status were powerful and independent prognostic factors. Dynamic (18)F-FET PET might be an important and independent imaging biomarker for patients with suspected WHO grade II gliomas and offers perspectives for stratified diagnostic and therapeutic strategies. Tumors with focal decreasing TAC need highly targeted surgical interventions to avoid undergrading and undertreatment.
authors.affiliation: Department of Neurosurgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Thon
authors.forename: Mathias
authors.initials: M
authors.lastname: Kunz
authors.forename: Lena
authors.initials: L
authors.lastname: Lemke
authors.forename: Nathalie L
authors.initials: NL
authors.lastname: Jansen
authors.forename: Sabina
authors.initials: S
authors.lastname: Eigenbrod
authors.forename: Simone
authors.initials: S
authors.lastname: Kreth
authors.forename: Jürgen
authors.initials: J
authors.lastname: Lutz
authors.forename: Rupert
authors.initials: R
authors.lastname: Egensperger
authors.forename: Armin
authors.initials: A
authors.lastname: Giese
authors.forename: Jochen
authors.initials: J
authors.lastname: Herms
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.forename: Hans
authors.initials: H
authors.lastname: Kretzschmar
authors.forename: Jörg-Christian
authors.initials: JC
authors.lastname: Tonn
authors.forename: Christian
authors.initials: C
authors.lastname: la Fougère
authors.forename: Friedrich-Wilhelm
authors.initials: FW
authors.lastname: Kreth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D014443:Tyrosine / Q000031:analogs & derivatives*; D055815:Young Adult
chemical_list: D019275:Radiopharmaceuticals; C545932:(18F)fluoroethyltyrosine; D014443:Tyrosine; D007521:Isocitrate Dehydrogenase; D019853:O(6)-Methylguanine-DNA Methyltransferase
keywords: 18F-FET PET; grading; imaging; low-grade glioma; prognosis