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Dynamic (18) F-FET PET in suspected WHO grade II gliomas defines distinct biological subgroups with different clinical courses


Thon, N; Kunz, M; Lemke, L; Jansen, N L; Eigenbrod, S; Kreth, S; Lutz, J; Egensperger, R; Giese, A; Herms, J; Weller, M; Kretzschmar, H; Tonn, J C; laFougère, C; Kreth, F W (2015). Dynamic (18) F-FET PET in suspected WHO grade II gliomas defines distinct biological subgroups with different clinical courses. International Journal of Cancer, 136(9):2132-2145.

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 one-year (two-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 18F-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. © 2014 Wiley Periodicals, Inc.

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 one-year (two-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 18F-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. © 2014 Wiley Periodicals, Inc.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Date:2015
Deposited On:06 Nov 2014 09:45
Last Modified:05 Apr 2016 18:28
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0020-7136
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1002/ijc.29259
PubMed ID:25311315

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