title: Late Pseudoprogression in Glioblastoma: Diagnostic Value of Dynamic O-(2-[18F]fluoroethyl)-L-Tyrosine PET.
abstract: Pseudoprogression (PsP) is characterized by therapy-associated but not tumor growth-associated increases of contrast-enhancing glioblastoma lesions on MRI. Although typically occurring during the first 3 months after radiochemotherapy, PsP may occur later in the course of the disease and may then be particularly difficult to distinguish from true tumor progression. We explored PET using O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET-PET) to approach the diagnostic dilemma.
  
  
  
  Twenty-six patients with glioblastoma that presented with increasing contrast-enhancing lesions later than 3 months after completion of radiochemotherapy underwent (18)F-FET-PET. Maximum and mean tumor/brain ratios (TBRmax and TBRmean) of (18)F-FET uptake as well as time-to-peak (TTP) and patterns of the time-activity curves were determined. The final diagnosis of true progression versus late PsP was based on follow-up MRI using RANO criteria.
  
  
  
  Late PsP occurred in 7 patients with a median time from radiochemotherapy completion of 24 weeks while the remaining patients showed true tumor progression. TBRmax and TBRmean were significantly higher in patients with true progression than in patients with late PsP (TBRmax 2.4 ± 0.1 vs. 1.5 ± 0.2, P = 0.003; TBRmean 2.1 ± 0.1 vs. 1.5 ± 0.2, P = 0.012) whereas TTP was significantly shorter (mean TTP 25 ± 2 vs. 40 ± 2 min, P < 0.001). ROC analysis yielded an optimal cutoff value of 1.9 for TBRmax to differentiate between true progression and late PsP (sensitivity 84%, specificity 86%, accuracy 85%, P = 0.015).
  
  
  
  O-(2-[(18)F]fluoroethyl)-L-tyrosine PET provides valuable information in assessing the elusive phenomenon of late PsP. Clin Cancer Res; 22(9); 2190-6. ©2015 AACR.
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Centre, Bonn, Germany. Stem Cell Pathologies, Institute of Reconstructive Neurobiology, University of Bonn, Bonn, Germany. Center of Integrated Oncology (CIO), Universities of Cologne and Bonn, Bonn, Germany. sied.kebir@ukb.uni-bonn.de.
authors.forename: Sied
authors.initials: S
authors.lastname: Kebir
authors.affiliation: Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn Medical Centre, Bonn, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Fimmers
authors.affiliation: Center of Integrated Oncology (CIO), Universities of Cologne and Bonn, Bonn, Germany. Deptartment of Neurology, University of Cologne, Cologne, Germany. Institute of Neuroscience and Medicine, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Galldiks
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Centre, Bonn, Germany. Stem Cell Pathologies, Institute of Reconstructive Neurobiology, University of Bonn, Bonn, Germany. Center of Integrated Oncology (CIO), Universities of Cologne and Bonn, Bonn, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Schäfer
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Centre, Bonn, Germany. Center of Integrated Oncology (CIO), Universities of Cologne and Bonn, Bonn, Germany.
authors.forename: Frederic
authors.initials: F
authors.lastname: Mack
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Centre, Bonn, Germany. Center of Integrated Oncology (CIO), Universities of Cologne and Bonn, Bonn, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Schaub
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Centre, Bonn, Germany. Center of Integrated Oncology (CIO), Universities of Cologne and Bonn, Bonn, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Stuplich
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Centre, Bonn, Germany. Center of Integrated Oncology (CIO), Universities of Cologne and Bonn, Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Niessen
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Centre, Bonn, Germany. Center of Integrated Oncology (CIO), Universities of Cologne and Bonn, Bonn, Germany.
authors.forename: Theophilos
authors.initials: T
authors.lastname: Tzaridis
authors.affiliation: Center of Integrated Oncology (CIO), Universities of Cologne and Bonn, Bonn, Germany. Department of Neurosurgery, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Simon
authors.affiliation: Institute of Neuroscience and Medicine, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Stoffels
authors.affiliation: Institute of Neuroscience and Medicine, Forschungszentrum Jülich, Jülich, Germany. Department of Nuclear Medicine, University of Aachen, Aachen, Germany.
authors.forename: Karl-Josef
authors.initials: KJ
authors.lastname: Langen
authors.affiliation: Stem Cell Pathologies, Institute of Reconstructive Neurobiology, University of Bonn, Bonn, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Scheffler
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Centre, Bonn, Germany. Stem Cell Pathologies, Institute of Reconstructive Neurobiology, University of Bonn, Bonn, Germany. Center of Integrated Oncology (CIO), Universities of Cologne and Bonn, Bonn, Germany. Clinical Cooperation Unit Neurooncology, MediClin Robert Janker Klinik, Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Glas
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Centre, Bonn, Germany. Center of Integrated Oncology (CIO), Universities of Cologne and Bonn, Bonn, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Herrlinger
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D059248:Chemoradiotherapy / Q000379:methods; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000009:adverse effects; D019275:Radiopharmaceuticals / Q000009:adverse effects; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D014443:Tyrosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D055815:Young Adult
chemical_list: C117289:O-(2-fluoroethyl)tyrosine; D019275:Radiopharmaceuticals; D014443:Tyrosine