title: Biological tumor volume in 18FET-PET before radiochemotherapy correlates with survival in GBM.
abstract: OBJECTIVE
  The aim of this prospective longitudinal study was to identify static and dynamic O-(2-[(18)F]fluoroethyl)-L-tyrosine PET ((18)FET-PET)-derived imaging biomarkers in patients with glioblastoma (GBM).
  
  
  METHODS
  Seventy-nine patients with newly diagnosed GBM were included; 42 patients underwent stereotactic biopsy (unresectable tumors) and 37 patients microsurgical tumor resection. All patients were scheduled to receive radiotherapy plus concomitant and adjuvant temozolomide (RCx/TMZ). (18)FET-PET evaluation using static and dynamic analysis was done before biopsy/resection, after resection, 4 to 6 weeks following RCx, and after 3 cycles of TMZ. Endpoints were survival and progression-free-survival. Prognostic factors were obtained from proportional hazards models.
  
  
  RESULTS
  Biological tumor volume before RCx (BTV(preRCx)) was the most important (18)FET-PET-derived imaging biomarker and was independent of MGMT promoter methylation and clinical prognostic factors: patients with smaller BTV(preRCx) had significantly longer progression-free and overall survival (OS). (18)FET time-activity curves (TACs) before treatment and their changes after RCx were also related to outcome; patients with initially increasing TACs experienced longer OS.
  
  
  CONCLUSIONS
  BTV(preRCx) and TAC represent important (18)FET-PET-derived imaging biomarkers in GBM. Increasing TACs are associated with prolonged OS. The BTV(preRCx) is a strong prognostic factor for progression-free survival and OS independent of the mode of surgery. Our data furthermore suggest that patients harboring resectable GBM might benefit from maximal PET-guided tumor resection.
authors.affiliation: From the Departments of Neurosurgery (B.S., F.W.K., J.C.T.), Nuclear Medicine (N.L.J.), Neuroradiology (J.L., H.J.), and Neuropathology (H.K., S.E.), Ludwig-Maximilians University Munich; Department of Neurosurgery (M.S.), University of Bonn; Department of Nuclear Medicine (G.P.), Katharinenhospital Stuttgart; Department of Nuclear Medicine (C.l.F.), University of Tuebingen, Germany; and Department of Neurology (M.W.), University Hospital Zurich, Switzerland.
authors.forename: Bogdana
authors.initials: B
authors.lastname: Suchorska
authors.affiliation: From the Departments of Neurosurgery (B.S., F.W.K., J.C.T.), Nuclear Medicine (N.L.J.), Neuroradiology (J.L., H.J.), and Neuropathology (H.K., S.E.), Ludwig-Maximilians University Munich; Department of Neurosurgery (M.S.), University of Bonn; Department of Nuclear Medicine (G.P.), Katharinenhospital Stuttgart; Department of Nuclear Medicine (C.l.F.), University of Tuebingen, Germany; and Department of Neurology (M.W.), University Hospital Zurich, Switzerland.
authors.forename: Nathalie L
authors.initials: NL
authors.lastname: Jansen
authors.affiliation: From the Departments of Neurosurgery (B.S., F.W.K., J.C.T.), Nuclear Medicine (N.L.J.), Neuroradiology (J.L., H.J.), and Neuropathology (H.K., S.E.), Ludwig-Maximilians University Munich; Department of Neurosurgery (M.S.), University of Bonn; Department of Nuclear Medicine (G.P.), Katharinenhospital Stuttgart; Department of Nuclear Medicine (C.l.F.), University of Tuebingen, Germany; and Department of Neurology (M.W.), University Hospital Zurich, Switzerland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Linn
authors.affiliation: From the Departments of Neurosurgery (B.S., F.W.K., J.C.T.), Nuclear Medicine (N.L.J.), Neuroradiology (J.L., H.J.), and Neuropathology (H.K., S.E.), Ludwig-Maximilians University Munich; Department of Neurosurgery (M.S.), University of Bonn; Department of Nuclear Medicine (G.P.), Katharinenhospital Stuttgart; Department of Nuclear Medicine (C.l.F.), University of Tuebingen, Germany; and Department of Neurology (M.W.), University Hospital Zurich, Switzerland.
authors.forename: Hans
authors.initials: H
authors.lastname: Kretzschmar
authors.affiliation: From the Departments of Neurosurgery (B.S., F.W.K., J.C.T.), Nuclear Medicine (N.L.J.), Neuroradiology (J.L., H.J.), and Neuropathology (H.K., S.E.), Ludwig-Maximilians University Munich; Department of Neurosurgery (M.S.), University of Bonn; Department of Nuclear Medicine (G.P.), Katharinenhospital Stuttgart; Department of Nuclear Medicine (C.l.F.), University of Tuebingen, Germany; and Department of Neurology (M.W.), University Hospital Zurich, Switzerland.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Janssen
authors.affiliation: From the Departments of Neurosurgery (B.S., F.W.K., J.C.T.), Nuclear Medicine (N.L.J.), Neuroradiology (J.L., H.J.), and Neuropathology (H.K., S.E.), Ludwig-Maximilians University Munich; Department of Neurosurgery (M.S.), University of Bonn; Department of Nuclear Medicine (G.P.), Katharinenhospital Stuttgart; Department of Nuclear Medicine (C.l.F.), University of Tuebingen, Germany; and Department of Neurology (M.W.), University Hospital Zurich, Switzerland.
authors.forename: Sabina
authors.initials: S
authors.lastname: Eigenbrod
authors.affiliation: From the Departments of Neurosurgery (B.S., F.W.K., J.C.T.), Nuclear Medicine (N.L.J.), Neuroradiology (J.L., H.J.), and Neuropathology (H.K., S.E.), Ludwig-Maximilians University Munich; Department of Neurosurgery (M.S.), University of Bonn; Department of Nuclear Medicine (G.P.), Katharinenhospital Stuttgart; Department of Nuclear Medicine (C.l.F.), University of Tuebingen, Germany; and Department of Neurology (M.W.), University Hospital Zurich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Simon
authors.affiliation: From the Departments of Neurosurgery (B.S., F.W.K., J.C.T.), Nuclear Medicine (N.L.J.), Neuroradiology (J.L., H.J.), and Neuropathology (H.K., S.E.), Ludwig-Maximilians University Munich; Department of Neurosurgery (M.S.), University of Bonn; Department of Nuclear Medicine (G.P.), Katharinenhospital Stuttgart; Department of Nuclear Medicine (C.l.F.), University of Tuebingen, Germany; and Department of Neurology (M.W.), University Hospital Zurich, Switzerland.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pöpperl
authors.affiliation: From the Departments of Neurosurgery (B.S., F.W.K., J.C.T.), Nuclear Medicine (N.L.J.), Neuroradiology (J.L., H.J.), and Neuropathology (H.K., S.E.), Ludwig-Maximilians University Munich; Department of Neurosurgery (M.S.), University of Bonn; Department of Nuclear Medicine (G.P.), Katharinenhospital Stuttgart; Department of Nuclear Medicine (C.l.F.), University of Tuebingen, Germany; and Department of Neurology (M.W.), University Hospital Zurich, Switzerland.
authors.forename: Friedrich W
authors.initials: FW
authors.lastname: Kreth
authors.affiliation: From the Departments of Neurosurgery (B.S., F.W.K., J.C.T.), Nuclear Medicine (N.L.J.), Neuroradiology (J.L., H.J.), and Neuropathology (H.K., S.E.), Ludwig-Maximilians University Munich; Department of Neurosurgery (M.S.), University of Bonn; Department of Nuclear Medicine (G.P.), Katharinenhospital Stuttgart; Department of Nuclear Medicine (C.l.F.), University of Tuebingen, Germany; and Department of Neurology (M.W.), University Hospital Zurich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: la Fougere
authors.affiliation: From the Departments of Neurosurgery (B.S., F.W.K., J.C.T.), Nuclear Medicine (N.L.J.), Neuroradiology (J.L., H.J.), and Neuropathology (H.K., S.E.), Ludwig-Maximilians University Munich; Department of Neurosurgery (M.S.), University of Bonn; Department of Nuclear Medicine (G.P.), Katharinenhospital Stuttgart; Department of Nuclear Medicine (C.l.F.), University of Tuebingen, Germany; and Department of Neurology (M.W.), University Hospital Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.affiliation: From the Departments of Neurosurgery (B.S., F.W.K., J.C.T.), Nuclear Medicine (N.L.J.), Neuroradiology (J.L., H.J.), and Neuropathology (H.K., S.E.), Ludwig-Maximilians University Munich; Department of Neurosurgery (M.S.), University of Bonn; Department of Nuclear Medicine (G.P.), Katharinenhospital Stuttgart; Department of Nuclear Medicine (C.l.F.), University of Tuebingen, Germany; and Department of Neurology (M.W.), University Hospital Zurich, Switzerland. joerg.christian.tonn@med.uni-muenchen.de.
authors.forename: Joerg C
authors.initials: JC
authors.lastname: Tonn
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008866:Microsurgery; D008875:Middle Aged; D019635:Neurosurgical Procedures; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D000077204:Temozolomide; D016896:Treatment Outcome; D047368:Tumor Burden; D014443:Tyrosine / Q000031:analogs & derivatives
chemical_list: D018906:Antineoplastic Agents, Alkylating; C545932:(18F)fluoroethyltyrosine; D014443:Tyrosine; D003606:Dacarbazine; D000077204:Temozolomide