Bogdana Suchorska1, Nathalie L Jansen1, Jennifer Linn1, Hans Kretzschmar1, Hendrik Janssen1, Sabina Eigenbrod1, Matthias Simon1, Gabriele Pöpperl1, Friedrich W Kreth1, Christian la Fougere1, Michael Weller1, Joerg C Tonn2. 1. 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. 2. 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.
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. CONCLUSION: 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.
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. CONCLUSION: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.
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