title: Amino acid positron emission tomography to monitor chemotherapy response and predict seizure control and progression-free survival in WHO grade II gliomas.
abstract: Patients with WHO grade II glioma may respond to chemotherapy that is currently not standardized regarding timing and treatment duration. Metabolic changes during chemotherapy may precede structural tumor volume reductions. We therefore compared time courses of amino acid PET and MRI responses to temozolomide (TMZ) and assessed whether responses correlated with seizure control and progression-free survival (PFS).
  
  
  
  PET and MRI were performed before and during TMZ chemotherapy. Tumor volumes were calculated using regions-of-interest analysis. Amino acid uptake was also quantified as metabolically active tumor volume and tumor-to-cerebellum uptake ratio.
  
  
  
  One hundred twenty-five PET and 125 MRI scans from 33 patients were analyzed. Twenty-five patients showed metabolic responses that exhibited an exponential time course with a 25% reduction of the active volume on average after 2.3 months. MRI responses followed a linear course with a 25% reduction after 16.8 months. Reduction of metabolically active tumor volumes, but not reduction of PET uptake ratios or MRI tumor volumes, correlated with improved seizure control following chemotherapy (P = .012). Receiver-operating-characteristic curve analysis showed that a decrease of the active tumor volume of ≥80.5% predicts a PFS of ≥60 months (P = .018) and a decrease of ≥64.5% a PFS of ≥48 months (P = .037).
  
  
  
  Amino acid PET is superior to MRI for evaluating TMZ responses in WHO grade II glioma patients. The response delay between both imaging modalities favors amino acid PET for individually tailoring the duration of chemotherapy. Additional studies should investigate whether this personalized approach is appropriate with regard to outcome.
authors.affiliation: Department of Neurology and Brain Tumor Center, Cantonal Hospital, Aarau, Switzerland (U.R.); Institute for Pharmacology and Toxicology, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Neuroscience Center, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Department of Neurology, Medical University, Innsbruck, Austria (M.N.); Department of Neuro-Oncology, University Hospital, Torino, Italy (R.R., R.S.); Department of Neurology, University Hospital, Switzerland (P.R., M.W.); Department of Oncology, University Hospital, Zürich, Switzerland (S.H.); Department of Neurology, University Hospital, Cologne, Germany, and Research Center, Jülich, Germany (N.G.); Medicina Nucleare, Istituto Nazionale dei Tumori, Milano, Italy (F.C.).
authors.forename: Ulrich
authors.initials: U
authors.lastname: Roelcke
authors.affiliation: Department of Neurology and Brain Tumor Center, Cantonal Hospital, Aarau, Switzerland (U.R.); Institute for Pharmacology and Toxicology, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Neuroscience Center, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Department of Neurology, Medical University, Innsbruck, Austria (M.N.); Department of Neuro-Oncology, University Hospital, Torino, Italy (R.R., R.S.); Department of Neurology, University Hospital, Switzerland (P.R., M.W.); Department of Oncology, University Hospital, Zürich, Switzerland (S.H.); Department of Neurology, University Hospital, Cologne, Germany, and Research Center, Jülich, Germany (N.G.); Medicina Nucleare, Istituto Nazionale dei Tumori, Milano, Italy (F.C.).
authors.forename: Matthias T
authors.initials: MT
authors.lastname: Wyss
authors.affiliation: Department of Neurology and Brain Tumor Center, Cantonal Hospital, Aarau, Switzerland (U.R.); Institute for Pharmacology and Toxicology, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Neuroscience Center, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Department of Neurology, Medical University, Innsbruck, Austria (M.N.); Department of Neuro-Oncology, University Hospital, Torino, Italy (R.R., R.S.); Department of Neurology, University Hospital, Switzerland (P.R., M.W.); Department of Oncology, University Hospital, Zürich, Switzerland (S.H.); Department of Neurology, University Hospital, Cologne, Germany, and Research Center, Jülich, Germany (N.G.); Medicina Nucleare, Istituto Nazionale dei Tumori, Milano, Italy (F.C.).
authors.forename: Martha
authors.initials: M
authors.lastname: Nowosielski
authors.affiliation: Department of Neurology and Brain Tumor Center, Cantonal Hospital, Aarau, Switzerland (U.R.); Institute for Pharmacology and Toxicology, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Neuroscience Center, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Department of Neurology, Medical University, Innsbruck, Austria (M.N.); Department of Neuro-Oncology, University Hospital, Torino, Italy (R.R., R.S.); Department of Neurology, University Hospital, Switzerland (P.R., M.W.); Department of Oncology, University Hospital, Zürich, Switzerland (S.H.); Department of Neurology, University Hospital, Cologne, Germany, and Research Center, Jülich, Germany (N.G.); Medicina Nucleare, Istituto Nazionale dei Tumori, Milano, Italy (F.C.).
authors.forename: Roberta
authors.initials: R
authors.lastname: Rudà
authors.affiliation: Department of Neurology and Brain Tumor Center, Cantonal Hospital, Aarau, Switzerland (U.R.); Institute for Pharmacology and Toxicology, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Neuroscience Center, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Department of Neurology, Medical University, Innsbruck, Austria (M.N.); Department of Neuro-Oncology, University Hospital, Torino, Italy (R.R., R.S.); Department of Neurology, University Hospital, Switzerland (P.R., M.W.); Department of Oncology, University Hospital, Zürich, Switzerland (S.H.); Department of Neurology, University Hospital, Cologne, Germany, and Research Center, Jülich, Germany (N.G.); Medicina Nucleare, Istituto Nazionale dei Tumori, Milano, Italy (F.C.).
authors.forename: Patrick
authors.initials: P
authors.lastname: Roth
authors.affiliation: Department of Neurology and Brain Tumor Center, Cantonal Hospital, Aarau, Switzerland (U.R.); Institute for Pharmacology and Toxicology, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Neuroscience Center, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Department of Neurology, Medical University, Innsbruck, Austria (M.N.); Department of Neuro-Oncology, University Hospital, Torino, Italy (R.R., R.S.); Department of Neurology, University Hospital, Switzerland (P.R., M.W.); Department of Oncology, University Hospital, Zürich, Switzerland (S.H.); Department of Neurology, University Hospital, Cologne, Germany, and Research Center, Jülich, Germany (N.G.); Medicina Nucleare, Istituto Nazionale dei Tumori, Milano, Italy (F.C.).
authors.forename: Silvia
authors.initials: S
authors.lastname: Hofer
authors.affiliation: Department of Neurology and Brain Tumor Center, Cantonal Hospital, Aarau, Switzerland (U.R.); Institute for Pharmacology and Toxicology, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Neuroscience Center, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Department of Neurology, Medical University, Innsbruck, Austria (M.N.); Department of Neuro-Oncology, University Hospital, Torino, Italy (R.R., R.S.); Department of Neurology, University Hospital, Switzerland (P.R., M.W.); Department of Oncology, University Hospital, Zürich, Switzerland (S.H.); Department of Neurology, University Hospital, Cologne, Germany, and Research Center, Jülich, Germany (N.G.); Medicina Nucleare, Istituto Nazionale dei Tumori, Milano, Italy (F.C.).
authors.forename: Norbert
authors.initials: N
authors.lastname: Galldiks
authors.affiliation: Department of Neurology and Brain Tumor Center, Cantonal Hospital, Aarau, Switzerland (U.R.); Institute for Pharmacology and Toxicology, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Neuroscience Center, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Department of Neurology, Medical University, Innsbruck, Austria (M.N.); Department of Neuro-Oncology, University Hospital, Torino, Italy (R.R., R.S.); Department of Neurology, University Hospital, Switzerland (P.R., M.W.); Department of Oncology, University Hospital, Zürich, Switzerland (S.H.); Department of Neurology, University Hospital, Cologne, Germany, and Research Center, Jülich, Germany (N.G.); Medicina Nucleare, Istituto Nazionale dei Tumori, Milano, Italy (F.C.).
authors.forename: Flavio
authors.initials: F
authors.lastname: Crippa
authors.affiliation: Department of Neurology and Brain Tumor Center, Cantonal Hospital, Aarau, Switzerland (U.R.); Institute for Pharmacology and Toxicology, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Neuroscience Center, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Department of Neurology, Medical University, Innsbruck, Austria (M.N.); Department of Neuro-Oncology, University Hospital, Torino, Italy (R.R., R.S.); Department of Neurology, University Hospital, Switzerland (P.R., M.W.); Department of Oncology, University Hospital, Zürich, Switzerland (S.H.); Department of Neurology, University Hospital, Cologne, Germany, and Research Center, Jülich, Germany (N.G.); Medicina Nucleare, Istituto Nazionale dei Tumori, Milano, Italy (F.C.).
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.affiliation: Department of Neurology and Brain Tumor Center, Cantonal Hospital, Aarau, Switzerland (U.R.); Institute for Pharmacology and Toxicology, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Neuroscience Center, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Department of Neurology, Medical University, Innsbruck, Austria (M.N.); Department of Neuro-Oncology, University Hospital, Torino, Italy (R.R., R.S.); Department of Neurology, University Hospital, Switzerland (P.R., M.W.); Department of Oncology, University Hospital, Zürich, Switzerland (S.H.); Department of Neurology, University Hospital, Cologne, Germany, and Research Center, Jülich, Germany (N.G.); Medicina Nucleare, Istituto Nazionale dei Tumori, Milano, Italy (F.C.).
authors.forename: Riccardo
authors.initials: R
authors.lastname: Soffietti
mesh_terms: D000328:Adult; D000596:Amino Acids; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019540:Area Under Curve; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000401:mortality; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D049268:Positron-Emission Tomography / Q000379:methods*; D012372:ROC Curve; D012640:Seizures / Q000209:etiology; D012680:Sensitivity and Specificity; D000077204:Temozolomide; D055815:Young Adult
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D003606:Dacarbazine; D000077204:Temozolomide
keywords: MRI; PET; chemotherapy; epilepsy; low-grade glioma