title: The Diagnostic Ability of Follow-Up Imaging Biomarkers after Treatment of Glioblastoma in the Temozolomide Era: Implications from Proton MR Spectroscopy and Apparent Diffusion Coefficient Mapping.
abstract: OBJECTIVE
  To prospectively determine institutional cut-off values of apparent diffusion coefficients (ADCs) and concentration of tissue metabolites measured by MR spectroscopy (MRS) for early differentiation between glioblastoma (GBM) relapse and treatment-related changes after standard treatment.
  
  
  METHODS
  Twenty-four GBM patients who received gross total resection and standard adjuvant therapy underwent MRI examination focusing on the enhancing region suspected of tumor recurrence. ADC maps, concentrations of N-acetylaspartate, choline, creatine, lipids, and lactate, and metabolite ratios were determined. Final diagnosis as determined by biopsy or follow-up imaging was correlated to the results of advanced MRI findings.
  
  
  RESULTS
  Eighteen (75%) and 6 (25%) patients developed tumor recurrence and pseudoprogression, respectively. Mean time to radiographic progression from the end of chemoradiotherapy was 5.8 ± 5.6 months. Significant differences in ADC and MRS data were observed between those with progression and pseudoprogression. Recurrence was characterized by N-acetylaspartate ≤ 1.5 mM, choline/N-acetylaspartate ≥ 1.4 (sensitivity 100%, specificity 91.7%), N-acetylaspartate/creatine ≤ 0.7, and ADC ≤ 1300 × 10(-6) mm(2)/s (sensitivity 100%, specificity 100%).
  
  
  CONCLUSIONS
  Institutional validation of cut-off values obtained from advanced MRI methods is warranted not only for diagnosis of GBM recurrence, but also as enrollment criteria in salvage clinical trials and for reporting of outcomes of initial treatment.
authors.affiliation: Department of Diagnostic Imaging, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic ; Department of Diagnostic Imaging, St. Anne's University Hospital Brno, 656 91 Brno, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Bulik
authors.affiliation: International Clinical Research Center, St. Anne's University Hospital Brno, 656 91 Brno, Czech Republic ; Department of Radiation Oncology, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic ; Department of Radiation Oncology, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Kazda
authors.affiliation: Department of Radiation Oncology, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic ; Department of Radiation Oncology, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Slampa
authors.affiliation: International Clinical Research Center, St. Anne's University Hospital Brno, 656 91 Brno, Czech Republic ; Department of Neurosurgery, St. Anne's University Hospital Brno, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic ; Department of Neurosurgery, St. Anne's University Hospital Brno, 656 91 Brno, Czech Republic.
authors.forename: Radim
authors.initials: R
authors.lastname: Jancalek
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D056324:Diffusion Tensor Imaging; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control; D017063:Outcome Assessment, Health Care / Q000379:methods; D011379:Prognosis; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D003606:Dacarbazine; D000077204:Temozolomide