title: Secondary Glioblastoma: Molecular and Clinical Factors That Affect Outcome After Malignant Progression of a Lower Grade Tumor.
abstract: OBJECTIVE
  There is limited information on prognostic factors and outcomes in patients with secondary glioblastoma (sGBM). Herein we report on the outcomes of patients with sGBM and identify clinically relevant prognostic factors.
  
  
  METHODS
  We retrospectively analyzed our institutional database for patients with histologic evidence of World Health Organization (WHO) grade II-III gliomas that went on to develop WHO grade IV sGBM. The assessment of the isocitrate dehydrogenase-1 (IDH1) R132H mutation was performed by immunohistochemical staining.
  
  
  RESULTS
  Forty-five patients with sGBM were included within our analysis (median age, 41 years). Mutated IDH1 (R132H) protein was present within the gliomas of 24 patients and was absent in 17. Immunohistochemistry assessment could not be performed for 4 patients. The median time between first diagnosis of glioma and sGBM was 158.9 weeks. Median overall survival (OS) after a diagnosis of sGBM was 63.6 weeks. When assessing patient-specific (i.e., therapy-independent) factors, mutated IDH1 (R132H) protein (P = 0.01; hazard ratio (HR), 0.54; confidence interval (CI) 0.33-0.87), WHO grade II tumor as precursor lesion (P = 0.05; HR, 0.49; CI 0.25-0.97), and a frontal tumor location (P = 0.04; HR, 0.48; CI 0.23-0.99) were found to be associated with better OS by multivariate analysis. Our data further indicate that complete tumor removal is associated with better patient survival in sGBM patients within certain risk groups (time period to development of sGBM, >104 weeks; initial WHO grade II tumor, IDH1 mutation, and time period to development of sGBM, >104 weeks; initial WHO grade II or III tumor, IDH1 wild type, frontal lobe localization).
  
  
  CONCLUSIONS
  Our retrospective analysis suggested that the presence of an IDH1 (R132H) mutation, frontal tumor location, and WHO grade of the initial tumor are associated with OS after progression to sGBM. In addition, some patients with sGBM may benefit from complete tumor resection depending on these patient-specific parameters. This is a finding that will ultimately need prospective validation.
authors.affiliation: Department of Neurosurgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany. Electronic address: f.gessler@med.uni-frankfurt.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Gessler
authors.affiliation: Department of Neurosurgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zappi
authors.affiliation: Department of Neurosurgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Konczalla
authors.affiliation: Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS/NIH), Bethesda, Maryland, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Bernstock
authors.affiliation: Department of Neurosurgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany.
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Forster
authors.affiliation: Institute of Neuroradiology, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany.
authors.forename: Marlies
authors.initials: M
authors.lastname: Wagner
authors.affiliation: Institute of Neurology (Edinger-Institute), University Hospital Frankfurt, Goethe-University, Frankfurt, Germany.
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.affiliation: Department of Neurosurgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Seifert
authors.affiliation: Department of Neurosurgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Senft
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000556:secondary* / Q000628:therapy; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000556:secondary* / Q000628:therapy; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D012189:Retrospective Studies; D018709:Statistics, Nonparametric
chemical_list: D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: IDH1 mutation (R132H); Predictive scoring system; Prognostic factors; Secondary glioblastoma (sGBM)