title: Progression types after antiangiogenic therapy are related to outcome in recurrent glioblastoma.
abstract: OBJECTIVE
  This retrospective study analyzed whether the type of radiologic progression, classified according to contrast enhancement on MRI T1-weighted sequences and changes in T2-hyperintense signal, is relevant for outcome in patients with progressive glioblastoma (pGB) treated with bevacizumab.
  
  
  METHODS
  MRI scans of 83 patients with pGB treated with bevacizumab were evaluated prior to and at disease progression. Based on initial decrease in and subsequent flare-up of contrast enhancement in T1 and 2 patterns of T2-hyperintense tumor progression, progression types (PTs) were categorized as cT1 flare-up, T2-diffuse, T2-circumscribed, or primary nonresponder. Overall survival (OS), survival from start of bevacizumab therapy (OS_Bev), survival after bevacizumab failure (OS_PostBev), time from initial diagnosis until initiation of bevacizumab therapy (StartBevT), and time to bevacizumab progression were evaluated using Kaplan-Meier curves, log-rank test, and Cox regression analyses.
  
  
  RESULTS
  The time observed for development of a T2-diffuse (n = 15) or a cT1 flare-up (n = 35) progression was longer than for progression in primary nonresponders (n = 16) or T2-circumscribed progression (n = 17). The T2-diffuse PT showed longer OS, OS_Bev, OS_PostBev, and StartBevT compared to the other PTs. Postprogression therapy tended to be relevant only for patients with a T2-circumscribed PT.
  
  
  CONCLUSIONS
  Radiologic PTs following bevacizumab treatment failure show differences in time to development and are related to outcome. We therefore hypothesize that these PTs reflect a different glioma biology, including differential resistance mechanisms to bevacizumab, and may be associated with different responses to postprogression therapy.
authors.affiliation: From the Departments of Neurology (M.N., M.H., G.S.) and Medical Statistics, Informatics and Health Economics (G.G.), Innsbruck Medical University, Austria; the Department of Neurooncology (B.W., W.W.), Neurology Clinic and National Center for Tumor Diseases, and the Department of Neuroradiology (M.N., M.B., A.R.), University of Heidelberg; the Department of Neurology (M.H.), Regensburg Medical University; the Department of Radiology (H.P.S.), the Clinical Cooperation Unit Neurooncology (B.W., W.W.), and Department of Radiology, Neurooncologic Imaging (E012) (A.R.), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Martha
authors.initials: M
authors.lastname: Nowosielski
authors.forename: Benedikt
authors.initials: B
authors.lastname: Wiestler
authors.forename: Georg
authors.initials: G
authors.lastname: Goebel
authors.forename: Markus
authors.initials: M
authors.lastname: Hutterer
authors.forename: Heinz P
authors.initials: HP
authors.lastname: Schlemmer
authors.forename: Günther
authors.initials: G
authors.lastname: Stockhammer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.forename: Martin
authors.initials: M
authors.lastname: Bendszus
authors.forename: Alexander
authors.initials: A
authors.lastname: Radbruch
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D059906:Neuroimaging; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab