title: Sustained focal antitumor activity of bevacizumab in recurrent glioblastoma.
abstract: OBJECTIVE
  To investigate the relevance of bevacizumab (BEV)-induced diffusion-restricted lesions and T1-hyperintense lesions in patients with recurrent glioblastoma.
  
  
  METHODS
  We prospectively screened 74 BEV-treated patients with recurrent glioblastoma for (1) diffusion-restricted lesions and/or, (2) lesions with a hyperintense signal on precontrast T1-weighted images. We further evaluated overall survival (OS), histopathology of the lesions, and patterns of progression.
  
  
  RESULTS
  Twenty-five of 74 patients (34%) developed T1-hyperintense lesions, whereas diffusion-restricted lesions could be detected in 35 of 74 patients (47%). In 21 of 74 patients (28%), the lesions displayed both features ("double-positive"). OS for patients with double-positive lesions was 13.0 months; patients with neither of these lesions had an OS of 6.6 months (p < 0.005). Histologic evaluation of double-positive lesions revealed extensive calcified necrosis in 4 of 4 patients. Notably, these double-positive lesions were rarely involved in further tumor progression. However, they were associated with an increase in distant recurrences at BEV failure.
  
  
  CONCLUSIONS
  BEV-induced double-positive MRI lesions are a predictive imaging marker associated with a substantial survival benefit and with improved local control in patients with recurrent glioblastoma. Our data suggest that these lesions are the result of a sustained focal antitumor activity of BEV.
authors.affiliation: From the Dr. Senckenberg Institute of Neurooncology (O.B., M.W.R., J.R., J.P.S.), Institute of Neurology (Edinger-Institute) (P.N.H., M.M.), Department of Neurosurgery (L.M.W.), and Institute of Neuroradiology (S.-J.Y., E.H.), University Hospital Frankfurt, Goethe University, Frankfurt; and German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) (O.B., P.N.H., L.M.W., S.-J.Y., M.M., M.W.R., J.R., J.P.S., E.H.), Heidelberg, Germany. oliver.baehr@med.uni-frankfurt.de.
authors.forename: Oliver
authors.initials: O
authors.lastname: Bähr
authors.affiliation: From the Dr. Senckenberg Institute of Neurooncology (O.B., M.W.R., J.R., J.P.S.), Institute of Neurology (Edinger-Institute) (P.N.H., M.M.), Department of Neurosurgery (L.M.W.), and Institute of Neuroradiology (S.-J.Y., E.H.), University Hospital Frankfurt, Goethe University, Frankfurt; and German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) (O.B., P.N.H., L.M.W., S.-J.Y., M.M., M.W.R., J.R., J.P.S., E.H.), Heidelberg, Germany.
authors.forename: Patrick N
authors.initials: PN
authors.lastname: Harter
authors.affiliation: From the Dr. Senckenberg Institute of Neurooncology (O.B., M.W.R., J.R., J.P.S.), Institute of Neurology (Edinger-Institute) (P.N.H., M.M.), Department of Neurosurgery (L.M.W.), and Institute of Neuroradiology (S.-J.Y., E.H.), University Hospital Frankfurt, Goethe University, Frankfurt; and German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) (O.B., P.N.H., L.M.W., S.-J.Y., M.M., M.W.R., J.R., J.P.S., E.H.), Heidelberg, Germany.
authors.forename: Lutz M
authors.initials: LM
authors.lastname: Weise
authors.affiliation: From the Dr. Senckenberg Institute of Neurooncology (O.B., M.W.R., J.R., J.P.S.), Institute of Neurology (Edinger-Institute) (P.N.H., M.M.), Department of Neurosurgery (L.M.W.), and Institute of Neuroradiology (S.-J.Y., E.H.), University Hospital Frankfurt, Goethe University, Frankfurt; and German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) (O.B., P.N.H., L.M.W., S.-J.Y., M.M., M.W.R., J.R., J.P.S., E.H.), Heidelberg, Germany.
authors.forename: Se-Jong
authors.initials: SJ
authors.lastname: You
authors.affiliation: From the Dr. Senckenberg Institute of Neurooncology (O.B., M.W.R., J.R., J.P.S.), Institute of Neurology (Edinger-Institute) (P.N.H., M.M.), Department of Neurosurgery (L.M.W.), and Institute of Neuroradiology (S.-J.Y., E.H.), University Hospital Frankfurt, Goethe University, Frankfurt; and German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) (O.B., P.N.H., L.M.W., S.-J.Y., M.M., M.W.R., J.R., J.P.S., E.H.), Heidelberg, Germany.
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.affiliation: From the Dr. Senckenberg Institute of Neurooncology (O.B., M.W.R., J.R., J.P.S.), Institute of Neurology (Edinger-Institute) (P.N.H., M.M.), Department of Neurosurgery (L.M.W.), and Institute of Neuroradiology (S.-J.Y., E.H.), University Hospital Frankfurt, Goethe University, Frankfurt; and German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) (O.B., P.N.H., L.M.W., S.-J.Y., M.M., M.W.R., J.R., J.P.S., E.H.), Heidelberg, Germany.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Ronellenfitsch
authors.affiliation: From the Dr. Senckenberg Institute of Neurooncology (O.B., M.W.R., J.R., J.P.S.), Institute of Neurology (Edinger-Institute) (P.N.H., M.M.), Department of Neurosurgery (L.M.W.), and Institute of Neuroradiology (S.-J.Y., E.H.), University Hospital Frankfurt, Goethe University, Frankfurt; and German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) (O.B., P.N.H., L.M.W., S.-J.Y., M.M., M.W.R., J.R., J.P.S., E.H.), Heidelberg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Rieger
authors.affiliation: From the Dr. Senckenberg Institute of Neurooncology (O.B., M.W.R., J.R., J.P.S.), Institute of Neurology (Edinger-Institute) (P.N.H., M.M.), Department of Neurosurgery (L.M.W.), and Institute of Neuroradiology (S.-J.Y., E.H.), University Hospital Frankfurt, Goethe University, Frankfurt; and German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) (O.B., P.N.H., L.M.W., S.-J.Y., M.M., M.W.R., J.R., J.P.S., E.H.), Heidelberg, Germany.
authors.forename: Joachim P
authors.initials: JP
authors.lastname: Steinbach
authors.affiliation: From the Dr. Senckenberg Institute of Neurooncology (O.B., M.W.R., J.R., J.P.S.), Institute of Neurology (Edinger-Institute) (P.N.H., M.M.), Department of Neurosurgery (L.M.W.), and Institute of Neuroradiology (S.-J.Y., E.H.), University Hospital Frankfurt, Goethe University, Frankfurt; and German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) (O.B., P.N.H., L.M.W., S.-J.Y., M.M., M.W.R., J.R., J.P.S., E.H.), Heidelberg, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Hattingen
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000068258:Bevacizumab; D054316:Biomarkers, Pharmacological; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D018316:Gliosarcoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D054316:Biomarkers, Pharmacological; D000068258:Bevacizumab