title: Evaluation of pseudoprogression rates and tumor progression patterns in a phase III trial of bevacizumab plus radiotherapy/temozolomide for newly diagnosed glioblastoma.
abstract: Evaluation of glioblastoma disease status may be complicated by treatment-induced changes and discordance between enhancing and nonenhancing MRI. Exploratory analyses are presented (prospectively assessed pseudoprogression and therapy-related tumor pattern changes) from the AVAglio trial (bevacizumab or placebo plus radiotherapy/temozolomide for newly diagnosed glioblastoma).
  
  
  
  MRI was done every 8 weeks (beginning 4 wk after chemoradiotherapy) using prespecified and standardized T1 and T2 protocols. Progressive disease (PD) at 10 weeks was reconfirmed at 18 weeks to distinguish pseudoprogression. Progression-free survival (PFS), excluding cases of confirmed pseudoprogression, was assessed (post-hoc/exploratory). Tumor progression patterns were determined at each disease assessment/PD (prespecified/exploratory).
  
  
  
  Of patients with PD in the bevacizumab and placebo arms, 143/354 (40.4%) and 155/387 (40.1%), respectively, had PD due to contrast-enhancing lesions, and 51/354 (14.4%) and 53/387 (13.7%) had PD due to nonenhancing lesions. Of all patients in the bevacizumab arm (n = 458), 2.2% had confirmed pseudoprogression versus 9.3% in the placebo arm (n = 463). Baseline characteristics did not differ between patients with/without pseudoprogression (including for MGMT status). Excluding confirmed pseudoprogression, PFS (hazard ratio: 0.65, 95% CI: 0.56-0.75; P < .0001, bevacizumab vs placebo) was comparable to the intent-to-treat population. At PD, most patients had the same tumor focus (local/multifocal, >84%) and infiltrative profile (>88%) as at baseline; no shift to a diffuse or multifocal phenotype was observed.
  
  
  
  Pseudoprogression complicated progression assessment in a small but relevant number of patients but had negligible impact on PFS. Bevacizumab did not appear to adversely impact tumor progression patterns.
authors: University Medical Center, Heidelberg, Germany (W.W., M.B.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Princess Margaret Hospital, * Toronto, Canada (W.M.); Regional Cancer Center Stockholm Gotland, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden (R.H.); The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Saitama Medical University, Iruma, Saitama Prefecture, Japan (R.N.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (C.R., Y.K.); University of California Los Angeles, Los Angeles, California (T.C.) wolfgang.wick@med.uni-heidelberg.de.
authors: Wolfgang
authors: W
authors: Wick
authors: University Medical Center, Heidelberg, Germany (W.W., M.B.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Princess Margaret Hospital, * Toronto, Canada (W.M.); Regional Cancer Center Stockholm Gotland, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden (R.H.); The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Saitama Medical University, Iruma, Saitama Prefecture, Japan (R.N.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (C.R., Y.K.); University of California Los Angeles, Los Angeles, California (T.C.).
authors: Olivier L
authors: OL
authors: Chinot
authors: University Medical Center, Heidelberg, Germany (W.W., M.B.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Princess Margaret Hospital, * Toronto, Canada (W.M.); Regional Cancer Center Stockholm Gotland, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden (R.H.); The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Saitama Medical University, Iruma, Saitama Prefecture, Japan (R.N.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (C.R., Y.K.); University of California Los Angeles, Los Angeles, California (T.C.).
authors: Martin
authors: M
authors: Bendszus
authors: University Medical Center, Heidelberg, Germany (W.W., M.B.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Princess Margaret Hospital, * Toronto, Canada (W.M.); Regional Cancer Center Stockholm Gotland, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden (R.H.); The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Saitama Medical University, Iruma, Saitama Prefecture, Japan (R.N.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (C.R., Y.K.); University of California Los Angeles, Los Angeles, California (T.C.).
authors: Warren
authors: W
authors: Mason
authors: University Medical Center, Heidelberg, Germany (W.W., M.B.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Princess Margaret Hospital, * Toronto, Canada (W.M.); Regional Cancer Center Stockholm Gotland, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden (R.H.); The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Saitama Medical University, Iruma, Saitama Prefecture, Japan (R.N.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (C.R., Y.K.); University of California Los Angeles, Los Angeles, California (T.C.).
authors: Roger
authors: R
authors: Henriksson
authors: University Medical Center, Heidelberg, Germany (W.W., M.B.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Princess Margaret Hospital, * Toronto, Canada (W.M.); Regional Cancer Center Stockholm Gotland, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden (R.H.); The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Saitama Medical University, Iruma, Saitama Prefecture, Japan (R.N.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (C.R., Y.K.); University of California Los Angeles, Los Angeles, California (T.C.).
authors: Frank
authors: F
authors: Saran
authors: University Medical Center, Heidelberg, Germany (W.W., M.B.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Princess Margaret Hospital, * Toronto, Canada (W.M.); Regional Cancer Center Stockholm Gotland, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden (R.H.); The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Saitama Medical University, Iruma, Saitama Prefecture, Japan (R.N.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (C.R., Y.K.); University of California Los Angeles, Los Angeles, California (T.C.).
authors: Ryo
authors: R
authors: Nishikawa
authors: University Medical Center, Heidelberg, Germany (W.W., M.B.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Princess Margaret Hospital, * Toronto, Canada (W.M.); Regional Cancer Center Stockholm Gotland, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden (R.H.); The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Saitama Medical University, Iruma, Saitama Prefecture, Japan (R.N.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (C.R., Y.K.); University of California Los Angeles, Los Angeles, California (T.C.).
authors: Cedric
authors: C
authors: Revil
authors: University Medical Center, Heidelberg, Germany (W.W., M.B.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Princess Margaret Hospital, * Toronto, Canada (W.M.); Regional Cancer Center Stockholm Gotland, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden (R.H.); The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Saitama Medical University, Iruma, Saitama Prefecture, Japan (R.N.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (C.R., Y.K.); University of California Los Angeles, Los Angeles, California (T.C.).
authors: Yannick
authors: Y
authors: Kerloeguen
authors: University Medical Center, Heidelberg, Germany (W.W., M.B.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Princess Margaret Hospital, * Toronto, Canada (W.M.); Regional Cancer Center Stockholm Gotland, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden (R.H.); The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Saitama Medical University, Iruma, Saitama Prefecture, Japan (R.N.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (C.R., Y.K.); University of California Los Angeles, Los Angeles, California (T.C.).
authors: Timothy
authors: T
authors: Cloughesy
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D000068258:Bevacizumab / Q000008:administration & dosage / Q000009:adverse effects; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000077204:Temozolomide
chemical_list: D000068258:Bevacizumab; D003606:Dacarbazine; D000077204:Temozolomide
keywords: glioblastoma; pseudoprogression; response; tumor pattern