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Evaluation of pseudoprogression rates and tumor progression patterns in a phase III trial of bevacizumab plus radiotherapy/temozolomide for newly diagnosed glioblastoma.

Al's Comment:

 There has always been the fear that using Avastin would cause the tumor to become more invasive as the blood supply to the tumor gets cut off.  This article shows in a large number of patients that this fear is not justified.

Posted on: 08/18/2016

  Neuro Oncol. 2016 Aug 11. pii: now091. [Epub ahead of print]
Evaluation of pseudoprogression rates and tumor progression patterns in a phase III trial of bevacizumab plus radiotherapy/temozolomide for newly diagnosed glioblastoma.
Wick W1, Chinot OL1, Bendszus M1, Mason W 1, Henriksson R1, Saran F1, Nishikawa R1, Revil C1, Kerloeguen Y1, Cloughesy T1.
Author information:
1University 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.).
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.
© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail:


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