Evidence map›Paper›PMID 27515827›Full record

Trial reportNeuro-oncology2016

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

Wolfgang Wick, Olivier L Chinot, Martin Bendszus, Warren Mason, Roger Henriksson, Frank Saran, Ryo Nishikawa, Cedric Revil, Yannick Kerloeguen, Timothy Cloughesy

Abstract readClinical Trial, Phase IIIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 5 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
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  4. Anti-epidermal growth factor receptor therapy for glioblastoma in adults.The Cochrane database of systematic reviews · 2020
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1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Wolfgang WickUniversity 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.
Olivier L ChinotUniversity 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.).
Martin BendszusUniversity 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.).
Warren MasonUniversity 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.).
Roger HenrikssonUniversity 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.).
Frank SaranUniversity 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.).
Ryo NishikawaUniversity 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.).
Cedric RevilUniversity 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.).
Yannick KerloeguenUniversity 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.).
Timothy CloughesyUniversity 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.).

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEvaluation 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).

methodsMRI 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).

resultsOf 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.

conclusionsPseudoprogression 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.

Indexed as

AdultAgedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBrain NeoplasmsChemoradiotherapyDacarbazineDisease-Free SurvivalDisease ProgressionDouble-Blind MethodFemaleGlioblastomaHumansImage Interpretation, Computer-AssistedKaplan-Meier EstimateMagnetic Resonance ImagingBevacizumabDacarbazineTemozolomideglioblastomapseudoprogressionresponsetumor pattern

Identifiers

PMID27515827
PMCPMC5035525

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.