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Radiologic progression of glioblastoma under therapy-an exploratory analysis of AVAglio.

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Date
2018-03
ICR Author
Marsden,
Author
Nowosielski, M
Ellingson, BM
Chinot, OL
Garcia, J
Revil, C
Radbruch, A
Nishikawa, R
Mason, WP
Henriksson, R
Saran, F
Kickingereder, P
Platten, M
Sandmann, T
Abrey, LE
Cloughesy, TF
Bendszus, M
Wick, W
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Type
Journal Article
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Abstract
Background In this exploratory analysis of AVAglio, a randomized phase III clinical study that investigated the addition of bevacizumab (Bev) to radiotherapy/temozolomide in newly diagnosed glioblastoma, we aim to radiologically characterize glioblastoma on therapy until progression and investigate whether the type of radiologic progression differs between treatment arms and is related to survival and molecular data.Methods Five progression types (PTs) were categorized using an adapted algorithm according to MRI contrast enhancement behavior in T1- and T2-weighted images in 621 patients (Bev, n = 299; placebo, n = 322). Frequencies of PTs (designated as classic T1, cT1 relapse, T2 diffuse, T2 circumscribed, and primary nonresponder), time to progression (PFS), and overall survival (OS) were assessed within each treatment arm and compared with molecular subtypes and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status.Results PT frequencies differed between the Bev and placebo arms, except for "T2 diffuse" (12.4% and 7.1%, respectively). PTs showed differences in PFS and OS; with "T2 diffuse" being associated with longest survival. Complete disappearance of contrast enhancement during treatment ("cT1 relapse") showed longer survival than only partial contrast enhancement decrease ("classic T1"). "T2 diffuse" was more commonly MGMT hypermethylated. Only weak correlations to molecular subtypes from primary tissue were detected.Conclusions Progression of glioblastoma under therapy can be characterized radiologically. These radiologic phenotypes are influenced by treatment and develop differently over time with differential outcomes. Complete resolution of contrast enhancement during treatment is a favorable factor for outcome.
URI
https://repository.icr.ac.uk/handle/internal/1234
DOI
https://doi.org/10.1093/neuonc/nox162
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Subject
Humans
Glioblastoma
Brain Neoplasms
Neoplasm Recurrence, Local
Disease Progression
Antineoplastic Combined Chemotherapy Protocols
Magnetic Resonance Imaging
Prognosis
Survival Rate
Retrospective Studies
Follow-Up Studies
Double-Blind Method
DNA Methylation
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Promoter Regions, Genetic
Chemoradiotherapy
Biomarkers, Tumor
Bevacizumab
Temozolomide
Language
eng
License start date
2018-03
Citation
Neuro-oncology, 2018, 20 (4), pp. 557 - 566

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