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@ARTICLE{Kessler:277801,
author = {T. Kessler$^*$ and D. Schrimpf$^*$ and L. Doerner and L.
Hai$^*$ and L. Kaulen$^*$ and J. Ito$^*$ and M. van den Bent
and M. Taphoorn and A. A. Brandes and A. Idbaih and J.
Dômont and P. M. Clement and M. Campone and M. Bendszus and
A. von Deimling$^*$ and F. Sahm$^*$ and M. Platten$^*$ and
W. Wick$^*$ and A. Wick},
title = {{P}rognostic markers of {DNA} methylation and {NGS}
sequencing in progressive glioblastoma from the
{EORTC}-26101 trial.},
journal = {Clinical cancer research},
volume = {29},
number = {19},
issn = {1078-0432},
address = {Philadelphia, Pa. [u.a.]},
publisher = {AACR},
reportid = {DKFZ-2023-01512},
pages = {3892-3900},
year = {2023},
note = {#EA:B320# / 2023 Oct 2;29(19):3892-3900},
abstract = {The EORTC-26101 study was a randomized phase 2 and 3
clinical trial of bevacizumab in combination with lomustine
versus lomustine alone in progressive glioblastoma. Other
than for progression-free survival (PFS), there was no
benefit from addition of bevacizumab for overall survival
(OS). However, molecular data allows for the rare
opportunity to assess prognostic biomarkers from primary
surgery for their impact in progressive glioblastoma.We
analyzed DNA methylation array data and panel sequencing
from 170 genes of 380 tumor samples of the EORTC-26101
study. These patients were comparable to the overall study
cohort in regards of baseline characteristics, study
treatment and survival.295/380 $(78\%)$ of patients' samples
were classified into one of the main glioblastoma groups
receptor tyrosine kinase (RTK)1, RTK2 and mesenchymal. There
were 10 patients $(2.6\%)$ with isocitrate dehydrogenase
(IDH) mutant tumors in the biomarker cohort. Patients with
RTK1 and RTK2 classified tumors had lower median OS compared
to mesenchymal (7.6 vs. 9.2 vs. 10.5 months).
O6-methylguanine DNA-methyltransferase (MGMT) promotor
methylation was prognostic for PFS and OS. Neurofibromin
(NF)1 mutations were predictive of response to bevacizumab
treatment.Thorough molecular classification is important for
brain tumor clinical trial inclusion and evaluation. MGMT
promoter methylation and RTK1 classifier assignment were
prognostic in progressive glioblastoma. NF1 mutation may be
a predictive biomarker for bevacizumab treatment.},
cin = {B320 / HD01 / B300 / D170},
ddc = {610},
cid = {I:(DE-He78)B320-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B300-20160331 / I:(DE-He78)D170-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37494539},
doi = {10.1158/1078-0432.CCR-23-0926},
url = {https://inrepo02.dkfz.de/record/277801},
}