Journal Article

DKFZ-2023-01512

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Prognostic markers of DNA methylation and NGS sequencing in progressive glioblastoma from the EORTC-26101 trial.

Kessler, T. (First author)DKFZ* ; Schrimpf, D.DKFZ* ; Doerner, L. ; Hai, L.DKFZ* ; Kaulen, L.DKFZ* ; Ito, J.DKFZ* ; van den Bent, M. ; Taphoorn, M. ; Brandes, A. A. ; Idbaih, A. ; Dômont, J. ; Clement, P. M. ; Campone, M. ; Bendszus, M. ; von Deimling, A.DKFZ* ; Sahm, F.DKFZ* ; Platten, M.DKFZ* ; Wick, W.DKFZ* ; Wick, A.

2023
AACR Philadelphia, Pa. [u.a.]

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Please use a persistent id in citations: doi:10.1158/1078-0432.CCR-23-0926

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.

Note: #EA:B320# / 2023 Oct 2;29(19):3892-3900

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Contributing Institute(s):

1. KKE Neuroonkologie (B320)
2. DKTK HD zentral (HD01)
3. KKE Neuropathologie (B300)
4. KKE Neuroimmunologie und Hirntumorimmunologie (D170)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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