Journal Article

DKFZ-2018-00623

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial.

Mackay, A. ; Burford, A. ; Molinari, V. ; Jones, D.DKFZ* ; Izquierdo, E. ; Brouwer-Visser, J. ; Giangaspero, F. ; Haberler, C. ; Pietsch, T. ; Jacques, T. S. ; Figarella-Branger, D. ; Rodriguez, D. ; Morgan, P. S. ; Raman, P. ; Waanders, A. J. ; Resnick, A. C. ; Massimino, M. ; Garrè, M. L. ; Smith, H. ; Capper, D.DKFZ* ; Pfister, S.DKFZ* ; Würdinger, T. ; Tam, R. ; Garcia, J. ; Thakur, M. D. ; Vassal, G. ; Grill, J. ; Jaspan, T. ; Varlet, P. ; Jones, C.

2018
Cell Press Cambridge, Mass.

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Please use a persistent id in citations: doi:10.1016/j.ccell.2018.04.004

Abstract: The HERBY trial was a phase II open-label, randomized, multicenter trial evaluating bevacizumab (BEV) in addition to temozolomide/radiotherapy in patients with newly diagnosed non-brainstem high-grade glioma (HGG) between the ages of 3 and 18 years. We carried out comprehensive molecular analysis integrated with pathology, radiology, and immune profiling. In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency and somatic POLE/POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytoma ([PXA]-like, driven by BRAF_V600E or NF1 mutation) had significantly more CD8+ tumor-infiltrating lymphocytes, and longer survival with the addition of BEV. Histone H3 subgroups (hemispheric G34R/V and midline K27M) had a worse outcome and were immune cold. Future clinical trials will need to take into account the diversity represented by the term 'HGG' in the pediatric population.

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Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. DKTK Heidelberg (L101)
3. KKE Neuropathologie (G380)
4. DKTK Berlin (L201)

Research Program(s):

1. 319H - Addenda (POF3-319H) (POF3-319H)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 20 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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