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. In a pediatric high-grade non-brainstem glioma cohort, Mackay et al. show that hypermutator tumors and those resembling pleomorphic xanthoastrocytoma are highly infiltrated by CD8+ lymphocytes and benefit from the addition of bevacizumab, whereas the histone H3 subgroups are immune cold and have a poor outcome.
| Original language | English |
|---|---|
| Pages (from-to) | 829-842.e5 |
| Journal | Cancer Cell |
| Volume | 33 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 14 2018 |
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Keywords
- CD8
- H3F3A
- hypermutator
- immune
- MAPK
- pediatric high-grade glioma
ASJC Scopus subject areas
- Oncology
- Cell Biology
- Cancer Research
Cite this
Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial. / Mackay, Alan; Burford, Anna; Molinari, Valeria; Jones, David T.W.; Izquierdo, Elisa; Brouwer-Visser, Jurriaan; Giangaspero, Felice; Haberler, Christine; Pietsch, Torsten; Jacques, Thomas S.; Figarella-Branger, Dominique; Rodriguez, Daniel; Morgan, Paul S.; Raman, Pichai; Waanders, Angela J.; Resnick, Adam C.; Massimino, Maura; Garrè, Maria Luisa; Smith, Helen; Capper, David; Pfister, Stefan M.; Würdinger, Thomas; Tam, Rachel; Garcia, Josep; Thakur, Meghna Das; Vassal, Gilles; Grill, Jacques; Jaspan, Tim; Varlet, Pascale; Jones, Chris.
In: Cancer Cell, Vol. 33, No. 5, 14.05.2018, p. 829-842.e5.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial
AU - Mackay, Alan
AU - Burford, Anna
AU - Molinari, Valeria
AU - Jones, David T.W.
AU - Izquierdo, Elisa
AU - Brouwer-Visser, Jurriaan
AU - Giangaspero, Felice
AU - Haberler, Christine
AU - Pietsch, Torsten
AU - Jacques, Thomas S.
AU - Figarella-Branger, Dominique
AU - Rodriguez, Daniel
AU - Morgan, Paul S.
AU - Raman, Pichai
AU - Waanders, Angela J.
AU - Resnick, Adam C.
AU - Massimino, Maura
AU - Garrè, Maria Luisa
AU - Smith, Helen
AU - Capper, David
AU - Pfister, Stefan M.
AU - Würdinger, Thomas
AU - Tam, Rachel
AU - Garcia, Josep
AU - Thakur, Meghna Das
AU - Vassal, Gilles
AU - Grill, Jacques
AU - Jaspan, Tim
AU - Varlet, Pascale
AU - Jones, Chris
PY - 2018/5/14
Y1 - 2018/5/14
N2 - 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. In a pediatric high-grade non-brainstem glioma cohort, Mackay et al. show that hypermutator tumors and those resembling pleomorphic xanthoastrocytoma are highly infiltrated by CD8+ lymphocytes and benefit from the addition of bevacizumab, whereas the histone H3 subgroups are immune cold and have a poor outcome.
AB - 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. In a pediatric high-grade non-brainstem glioma cohort, Mackay et al. show that hypermutator tumors and those resembling pleomorphic xanthoastrocytoma are highly infiltrated by CD8+ lymphocytes and benefit from the addition of bevacizumab, whereas the histone H3 subgroups are immune cold and have a poor outcome.
KW - CD8
KW - H3F3A
KW - hypermutator
KW - immune
KW - MAPK
KW - pediatric high-grade glioma
UR - http://www.scopus.com/inward/record.url?scp=85046812565&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046812565&partnerID=8YFLogxK
U2 - 10.1016/j.ccell.2018.04.004
DO - 10.1016/j.ccell.2018.04.004
M3 - Article
AN - SCOPUS:85046812565
VL - 33
SP - 829-842.e5
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 5
ER -