WHO grade has no prognostic value in the pediatric high-grade glioma included in the HERBY trial.
Adolescent
Antineoplastic Agents
/ administration & dosage
Bevacizumab
/ administration & dosage
Brain Neoplasms
/ pathology
Chemoradiotherapy
/ methods
Child
Child, Preschool
Clinical Trials, Phase II as Topic
Datasets as Topic
Female
Glioma
/ pathology
Humans
Male
Multicenter Studies as Topic
Neoplasm Grading
/ standards
Prognosis
Randomized Controlled Trials as Topic
Temozolomide
/ administration & dosage
World Health Organization
Ki-67
grading criteria
high-grade glioma
pediatric
Journal
Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420
Informations de publication
Date de publication:
11 01 2020
11 01 2020
Historique:
pubmed:
17
8
2019
medline:
11
2
2021
entrez:
17
8
2019
Statut:
ppublish
Résumé
The World Health Organization (WHO) adult glioma grading system is questionable in pediatric high-grade gliomas (pHGGs), which are biologically distinct from adult HGGs. We took advantage of the neuropathological review data obtained during one of the largest prospective randomized pHGG trials, namely HERBY (NCT01390948), to address this issue in children with newly diagnosed non-brainstem HGG. HGG diagnosis was confirmed by pre-randomization, real-time central pathology review using WHO 2007 criteria, followed by a consensus review blinded to clinical factors and outcomes. We evaluated association between WHO 2007 grade and other clinical/radiological/biological characteristics and the prognostic value of WHO 2007 grade, midline location, and selected biomarkers (Ki-67 index/Olig2/CD34/EGFR/p53/H3F3A K27M mutation) on overall survival. Real-time central neuropathological review was feasible in a multicenter study, with a mean time of 2.4 days, and led to the rejection of HGG diagnosis in 20 of 163 cases (12.3%). The different grading criteria and resulting WHO grade were not significantly associated with overall survival in the entire population (n = 118) or in midline and non-midline subgroups. H3F3A K27M mutation was significantly associated with poor outcome. No significant prognostic value was observed for grade, even after regrading H3F3A K27M-mutated midline glioma as grade IV (WHO 2016). Midline location and a high Ki-67 index (≥20%) were associated with poor outcome (P = 0.004 and P = 0.04, respectively). A 10% increase in Ki-67 index was associated with a hazard ratio of 1.53 (95% CI: 1.27-1.83; P < 0.0001). Our findings suggest that WHO grade III versus IV has no prognostic value in pediatric HGG.
Sections du résumé
BACKGROUND
The World Health Organization (WHO) adult glioma grading system is questionable in pediatric high-grade gliomas (pHGGs), which are biologically distinct from adult HGGs. We took advantage of the neuropathological review data obtained during one of the largest prospective randomized pHGG trials, namely HERBY (NCT01390948), to address this issue in children with newly diagnosed non-brainstem HGG.
METHODS
HGG diagnosis was confirmed by pre-randomization, real-time central pathology review using WHO 2007 criteria, followed by a consensus review blinded to clinical factors and outcomes. We evaluated association between WHO 2007 grade and other clinical/radiological/biological characteristics and the prognostic value of WHO 2007 grade, midline location, and selected biomarkers (Ki-67 index/Olig2/CD34/EGFR/p53/H3F3A K27M mutation) on overall survival.
RESULTS
Real-time central neuropathological review was feasible in a multicenter study, with a mean time of 2.4 days, and led to the rejection of HGG diagnosis in 20 of 163 cases (12.3%). The different grading criteria and resulting WHO grade were not significantly associated with overall survival in the entire population (n = 118) or in midline and non-midline subgroups. H3F3A K27M mutation was significantly associated with poor outcome. No significant prognostic value was observed for grade, even after regrading H3F3A K27M-mutated midline glioma as grade IV (WHO 2016). Midline location and a high Ki-67 index (≥20%) were associated with poor outcome (P = 0.004 and P = 0.04, respectively). A 10% increase in Ki-67 index was associated with a hazard ratio of 1.53 (95% CI: 1.27-1.83; P < 0.0001).
CONCLUSION
Our findings suggest that WHO grade III versus IV has no prognostic value in pediatric HGG.
Identifiants
pubmed: 31419298
pii: 5550833
doi: 10.1093/neuonc/noz142
pmc: PMC6954414
doi:
Substances chimiques
Antineoplastic Agents
0
Bevacizumab
2S9ZZM9Q9V
Temozolomide
YF1K15M17Y
Banques de données
ClinicalTrials.gov
['NCT01390948']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
116-127Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.
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