PMID- 33068421
OWN - NLM
STAT- MEDLINE
DCOM- 20210520
LR  - 20211204
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 23
IP  - 5
DP  - 2021 May 5
TI  - Associations of meningioma molecular subgroup and tumor recurrence.
PG  - 783-794
LID - 10.1093/neuonc/noaa226 [doi]
AB  - BACKGROUND: We and others have identified mutually exclusive molecular subgroups 
      of meningiomas; however, the implications of this classification for clinical 
      prognostication remain unclear. Integrated genomic and epigenomic analyses 
      implicate unique oncogenic processes associated with each subgroup, suggesting 
      the potential for divergent clinical courses. The aim of this study was to 
      understand the associated clinical outcomes of each subgroup, as this could 
      optimize treatment for patients. METHODS: We analyzed outcome data for 469 
      meningiomas of known molecular subgroup, including extent of resection, 
      postoperative radiation, surveillance imaging, and time to recurrence, when 
      applicable. Statistical relationships between outcome variables and subgroup were 
      assessed. Features previously associated with recurrence were further 
      investigated after stratification by subgroup. We used Kaplan-Meier analyses to 
      compare progression-free survival, and identified factors significantly 
      associated with recurrence using Cox proportional hazards modeling. RESULTS: 
      Meningioma molecular subgroups exhibited divergent clinical courses at 2 years of 
      follow-up, with several aggressive subgroups (NF2, PI3K, HH, tumor necrosis 
      factor receptor-associated factor 7 [TRAF7]) recurring at an average rate of 22 
      times higher than others (KLF4, POLR2A, SMARCB1). PI3K-activated tumors recurred 
      earlier than other subgroups but had intermediate long-term outcome. Among 
      low-grade tumors, HH and TRAF7 meningiomas exhibited elevated recurrence compared 
      with other subgroups. Recurrence of NF2 tumors was associated with male sex, high 
      grade, and elevated Ki-67. Multivariate analysis identified molecular subgroup as 
      an independent predictor of recurrence, along with grade and previous recurrence. 
      CONCLUSION: We describe distinct clinical outcomes and recurrence rates 
      associated with meningioma molecular subgroups. Our findings emphasize the 
      importance of genomic characterization to guide postoperative management 
      decisions for meningiomas.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of the 
      Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Youngblood, Mark W
AU  - Youngblood MW
AUID- ORCID: 0000-0002-1044-8015
AD  - Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, 
      Connecticut, USA.
AD  - Department of Neurological Surgery, Northwestern University, Chicago, Illinois, 
      USA.
FAU - Miyagishima, Danielle F
AU  - Miyagishima DF
AD  - Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, 
      Connecticut, USA.
AD  - Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut, USA.
AD  - Department of Genetics, Yale School of Medicine, New Haven, Connecticut, USA.
FAU - Jin, Lan
AU  - Jin L
AD  - Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, 
      Connecticut, USA.
FAU - Gupte, Trisha
AU  - Gupte T
AD  - Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, 
      Connecticut, USA.
AD  - Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut, USA.
FAU - Li, Chang
AU  - Li C
AD  - Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, 
      Connecticut, USA.
AD  - Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 
      China.
AD  - The Third Xiangya Hospital, Central South University, Changsha, China.
FAU - Duran, Daniel
AU  - Duran D
AD  - Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, 
      Connecticut, USA.
AD  - Department of Neurosurgery, University of Mississippi Medical Center, Jackson, 
      Mississippi, USA.
FAU - Montejo, Julio D
AU  - Montejo JD
AD  - Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, 
      Connecticut, USA.
AD  - Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, One Medical Center 
      Drive, Lebanon, New Hampshire, USA.
FAU - Zhao, Amy
AU  - Zhao A
AD  - Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, 
      Connecticut, USA.
FAU - Sheth, Amar
AU  - Sheth A
AD  - Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, 
      Connecticut, USA.
FAU - Tyrtova, Evgeniya
AU  - Tyrtova E
AD  - Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, 
      Connecticut, USA.
AD  - Department of Neurological Surgery, The University of Washington, Seattle, 
      Washington, USA.
FAU - Ozduman, Koray
AU  - Ozduman K
AD  - Department of Neurosurgery, Acibadem Mehmet Ali Aydinlar University, School of 
      Medicine, Istanbul, Turkey.
FAU - Iacoangeli, Francesco
AU  - Iacoangeli F
AD  - Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut, USA.
AD  - Department of Neurosurgery, Pitie-Salpetriere Hospital and Sorbonne University, 
      Paris, France.
FAU - Peyre, Matthieu
AU  - Peyre M
AD  - Department of Neurosurgery, Pitie-Salpetriere Hospital and Sorbonne University, 
      Paris, France.
AD  - Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, 
      Pennsylvania, USA.
FAU - Boetto, Julien
AU  - Boetto J
AD  - Department of Neurosurgery, Pitie-Salpetriere Hospital and Sorbonne University, 
      Paris, France.
FAU - Pease, Matthew
AU  - Pease M
AD  - Department of Neurosurgery, Pitie-Salpetriere Hospital and Sorbonne University, 
      Paris, France.
FAU - Avsar, Timucin
AU  - Avsar T
AD  - Department of Medical Biology, Bahcesehir University (BAU) Faculty of Medicine, 
      Istanbul, Turkey.
FAU - Huttner, Anita
AU  - Huttner A
AD  - Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, 
      Connecticut, USA.
AD  - Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
FAU - Bilguvar, Kaya
AU  - Bilguvar K
AD  - Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, 
      Connecticut, USA.
AD  - Yale Center for Genome Analysis, Yale University West Campus, Orange, 
      Connecticut, USA.
FAU - Kilic, Turker
AU  - Kilic T
AD  - Department of Neurosurgery, BAU, School of Medicine, Istanbul, Turkey.
FAU - Pamir, M Necmettin
AU  - Pamir MN
AD  - Department of Neurosurgery, Acibadem Mehmet Ali Aydinlar University, School of 
      Medicine, Istanbul, Turkey.
FAU - Amankulor, Nduka
AU  - Amankulor N
AD  - Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, 
      Pennsylvania, USA.
FAU - Kalamarides, Michel
AU  - Kalamarides M
AD  - Department of Neurosurgery, Pitie-Salpetriere Hospital and Sorbonne University, 
      Paris, France.
FAU - Erson-Omay, E Zeynep
AU  - Erson-Omay EZ
AD  - Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, 
      Connecticut, USA.
AD  - Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut, USA.
FAU - Gunel, Murat
AU  - Gunel M
AD  - Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, 
      Connecticut, USA.
AD  - Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut, USA.
AD  - Yale Center for Genome Analysis, Yale University West Campus, Orange, 
      Connecticut, USA.
FAU - Moliterno, Jennifer
AU  - Moliterno J
AD  - Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, 
      Connecticut, USA.
AD  - Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut, USA.
LA  - eng
GR  - F30 CA213666/CA/NCI NIH HHS/United States
GR  - T32 GM136651/GM/NIGMS NIH HHS/United States
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
GR  - T32 GM007205/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
SB  - IM
MH  - Epigenomics
MH  - Genomics
MH  - Humans
MH  - Kruppel-Like Factor 4
MH  - Male
MH  - *Meningeal Neoplasms/genetics
MH  - *Meningioma/genetics
MH  - Neoplasm Recurrence, Local/genetics
MH  - Retrospective Studies
PMC - PMC8099468
OTO - NOTNLM
OT  - meningioma genomics
OT  - molecular subgroups
OT  - precision medicine
OT  - tumor prognosis
EDAT- 2020/10/18 06:00
MHDA- 2021/05/21 06:00
PMCR- 2021/10/17
CRDT- 2020/10/17 17:04
PHST- 2020/10/18 06:00 [pubmed]
PHST- 2021/05/21 06:00 [medline]
PHST- 2020/10/17 17:04 [entrez]
PHST- 2021/10/17 00:00 [pmc-release]
AID - 5928913 [pii]
AID - noaa226 [pii]
AID - 10.1093/neuonc/noaa226 [doi]
PST - ppublish
SO  - Neuro Oncol. 2021 May 5;23(5):783-794. doi: 10.1093/neuonc/noaa226.