PMID- 29718366
OWN - NLM
STAT- MEDLINE
DCOM- 20191018
LR  - 20191023
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 20
IP  - 11
DP  - 2018 Oct 9
TI  - Intratumoral heterogeneity of oxygen metabolism and neovascularization uncovers 2 
      survival-relevant subgroups of IDH1 wild-type glioblastoma.
PG  - 1536-1546
LID - 10.1093/neuonc/noy066 [doi]
AB  - BACKGROUND: The intratumoral heterogeneity of oxygen metabolism in combination 
      with variable patterns of neovascularization (NV) as well as reprogramming of 
      energy metabolism affects the landscape of tumor microenvironments (TMEs) in 
      glioblastoma. Knowledge of the hypoxic and perivascular niches within the TME is 
      essential for understanding treatment failure. METHODS: Fifty-two patients with 
      untreated glioblastoma (isocitrate dehydrogenase 1 wild type [IDH1wt]) were 
      examined with a physiological MRI protocol including a multiparametric 
      quantitative blood oxygen level dependent (qBOLD) approach and vascular 
      architecture mapping (VAM). Imaging biomarker information about oxygen metabolism 
      (mitochondrial oxygen tension) and neovascularization (microvascular density and 
      type) were fused for classification of 6 different TMEs: necrosis, hypoxia 
      with/without neovascularization, oxidative phosphorylation (OxPhos), and 
      glycolysis with/without neovascularization. Association of the different TME 
      volume fractions with progression-free survival (PFS) was assessed using 
      Kaplan-Meier analysis and Cox proportional hazards models. RESULTS: A common 
      spatial structure of TMEs was detected: central necrosis surrounded by tumor 
      hypoxia (with defective and functional neovasculature) and different TMEs with a 
      predominance of OxPhos and glycolysis for energy production, respectively. The 
      percentage of the different TMEs on the total tumor volume uncovered 2 clearly 
      different subtypes of glioblastoma IDH1wt: a glycolytic dominated phenotype with 
      predominantly functional neovasculature and a necrotic/hypoxic dominated 
      phenotype with approximately 50% of defective neovasculature. Patients with a 
      necrotic/hypoxic dominated phenotype showed significantly shorter PFS (P = 
      0.035). CONCLUSIONS: Our non-invasive mapping approach allows for classification 
      of the TME and detection of tumor-supportive niches in glioblastoma which may be 
      helpful for both clinical patient management and research.
FAU - Stadlbauer, Andreas
AU  - Stadlbauer A
AD  - Department of Neurosurgery, University of Erlangen-Nurnberg, Erlangen, Germany.
AD  - Institute of Medical Radiology, University Clinic of St Polten, St Polten, 
      Austria.
FAU - Zimmermann, Max
AU  - Zimmermann M
AD  - Department of Neurosurgery, University of Erlangen-Nurnberg, Erlangen, Germany.
FAU - Doerfler, Arnd
AU  - Doerfler A
AD  - Department of Neuroradiology, University of Erlangen-Nurnberg, Erlangen, Germany.
FAU - Oberndorfer, Stefan
AU  - Oberndorfer S
AD  - Department of Neurology, University Clinic of St Polten, St Polten, Austria.
FAU - Buchfelder, Michael
AU  - Buchfelder M
AD  - Department of Neurosurgery, University of Erlangen-Nurnberg, Erlangen, Germany.
FAU - Coras, Roland
AU  - Coras R
AD  - Department of Neuropathology, University of Erlangen-Nurnberg, Erlangen, Germany.
FAU - Kitzwogerer, Melitta
AU  - Kitzwogerer M
AD  - Department of Pathology, University Clinic of St Polten, St Polten, Austria.
FAU - Roessler, Karl
AU  - Roessler K
AD  - Department of Neurosurgery, University of Erlangen-Nurnberg, Erlangen, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - EC 1.1.1.41 (Isocitrate Dehydrogenase)
RN  - EC 1.1.1.42. (IDH1 protein, human)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Brain Neoplasms/blood supply/genetics/*mortality/pathology
MH  - Energy Metabolism
MH  - Female
MH  - Follow-Up Studies
MH  - Glioblastoma/blood supply/genetics/*mortality/pathology
MH  - Humans
MH  - Isocitrate Dehydrogenase/*genetics
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - *Neovascularization, Pathologic
MH  - Oxygen/*metabolism
MH  - Prognosis
MH  - Prospective Studies
MH  - Retrospective Studies
MH  - Survival Rate
MH  - *Tumor Microenvironment
PMC - PMC6176796
EDAT- 2018/05/03 06:00
MHDA- 2019/10/19 06:00
PMCR- 2019/10/09
CRDT- 2018/05/03 06:00
PHST- 2018/05/03 06:00 [pubmed]
PHST- 2019/10/19 06:00 [medline]
PHST- 2018/05/03 06:00 [entrez]
PHST- 2019/10/09 00:00 [pmc-release]
AID - 4989834 [pii]
AID - noy066 [pii]
AID - 10.1093/neuonc/noy066 [doi]
PST - ppublish
SO  - Neuro Oncol. 2018 Oct 9;20(11):1536-1546. doi: 10.1093/neuonc/noy066.