Clinical & Experimental Metastasis

, Volume 30, Issue 4, pp 357–368 | Cite as

Extent of peritumoral brain edema correlates with prognosis, tumoral growth pattern, HIF1a expression and angiogenic activity in patients with single brain metastases

  • Thomas Spanberger
  • Anna S. Berghoff
  • Carina Dinhof
  • Aysegül Ilhan-Mutlu
  • Manuel Magerle
  • Markus Hutterer
  • Josef Pichler
  • Adelheid Wöhrer
  • Monika Hackl
  • Georg Widhalm
  • Johannes A. Hainfellner
  • Karin Dieckmann
  • Christine Marosi
  • Peter Birner
  • Daniela Prayer
  • Matthias PreusserEmail author
Research Paper


To analyze the prognostic value of the extent of peritumoral brain edema in patients operated for single brain metastases (BM), we retrospectively evaluated pre-operative magnetic resonance images in a discovery cohort of 129 patients and a validation cohort of 118 patients, who underwent neurosurgical resection of a single BM in two different hospitals. We recorded clinical parameters and immunohistochemically assessed the Ki67 index, the microvascularization patterns and the expression of hypoxia-induced factor 1 alpha (HIF1a) in the BM tissue specimens retrieved at neurosurgery. Statistical analysis including uni- and multivariate survival analyses were performed. Baseline characteristics were well balanced between the discovery and validation cohorts. In univariate analysis, we found a significant association of favorable overall survival time with young patient age, high Karnofsky performance score, low graded prognostic assessment (GPA) class, absence of extracranial metastases, adjuvant treatment with whole brain radiotherapy and, surprisingly, large brain edema. In multivariate analysis, only GPA and extent of brain edema remained independent prognostic parameters. The prognostic impact of the extent of brain edema was consistent in the two patient cohorts. Furthermore, we found a significant correlation of small brain edema with brain-invasive tumor growth pattern as assessed intraoperatively by the neurosurgeon, low neo-angiogenic activity and low expression of HIF1a. Extent of brain edema independently correlates with prognosis in patients operated for single BM. In conclusion, patients with small peritumoral edema have shorter survival times and their tumors are characterized by a more brain-invasive growth, lower HIF1a expression and less angiogenic activity.


Brain metastases Neuroradiology Edema Prognosis Single brain metastases 



Brain metastases


Hypoxia-induced factor 1 alpha


Graded prognostic assessment


Overall survival


Non-small cell lung cancer


Small cell lung cancer


In human epidermal growth factor receptor 2


Brain metastasis free survival


Magnetic resonance


Karnofsky performance score


Whole-brain radiation therapy


Central nervous system



This study was performed within the framework of the Society of Austrian Neurooncology (SANO, This study was supported by grant number 13457 of the Austrian National Bank (principle investigator: Matthias Preusser).

Conflict of interest

None declared.


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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Thomas Spanberger
    • 1
    • 10
  • Anna S. Berghoff
    • 2
    • 10
  • Carina Dinhof
    • 3
    • 10
  • Aysegül Ilhan-Mutlu
    • 3
    • 10
  • Manuel Magerle
    • 3
    • 10
  • Markus Hutterer
    • 4
  • Josef Pichler
    • 5
  • Adelheid Wöhrer
    • 2
    • 10
  • Monika Hackl
    • 6
  • Georg Widhalm
    • 7
    • 10
  • Johannes A. Hainfellner
    • 2
    • 10
  • Karin Dieckmann
    • 8
    • 10
  • Christine Marosi
    • 3
    • 10
  • Peter Birner
    • 9
    • 10
  • Daniela Prayer
    • 1
    • 10
  • Matthias Preusser
    • 3
    • 10
    Email author
  1. 1.Division of Neuroradiology, Department of RadiologyMedical University of ViennaViennaAustria
  2. 2.Institute of NeurologyMedical University of ViennaViennaAustria
  3. 3.Department of Medicine IMedical University of ViennaViennaAustria
  4. 4.Department of NeurologyChristian-Doppler-Klinik, Paracelsus Medical UniversitySalzburgAustria
  5. 5.Department of Medicine and NeurooncologyLandes-Nervenklinik Wagner-JaureggLinzAustria
  6. 6.Austrian National Cancer Registry, Statistics AustriaViennaAustria
  7. 7.Department of NeurosurgeryMedical University of ViennaViennaAustria
  8. 8.Department of RadiotherapyMedical University of ViennaViennaAustria
  9. 9.Institute of Clinical PathologyMedical University of ViennaViennaAustria
  10. 10.Comprehensive Cancer Center CNS Tumours UnitMedical University of ViennaViennaAustria

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