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

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Abstract

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.

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Abbreviations

BM:

Brain metastases

HIF1a:

Hypoxia-induced factor 1 alpha

GPA:

Graded prognostic assessment

OS:

Overall survival

NSCLC:

Non-small cell lung cancer

SCLC:

Small cell lung cancer

HER2:

In human epidermal growth factor receptor 2

BMFS:

Brain metastasis free survival

MR:

Magnetic resonance

KPS:

Karnofsky performance score

WBRT:

Whole-brain radiation therapy

CNS:

Central nervous system

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Acknowledgments

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

Conflict of interest

None declared.

Author information

Authors and Affiliations

  1. Division of Neuroradiology, Department of Radiology, Medical University of Vienna, Vienna, Austria

    Thomas Spanberger & Daniela Prayer

  2. Institute of Neurology, Medical University of Vienna, Vienna, Austria

    Anna S. Berghoff, Adelheid Wöhrer & Johannes A. Hainfellner

  3. Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria

    Carina Dinhof, Aysegül Ilhan-Mutlu, Manuel Magerle, Christine Marosi & Matthias Preusser

  4. Department of Neurology, Christian-Doppler-Klinik, Paracelsus Medical University, Salzburg, Austria

    Markus Hutterer

  5. Department of Medicine and Neurooncology, Landes-Nervenklinik Wagner-Jauregg, Linz, Austria

    Josef Pichler

  6. Austrian National Cancer Registry, Statistics Austria, Vienna, Austria

    Monika Hackl

  7. Department of Neurosurgery, Medical University of Vienna, Vienna, Austria

    Georg Widhalm

  8. Department of Radiotherapy, Medical University of Vienna, Vienna, Austria

    Karin Dieckmann

  9. Institute of Clinical Pathology, Medical University of Vienna, Vienna, Austria

    Peter Birner

  10. Comprehensive Cancer Center CNS Tumours Unit, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria

    Thomas Spanberger, Anna S. Berghoff, Carina Dinhof, Aysegül Ilhan-Mutlu, Manuel Magerle, Adelheid Wöhrer, Georg Widhalm, Johannes A. Hainfellner, Karin Dieckmann, Christine Marosi, Peter Birner, Daniela Prayer & Matthias Preusser

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  1. Thomas Spanberger
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  2. Anna S. Berghoff
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  11. Johannes A. Hainfellner
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  14. Peter Birner
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  15. Daniela Prayer
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Correspondence to Matthias Preusser.

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Spanberger, T., Berghoff, A.S., Dinhof, C. et al. Extent of peritumoral brain edema correlates with prognosis, tumoral growth pattern, HIF1a expression and angiogenic activity in patients with single brain metastases. Clin Exp Metastasis 30, 357–368 (2013). https://doi.org/10.1007/s10585-012-9542-9

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  • DOI: https://doi.org/10.1007/s10585-012-9542-9

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