Extent of peritumoral brain edema correlates with prognosis, tumoral growth pattern, HIF1a expression and angiogenic activity in patients with single brain metastases.
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.
Division of Neuroradiology, Department of Radiology, Medical University of Vienna, Vienna, Austria.
Thomas
T
Spanberger
Anna S
AS
Berghoff
Carina
C
Dinhof
Aysegül
A
Ilhan-Mutlu
Manuel
M
Magerle
Markus
M
Hutterer
Josef
J
Pichler
Adelheid
A
Wöhrer
Monika
M
Hackl
Georg
G
Widhalm
Johannes A
JA
Hainfellner
Karin
K
Dieckmann
Christine
C
Marosi
Peter
P
Birner
Daniela
D
Prayer
Matthias
M
Preusser
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001317:Austria / Q000453:epidemiology; D001929:Brain Edema / Q000453:epidemiology / Q000378:metabolism / Q000401:mortality*; D001932:Brain Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000556:secondary*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000401:mortality*; D059906:Neuroimaging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit