Article
First experiences with low dose anti-angiogenic treatment in gliomatosis cerebri with signs of angiogenic activity
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Authors
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M. Seiz
- Neurochirurgische Klinik, Universitätsklinikum Mannheim
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P. Kohlhof
- Institut für Neuropathologie, Ruprecht-Karls-Universität Heidelberg
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M. Brockmann
- Abteilung für Neuroradiologie, Universitätsklinikum Mannheim
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P. Vajkoczy
- Neurochirurgische Klinik, Charite - Universitätsmedizin Berlin
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K. Schmieder
- Neurochirurgische Klinik, Universitätsklinikum Mannheim
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J. Tüttenberg
- Neurochirurgische Klinik, Universitätsklinikum Mannheim
| Published: | May 20, 2009 |
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Outline
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Objective: Gliomatosis cerebri is a rare primary cerebral tumor entity characterized by diffuse infiltrative growth patterns representing a WHO grade III malignancy. The prognosis is dismal and therapeutical options are still controversial. In contrast to other high grade gliomas, angiogenesis is thought to be absent in gliomatosis cerebri.
Methods: Despite this assumption we performed histopathological analyses of samples of six patients with gliomatosis cerebri and found angiogenic activity with expression of VEGF and COX-2. We therefore decided to administer continuous low dose chemotherapy with temozolomide and celecoxib for anti-angiogenic treatment in the four patients that were in good clinical condition following external radiotherapy.
Results: In all patients treatment was well tolerated and MRI follow up showed no tumor progression for at least six months. Intracellular COX-2 expression was found in samples from four of the six patients. Cellular VEGF expression was divided into reaction in the cytosol and in the nuclei due to variable reaction patterns. Intracellular VEGF was detected by immunohistochemistry in GC samples from five of six patients. Immunohistochemical staining with a CD31 antibody showed a dense network of branching capillaries in parts of all analyzed tumors. In three patients, conglomerated vessels with prominent endothelia could be observed focally.
One patient died due to pulmonary embolism 9 months after diagnosis, another patient survived 15 months after diagnosis with progressive disease in the last follow up MRI before death. At present, two other patients are still in stable clinical condition without MRI signs of tumor progression (11 and 17 months).
Conclusions: From our initial experiences in a small number of patients with gliomatosis cerebri we conclude that signs of angiogenic activity with overexpression of angiogenic factors like VEGF and COX-2 seem to be more frequent than hitherto reported, and that low dose chemotherapy might provide a promising approach for treatment of these patients.
