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On the issue of early and aggressive treatment in grade 2 gliomas
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
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2003 (English)In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 129, no 3, 154-160 p.Article in journal (Refereed) Published
Abstract [en]

Purpose

To study the effects of surgery and timing of radiotherapy on patient survival in grade 2 gliomas.

Methods

One hundred and eighty-nine patients with diffuse astrocytomas, oligoastrocytomas, and oligodendrogliomas, World Health Organization grade 2, treated between 1982 and 2000 were identified. The impact of treatment given and clinical parameters were studied in univariate- and multivariate survival analyses.

Results

Median survival for the whole patient sample was 6.4 years and the 5-year survival rate was 60%. Macroscopic total resection was beneficial in the univariate analysis (P=0.03) but not when adjusting for confounders. Early subtotal resection did not prolong survival. Early radiotherapy was associated with a shorter survival time compared to delayed or no irradiation (P=0.004). However, this difference was mainly due to an unequal distribution of prognostic factors and was not significant in the multivariate analysis. The most important predictors for long survival time were young age (P<0.001), oligodendroglioma histology (P<0.001), and small tumour size (P=0.02).

Conclusions

Early conventional treatment with surgery and radiotherapy had no positive effect on patient survival. This opens up the possibility of trying and evaluating other first-line treatment regimens in this disease.

Place, publisher, year, edition, pages
2003. Vol. 129, no 3, 154-160 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-90046DOI: 10.1007/s00432-003-0423-0PubMedID: 12712330OAI: oai:DiVA.org:uu-90046DiVA: diva2:162102
Available from: 2002-10-25 Created: 2002-10-25 Last updated: 2017-12-14Bibliographically approved
In thesis
1. In Search of Prognostic Factors in Grade 2 Gliomas
Open this publication in new window or tab >>In Search of Prognostic Factors in Grade 2 Gliomas
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Grade 2 gliomas are malignant brain tumours affecting otherwise healthy adults. Although the long-term prognosis is poor, many patients are well and may have a high quality of life for several years. There is, however, a large variability in the natural course of the disease which makes it essential to identify patients who might benefit from early surgery or radio-therapy. The aim of the present thesis was to define new and clinically useful prognostic markers that may assist in the initial treatment decision and in patient follow-up.

A retrospective study of 189 patients with gliomas WHO grade 2 showed no advantage in survival of early tumour resection or radiotherapy, and confirmed that histological subtype and patient age are the most important predictors of survival (I). In 89 patients, the pre-treatment uptake of 11C-methionine (MET) measured with positron emission tomography (PET) was identified as a prognostic marker for survival (II). At the time of tumour progression, irradiated tumours demonstrated signs of a residual radiotherapeutic effect that correlated with the pre-treatment uptake of MET (III). Pre-treatment uptake of MET may, therefore, be important both in predicting the natural course of the disease and the response after treatment. Immunohistochemical staining of 40 tumour samples showed an inverse association between the number of tumour cells expressing platelet-derived growth factor alpha receptor (PDGFRa) and survival (IV). Also, a reduction was observed in the number of receptor-positive cells after malignant transformation, supporting the prognostic value of PDGFRa.

Lumbar puncture was performed in eight patients with newly diagnosed low-grade gliomas to identify three important growth factors in tumour development. Neither PDGF nor vascular endothelial growth factor (VEGF) were detected in the cerebrospinal fluid (CSF), and fibroblast growth factor 2 (FGF-2) was measurable at extremely low concentrations in two of the patients (V). A proteome screening of the CSF, using two-dimensional gel electrophoresis and mass spectrometry, detected alpha 2-HS glycoprotein at significantly higher concentrations than in a control group (VI). This glycoprotein emerges as a novel substance in glioma research and may be of great interest because of its suggested involvement in the embryonic development of the neocortex.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2002. 39 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1194
Keyword
Neurosciences, low-grade glioma, positron emission tomography, platelet-derived growth factor receptor, mass spectrometry, alpha 2-HS glycoprotein, Neurovetenskap
National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-2789 (URN)91-554-5435-6 (ISBN)
Public defence
2002-12-14, Rudbecksalen, Uppsala, 13:15
Opponent
Available from: 2002-10-25 Created: 2002-10-25 Last updated: 2013-05-23Bibliographically approved

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Smits, AnjaBlomquist, Erik

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