Treatment of glioblastoma multiforme in elderly patients. Clinico-therapeutic remarks in 22 patients older than 80 years.

We report our remarks on 22 patients, 80 years of age and older, who were treated for glioblastoma multiforme. The 16 patients who underwent a multimodality treatment (surgery + radiotherapy + chemotherapy) had an average survival of 16.7 months versus the 5.8 months of the 8 patients treated with biopsy followed by radiotherapy and/or chemotherapy (log-rank test, P < 0.001). Moreover, we point out the importance of MGMT hypermethylation as a significant prognostic factor: the 9 patients with nonmethylated MGMT had a mean survival of 7.7 months vs. 17.9 months of the 13 patients with the MGMT promoter methylated (log-rank test, P = 0.0006). Several studies have pointed out age as an important negative factor for the outcome of elderly patients affected by glioblastoma multiforme. Elderly patients with a diagnosis of glioblastoma multiforme are thus generally excluded from clinical trials of treatment for the neoplasm, because it is a common opinion that the prognosis for such patients is particularly poor. On the contrary, according to our clinical and surgical experience, we firmly believe that patients older than 80 years with a histologically proven diagnosis of glioblastoma multiforme and in good health conditions (Karnofsky performance status >60) should be treated in the same way as younger patients.

Inhibition of cell growth by EGR-1 in human primary cultures from malignant glioma.

BACKGROUND: The aim of this work was to investigate in vitro the putative role of EGR-1 in the growth of glioma cells. EGR-1 expression was examined during the early passages in vitro of 17 primary cell lines grown from 3 grade III and from 14 grade IV malignant astrocytoma explants. The explanted tumors were genetically characterized at the p53, MDM2 and INK4a/ARF loci, and fibronectin expression and growth characteristics were examined. A recombinant adenovirus overexpressing EGR-1 was tested in the primary cell lines. RESULTS: Low levels of EGR-1 protein were found in all primary cultures examined, with lower values present in grade IV tumors and in cultures carrying wild-type copies of p53 gene. The levels of EGR-1 protein were significantly correlated to the amount of intracellular fibronectin, but only in tumors carrying wild-type copies of the p53 gene (R = 0,78, p = 0.0082). Duplication time, plating efficiency, colony formation in agarose, and contact inhibition were also altered in the p53 mutated tumor cultures compared to those carrying wild-type p53. Growth arrest was achieved in both types of tumor within 1-2 weeks following infection with a recombinant adenovirus overexpressing EGR-1 but not with the control adenovirus. CONCLUSIONS: Suppression of EGR-1 is a common event in gliomas and in most cases this is achieved through down-regulation of gene expression. Expression of EGR-1 by recombinant adenovirus infection almost completely abolishes the growth of tumor cells in vitro, regardless of the mutational status of the p53 gene.

Extremely delayed cerebral metastasis from renal carcinoma: report of four cases and critical analysis of the literature.

Brain metastases from renal carcinoma may appear even a long time after surgical treatment of the primary tumor. The authors present 2 series of patients, one of which has already been published and the other new, for a total of 4 cases of brain metastasis from renal carcinoma with late onset, which occurred 13, 17, 26 and 12 years after primary surgical treatment. The other cases described in the literature were also critically reviewed.