No abstract

Purpose: Anaplastic gliomas constitute a heterogeneous group of tumors with different therapeutic responses to adjuvant chemotherapy with alkylating agents. O 6 -Methylguanine-DNA methyltransferase (MGMT), a DNA repair protein, is one of the implicated factors in glioma chemoresistance.The prognostic value of MGMTremains controversial due in part to the fact that previous published studies included heterogeneous groups of patients with different tumor grades. The aim of this study was to evaluate the prognostic significance of MGMT in patients with anaplastic glioma. Experimental Design: Ninety-three patients with anaplastic glioma were analyzed for MGMT protein expression by immunohistochemistry. In addition, for those patients from whom a good yield of DNA was obtained (n = 40), MGMT promoter methylation profile was analyzed by methylation-specific PCR. MGMT prognostic significance was evaluated together with other well-known prognostic factors. Results: Fifty-one tumors (54.8%) showed nuclear staining of MGMT. There was a trend towards longer overall survival for those patients with negative MGMT immunostaining (hazard ratio,1.66; P = 0.066). In a secondary analysis including those patients who actually received chemotherapy (n = 72), the absence of MGMTexpression was independently associated with better survival (hazard ratio, 2.12; P = 0.027). MGMT promoter methylation was observed in 50% of the analyzed tumors. No statistical correlation between MGMT expression and MGMT promoter hypermethylation was observed. Conclusions: Unlike previous studies, we did not find a correlation between MGMT promoter methylation and survival. However, we observed a correlation between MGMT protein expression and survival in those patients who received chemotherapy thus suggesting that the absence of MGMTexpression is a positive predictive marker in patients with anaplastic glioma.Anaplastic gliomas (WHO grade 3) show a wide variability of clinical outcome. Despite optimal treatment, mainly consisting of gross total resection followed by radiotherapy and chemotherapy with alkylating agents (1), therapeutic response and survival times vary considerably. This fact suggests that a large number of factors, including patient, tumor, and treatment characteristics, may influence the outcome (2 -4).Alkylating agents cause cell death by forming cross-links between adjacent strands of DNA due to alkylation of the O 6 position of guanine. The cellular DNA repair protein O 6 -methylguanine-DNA methyltransferase (MGMT) inhibits the cross-linking of double-stranded DNA by removing alkylating lesions (5 -7). A direct relationship between MGMT activity and resistance to alkylating nitrosoureas and methylating agents (i.e., ionizing radiations) has been well documented in cell lines and xenografts derived from a variety of human tumors, including gliomas (8). Moreover, depletion of MGMT activity with the substrate analogue inhibitor O 6

Performance status assessment, Karnofsky performance status (KPS), and Eastern Cooperative Oncology Group (ECOG) scales were performed in 100 consecutive patients independently by two physicians and by the patients themselves to evaluate the scales' validity and reliability. Findings of Kendall's correlation were highly significant between physicians (0.76 for KPS, 0.75 for ECOG) and between physicians and patients (0.65 for KPS, 0.59 for ECOG). The authors point out that patients' self evaluation could provide a valuable and reliable assessment.

No abstract

Palliative care is the management of patients with progressive, far-advanced disease for whom the prognosis is limited and the focus of care is quality of life. During the last days of life, it is important to redefine the goals, as previously present symptoms may increase and new symptoms may appear. To assess these symptoms, 176 patients were evaluated. A questionnaire evaluated symptoms during the last week of life and compared these prevalences with those at the first evaluation. The patients comprised 121 men and 55 women. The mean age was 67.7 years. Metastases were present in 66.5% and were multiple in 52%. The most frequent symptoms at the end of life (> 50%) were anorexia, asthenia, dry mouth, confusion, and constipation. The majority of patients died at home (64.2%). We observed good control of "reversible" symptoms, but many symptoms were difficult to control at the end of life. Symptom assessment is important in this population.