Potential Prognostic Value of GATA4 Depends on the p53 Expression in Primary Glioblastoma Patients.

BACKGROUND: Primary glioblastoma is characterized by an extremely poor prognosis. The promoter methylation of GATA4 leads to the loss of its expression in many cancer types. The formation of high-grade astrocytomas can be promoted by the concurrent loss of TP53 and GATA4 in normal human astrocytes. Nevertheless, the impact of GATA4 alterations with linkage to TP53 changes in gliomagenesis is poorly understood. This study aimed to evaluate GATA4 protein expression, GATA4 promoter methylation, p53 expression, TP53 promoter methylation, and mutation status in patients with primary glioblastoma and to assess the possible prognostic impact of these alterations on overall survival. MATERIALS AND METHODS: Thirty-one patients with primary glioblastoma were included. GATA4 and p53 expressions were determined immunohistochemically, and GATA4 and TP53 promoter methylations were analyzed via methylation-specific PCR. TP53 mutations were investigated via Sanger sequencing. RESULTS: The prognostic value of GATA4 depends on p53 expression. Patients without GATA4 protein expression were more frequently negative for TP53 mutations and had better prognoses than the GATA4 positive patients. In patients positive for GATA4 protein expression, p53 expression was associated with the worst outcome. However, in patients positive for p53 expression, the loss of GATA4 protein expression seemed to be associated with improved prognosis. GATA4 promoter methylation was not associated with a lack of GATA4 protein expression. CONCLUSIONS: Our data indicate that there is a possibility that GATA4 could function as a prognostic factor in glioblastoma patients, but in connection with p53 expression. A lack of GATA4 expression is not dependent on GATA4 promoter methylation. GATA4 alone has no influence on survival time in glioblastoma patients.

Retrospective analysis of the effectiveness of volumetric modulated arc therapy half­body irradiation in palliation of pain in patients with multiple bone metastases.

Bone metastases are the most common cause of cancer-related pain. It has been reported that radiotherapy is efficient in the palliation of pain caused by bone metastases. Half-body irradiation (HBI) is a method of palliative treatment in patients with multiple metastases to bones. The present study aimed to evaluate the efficiency of upper and lower HBI in reducing pain in patients with multiple bone metastases treated with volumetric modulated arc therapy (VMAT) HBI. A total of 22 patients received HBI based on the VMAT technique between July 2018 and July 2020. Treatment plans were subject to a dosimetric analysis. The absorbed doses ranged from 6 to 8 Gy in a single fraction. The patients rated pain on the 11-point (0-10) verbal numeric pain score (VNPS) before irradiation and after 1 month of follow-up. To assess the analgesic effect of HBI radiotherapy, data from 19 patients who attended the follow-up visit were analyzed. Before the treatment, the median VNPS of pain was 5 (IQR, 3-8); after the follow-up period, it was 3 (IQR, 1-4) (P=0.003). The median VNPS of the maximum pain within the last month before treatment was 8 (IQR, 7-10) and after irradiation it was 5 (IQR, 4-7) (P<0.001). The median VNPS of the average pain within the last month before the treatment was 5 (IQR, 4-7); after the treatment, it was 3 (IQR, 2-5) (P=0.003). In conclusion, conformal VMAT-intensity-modulated radiation therapy HBI is an effective method for reducing pain in patients with painful multiple bone metastases. Conformal techniques of radiation allow for the reduction of doses to organs at risk thus potentially reducing the toxicity of treatment.

MiR-21, miR-34a, miR-125b, miR-181d and miR-648 levels inversely correlate with MGMT and TP53 expression in primary glioblastoma patients.

INTRODUCTION: TP53 and MGMT alterations play a crucial role in glioblastoma (GB) pathogenesis. TP53 and MGMT function is affected by several pathologic mechanisms, such as point mutations or promoter methylation, which are well characterized. Expression of both genes can be regulated by other mechanisms as well, e.g., microRNAs (miRNAs). Moreover, cross-talk among various pathologic processes may occur, further affecting MGMT and TP53 functionality. MATERIAL AND METHODS: In 49 GB patients, we analyzed the possible associations between TP53 and its miRNA regulators miR-125b, miR-21, and miR-34a, as well as MGMT and its miRNA regulators miR-181d and miR-648. We evaluated the possible influence of mutational and methylation status on the pre-identified associations. RESULTS: In patients with immunohistochemistry-detected TP53 overexpression, expression levels of miR-34a and TP53 were negatively correlated (r = -0.56, p = 0.0195), and in patients with TP53 mutations, expression levels of TP53 and miR-21 were negatively correlated (r = -0.67, p = 0.0330). In patients with MGMT methylation, expression levels of MGMT were negatively correlated with miR-648 and miR-125b expression levels (r = -0.61, p = 0.0269 and r = -0.34, p = 0.0727, respectively). CONCLUSIONS: Our findings demonstrate that selected miRNAs are significantly correlated with MGMT and TP53 levels, but the extent of this correlation differs regarding the TP53 and MGMT mutational and promoter methylation status.

Stereotactic radiotherapy of the tumor bed compared to whole brain radiotherapy after surgery of single brain metastasis: Results from a randomized trial.

PURPOSE: To evaluate if neurological/cognitive function outcomes in patients with resected single brain metastasis (BM) after stereotactic radiotherapy of the tumor bed (SRT-TB) are not inferior compared to those achieved with whole-brain radiotherapy (WBRT). METHODS: Patients with total/subtotal resection of single BM were randomly assigned either to SRT-TB (n=29) or WBRT (n=30). SRT-TB arm consisted of 15Gy/1 fraction, or 5×5Gy. WBRT consisted of 30Gy/10 fractions. Neurological/cognitive failure was defined as a decrease of neurological score by one point or more, or a worsening of the MiniMental test by at least 3 points, or neurological death. Cumulative incidence of neurological/cognitive failure (CINCF), neurological death (CIND), and overall survival (OS) were compared. RESULTS: Median follow-up was 29months (range: 8-45) for 15 patients still alive. The difference in the probability of CINCF at 6months (primary endpoint) was -8% in favor of WBRT (95% confidence interval: +17% -35%; non-inferiority margin: -20%). In the intention-to-treat analysis, two-year CIND rates were 66% vs. 31%, for SRT-TB and WBRT arm, respectively, p=.015. The corresponding figures for OS were 10% vs. 37%, p=.046. CONCLUSIONS: Non-inferiority of SRT-TB was not demonstrated in our underpowered study. More data from randomized studies are needed for confirmation of the value of this method.