Isocitrate Dehydrogenase (IDH)1/2 Mutations as Prognostic Markers in Patients With Glioblastomas.

The purpose of this study was to perform a meta-analysis examining the association of isocitrate dehydrogenase (IDH)1/2 mutations with overall survival (OS) and progression-free survival (PFS) in patients with glioblastomas. Medline, Cochrane, EMBASE, and Google Scholar were searched from inception to January 28, 2015, using combinations of the following keywords: IDH mutation, brain tumor, glioma, glioblastoma, oligodendroglioma, prognosis. Randomized controlled trials, and prospective and retrospective studies of patients with glioblastomas that provided IDH mutation and survival data were included. OS and PFS were used to evaluate the association of IDH1 and IDH1/2 mutations and prognosis. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for OS and PFS were calculated and compared between patients with and without mutations. Of 165 studies that were identified, 136 nonrelevant studies were excluded. Twenty-nine full-text articles were assessed, and of these, 5 were excluded as they did not provide a quantitative outcome. Therefore, 24 studies were included in the qualitative synthesis. The pooled HR of 0.358 (95% CI 0.264-0.487, P < 0.001) indicated that IDH mutations were associated with better OS. Similarly, the pooled HR of 0.322 (95% CI 0.24200.455, P < 0.001) indicated that IDH mutations were associated with better PFS. When patients were stratified by surgery versus no surgery or IDH1 versus IDH1/2 mutations, the results also indicated that the presence of IDH mutations was associated with better OS and PFS. The IDH mutations are associated with improved survival in patients with glioblastomas.

Radiotherapy after hyperbaric oxygenation in malignant gliomas.

OBJECTIVE: This review was to evaluate the efficacy and toxicity of radiation therapy (RT) administered immediately after hyperbaric oxygen (HBO) therapy in patients with high grade gliomas. RESEARCH DESIGN AND METHODS: PubMed, Embase, ISI Web of Knowledge, and Cochrane databases were searched using combinations of the following search terms: radiotherapy, hyperbaric oxygenation, chemotherapy, glioma, brain tumor. Selection was limited to prospective studies involving patients given HBO followed by RT for high-grade gliomas. Data extracted from studies included the clinical research phase of the study, number of study arms, number of patients, patient age and gender, glioma type and grade, pressure and length of HBO, protocol of radiation therapy, duration of follow-up, and the outcomes. MAIN OUTCOME MEASURES: Overall survival, time to progression, response rate, tumor regression, and toxic effects associated with HBO plus RT treatment. RESULTS: Literature search/screening yielded eight studies for analysis. Six of the studies were single-arm in design and enrolled a total of 203 patients, of whom 142 had grade IV gliomas and 61 had grade III gliomas. In these six studies, all patients received HBO then RT. Two studies were double-arm in design, with 24 patients treated with HBO followed by RT and 26 patients treated with RT alone. The findings from both the single- and double-arm studies indicated improved outcomes (survival rate, progression free survival, time to progression, response rate) with HBO and RT therapy. Reported toxicity included leucopenia, anemia, thrombocytopenia, fever, loss of appetite, constipation, nausea, vomiting, and liver dysfunction. The addition of HBO had minimal effect on toxicity or side effects; across the eight studies, only one patient with severe middle ear barotrauma had a complication directly related to HBO exposure. CONCLUSION: This systematic reviews suggests that the addition of HBO to RT is tolerated and may be beneficial in patients with high-grade gliomas.

Effect of Hyperbaric Oxygen on the Growth of Intracranial Glioma in Rats.

BACKGROUND: Numerous studies have confirmed that hyperbaric oxygen (HBO) in combination with radiotherapy or chemotherapy may increase the efficacy of radiotherapy or chemotherapy in patients with glioma. However, whether HBO therapy alone may inhibit or promote the growth of malignant tumors remains controversial. This study aimed to investigate the effect of HBO on the growth of glioma in rats, and the impact of HBO on the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-alpha (HIF-1α), angiogenesis, and apoptosis of glioma cells. METHODS: Male Sprague-Dawley rats were treated with or without HBO after glioma cell inoculation and followed for up to 16 days postinoculation. Rats were randomized to receive bilateral forelimb function tests (n = 20 per group) and head magnetic resonance imaging (n = 5 per group). Differences between HBO and control groups were tested using 2-sample independent t-tests and changes over time within treatment groups were analyzed using a repeated measurement analysis of variance with Bonferroni correction. The effect of HBO on the expression of VEGF, HIF-1α, von Willebrand factor, angiogenesis, and tumor cell apoptosis were also examined (n = 5 per group). RESULTS: Forelimb function scores were reduced in both HBO-treated and control groups. HBO-treated rats had significantly larger tumor volume and more water in the cerebellum compared with control rats. The intratumoral expression of VEGF was significantly higher in HBO-treated rats compared with control rats (23.2% vs. 13.3%, P = 0.002). HIF-1α was significantly increased in HBO-treated rats compared with controls in the expression of both intratumoral (72.7% vs. 54.9%, P = 0.001) and peritumoral (2.6% vs. 1.9%, P = 0.003) cells. The intratumoral microvessel density (MVD) was significantly higher in the HBO group (15.6 vessels/field vs. 4.4 vessels/field, P < 0.001), and the peritumoral MVD was not significantly different between the two groups (P > 0.05). Apoptosis was significantly lower in HBO-treated rats compared with controls (44.4% vs. 82.8% for intratumoral; 10.1% vs. 77.5% for peritumoral, both P < 0.001). CONCLUSIONS: The current results demonstrate that HBO alone may promote tumor growth, and is therefore not suitable to treat patients with gliomas with neurological deficits or disorders with HBO alone. If HBO must be used as a mean of rehabilitation, it is recommended that HBO should be combined with radiotherapy or chemotherapy.