PD0325901 PD325901 were treated with radiotherapy alone and found that methylation

treated with radiotherapy alone, MGMT promoter methylation showed a strong correlation with improved survival. This finding suggested that MGMT promoter methylation was a general prognostic marker for radiosensitivity, in addition to being a predictive marker for chemosensitivity. Rivera et al. assessed the MGMT methylation PD0325901 PD325901 status and treatment outcome in 225 patients with GBM who were treated with radiotherapy alone and found that methylation of the MGMT gene promoter correlated with improved OS. In our current study, 39 patients received radiotherapy with inconsistent TMZ.We questioned whether the outcome was different according to the TMZ regimen. We observed that OS was consistently better in patients with a methylated MGMT promoter than in those with an unmethylated MGMT promoter, irrespective of the TMZ regimen.
Our results suggest that MGMT promoter methylation might be predictive of response to radiation and a general prognostic factor in GBM. In conclusion, we confirm that MGMT gene methylation status and age are potent prognostic factors in patients with GBM. Our results also suggest that maximum surgical resection and early start of postoperative radiotherapy might further improve the outcome. Glioblastoma multiforme, or World Health Organization grade 4 glioma, is the most common adult primary brain tumor, with more than 12,000 cases diagnosed annually by American Cancer Society estimates. In randomized trials of patients with GBM, after maximal safe surgical resection, radiotherapy to doses of 60 Gy in conventional 1.
8e2 Gy/d fractionation, as well as addition of chemotherapy to select younger patients, has been shown to improve survival. Unfortunately, despite multimodality treatment, patients diagnosed with GBM have a poor prognosis, with median survivals averaging less than 1 year for most patients. Clearly, current therapy is suboptimal. Stereotactic radiosurgery, which allows the delivery of very high dose, precise radiotherapy, has increased control and survival of patients with high grade gliomas in retrospective and Phase II trials. A multi institutional retrospective analysis of patients with high grade gliomas reported that those patients receiving SRS in addition to surgery and conventional radiotherapy had a significantly improved 2 year and median survival compared with historical controls of patients treated without SRS.
In a study of 37 patients with high grade gliomas 4 cm, treatment with SRS in addition to conventional radiotherapy resulted in 75% of patients being alive and stable at a median follow up of 19 months. Results of another Phase II study of patients with high grade gliomas receiving three weekly concomitant boosts in addition to lower dose conventional radiotherapy showed median survivals of 33 months for anaplastic astrocytomas and 16 months for GBM, which were higher than for historical non SRS controls. Because retrospective and Phase II data determined that an SRS boost in addition to conventional radiotherapy for patients with high grade gliomas was feasible and probably efficacious, a national Phase III trial was undertaken by the Radiation Therapy Oncology Group, in which patients with small supratentorial GBM were randomized to conventional radiotherapy with or without a stereotactic radios

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