BACKGROUND: Concurrent radiation (RT) and temozolomide (TMZ) has been accepted as standard first-line therapy for glioblastoma since publication of results of the phase III EORTC/NCIC trial in 2005. In the same NEJM issue, data were presented which showed the prognostic significance of MGMT methylation status in these patients. Trials for first-line treatment of anaplastic (grade III) glioma are currently underway, but until these trials complete accrual and mature, the role of concurrent chemotherapy and the prognostic significance of MGMT methylation status for patients with anaplastic glioma is unclear. METHODS: We hypothesized that methylated MGMT promoter may be a prognostic factor for anaplastic astrocytomas treated with chemoradiation (RT+ TMZ). We retrospectively reviewed data from 53 patients with anaplastic astrocytoma tested for MGMT methylation status by Methylation-Specific PCR (MSP) in our Neuro-oncology laboratory from 2007- 2014. Most patients were treated with concurrent TMZ and RT as first-line therapy (with a few selected cases treated with radiation alone). Survival curves of the groups of methylated and unmethylated tumors were compared using Logrank test. RESULTS: Twenty-one of 53 patients (39%) had MGMT methylation. The median survival in patients with MGMT methylation was 32.2 months and for unmethylated tumors, 23.7 months (p = 0.0947). Patients 45 years and younger showed more favorable prognosis with a median survival of 33.9 months compared to 24.3 in patients older than 45. CONCLUSIONS: The results of this study support the hypothesis that patients with anaplastic astrocytoma who have MGMT methylation have a more favorable prognosis when treated with concomitant TMZ and RT than do their unmethylated counterparts. Further analysis regarding progression- free survival; the effect of other chemotherapy or biologic agents given as second-line or adjuvant therapy; the pattern of response in anaplastic gliomatosis; and the impact of 1p19q and IDH status in these patients will be presented.