MGMT promoter methylation status and prognosis of patients with primary or recurrent glioblastoma treated with carmustine wafers

May 14, 2013British journal of neurosurgery

MGMT gene methylation and outlook for patients with first-time or returning glioblastoma treated with carmustine wafers

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Abstract

Median overall survival for patients with MGMT promoter methylated tumors was 18.9 months, compared to 15.0 months for those with unmethylated tumors.

No significant difference in median overall survival was observed between patients with MGMT promoter methylated and unmethylated tumors in the overall cohort.
In the first-line BCNU + TMZ group, MGMT promoter methylation was associated with longer overall survival (21.0 vs 11.1 months).
Progression-free survival did not significantly differ between patients with and without MGMT promoter methylated tumors across all patient groups.
The first-line BCNU + TMZ group did not show a significant difference in overall survival compared to the first-line BCNU group.
The combination of TMZ radiochemotherapy with local delivery of BCNU was linked to a higher rate of therapy-related adverse effects.

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The prognostic role of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastoma patients treated with carmustine (BCNU) wafer implantation is unclear. Here, we report on a retrospective study of 47 patients with either newly diagnosed (30 patients) or recurrent (17 patients) glioblastoma (WHO grade IV) treated with BCNU (bis-chloroethylnitrosourea) wafers. Thirteen of the newly diagnosed patients received local BCNU and irradiation only (first-line BCNU), while 17 patients additionally received concomitant and adjuvant temozolomide (TMZ) radiochemotherapy (first-line BCNU + TMZ). Of the 17 patients treated for recurrent glioblastoma (second-line BCNU), 16 had received radiotherapy with concomitant and adjuvant TMZ as an initial treatment. Median overall survival (OS) did not significantly differ between 19 patients with MGMT promoter methylated tumors when compared to 28 patients with unmethylated tumors (18.9 vs 15.0 months; p = 0.1054). In the first-line BCNU + TMZ group, MGMT promoter methylation was associated with longer OS (21.0 vs 11.1 months, p = 0.0127), while no significant survival differences were detected in the other two subgroups. Progression-free survival did not significantly differ between patients with and without MGMT promoter methylated tumors in the entire patient cohort or any of the three subgroups. The first-line BCNU + TMZ group showed no significant difference in OS when compared to the first-line BCNU group (18.9 vs 14.7 months), but tended to have more therapy-related adverse effects (53% vs 24%, p = 0.105). In summary, MGMT promoter methylation showed a non-significant trend toward longer survival in our patient cohort. The combination of TMZ radiochemotherapy with local delivery of BCNU did not provide a significant survival benefit compared to local BCNU alone, but was associated with a higher rate of adverse effects. Owing to the small number of patients investigated, however, these findings would need to be corroborated in larger patient cohorts.

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MGMT promoter methylation status and prognosis of patients with primary or recurrent glioblastoma treated with carmustine wafers

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