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

TY - JOUR

T1 - MGMT promoter methylation status and prognosis of patients with primary or recurrent glioblastoma treated with carmustine wafers

AU - Gutenberg, A

AU - Bock, H C

AU - Brück, W

AU - Doerner, L

AU - Mehdorn, H M

AU - Roggendorf, W

AU - Westphal, M

AU - Felsberg, J

AU - Reifenberger, G

AU - Giese, A

PY - 2013/12/1

Y1 - 2013/12/1

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Antineoplastic Agents, Alkylating

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Brain Neoplasms

KW - Carmustine

KW - Chemoradiotherapy

KW - Combined Modality Therapy

KW - DNA Methylation

KW - Dacarbazine

KW - Disease-Free Survival

KW - Female

KW - Glioblastoma

KW - Humans

KW - Karnofsky Performance Status

KW - Male

KW - Middle Aged

KW - O(6)-Methylguanine-DNA Methyltransferase

KW - Prognosis

KW - Promoter Regions, Genetic

KW - Retrospective Studies

KW - Survival Analysis

U2 - 10.3109/02688697.2013.791664

DO - 10.3109/02688697.2013.791664

M3 - SCORING: Journal article

C2 - 23662801

VL - 27

SP - 772

EP - 778

JO - BRIT J NEUROSURG

JF - BRIT J NEUROSURG

SN - 0268-8697

IS - 6

ER -