The impact of sequential vs. combined radiochemotherapy with temozolomide, resection and MGMT promoter hypermethylation on survival of patients with primary glioblastoma - a single centre retrospective study

Feb 20, 2013British journal of neurosurgery

How timing of combined chemotherapy, radiation, surgery, and gene methylation relate to survival in primary glioblastoma patients

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Abstract

Overall survival (OS) was 18.6 months and progression-free survival (PFS) was 5.6 months for patients with glioblastoma multiforme.

Patients treated with concomitant chemotherapy did not show improved OS or PFS compared to those receiving only radiotherapy followed by chemotherapy.
The extent of tumor resection was significantly associated with improved OS (21.5 months vs. 16.1 months) and PFS (11.0 months vs. 3.9 months).
MGMT methylation status was significantly associated with OS, indicating its potential importance in treatment outcomes.
No significant differences were found between the two treatment cohorts regarding established prognostic markers such as age and performance status.

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BACKGROUND: The benefit of the introduction of alkylating chemotherapy in the treatment of glioblastoma multiforme (GBM) patients has been demonstrated by comparing radiotherapy with concomitant plus intermittent temozolomide (iTMZ) to radiation therapy. The isolated impact of the concomitant part of this protocol on survival was not investigated. We were therefore interested in the impact of the effect of the concomitant therapy part on survival. Hence, we compared patients treated with open surgery followed by radiotherapy and iTMZ with patients treated with concomitant plus iTMZ chemotherapy regarding overall (OS) and progression-free survival (PFS).

METHODS: We performed a retrospective database search for the period between 2002 and 2007 and aimed at the identification of patients with primary GBM treated by open resection, radiotherapy (only radiotherapy = Group A and plus concomitant TMZ = Group B) and at least two cycles of TMZ. Patients were stratified for established prognostic markers like extent of resection, MGMT promoter methylation, Karnofsky Performance Scale (KPS), and age.

RESULTS: Eighty-five patients were analysed, among which 42 patients (49%) were affiliated with Cohort A and 43 patients (51%) with Cohort B. Between both cohorts there was no significant difference regarding MGMT methylation status (p = 0.929), extend of resection (p = 0.102), KPS (p = 0.197) and age (p = 0.327). For the entire patient population, median OS was 18.6 months and PFS was 5.6 months. The extent of resection was significantly correlated with survival (OS: 21.5 vs. 16.1 months (p = 0.001) and PFS: 11.0 vs. 3.9 months (p = 0.044)). MGMT methylation status revealed a significant impact on OS (p = 0.008). Affiliation to Cohort A or B was neither correlated with PFS (p = 0.168) nor with OS (p = 0.343).

CONCLUSION: Our study demonstrates that PFS and OS are strongly determined by the MGMT status and the extent of resection. Interestingly, concomitant radiochemotherapy was not superior to radiotherapy followed by iTMZ chemotherapy regarding OS and PFS.

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The impact of sequential vs. combined radiochemotherapy with temozolomide, resection and MGMT promoter hypermethylation on survival of patients with primary glioblastoma - a single centre retrospective study

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