B8
A single UK centre study of temozolomide and radiotherapy in glioblastoma patients
Julie Dunn1, Farida Allam2, Kathy Joyce1, Helen Wong2, Atik Baborie3, Andrew Brodbelt3, Ross Sibson1, Daniel Crooks3, David Husband2, Aditya Shenoy2, Triantfillous Liloglou1, Brian Haylock2, Carol Walker1
1University of Liverpool, Liverpool, UK, 2Clatterbridge Centre for Oncology, Wirral, UK, 3The Walton Centre for Neurology and Neurosurgery, Liverpool, UK
Background
The NICE guidelines adopted concurrent and adjuvant temozolomide with radiotherapy for good performance glioblastoma patients, following a phase III trial (EORTC 22981/NCICCE.3), showing increased survival and good outcome associated with MGMT promoter hypermethylation. In this study we have investigated outcome and MGMT promoter hypermethylation in glioblastoma patients treated according to the Stupp protocol in a single UK treatment centre.
Method
Patients were referred for chemoradiotherapy following biopsy or resection. Overall (OS) and progression free survival (PFS) were analysed retrospectively. MGMT promoter methylation analysis was by MSP assay or pyrosequencing using archival or frozen tissues.
Results
109 patients were treated between June 2004-2007. With a median follow-up of 13.4 months, the median survival was 12 months (95%CI 10.6-13.4) and 8.5 months for similar historical patients. The 2-year survival was 15%. Median PFS was 10 months (95%CI 8.7-11.3). MSP and pyrosequencing data agreed in 29/34 cases. Pyrosequencing was reproducible and more reliable for archival and frozen tissues. 33/54 cases were methylated, while 6/38 showed heterogeneity between multiple samples from different parts of the tumour. In 41 patients treated with temozolomide and radiotherapy, MGMT promoter methylation was significantly associated with prolonged PFS (P=0.0000) and OS (P=0.0003) and was an independent prognostic variable.
Conclusion
Combined temozolomide and radiotherapy for glioblastoma patients benefited over previous standard treatment. MGMT pyrosequencing provides a reliable assay; methylation was associated with prolonged survival in a subset of the series. Further analysis will reveal the clinical utility of MGMT promoter methylation as a prognostic biomarker in the routine clinic.
