Association of molecular marker O6Methylguanine DNA methyltransferase and concomitant chemoradiotherapy with survival in Southern Chinese glioblastoma patients

Abstract

Objectives (1) To compare the survival of concomitant chemotherapy and radiotherapy with radiotherapy alone in Chinese patients with primary glioblastoma. (2) To determine the methylation status of O6Methylguanine DNA methyltransferase in Chinese primary glioblastoma, and to assess the prognostic value of O6Methylguanine DNA methyltransferase methylation status in such patients. Design Retrospective correlative analysis. Setting University teaching hospital, Hong Kong. Patients Patients diagnosed with histologically proven primary glioblastoma in the period of March 2005 to June 2007 were recruited. Genomic DNA was isolated from formalin-fixed and paraffin-em bedded sections of glioblastoma tissues. Methylation-specific polymerase chain reaction for O6Methylguanine DNA methyltransferase was performed. Patients' information at presentation was collected (age, performance status, steroid use, extent of resection, complications, radiotherapy data, use of chemotherapy). Primary outcome was measured by overall survival while secondary outcome was measured by progression-free survival. Overall and progression-free survivals were estimated by the Kaplan-Meier technique. Outcomes were assessed for groups with and without concomitant chemoradiotherapy and for groups with and without O6Methylguanine DNA methyltransferase methylation. Results A total of 35 glioblastoma patients were recruited; 27 were male and 8 female. Their mean age was 50 years. In all, 17 received concomitant chemoradiotherapy, and 18 received radiotherapy only. Their median overall survival was 12 (range, 7-17) months and the median progression-free survival was 5 (range, 3-6) months. In the radiotherapy alone group, the median progression-free survival and overall survival was 4 (range, 3-5) months and 6 (range, 2-10) months, respectively. In the concomitant radiochemotherapy group, the median progression-free survival and overall survival was 6 (range, 2-10) months and 13 (range, 8-18) months, respectively. Fifteen (43%) of the tumour samples showed methylation of O6Methylguanine DNA methyltransferase. There was a trend towards overall longer survival in the group with methylated tumours compared to those with unmethylated tumours; respective values for median survival (ranges) were 17 (13-21) versus 10 (6-14) months (P=0.105). Conclusions Our single-centre results indicated that Chinese glioblastoma patients who had received concomitant chemoradiotherapy showed a trend towards longer overall survival compared to those receiving radiotherapy alone. Approximately 43% of our Chinese glioblastoma samples showed methylation of O6Methylguanine DNA methyltransferase. O6Methylguanine DNA methyltransferase methylation may be a signifcant prognostic factor in Chinese glioblastoma patients.