ylated MGMT gene promoter. In our study, the median OS was 29 months with MGMT gene methylation and 20 months with unmethylation. One possible explanation for improved survival in our current study is the superior GTR/STR rate. Approximately three fourths of ourpatients underwent GTR or STR, and their median survival time was 23 months. In Panobinostat LBH-589 the EORTC trial 26981/22891 and NCIC trial CE.3, the extent of resection was categorized into biopsy, partial debulking surgery, and complete debulking surgery. Approximately 40% of patients underwent complete debulking surgery, although the definitions of complete removal and partial removal were not clearly described. By contrast, in our institution, the extent of resection was determined by postoperative MRI taken within 48 hours of operation in all patients.
Another possible explanation of better survival in our current study is the early start of postoperative radiotherapy. The median estimated cellular doubling time of GBM is 17 days. As the tumor enlarges and sends out satellite growths a regional miss is more likely in the radiation treatment. Some authors have reported that delay in time from surgery to start of radiotherapy is associated with a poor survival rate. Irwin et al. reported that every additional week of delay until start of radiotherapy increases the risk of death by 8.9%. In the EORTC trial 26981/22891 and NCIC trial CE.3, the median time from diagnosis to the start of radiotherapy was 5 weeks. In our current study, postoperative radiotherapy was started within 3 weeks of operation in 87% of patients.
The current study was conducted in a single institution, and consistent surgical and radiotherapy techniques may have contributed to better survival compared with reports from multiinstitution studies. Most previous dose escalation studies for GBM have failed to show an improvement in survival. Before introducing TMZ, we tried to escalate the radiation dose from 60 Gy to 70.2 Gy. In the report by Cho et al, the median survival in 42 patients who received a higher dose of radiation was 21 5.03 months, whereas the median survival in 33 patients who received a lower radiation dose was 14 0.94 months. Because Cho et al. conducted a retrospective study with historical comparison, improved survival could possibly be attributed not only to a higher radiation dose but also to improved surgical and radiotherapy techniques.
In the current study, there was no significant difference in the median OS between patients who received 60 Gy radiation plus TMZ and patients who received over 60 Gy radiation plus TMZ. One possible explanation is that the higher radiotherapy dose effect may have been compromised by the addition of TMZ. The effects of adding TMZ and escalating the radiation dose require further investigation. From the EORTC trial 26981/22891 and NCIC trial CE.3, MGMT gene promoter methylation has gained interest as a potential predictive marker for improved response to chemotherapy, particularly alkylating agents such as TMZ. However, it is still not entirely clear whether MGMT promoter methylation is truly a prognostic marker, indicative of the natural history of disease, or truly a predictive marker of sensitivity to chemotherapy or radiation. In the same EORTC trial, in patients who were