gms | German Medical Science

Objective: For patients with unresectable glioblastomas, length of survival (OS) after primary radiotherapy in combination with concomitant and adjuvant temozolomide is poorly defined. A previously published prospective study of our group has indicated a surprisingly long progression-free survival (PFS) in case of a methylated MGMT promoter. In the current updated study we focused on OS, post-recurrence survival (PRS) and prognostic/predictive factors associated with these endpoints.

Method: Previously published prospective data of 56 adult patients (aged 18-85, KPS>60) with supratentorial, unresectable glioblastomas were updated. Reference point was the date of the biopsy. Date of last follow-up was september 2014. Patients were grouped according to the Radiation Therapy Oncology Group (RTOG)-recursive partitioning analysis (RPA) classes. PFS, OS and PRS were estimated with the Kaplan-Meier method. Prognostic factors were obtained from proportional hazards models. Patients gave informed consent and the study was approved by the institutional review board (AZ 216/14).

Results: At the time of study closure 51 out of 56 patients had died. One patient was lost to follow-up. Overall, median OS, PFS and PRS were 49, 32, and 14 weeks, respectively. Patients with a methylated tumor exhibited significantly longer median PFS (45 vs. 24 weeks, p<0.0001), OS (81 vs. 29 weeks, p<0.0001) and PRS (20 vs 7 weeks, p<0.001). Patients with a Karnofsky performance score >70 at the time of tumor recurrence (KPSrez) received significantly more often salvage treatment (16/22 vs 6/22, p<0.0001). In multivariate models, favorable prognostic factors for OS were MGMT promoter methylation (p<0.0001) and RTOG-RPA classes III+IV (p=0.0031); favorable prognostic factors for PRS were an initial KPS>80 (p=0.02), a KPSrez>70 (p=0.001), and a methylated MGMT promoter (p=0.001); the prognostic impact of MGMT methylation pertained independent from the mode of the chosen salvage therapy. The study confirmed the previously reported predominant prognostic impact of MGMT methylation status on PFS (p=0.0002).

Conclusions: Even in unresectable glioblastoma, the prognosis of patients with methylated MGMT promoter has dramatically improved in the era of radiotherapy plus concomitant and adjuvant TMZ. The prognostic influence of this biomarker pertained even after tumor progression irrespective of the applied salvage therapy. Thus, there is no reason for therapeutic nihilism in these patients.