Treatment of unresectable glioblastoma multiforme

Uncertainty exists about the adequate treatment of adult patients with unresectable, primary, biopsy-proven glioblastoma multiforme (GBM), because the different options for this group of patients have not been evaluated in randomized clinical trials to date. Usually, these patients are lumped together in studies of radiotherapy or combined modality treatment with patients who have undergone extensive surgical resection, although they represent an unfavorable subgroup. This fact led us to review the recently published results for combined radio- and chemotherapy and to compare them with historical data. Management with best supportive care after biopsy resulted in a median survival time of 3 months. Median survival in a historical series of radiotherapy was of the order of 6-7 months and 2-year survival was less than 10%. Combined treatment consistently resulted in a 2-year survival rate of 10-18%. However, the median survival in contemporary series is highly variable, still ranging from 5 to 13 months. Even with the same regimen, large differences in outcome were observed (median survival 5 vs. 9.4 months). In a large randomized trial of radiotherapy vs. radiotherapy plus temozolomide, the subgroup with biopsy only did not benefit significantly from combined treatment. With different radio-chemotherapy approaches, the median survival was approximately 5 months in recursive partitioning analysis (RPA) class VI, but 8-14 months in classes IV and V. Thus, careful patient selection is necessary to avoid overtreatment in prognostically unfavorable groups with unresectable GBM. In patients qualifying for lengthy regimens of radio-chemotherapy, prospective randomized trials should study whether simultaneous radio- and chemotherapy is superior to radiotherapy alone and, if so, what are the effects of addition of either upfront chemotherapy or postradiation chemotherapy. Recent data suggest that class prediction models, based on defined molecular profiles, and assessment of MGMT promoter methylation might contribute to improved patient stratification and decision making.