Management of GBM: a problem of local recurrence.

Forty years ago, adjuvant treatment of patients with GBM using fractionated radiotherapy following surgery was shown to substantially improve survival compared to surgery alone. However, even with the addition of temozolomide to radiotherapy, overall survival is quite limited and local failure remains a fundamental problem, despite multiple attempts to increase dose to the tumor target. This review presents the historical background and clinical rationale leading to the current standard of care consisting of 60 Gy total dose in 2 Gy fractions to the MRI-defined targets in younger, high performance status patients and more hypofractionated regimens in elderly and/or debilitated patients. Particle therapies offer the potential to increase local control while reducing dose and, potentially, long-term neurocognitive toxicity. However, improvements in systemic therapies for GBM will need to be implemented before the full benefits of improved local control can be realized.