Reevaluating stereotactic radiosurgery for glioblastoma: new potential for targeted dose-escalation

Countless therapeutic strategies have been explored over many decades to prevent or slow the progression of glioblastoma. Despite radical changes in radiation management in other malignancies, there have been no major advances in the radiotherapeutic approach to glioblastoma in over 30 years. Past hopes to overcome inherent radioresistance with escalating doses have been met with frustration. However, prior clinical trials were performed before temozolomide, a radiosensitizer, altered the standard of care and this has renewed interest in dose escalation. Immunotherapy has led to further excitement, given the substantial responses that have been observed in other cancers when combined with high-dose radiation. In addition, advances in molecular profiling and neuroimaging have created new opportunities to improve patient selection for the most appropriate course of treatment. In this review, we outline past attempts to utilize radiosurgery in glioblastoma and focus on the potential to reintroduce this modality of dose escalation in the setting of modern and emerging systemic agents, molecular studies and imaging analyses.