Stereotactic radiosurgery: adjacent tissue injury and response after high-dose single fraction radiation. Part II: Strategies for therapeutic enhancement, brain injury mitigation, and brain injury repair.

Overview

In the first part of this series, we reviewed the histological, radiographic, and molecular data gathered regarding the brain parenchymal response to radiosurgery and suggested future studies that could enhance our understanding of the topic. With this article, we begin by addressing methods of potentiating the effect of radiosurgery on target lesions of the central nervous system. Much of the work on potentiating the effects of cranial radiation has been performed in the field of whole-brain radiotherapy. Data from Phase III trials evaluating the efficacy of various agents as radiosensitizers or radioenhancers in whole-brain radiotherapy are reviewed, and trials for investigating certain agents as enhancers of radiosurgery are suggested. The roles of gene therapy and nanotechnology in enhancing the therapeutic efficacy of radiosurgery are then addressed. Focus is then shifted to a discussion of strategies of protecting healthy tissue from the potentially deleterious aspects of the brain's response to radiosurgery that were presented in the first article of this series. Finally, comments are made regarding the role of neural progenitor or stem cells in the repair of radiation-induced brain injury after radiosurgery. The importance of both the role of the extracellular matrix and properly directed axonal regrowth leading to appropriate target reinnervation is highlighted.