Principles of radiobiology of stereotactic radiosurgery and clinical applications in the central nervous system.

Stereotactic radiosurgery (SRS) has become an important treatment option for intracranial lesions and has recently been adapted to treat lesions outside the brain. Many studies have shown the effectiveness of SRS for the treatment of benign and metastatic tumors. Although DNA damage has been thought to be the principal form of radiation-induced damage, recent studies have shown that vascular endothelial damage is perhaps more important in the setting of high radiation doses per fraction such as those used in SRS. Furthermore, it has been shown that molecular responses to radiation differ based on dose per fraction. The principles of classical radiobiology are reviewed with explanation on why fractionation of radiotherapy allows optimization of the therapeutic ratio. The current understanding of the molecular responses that occur soon after the delivery of high radiation doses per fraction is also reviewed. A summary of current clinical evidence of radiation tolerance to SRS of brain, brainstem, optic chiasm and spinal cord is also provided. Recent advances in understanding the molecular basis of SRS response have uncovered a different biological response than previously thought. Further understanding of these molecular mechanisms will allow for the development of targeted radiosensitizers and radioprotectors to optimize the therapeutic ratio.