over larger areas are more likely to be used (for example as in VMAT treatments). Fractionated radiotherapy relies more heavily on the different radiosensitivity of the target and the surrounding normal tissue to the total accumulated radiation dose. Historically, the field of fractionated radiotherapy evolved from the original concept of stereotactic radiosurgery following discovery of the principles of radiobiology: repair, reassortment, repopulation, and reoxygenation. Today, both treatment techniques are complementary, as tumors that may be resistant to fractionated radiotherapy may respond well to radiosurgery, and tumors that are too large or too close to critical organs for safe radiosurgery may be suitable candidates for fractionated radiotherapy. Today, both Gamma Knife and Linac radiosurgery programs are commercially available worldwide. While the Gamma Knife is dedicated to radiosurgery, many Linacs are built for conventional fractionated radiotherapy and require additional technology and expertise to become dedicated radiosurgery tools. There is not a clear difference in efficacy between these different approaches. The major manufacturers, Varian and Elekta offer dedicated radiosurgery Linacs as well as machines designed for conventional treatment with radiosurgery capabilities. Systems designed to complement conventional Linacs with beam-shaping technology, treatment planning, and image-guidance tools to provide. An example of a dedicated radiosurgery Linac is the CyberKnife, a compact Linac mounted onto a robotic arm that moves around the patient and irradiates the tumor from a large set of fixed positions, thereby mimicking the Gamma Knife concept. Mechanism of action The fundamental principle of radiosurgery is that of selective ionization of tissue, by means of high-energy beams of radiation. Ionization is the production of ions and free radicals which are damaging to the cells. These ions and radicals, which may be formed from the water in the cell or biological materials, can produce irreparable damage to DNA, proteins, and lipids, resulting in the cell's death. Thus, biological inactivation is carried out in a volume of tissue to be treated, with a precise destructive effect. The radiation dose is usually measured in grays (one gray (Gy) is the absorption of one joule of energy per kilogram of mass). A unit that attempts to take into account both the different organs that are irradiated and the type of radiation is the sievert, a unit that describes both the amount of energy deposited and the biological effectiveness. Clinical applications When used outside the CNS it may be called stereotactic body radiation therapy (SBRT) or stereotactic ablative