The radiobiological concepts of intrinsic radiation sensitivity, oxygenation, and dose-volume effects have been reasonably delineated in the context of conventional radiotherapy (RT). Yet, for circumstances in which large doses are delivered in single-fraction or hypofractionated regimens, these intrinsic radiobiological concepts are relatively poorly understood. Stereotactic radiosurgery (SRS) is a radical departure from the current RT approach in which large fields, cone downs, and protracted therapies are used for normal tissue preservation and to maximize the therapeutic ratio. SRS is the precise, highly focused delivery of radiation beams to lesions whereby only a fraction of the total dose is received by surrounding normal tissues. The usage of SRS is currently expanding well beyond its roots as an ablative tool for thalamotomies, arteriovenous malformations, and cranial vault tumors. Hence, widely believed dogmas concerning the tolerance of critical structures to conventionally fractionated doses, such as the dose-volume effect, total dose, and time (latency) dependency, have to be reevaluated for hypofractionated radiation therapy.
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