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A method for extracranial stereotactic radiosurgery (ESRS) is described. For this treatment method a stereotactic body frame was developed and is described here. The ESRS method uses a hypofractionation schedule with 2–3 fractions with 10–20 Gy/fraction to the periphery of the target volume, at the 65% isodose. The heterogeneous target dose is used as a means to increase the probability of killing the hypoxic tumor cells. It is argued from in vitro cell survival data that the dose increase used will give a reasonable probability to eradicate at least moderate concentrations of hypoxic cells. A high reproducibility of the target position with the ESRS method is based on the definition of the patient reference system to the stereotactic system and not to the bony anatomical reference points as used in conventional radiotherapy. Important to the ESRS method is that the target position is verified by computed tomography (CT) examinations. The positional accuracy of the target in the stereotactic system is 3.1 mm (mean deviation) in the transversal plane and 5.5 mm (mean deviation) in the longitudinal direction. The setup accuracy, i.e., the correct alignment of the stereotactic system to the isocenter of the treatment unit, is within 1 mm. Other aspects of the ESRS method that are discussed are the treatment technique including collimation methods and dose distributions used, as well as target margins. ESRS has been in clinical use for several years at Radiumhemmet, Karolinska Hospital.