© 1996 Nature Publishing Group http://www.nature.com/naturemedicine • NEW TECHNOLOGY Stereotactic radiosurgery ROBERT). MACIUNAS Department of Neurological Surgery, Vanderbilt University Medical Center, T-4224 Medical Center North, Nashville, Tennessee 37232-2380, USA In 1951, Lars Leksell, a Swedish neuro­ nisms to be engaged in normal tissue. tons, whether produced by radioactive surgeon at the Karolinska Institute in Stereotactic radiosurgery relies instead cobalt or by linear accelerators, may be Stockholm, described a method of pre­ on the accurate localization of abnormal considered to be effectively identical'. cisely guiding beams of radiation to treat tissue and complex treatment planning The revolution in computer image surgically inaccessible lesions within the to restrict the peak of delivered radiation processing has provided powerful tools brain1. In order to locate the target, he to this region. By delivering radiation for expediting the complex treatment relied upon stereotaxy, a technique from many different orientations using plans required by radiosurgery. The devised by Clarke and Horsley in 1906 a crossfire technique, the cumulative grease pencil calculations on skull radi- Fig. 1 Pseudo-three-dimensional surface rendering of critical anatomy • structures, target lesion and radiosurgery dose delivery areas. dose at the isocenter is ographs by Leksell have been replaced enormously multiplied with three-dimensional surface render­ over the background ings overlaid by dose-volume histograms peripheral dose'·". (Fig. l)u'. Accurate mapping, or registration, of image-to­ Applications physical space has been Stereotactic radiosurgery has been ap­ achieved by the use plied to a broad spectrum of intracranial of stereotactic frames. lesions. Although initially conceived as a Imaging modalities typ­ technique for performing minimally in­ ically employed include vasive psychosurgery''6'19, it has found its digital tomograms such greatest utility in the treatment of arteri­ as computed tomogra­ ovenous malformations, benign cranial phy (CT) and magnetic base tumors, metastatic cancers and a resonance (MR) imag­ variety of other lesions. ing, and transfemoral Intracranial arteriovenous malforma­ cerebral angiograms. tions less than 30 mm in size are increas­ (ref. 2), whereby a coordinate frame was Although angiography is inherently a ingly treated with this modality. Gradual attached to the skull so as to register di­ two-dimensional projection image, its sclerosis of the aberrant vasculature re­ agnostic images and the patient's superior resolution of relevant vascular sults in occlusion of arteriovenous mal­ anatomy. Initially, the radiation source anatomy provides critical information formations in approximately 85 percent used was proton beams generated by a when dealing with vascular anomalies•. of cases, yielding results similar to those 34 10 13 cyclotron ' • Because of the complexity Several different sources of radiation of open craniotomy and resection ' • and limited availability of this tech­ are employed. Radioactive cobalt rods Particle beam therapy has been champi­ nique, Leksell eventually settled on continue to be used in "gamma knives," oned by some for the treatment of larger cobalt-60 ('°CO rods)•-•. The first which have evolved from the original arteriovenous malformations17'18 . Often, 5 10 "gamma unit" was installed in 1968 at Karolinska unit ' • Most institutions rely endovascular approaches to emboliza­ the Karolinska Institute, ushering in upon linear accelerator sources for tion with particulate material, coils, or 11 16 an era of explosive growth in the clinical photons"· - , Several sites, including glue are used to prepare the arterio­ use of this technology. the Massachusetts General Hospital venous malformation by reducing its size and Lawrence Livermore Hospital at and diminishing its flowzo. Angio­ The technique Berkeley, have employed charged parti­ graphically occult arteriovenous mal­ Traditional, fractionated external beam cleS3'4'17'18. In theory, charged particles formations appear to respond to radiotherapy relies upon the differential offer better dose homogeneity for larger treatment with a lower annual incidence sensitivity of normal parenchyma ver­ lesions and potentially are more con­ of hemorrhage21 . sus neoplastic tissue. Radiation is strained in their site of energy deposi­ Benign cranial base tumors amenable delivered to a broad field encompassing tion due to the "Bragg peak" effect, to this therapy include acoustic neuri­ the tumor, with sufficient time elapsing although some have questioned the sig­ nomas, cavernous sinus meningiomas, between individual dose fractions to nificance of these effectS 18. For pur­ pituitary tumors, and other tumors allow effective nuclear repair mecha- poses of this discussion, 4-MeV pho- that are inaccessible, residual or recur- 712 NATURE MEDICINE, VOLUME 2, NUMBER 6, JUNE 1996 © 1996 Nature Publishing Group http://www.nature.com/naturemedicine • ·············NEW TECHNOLOGY Fig. 2 Two-dimen­ for prediction of complications from radio­ sional slice display of surgery. Int. f. Radiat. Oneal. Bioi. Phys. 17, 8 79-885 (1989). radiosurgical isodose 8. Podgorsak, E.B. et al. Dynamic stereotactic lines, demonstrating radiosurgery. Int. f. Radiat. Oneal. Bioi. Phys. 14, abrupt dosimetric fall­ 115-120 (1988). 9. Spiegelman, R., Friedman, W.A. & Bova, F.J. off at the edge of the Limitations of angiographic target localiza­ target lesion. tion in radiosurgical treatment planning. Neurosurgery 30, 619-624 (1992). 10. Lunsford, L.D. et al. Stereotactic radiosurgery of the brain using the first United States 201 cobalt-60 source gamma knife. Neurosurgery 24, 151-159 (1989). 11. Betti, 0.0. & Derechinsky, V.E. Hyperselective encephalic irradiation with a linear accelerator. Acta Neuroehir. Suppl. (Wien) 33, 385-390 (1984). 12. Colombo, F. et al. External stereotactic irradia­ tion by linear accelerator. Neurosurgery 16, 154-160 (1985). 13. Friedman, W.A. & Bova, F.J. LINAC radio­ surgery for arteriovenous malformations. f. Neurosurg. 77, 832-841 (1992). 14. Lutz, W., Winston, K.R. & Maleki, N. A system for stereotactic radiosurgery with a linear accel­ erator. Int. f. Radiat. Oneal. Bioi. Phys. 14, 373-381 (1988). 15. Ozkan, M., Maciunas, R.J. & Eisert, D. Automated planning for stereotactic radio­ surgery. Proc. of the Intelligent Autonomous Systems Conf., Karlsruhe, Germany, March rent after maximal efforts at surgical the treatment of medically intract­ 27-30, 1995. 10 22 25 extirpation ' - • able epilepsy and functional ablative 16. Winston, K.R. & Lutz, W. Linear accelerator as Intracranial metastases are generally procedures. a neurosurgical tool for stereotactic radio­ surgery. Neurosurgery 22, 454-464 (1988). felt to be optimally treated with stereo­ Radiation sensitizers have been pro­ 17. Hosobuchi, Y., Fabrikant. J.I. & Lyman, J.T. tactic radiosurgery, often in conjunction posed to increase the therapeutic index Stereotactic heavy-particle irradiation of in­ 27 tracranial arteriovenous malformations. Appl. with external beam radiation therapf'· • between normal and pathologic tissue Neurophysiol. 50, 248-252 (1987). This palliative therapy sustains neuro­ treated with radiation. Clinical trials are 18. Kjellberg, R.N. et al. Bragg-peak proton-beam logic function until the patient suc­ underway to investigate whether their therapy for arteriovenous malformations of the cumbs to the primary systemic disease use can minimize required doses and im­ brain. N. Engl. f. Med. 309, 269-274 (1983). 19. Steiner, L. et al. Gammathalamotomy in (Fig. 2). prove clinical outcome after stereotactic tractable pain. Acta Neurochir. (Wien) 52, radiosurgery. 173-184 (1980). Future directions A considerable cumulative clinical ex­ 20. Dawson, R.C. III et al. Treatment of arteriove­ nous malformations of the brain with Frameless techniques of interactive perience with stereotactic radiosurgery combined embolization and stereotactic radio­ image-guided radiosurgery promise to exists, with perhaps as many as 25,000 surgery: Results after 1 and 2 years. Am. f. Neuroradiol. 11, 857-864 (1990). allow greater clinical flexibility, while patients having been treated since 1968. 21. Konziolka, D. et al. Stereotactic radiosurgery of maintaining high levels of system Perhaps the most significant advance in angiographically occult vascular malforma­ accuracy. By eliminating the need to this field will be the careful analysis tions: Indications and preliminary experience. Neurosurgery 27, 892-900 (1990). attach a cranial coordinate frame, of prospective controlled multicenter 22. Degerblad, M. et al. Long-term results of stereo­ fractionated dose schedules of highly studies employing outcome analysis to tactic radiosurgery to the pituitary gland in precise, complex radiosurgical treat­ determine the proper indications for this Cushing's disease. Acta Endocrinol. (Copenh.) 28 112, 310-314 (1986). ment plans may be investigated • therapy in the context of minimally 23. Flickinger, ].C. eta/. Radiosurgery of acoustic Ultimately, the practice of traditional invasive neurosurgery and radiation neurinomas. Cancer 67, 345-353 (1991). external beam fractionated radiother­ oncology. 24. Kondziolka, D. et al. Stereotactic radiosurgery of meningiomas. f. Neurosurg. 74, 552-559 apy will likely become more refined as (1991). 29 these techniques become widespread • 1. Leksell, L. The stereotaxic method and radio­ 25. Kondziolka, D., Lunsford, L.D. & Flickinger, Extracranial