The Mayo Clinic Gamma Knife Experience: Indications and Initial Results

Mayo Clinic Proceedings

January 1999

Volume 74 Number 1

The Mayo Clinic Gamma Knife Experience: Indications and Initial Results BRUCE

E. POLLOCK, M.D., DEBORAH A. GORMAN, R.N., W. KLINE, PH.D.

PAULA

J. SCHOMBERG, M.D., AND

ROBERT

growth control was noted in 200 (96%). Tumor growth was also controlled in 90% of brain metastatic lesions at a median of 7 months after radiosurgery. Of 20 patients with trigeminal neuralgia and follow-up for more than 2 months, 14 (70%) were free of pain after radiosurgery. • Conclusion: Radiosurgery is a safe and effective management strategy for a wide variety of intracranial disorders. Use of radiosurgical treatment should continue to increase as more data become available on the long-term results of this procedure.

• Objective: To review the results and expectations of contemporary stereotactic radiosurgery. • Material and Methods: We conducted a retrospective analysis of 1,033 consecutive patients who underwent gamma knife radiosurgery at Mayo Clinic Rochester between January 1990 and January 1998. • Results: The number of patients undergoing radiosurgery increased from 57 in 1990 to 216 in 1997. Of 97 patients with arteriovenous malformations who underwent follow-up angiography 2 years or more after a single radiosurgical procedure, 72 (74%) had complete obliteration of the vascular malformation. Of 209 patients who underwent radiosurgery for benign tumors (schwannomas, meningiomas, or pituitary adenomas) and had radiologic studies after 2 years or more of follow-up, tumor

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AVMs =arteriovenous malformations; CMs =cavernous malformations; DAVFs = dural arteriovenous fistulas; MRI = magnetic resonance imaging

S

and functional disorders such as trigeminal neuralgia.'? The purpose of this article is to discuss the indications for and the results of gamma knife radiosurgery based on the initial 8-year Mayo Clinic experience.

tereotactic radiosurgery is the precise delivery of a single fraction of high-dose ionizing radiation to an imaging-defined target. Conceived by Lars Leksell' in 1951, radiosurgery coupled advances in stereotactic localization with use of various radiation sources to decrease the morbidity associated with conventional intracranial surgical procedures. During the past 4 decades, major refinements have occurred in this technology to improve its safety and clinical applicability. The development that facilitated the growth of radiosurgery, however, was the introduction of computed tomography and magnetic resonance imaging (MRI). With the advent of advanced neuroimaging capability, radiosurgery was no longer limited to targets that could be defined by either plain skull radiography or cerebral angiography. Today, radiosurgery is used in the management of a wide variety of vascular malformations.i? benign and malignant brain tumors."?

DESCRIPTION OF GAMMA KNIFE RADIOSURGERY Stereotactic radiosurgery is a multidisciplinary procedure that relies on the expertise of specialists from several fields (neurologic surgery, radiation oncology, medical physics, radiology, and nursing). Radiosurgery is performed as an outpatient procedure; in most patients, only local anesthesia is needed. General anesthesia is usually necessary for pediatric patients younger than 12 years old. Radiosurgery

For accompanying editorial, see page 101 involves four steps. First, a stereotactic headframe is attached to the patient's skull. Second, the patient undergoes computed tomography, MRI, cerebral angiography, or a combination of these neuroimaging modalities, depending on the indication for the procedure. Stereotactic MRI has become the primary imaging technique because of its higher resolution for target definition. Third, a "dose plan" is created that closely matches the margins of the imagingdefined target. Typically, multiple isocenter dose plans are

From the Department of Neurologic Surgery (B.E.P., D.A.G.) and Division of Radiation Oncology (P.J.S., R.W.K.), Mayo Clinic Rochester, Rochester, Minnesota. Address reprint requests and correspondence to Dr. B. E. Pollock, Department of Neurologic Surgery, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN 55905.

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© 1999 Mayo Foundation for Medical Education and Research

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The number of patients undergoing radiosurgery increased from 57 in 1990 to 216 in 1997. The diagnoses of the first 1,033 patients undergoing radiosurgery at Mayo Clinic Rochester are summarized in Tab le 1. Of these patients, 33% had vascular malformations, 36% had benign intracranial tumors, and 28% had malignant intracranial tumors . Twenty-seven patients (3%) underwent radiosurgery for trigeminal neuralgia. VASCULAR MALFORMATIONS

Fig. I. Depiction of radiosurgery dose plan for vestibular schwannoma in 37-year-old woman. A conformal dose plan with use of 13 isocenters of radiation treatment was used to cover tumorat 50% isodoseline. used to minimize the radiation dose to the surrounding structures. Improved computer dose-planning software has also contributed substantially to the prod uction of dose plans more conformal to the irreg ular shapes of many tumors and vascular malformations (Fig. I). Conformal" radiosurgery is essential to minimize radiation-related complications after radiosurgery. Fourth, the radiation dose is delivered to the patient. The Leksell gamma knife (Elekta Instruments, Inc., Atlanta, Georgia) consists of 20 I cobalt-60 sources surrounded by an 18,000-kg shield. At Mayo Clinic Rochester, the model B unit was recently installed to replace the original model U unit. The newer model B unit can be used to treat some regions of the head and neck that previously could not be reached with the model U unit. The overall time of radiation delivery varies depending on the prescribed dose, but it generally ranges from 15 to 45 minutes. The mechanical accuracy of radiation delivery with use of the gamma knife is less than 0.3mm variation. After radiation delivery, the stereotactic headframe is removed, and the patient is returned to the outpatient area. Most patients are dismissed from the hospital on the day of the procedure. INDICATIONS

Appropriate selection of patients is critical for good patient outcomes after radiosurgery. In general, patients with lesions that exceed 35 mm in mean diameter are not considered good candi dates for radiosurgery for several reasons . At larger volumes, the radiation falloff into the surrounding normal tissues is not as steep as with smaller volumes, and the risk of delayed radiation-related complications increases exponentially. Furthermore, patients with larger lesions often have symptoms directly related to mass effect. For such patients, radiosurgery is ineffective, and surgical resection is the preferred management strategy.

Arteriovenous malformations (AVMs) were one of the first indications for radiosurgery because they could be visualized with use of cerebral angiography. Radiosurgery leads to the progressive obliteration of AVMs by endothelial cell proliferation, which results in luminal closure. II Complete obliteration generally occurs during a latency interval of 1 to 3 years after radiosurgery. Radiosurgery has also been used to manage dural arteriovenous fistulas (DA VFs) 3 and cavernous malformations (CMs) .2.1 2 Radiosurgery has not proved effective for cerebral aneu rysms . Venous malformations are common aberrations of the cerebral venous system with a very low ~l risk of hemorrhage." Consequently, radiosurgery provides little benefit for management of venous malformations and is not recommended." Table I.-Diagnoses of Patients Undergoing Gamma Knife Radiosurgery at Mayo Clinic Rochester Between 1990 and 1998(N = 1,033) Indication Vascular malformations Arteriovenous malformation Duralarteriovenous fistula Cavernous malformation Benigntumors Vestibular schwannoma Meningioma Pituitary adenoma Other schwannoma Hemangioblastoma Malignant tumors Brain metastatic lesions Glial tumors* Other tumorst Trigeminal neuralgia

Patients No. % 249 77

17

116

24 7 2 11

179 45 15 15

17 4

100 84 109 27

10 8

I

I

11

3

*Includes patients with astrocytoma. anaplastic astrocytoma. glioblastoma multiforme, oligodendroglioma. ependymoma, medulloblastoma, neurocytoma, and pilocytic astrocytoma. [Includes patients with chordoma. chondrosarcoma, glomus tumor, craniopharyngioma. hemangiopericytoma, and nasopharyngeal carcinoma.

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Arteriovenous Malformations The goals of management of AVMs are to eliminate the risk of future intracranial bleeding and to minimize morbidity. Options for patients with AVMs include embolization, surgical resection, radiosurgery, or a combination of these techniques. Radiosurgery has been shown to be an important management strategy for appropriately selected patients with AVM. Radiosurgery is especially useful for AVMs in deep brain sites (the basal ganglia, internal capsule, thalamus, or brain stem)15,16 and for critical lobar areas (sensorimotor or visual cortex).'? The primary drawback of radiosurgery for AVM is that patients remain at risk for bleeding until the AVM is obliterated. Several recently published reports have documented that the annual risk of AVM bleeding is either unchanged during the latency interval":" or decreased within 6 months after radiosurgery." At Mayo Clinic Rochester between 1990 and 1998, 227 patients with AVM underwent radiosurgery. The initial clinical manifestation was hemorrhage in 92 patients (41%), seizures in 72 (32%), and headaches in 90 (40%). Embolization was performed in 15 patients (7%) before radiosurgery. Seventy-three AVMs (32%) were located in the basal ganglia, thalamus, brain stem, or cerebellum; 170 AVMs (75%) were Spetzler-Martin grade III or greater." Of 97 patients who underwent follow-up angiography 2 years or more after a single radiosurgical procedure, 72 (74%) had complete obliteration of their AVM (Fig. 2). In 12 patients (5%), radiation-related complications devel-

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oped after radiosurgery. Two patients had complete resolution of their symptoms; thus, the incidence of new permanent neurologic deficits was 4%. Thirteen patients (6%) suffered an AVM hemorrhage after radiosurgery: four died, six sustained new deficits, and three recovered completely. In 22 patients, radiosurgery was repeated because of incomplete obliteration of the AVM. Six of eight patients in whom follow-up angiography was done after AVM-related radiosurgery was repeated had complete obliteration of the vascular malformation, an overall AVM cure rate of 80%. Dural Arteriovenous Fistulas DAVFs are rare lesions that typically manifest in adulthood and are more common in women than in men. Most are believed to be acquired lesions attributable to thrombosis of an adjacent venous sinus. Patients with DAVFs often complain of pulsatile tinnitus, headaches, seizures, or ocular problems, depending on the site of the fistula. Intracranial hemorrhage is less common as the initial symptom in patients who have DAVFs in comparison with patients who have AVMs. The most frequent sites of involvement are the transverse and sigmoid sinuses, but DAVFs occur as well at the cavernous sinus, the anterior cranial base, and the tentorium. Factors predisposing patients with DAVFs to hemorrhage include cortical venous drainage, venous dilatations, and deep venous drainage.P-" Treatment is necessary for DAVFs if they have angiographic characteristics associated with an in-

A

Fig. 2. Lateral vertebral angiograms of 15-year-old girl with right thalamic arteriovenous malformation (AVM) who sustained an intracerebral hemorrhage. A, Angiogram at time of radiosurgery. B, Angiogram 36 months later, showing complete obliteration of AVM.

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creased bleeding risk (cortical venous drainage) or symptoms that impair the patient's normal activities of daily living . At our institution, 77 patients with DAVFs have undergone radiosurgery.' Whenever possible, radiosurgery is combined with transarterial particulate embolization in the management of DAVFs. Radiosurgery is generally performed before embolization so that all the components of the DAVF are well visualized and included within the radiosurgical treatment volume. The patient then undergoes embolization (primarily through branches of the external carotid artery or other hypertrophied arteries supplying the dura) in the days after the radiosurgical procedure. This multimodality approach provides rapid alleviation of the patient's symptoms, reduction in risk of hemorrhage by the embolization procedures, and long-term cure of the fistula by progressive radiosurgical obliteration of the involved vasculature. Most patients (91%) with DAVFs had symptoms related to the fistula (for example, pulsatile tinnitus , chemosis, and proptosis); only seven patients (9%) had a prior hemorrhage. The sites of the DA VFs were as follows: transverse or sigmoid sinus in 26 patients, cavernous sinus in 20, petrosal sinus or tentorium in 16, jugular foramen in 6, cerebral hemisphere in 6, and superior sagittal sinus in 3. Forty-six patients (60%) underwent one or more embolization procedures after radiosurgery. Relief of symptoms occurred in more than 70% of patients. Morbidity related to either radiosurgery or embolization has been minimal. One patient (l %) had a venous infarct that resulted in a mild dysphasia. Two patients sustained an occlusion of the middle cerebral artery, either during angiography for stereotactic localization (N = 1) or during follow-up embolization 1 year after the initial treatment (N = 1). Both patients were treated with immediate intraarterial thrombolysis. One patient recovered completely, whereas the other patient had a permanent mild hemiparesis and aphasia. Follow-up angiography in 37 patients I year or more after radiosurgery showed that 28 (76%) had total or near-total (more than 95%) obliteration of their DAVFs. Of note, 12 of 14 patients (86%) with DAVFs involving the cavernous sinus had total or neartotal obliteration of the fistula.

Cavernous Malformations Radiosurgery for CMs remains controversial. Assessing the effect of radiosurgery on CMs is difficult for several reasons. First, the incidence and natural history of these lesions remain poorly understood. Second, unlike radiosurgery for AVMs, wherein the effects can be seen on either MRI or angiography, CMs show no changes on MRI after radiosurgery and are not visualized on cerebral

angiography. Consequently, we are forced to rely on the clinical course of the patient to assess whether radiosurgery has reduced either the risk of bleeding or the occurrence of new neurologic events. For these reasonsand because most CMs are not difficult to resect safelythe criteria for use of radiosurgery for CMs have been strict. To date, only patients with a hemorrhagic (at least two separate bleeding episodes) CM located at a highrisk surgical site have been considered good candidates for radiosurgery. During the study period, 17 patients underwent radiosurgery for CMs-I0 in the brain stem, 6 in the basal ganglia or thalamus, and 1 in the corpus callosum. Currently, the Mayo Clinic is participating in a multicenter, prospective randomized trial in which the safety and efficacy of radiosurgery for CMs are being assessed. BENIGN TUMORS

Although many intracranial tumors are histologically benign , they can behave aggressively because of their location at the base of the skull. Advances in neuroimaging, anesthesia, and microsurgical techniques have allowed many tumors in this region to be resected with acceptable morbidity. Often , however, the intimate relationship between these tumors and the adjacent brain stem, cranial nerves, and major vessels precludes complete resection of the neoplasm without causing severe neurologic deficits. As a result, radiosurgery of benign intracranial tumors (schwannomas, meningiomas, and pituitary adenomas) has been increasingly used as an alternative to surgical resection. Two factors make these benign tumors good candidates for radiosurgery. First , because the tumors do not invade the surrounding normal tissues and can generally be well visualized on MRI, the entire tumor can be included within the targeted radiosurgical volume. Second, the radiobiologic characteristics of a late responding target (benign tumor) surrounded by a late responding normal tissue (the brain) are favorable for radiosurgery." In such cases, the radiosurgical target receives a much greater radiation dose than do the adjacent normal structures. Within a few millimeters of the tumor periphery, the radiation dose to the tumor increases from the range of 12 to 20 Gy to the maximal tumor dose of 24 to 40 Gy, whereas outside the tumor margin the radiation dose declines to 5 to 10 Gy over a similar distance. As a result, the tumor experiences the radiobiologic effect of more than 100 Gy of fractionated irradiation. In contrast, the normal surrounding tissue has the radiobiologic effect of only 10 to 30 Gy of fractionated irradiation. Of course, these principles apply only with use of conformal dose plans so that the adjacent tissue is not exposed to the same high radiation dose as the tumor itself.

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Schwannomas One hundred twelve patients with 116 vestibular schwannomas (acoustic neuromas) underwent radiosurgery. Fifteen additional patients had radiosurgery for schwannomas involving other cranial nerves (trochlear, trigeminal, and facial nerves and the jugular foramen region). Of these 127 patients, 34 (27%) had undergone one or more prior surgical resections of their tumor. Eight patients had neurofibromatosis type 2. Of 80 patients with imaging follow-up for at least 2 years, 74 (92%) had control of tumor growth (Fig. 3). Of the 74 patients with vestibular schwannomas who received less than 16 Gy (the currently prescribed dose regimen), facial weakness developed in 9 (12%)-2 with mild to moderate facial dysfunction, and 7 with severe facial weakness. Three of these seven patients later had appreciable improvement in their facial movement. Facial numbness or paresthesias occurred after radiosurgery in four patients (5%). Meningiomas We have used radiosurgery in 157 patients with 179 meningiomas either as a primary management strategy (N =58) or as an adjunct after prior surgical resection (N = 99). Twenty patients had undergone prior fractionated external beam radiotherapy. In 20 patients (23 tumors), the

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meningiomas were atypical or malignant. Most patients had meningiomas of the skull base including the cavernous sinus (N = 55)25 or petroclival (N = 27) regions. Progression of tumor was seen in nine cases (5%). Seven of these nine cases involved atypical or malignant meningiomas; previous surgical treatment had failed in all these patients. Ninety-eight of 100 patients (98%) with typical meningiomas and 2 years or more of follow-up had control of tumor growth (Fig. 4). Involvement of the trigeminal nerve was the most common postradiosurgical cranial neuropathy (N = 9). Clinical improvement was evident in 25 patients (16%). Pituitary Adenomas Radiosurgery was used for 45 pituitary adenomas. The goals for use of radiosurgery in the sellar-parasellar region are fourfold: (1) to prevent progression of tumor, (2) to minimize the possibility of pituitary dysfunction, (3) to normalize hormonal overproduction syndromes whenever present, and (4) to avoid damage to the adjacent cranial nerves and temporal lobes. Patients with large tumors that distort the optic chiasm or nerves are generally not considered good candidates for radiosurgery. Because the optic nerves are the most radiosensitive of the cranial nerves,26,27 MRI and multiple isocenter dose planning have been essen-

Fig. 3. Gadolinium-enhanced axial magnetic resonance images (MRls) of 73-year-old woman with right-sided vestibular schwannoma. A, MRI at time of radiosurgery. B, MRI 60 months later, demonstrating decreased size of tumor.

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Fig. 4. Gadolinium-enhanced axial magnetic resonance images (MRls) of 33-year-old woman with recurrent right petroclival meningioma. Patient had undergone surgical resection 6 years earlier and had preoperative facial pain. A, MRI at time of radiosurgery. B, MRI 79 months after radiosurgery, showing decreased size of tumor. Facial pain had persisted but was diminished.

tial to achieve improvement in patient outcomes for tumors in this region. To minimize the incidence of postradiosurgical visual deficits, we limit the radiation dose to the optic nerves to less than 12 Gy. Such a dose prescription has resulted in less than 3% visual morbidity. Control of tumor growth has been achieved in 28 of 29 patients (97%) with pituitary adenoma who had follow-up imaging 2 years or more after radiosurgery. Normalization of hormone levels has been achieved in approximately 70% of patients with acromegaly and 30% of patients with Cushing's disease. These figures are similar to those in other published series.v" Two probable explanations have been offered for the higher success rate in patients with growth hormone-producing tumors. First, growth hormone-producing tumors may be more sensitive to the effects of radiation therapy . Second, and more likely, growth hormone-secreting tumors tend to be larger and are simply better visualized for stereotactic targeting. In an attempt to improve the hormonal response rate, we now base the radiosurgical dose to the tumor on the calculated radiation dose to the optic apparatus. It is hoped that our results will improve with higher radiation doses. In three patients (7%), anterior pituitary insufficiency developed after radiosurgery. No cases of diabetes insipidus have developed.

MALIGNANT TUMORS

Glial Neoplasms High-grade gliomas (anaplastic astrocytomas, glioblastoma multiforme) are the most common primary brain tumors. Despite aggressive surgical resection, fractionated radiation therapy, and chemotherapy for such tumors, patient outcomes continue to be poor. Over the years, radiation therapy has been shown to be the most effective treatment for these aggressive tumors. Brachytherapy has been used to increase the radiation delivery to the tumor." Radiosurgery offers a less invasive method to boost the tumor radiation dose. 29 •3o Radiosurgery seems to be most effective for younger patients with small tumors and a good performance status (capable of caring for themselves). The Mayo Clinic is part of the ongoing Radiation Therapy Oncology Group protocol to evaluate the efficacy of upfront radiosurgery as part of the initial management of high-grade gliomas. Patients with pilocytic astrocytomas that are recurrent or unresectable have also been shown to benefit from radiosurgery." Brain Metastatic Lesions Radiosurgery has its greatest potential use in the management of patients with brain metastatic lesions.F-" Metastatic tumors are the most common brain tumors dis-

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Mayo Clin Proc , January 1999, Vol 74

covered each year. Approximately 100,000 patients are diagnosed with metastatic brain tumors annually. Among this group of patients, an estimated 25,000 to 50,000 patients would benefit from more aggress ive intervention (either surgical resection or stereotactic radiosurgery). Severa] published studies have shown that the addition of surgical treatment (resection or radiosurgery) to conventional fractionated radiation therapy can significantl y improve patient survival. P'" The optimal patients for aggressive intervention have absent or stable systemic disease, good performance status, and a single brain metastati c lesion. To date, we have used radiosurgery in the management of 100 patients with l 69 metastatic brain tumors (range, I to 12 tumors each). In our experience, the crude tumor control rate has been 90% at a median of 7 months after radiosurgery. Of note, some types of tumors that traditionally have been considered resistant to radiation therapy (for example, melanoma or renal cell carcinoma) seem to respond especially well to radiosurgery (Fig. 5).36 Patients with large tumors (in excess of 3.5 em) often require surgical resection to reduce mass effect. Such patients are not considered candidates for radiosurgery. Radiosurgery has several distinct advantages over surgical resection for metastatic brain disease. First, and most obvious, the patient is able to avoid the pain and discomfort of a craniotomy. Second, because the procedure is per-

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formed under local anesthesia and does not necessitate any time in an intensive-care unit, the medical risks are minimal. Third , radiosurgery is an outpatient procedure that involves little or no convalescent time. Consequentl y, patients are able to resume their normal activities the day after radiosurgery. Fourth, radiosurgery can be used for patients with metastatic lesions in brain sites that are considered at high risk for surgical resection. Fifth, patients with multiple brain metastatic tumors can be managed in a single radiosurgical procedure. Finally, radiosurgery has been shown to be more cost-effective than surgical resection in the management of patients with a solitary brain metastatic lesion." Malignant Tumors of the Skull Base Radiosurgery has also been found to have an important role in the management of patients with malignant tumors of the skull base." Such tumors are frequently inoperable , and chemotherapy is generally of little benefit. Management of such tumors with external beam radiation therapy is constrained by the radiation tolerance of adjacent brain tissue and cranial nerves. Local control remains greater than 90% 2 or more years after radio surgery for these difficult lesions. Most patients experience clinical improvement after radiosurgery- most commonly, a reduction in facial pain.

Fig. 5. Gadolinium-enhanced axial magnetic resonance images (MRls) of 54-year-old man with recurrent left temporal metastatic melanoma. Patient had undergone surgical resection and external beam radiation therapy 10 months before radiosurgery (45 Gy). A, MRI at time ofradios urgery. B, MRI 58 months after radiosurgery, showing decreased size of tumor.

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Gamma Knife Radiosurgery

TRIGEMINAL NEURALGIA Stereotactic radiosurgery was originally conceived by Dr. Leksell as a technique to perform functional procedures noninvasively. With the advent of improved neuroimaging, however, radiosurgery found increasing application in the management of intracranial neoplasms and vascular malformations. Recently, interest has been renewed in the use of radiosurgery for the treatment of patients with trigeminal neuralgia. A multi-institutional, prospective trial found that almost 80% of patients with trigeminal neuralgia had some relief of their facial pain after radiosurgery.'? At a median of 3 weeks after the procedure, 60% of patients became free of pain. New-onset facial numbness or paresthesias were noted in less than 10% of patients. The Mayo Clinic experience has been similar to the published results. To date, we have managed 27 patients with trigeminal neuralgia with radiosurgery. The mean age of these patients has been 67 years, and in most (86%), one or more prior operations (mean, 2.2 procedures per patient) had failed. Fourteen of 20 patients (70%) with follow-up for more than 2 months are free of pain; another 4 patients continue to have some pain but would repeat the procedure to achieve their current level of alleviation of pain. The Mayo Clinic is currently performing a prospective, randomized trial together with the University of Pittsburgh to examine the effect of irradiation of a longer length of the trigeminal nerve during radiosurgery on pain relief and associated complications. CONCLUSION Radiosurgery has proved to be a safe and effective management strategy for a wide variety of intracranial disorders. Radiosurgery appeals to both patients and physicians because of its noninvasive nature and low associated morbidity. ACKNOWLEDGMENT We thank the following persons for their support and contributions to the Mayo Clinic Gamma Knife Project: Mary H. Sawyer, Angela K. Kollasch, Lorna N. Stevens, R.N., David G. Piepgras, M.D., ThoralfM. Sundt, Jr., M.D. (now deceased), Robert J. Coffey, M.D., Dudley H. Davis, M.D., Patrick J. Kelly, M.D., Robert L. Foote, M.D., Diana F. Nelson, M.D., Scott L. Stafford, M.D., John D. Earle, M.D., Edward G. Shaw, M.D., John Huston III, M.D., Douglas A. Nichols, M.D., Edwin C. McCullough, Ph.D., and J. Daniel Bourland, Ph.D. REFERENCES 1. 2.

Leksell L. The stereotaxic method and radiosurgery of the brain. Acta Chir Scand 1951-1952;102:316-319 Kondzlolka D, Lunsford LD, Flickinger JC, Kestle JRW. Reduction of hemorrhage risk after stereotactic radiosurgery for cavernous malformations. ) Neurosurg 1995;83:825-831

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3.

4.

5.

6. 7. 8.

9.

10.

11.

12.

13.

14. 15.

16. 17.

18. 19.

20.

21. 22.

23.

24. 25.

26.

Link MJ, Coffey RJ, Nichols DA, Gorman DA. The role of radiosurgery and particulate embolization in the treatment of dural arteriovenous fistulas. ) Neurosurg 1996;84:804-809 Pollock BE, Flickinger JC, Lunsford LD, Maltz A, Kondzlolka D. Factors associated with successful arteriovenous malformation radiosurgery. Neurosurgery 1998;42:1239-1244 Yamamoto Y, Coffey RJ, Nichols DA, Shaw EG. Interim report on the radiosurgical treatment of cerebral arteriovenous malformations: the influence of size, dose, time, and technical factors on obliteration rate. ) Neurosurg 1995;83:832-837 Foote RL, Coffey RJ, Swanson JW, Harner SG, Beatty CW, Kline RW, et al. Stereotactic radiosurgery using the gamma knife for acoustic neuromas. tnt J Radiat Oneal Blo! Phys 1995;32:1153-1160 Kondzlolka D, Lunsford LD, Coffey RJ, Flickinger JC. Stereotactic radiosurgery of meningiomas. ) Neurosurg 1991;74:552-559 Pollock BE, Kondzlolka D, Lunsford LD, Flickinger JC. Stereotactic radiosurgery for pituitary adenomas: imaging, visual and endocrine results. Acta Neurochir Suppl (Wien) 1994;62:33-38 Pollock BE, Lunsford LD, Kondzlolka D, Flickinger JC, Bissonette DJ, Kelsey SF, et al. Outcome analysis of acoustic neuroma management: a comparison of microsurgery and stereotactic radiosurgery. Neurosurgery 1995;36:215-224 Kondzlolka D, Lunsford LD, Flickinger JC, Young RF, Vermeulen S, Duma CM, et al. Stereotactic radiosurgery for trigeminal neuralgia: a multiinstitutional study using the gamma unit. ) Neurosurg 1996; 84:940-945 Schneider BF, Eberhard DA, Steiner LE. Histopathology of arteriovenous malformations after gamma knife radiosurgery. ) Neurosurg 1997;87:352-357 Karlsson B, Kihlstrom L, Lindquist C, Ericson K, Steiner L. Radiosurgery for cavernous malformations. ) Neurosurg 1998; 88:293-297 Kondzlolka D, Dempsey PK, Lunsford LD. The case for conservative management of venous angiomas. Can) Neurol Sci 1991;18:295299 Lindquist C, Guo WY, Karlsson B, Steiner L. Radiosurgeryfor venous angiomas. ) Neurosurg 1993;78:531-536 Lawton MT, Hamilton MG, Spetzler RF. Multimodality treatment of deep arteriovenous malformations: thalamus, basal ganglia, and brain stem. Neurosurgery 1995;37:29-35 Sasaki T, Kurita H, Saito I, Kawamoto S, Nemoto S, Terahara A, et al. Arteriovenous malformations in the basal ganglia and thalamus: management and results in 101 cases. ) Neurosurg 1998;88:285-292 Pollock BE, Lunsford LD, Kondzlolka D, Bissonette DJ, Flickinger JC. Stereotactic radiosurgery for postgenlculate visual pathway arteriovenous malformations. ) Neurosurg 1996;84:437-441 Friedman WA, Blatt DL, Bova FJ, Buattl JM, Mendenhall WM, Kubllls PS. The risk of hemorrhage after radiosurgery for arteriovenous malformations. ) Neurosurg 1996;84:912-919 Pollock BE, Flickinger JC, Lunsford LD, Bissonette DJ, Kondzlolka D. Hemorrhage risk after stereotactic radiosurgery of cerebral arteriovenous malformations. Neurosurgery 1996;38:652-659 Karlsson B, Lindquist C, Steiner L. Effect of Gamma Knife surgery on the risk of rupture prior to AVM obliteration. Minim Invasive Neurosurg 1996;39:21-27 Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. ) Neurosurg 1986;65:476-483 Awad lA, Little JR, Akarawl WP, Ahl J. Intracranial dural arteriovenous malformations: factors predisposing to an aggressive neurologlcal course. ) Neurosurg 1990;72:839-850 Brown RD Jr, Wlebers DO, Nichols DA. Intracranial dural arteriovenous fistulae: angiographic predictors of intracranial hemorrhage and clinical outcome in nonsurgical patients. ) Neurosurg 1994;81:531-538 Larson DA, Flickinger JC, Loeffler JS. The radiobiology of radiosurgery [editorial]. tnt ) Radiat Oncol BioI Phys 1993;25:557-561 Duma CM, Lunsford LD, Kondzlolka D, Harsh GR IV, Flickinger JC. Stereotactic radiosurgery of cavernous sinus meningiomas as an addition or alternative to microsurgery. Neurosurgery 1993;32:699704 Leber KA, Bergloff J, Pendl G. Dose-response tolerance of the visual pathways and cranial nerves of the cavernous sinus to stereotactic radiosurgery. ) Neurosurg 1998;88:43-50

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27.

28.

29.

30. 31.

32.

Tishler RB, Loeffler JS, Lunsford LD, Duma C, Alexander E III, Kooy HM, et al. Tolerance of cranial nerves of the cavernous sinus to radiosurgery. Int J Radiat Oncol BioI Phys 1993;27:215221 Thoren M, Riihn T, Guo WY, Werner S. Stereotactic radiosurgery with the cobalt-60 gamma unit in the treatment of grow,th hormone-producing pituitary tumors. Neurosurgery 1991;29:663'e68 Shrleve DC, Alexander E III, Wen PY, Rne HA, Kooy HM, Black PM, et al. Comparison of stereotactic radiosurgery and brachytherapy in the treatment of recurrent glioblastoma multiforme. Neurosurgery 1995;36:275-282 Kondzlolka D, Rlcklnger JC, Bissonette DJ, Bozlk M, Lunsford LD. Survival benefit of stereotactic radiosurgery for patients with malignant glial neoplasms. Neurosurgery 1997;41:776-783 Somaza SC, Kondzlolka D, Lunsford LD, Rlcklnger JC, Bissonette DJ, Albright AL. Earlyoutcomes after stereotactic radiosurgery for growing pilocytic astrocytomas in children. Pediatr Neurosurg 1996;25:109115 Auchter RM, Lamond JP, Alexander E, Buattl JM, Chappell R, Friedman WA, et al. A multi institutional outcome and prognostic factor analysis of radiosurgery for resectable single brain metastasis. Int J Radiat Oneal BioI Phys 1996;35:27-35

33.

34.

35.

36. 37.

38.

13

Rlckinger JC, Kondzlolka D, Lunsford LD, Coffey RJ, Goodman ML, Shaw EG, et al. A multi-institutional experience with stereotactic radiosurgery for solitary brain metastasis. Int J Radiat Oneal BioI Phys 1994;28:797-802 Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Krysclo RJ, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990;322:494-500 Vecht CJ, Haaxma-Relche H, Noordljk EM, Padberg GW, Voormolen JHC, Hoekstra FH, et al. Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? Ann Neural 1993;33:583-590 Somaza 5, Kondzlolka D, Lunsford LD, Kirkwood JM, Rlcklnger JC. Stereotactic radiosurgery for cerebral metastatic melanoma. J Neurosurg 1993;79:661-666 Rutigliano MJ, Lunsford LD, Kondzlolka D, Strauss MJ, Khanna V, Green M. The cost effectiveness of stereotactic radiosurgery versus surgical resection in the treatment of solitary metastatic brain tumors. Neurosurgery 1995;37:445-453 Miller RC, Foote RL, Coffey RJ, Gorman DA, Earle JD, Schomberg PJ, et al. The role of stereotactic radiosurgery in the treatment of malignant skull base tumors. Int J Radiat Oneal BioI Phys 1997;39:977-981

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