Gamma knife surgery for skull base meningiomas

Gamma Knife Surgery for Skull Base Meningiomas THE EFFECTIVENESS OF LOW-DOSE TREATMENT Yoshiyasu Iwai, M.D., Kazuhiro Yamanaka, M.D., Toshihiro Yasui, M.D., Masaki Komiyama, M.D., Misao Nishikawa, M.D., Hideki Nakajima, M.D., and Hiroshige Kishi, M.D. Department of Neurosurgery, Osaka City General Hospital, Osaka, Japan

Iwai Y, Yamanaka K, Yasui T, Komiyama M, Nishikawa M, Nakajima H, Kishi H. Gamma knife surgery for skull base meningiomas. The effectiveness of low-dose treatment. Surg Neurol 1999; 52:40 –5. BACKGROUND

The surgical removal of skull base meningiomas has a high morbidity rate, even by modern microsurgical standards. We evaluated the results of gamma knife surgery for skull base meningiomas using a relatively low radiation dose for the tumor margins. METHODS

We reviewed 24 cases of skull base meningiomas during a 30-month period. The locations of the tumors were the petroclival region in 11 cases, the cavernous sinus region in 9 cases, and the cerebellopontine angle region in 4 cases. Eight patients (33%) had been operated on previously and fourteen patients (67%) had been treated by neuroimaging. The marginal doses for the tumors were 8 Gy to 15 Gy (median, 10.6 Gy). A large petroclival tumor 58 mm in diameter was treated with a staged treatment protocol with a 6-month interval between treatments. RESULTS

Tumor regression was observed in 46% of the patients imaged during the follow-up period (median, 17.1 months). No patients revealed tumor growth in the follow-up period (100% tumor control rate). Eleven patients (46%) had improved clinically by the time of the follow-up examinations. Preexisting cranial nerve deficit in one patient worsened because of radiation injury. CONCLUSION

Although a longer follow-up period is required, the relatively low minimum tumor radiation dose treatment for skull base meningiomas using a gamma knife seems to be an effective treatment with low morbidity. © 1999 by Elsevier Science Inc. KEY WORDS

Radiosurgery, gamma knife, cranial base, meningioma. Address reprint requests to: Dr. Yoshiyasu Iwai, Department of Neurosurgery, Osaka City General Hospital, 2-13-22, Miyakojima-hondori, Miyakojima-ku, Osaka, 534-0021, Japan. Received March 5, 1997; accepted April 27, 1998. 0090-3019/99/$–see front matter PII S0090-3019(99)00037-3

he operative results of surgery for skull base meningiomas have been improved by modern microsurgical techniques, but surgery is still accompanied by a high morbidity rate [1,2,17,18]. Radiosurgery achieves good tumor control (a lack of radiographic and clinical progression) with an 80% to 100% tumor control rate for meningiomas. Even so, previous reports of stereotactic radiosurgery showed a 5 to 13% morbidity rate because of radiation injury [3,4,8,9,20]. This report evaluates the effectiveness and morbidity rate of gamma knife treatment using low-dose radiation for skull base meningiomas.

T

Patients and Methods Between January 1994 and July 1996, 24 patients with skull base meningiomas underwent stereotactic radiosurgery with a 201-source cobalt-60 gamma knife. The locations of the tumors are listed in Table 1. No patients received external radiation before gamma knife treatment. The neurological deficits presented are listed in Table 2. The median age was 54 (range, 37 to 77). Six patients (25%) had neurological deficits that developed as complications of previous surgical procedures. Previous surgery had been performed in eight patients (33%). The Leksell Model G frame (Elekta Instruments, Stockholm, Sweden) was placed under local anesthesia. Magnetic resonance imaging was performed and the dose planning was done on a Gamma Plan. The median tumor diameter in this series was 27.3 mm (range, 13.4 mm–58.3 mm). The median tumor volume was 10,969 mm3 (range, 1248 mm3–28,597 mm3). The dose was based on the tumor volume and location. The minimal tumor radiation dose © 1999 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010

Radiosurgery for Cranial Base Meningiomas

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The Locations of Tumors

LOCATIONS

CASES

Petroclival Cavernous sinus Cerebellopontine angle

11 9 4

ranged from 8 Gy to 15 Gy (median, 10.6 Gy) (Figure 1). The isodose (mean 47.6%; range 30 – 60%) were used to cover the tumors. Multiple isocenters (mean, 13 isocenters; range, 5–18 isocenters) were used in all patients. One patient with a tumor with a median diameter of 58 mm underwent radiosurgery using a staged treatment protocol with a 6-month interval between treatments. All patients were discharged the day after radiosurgery. Follow-up imaging was requested at 6-month intervals. Tumor reduction was calculated as any measurable reduction in the anteroposterior or mediolateral dimensions of the tumor.

velopment of high T2 signal in the surrounding brain on MR imaging was observed in one patient who underwent two-staged gamma knife treatment without evidence of any new neurological deficits. Delayed transient radiation injury occurred in one patient (4%). This patient showed a worsening of a preexisting facial palsy after 12 Gy at the tumor margin.

Results

Discussion

The median follow-up period was 17.1 months (range, 6 –36 months). Twelve patients (50%) were unchanged clinically. Eleven patients (46%) improved clinically. Four patients had improved trigeminal function, two patients had improved oculomotor function, two had lessening of abducens palsy, two had improvement of cerebellar ataxia, and one had improvement of memory disturbance (Table 3). No patient had evidence of tumor growth after radiosurgery (tumor control rate, 100%). Table 4 shows the tumor control after radiosurgery. Eleven tumors (46%) regressed (Figure 2). The de-

Before discussing the therapeutic results of skull base meningiomas, we should discuss the natural history of meningiomas. Olivero et al reported the follow-up results of 57 cases of asymptomatic meningiomas with an average follow-up period of 32 months. Among these patients, 10 showed tumor growth during the follow-up period and the growth rate of these tumors was 0.24 cm/year, but no patient became symptomatic during the follow-up period [14]. Goodman et al followed up 24 patients with basal meningiomas during a period of 2–18 years; unequivocal tumor growth was observed in only three patients, and no patients required tumor debulking [6]. From these reports, newly diagnosed skull base meningiomas without symptoms can be observed during periods of follow-up. Surgery is the best treatment option for meningiomas, but surgery for skull base meningiomas has a relatively high morbidity rate and total removal has been achieved in only 60 –76% of cases, even when modern microsurgical techniques were used [1,2,

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Neurological Deficits before Radiosurgery for Skull Base Meningiomas

NEUROLOGICAL

DEFICITS

Visual disturbance Oculomotor palsy Trochlear nerve palsy Trigeminal nerve palsy Abducens nerve palsy Facial nerve palsy Hearing disturbance Hemiparesis Cerebellar dysfunction Aphasia Memory disturbance

NUMBER 1 3 1 7 5 3 6 1 5 1 1

There were 25% of neurological deficits reported to be the consequence of the approach, and 33% of the patients had undergone previous surgery.

Scattergram of Marginal Dose (Gy) versus Tumor Diameter (mm) for 24 patients with complications indicated by triangles.

1

3

Clinical Status after Radiosurgery of 24 Patients

NEUROLOGICAL

FINDINGS

Unchanged Improved Deteriorated

CASES

%

12 11 1

50 46 4

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4

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Iwai et al

Tumor Imaging Changes after Gamma Knife Treatment for Skull Base Meningiomas

TUMOR

SIZE

Decreased Unchanged Increased

NO.

%

11 13 0

46 54 0

17,18]. Most microsurgically operated tumors were large or giant-sized and there is some difficulty in comparing the results. Sekhar et al operated on 70 cases of clivus meningiomas; total removal was achieved in only 45 cases (60%). Forty-five cases (60%) deteriorated postoperatively and symptoms continued in 27% of the cases [18]. Cusimano et al reported the surgical results of 89 cases of cavernous sinus meningiomas. Total removal was attained in 68 cases (76%). Thirty percent of the patients had CSF rhinorrhea, 8% suffered large cerebral infarctions, 8% suffered extensive cerebral hemorrhage, and 4.5% of the patients had poor outcomes [2]. Samii et al reported 46% operative morbidity, but no mortality for petroclival meningiomas [17]. Couldwell et al also reported 32% significant complications and 3.6% mortality after surgery for petroclival meningiomas [1]. A total of 57% of parasellar meningiomas were totally removed and the recurrence and regrowth rate was 19% at 5-year follow-up in the series of cases treated by Milimanoff and associates. The latter recommended some adjuvant therapy such as radiation therapy and medical therapy [12]. Mathiesen et al followed up skull base meningiomas for 18 years after operation and Simpson Grades 1 and 2 had a 4% per 5-year period recurrence rate. Simpson Grades 4 and 5 operations had a 25% and a 45% recurrence rate per 5-year period. They emphasized the need to follow-up patients with skull base meningiomas with a 10- to 20-year perspective [11]. Ojemann recommended adjuvant therapy such as radiation therapy for skull base tumors in which total removal was difficult [13]. Petty et al reported the results of radiation therapy for meningiomas in 12 cases with a 54.5-month follow-up period. Nine of these cases showed no tumor growth, but three cases showed growth over this period. However, only one patient had recurrence after radiotherapy [16]. Goldsmith et al analyzed 140 patients treated by radiation therapy after subtotal resection of meningiomas. A 98% tumor control rate after radiation therapy was obtained and morbidity was only 3%. When the surgeon deemed the risk of morbidity associated with total resection to be unacceptably high, he recom-

(A) MRI before gamma knife treatment showing a right cavernous sinus meningioma in a 49-year-old woman. The patient was treated with 8 Gy to the 30% isodose tumor margin. (B) MRI 33 months after gamma knife treatment showing reduction of the tumor.

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mended a conservative approach of subtotal resection followed by radiation for meningiomas such as those in the petroclival or parasellar region, the cavernous sinus or orbit [5]. Steiner commented that the goal of surgery for skull base meningiomas should be the preservation of the quality of life of the patients; he recommended radiosurgery after subtotal removal of the tumors [19]. The treatment results of stereotactic radiosurgery for meningiomas were reported by several authors. Kida treated 42 cases of meningiomas using a

Radiosurgery for Cranial Base Meningiomas

gamma knife; only two patients showed growth after radiosurgery, and symptomatic edema occurred in only five cases (12%) [8]. Lunsford treated 94 cases of benign meningiomas using a gamma knife, and the tumor control rate was 92% with a 4-year period of follow-up [10]. Kida et al reported 18 cases of cavernous sinus meningiomas with 25.5 months of follow-up; tumor control had been obtained in 94.5% of the cases [9]. Duma et al also reported cavernous sinus meningiomas treated using a gamma knife; tumor control was obtained in 100% of the cases. A total of 56% showed regression in tumor size and 24% were improved clinically. Another 12% deteriorated after radiosurgery [13]. Tanaka et al treated 33 cases of skull base meningiomas using a gamma knife and tumor control was obtained in 94% of cases. A total of 36% of patients improved clinically and only 6% deteriorated because of radiation injury. They used a mean marginal dose of 15.1 Gy [20]. Pendl et al reported 92% tumor control for skull base meningiomas; 13% of patients deteriorated after being treated with a mean dose of 15 Gy to the tumor margin [15]. Ganz recommended above 12 Gy for the tumor margin, because patients treated below 12 Gy showed a 40% growth rate during a 1-year period of follow-up [4]. Duma used a 16-Gy marginal dose for cavernous sinus meningiomas [3] and Kida used a 13.9-Gy marginal dose for cavernous sinus meningiomas [9]. Tanaka used a 15.1 Gy mean marginal dose for skull base meningiomas [20]. We treated tumor margins with a relatively low radiation dose (mean dose of 10.8 Gy) and we obtained a 100% tumor control rate during a 17.1-month follow-up period. Only one case (4.5%) deteriorated because of radiation injury. We think the differences in morbidity rates depend on the radiation dose. We recommend a relatively low dose of radiation for skull base meningiomas. Tanaka reported four cases of skull base meningiomas with greater than 20 cm3 tumor volume treated by a two-staged gamma knife procedure; he obtained tumor control in three cases, whereas one patient showed peritumoral edema. In this case the interval between treatments was only 2 months. They recommended that the second gamma knife treatment should be performed 3 months after the first gamma knife treatment [20]. We also treated a large petroclival meningioma with a 28-cm3 tumor volume using a staged treatment protocol with a 6-month interval; the tumor size was unchanged during a 12-month follow-up. Large meningiomas can also be treated by radiosurgery with a staged treatment protocol. A median follow-up time of 17.1 months is too

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short to make any definitive statements about tumor control, so our results are very tentative and we still need further follow-up. But this study confirms that stereotactic radiosurgery has a very low morbidity rate and good tumor control using a relatively low radiation dose for the tumor margins. Stereotactic radiosurgery can be an alternative for surgical removal, and residual tumor after operation must be treated by this method. REFERENCES 1. Couldwell WT, Fukushima T, Giannotta SL, Weiss MH. Petroclival meningiomas: surgical experience in 109 cases. J Neurosurgery 1996;84:20 – 8. 2. Cusimano MD, Sekhar LN, Sen CN, Pomonis S, Wright DC, Biglan AW, Jannetta PJ. The results of surgery for benign tumors of the cavernous sinus. Neurosurgery 1995;37:1–10. 3. Duma CM, Lunsford LD, Kondziolka D, Harsh GR, Flickinger JC. Stereotactic radiosurgery of cavernous sinus meningiomas as an addition or alternative to microsurgery. Neurosurgery 1993;32:699 –705. 4. Ganz JC, Backlund EO, Thorsen FA. The results of gamma knife surgery of meningiomas, related to size of tumor and dose. Stereotactic Funct Neurosurg 1993;61(Suppl. 1):23–9. 5. Goldsmith BJ, Wara WM, Wilson CB, Larson DA. Postoperative irradiation for subtotally resected meningiomas. A retrospective analysis of 140 patients treated from 1967 to 1990. J Neurosurg 1994;80:195–201. 6. Goodman JM, Kuzma BB, Renkens KL. Natural history of basal meningiomas. In: Lunsford LD, ed. Stereotactic radiosurgery update. New York: Elsevier, 1992: 353–7. 7. Kallio M, Sankila R, Hakulinen T, Ja¨a¨skela¨inen J. Factors affecting operative and excess long-term mortality in 935 patients with intracranial meningioma. Neurosurgery 1992;31:2–12. 8. Kida Y, Kobayashi T, Tanaka T, Oyama H, Iwakoshi T. Stereotactic radiosurgery for intracranial meningiomas. No Shinkei Geka 1994;22:621– 6. 9. Kida Y, Kobayasi T, Tanaka T, Oyama H, Niwa M, Maesawa S. Radiosurgery of cavernous sinus meningiomas with gamma-knife. No Shinkei Geka 1996;24: 529 –33. 10. Lunsford LD. Contemporary management of meningiomas: radiation therapy as an adjuvant and radiosurgery as an alternative to surgical removal? J Neurosurg 1994;80:187–90. 11. Mathiesen T, Lindquist C, Kihlstro ¨ m L, Karlsson B. Recurrence of cranial base meningiomas. Neurosurgery 1996;39:2–9. 12. Milimanoff RO, Dosoretz DE, Linggood RM, Ojemann RG, Martuza RL. Meningiomas: analysis of recurrence and progression following neurosurgical resection. J Neurosurg 1985;62:18 –24. 13. Ojemann RG. Skull base surgery: a perspective. J Neurosurg 1992;76:569 –70. 14. Olivero WC, Lister JR, Elwood PW. The natural history and growth rate of asymptomatic meningiomas: a review of 60 patients. J Neurosurg 1995;83:222– 4. 15. Pendl G, Schro ¨ ttner O, Friehs GM, Feichtinger H. Ste-

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reotactic radiosurgery of skull base meningiomas. Stereotact Funct Neurosurg 1995;64(Suppl. 1):11–18. Petty AM, Kun LE, Meyer GA. Radiation therapy for incompletely resected meningiomas. J Neurosurgery 1985;62:502–7. Samii M, Ammirati M, Bini W, Sepehrnia A. Surgery of petroclival meningiomas: report of 24 cases. Neurosurgery 1989;24:12–17. Sekhar LN, Swamy NKS, Jaiswal V, Rubinstein E, Hirsh WE Jr, Wright DC. Surgical excision of meningiomas involving the clivus: preoperative and intraoperative features as predictors of postoperative functional deterioration. J Neurosurg 1994;81:860 – 8. Steiner L, Lindquist C, Steiner M. Radiosurgery. Symon L, ed. Advances and technical standards in neurosurgery. Vol 19. Wien: Springer-Verlag, 1992:70 –2. Tanaka T, Kobayashi T, Kida Y. Growth control of cranial base meningiomas by stereotactic radiosurgery with a gamma knife unit. Neurol Med Chir (Tokyo) 1996;36:7–10.

Iwai et al

2.

3.

COMMENTARY

In this article, Iwai et al report the results of gamma knife radiosurgery with a small dose (median tumor dose 10.6 Gy) in 24 patients with skull base meningiomas. The median tumor diameter was 2.7 cm. A total of 11 patients had petroclival meningiomas, 4 had cerebellopontine angle meningiomas, and 9 had cavernous sinus meningiomas. The authors’ median follow-up was 17.1 months, and any measurable reduction in the anteroposterior or mediolateral tumor diameter was considered “decreased.” Using these criteria, 11 (46%) decreased and 13 (54%) were unchanged. The authors have compared their data with several microsurgical series in the literature, as well as with two natural history studies of meningiomas, which indicate that of 81 asymptomatic meningiomas, only 13 showed tumor growth, and none required surgery. It is impossible to draw any definite conclusions from this study about the efficacy of gamma knife radiosurgery, or about the relative efficacy of microsurgery, for the following reasons: 1. All “skull base meningiomas” are not the same. Many factors, such as location, tumor size, vascular encasement or invasion, invasion of the brain stem, prior surgery or radiotherapy, and tumor biology (rate of growth) are important factors that determine outcome. The microsurgical series cited in this paper may include a number of tumors that are large or giant-sized, and had been previously operated or irradiated. It would therefore be difficult to compare the results of these tumors with the ones that were treated here by radiosurgery. Only a randomized, controlled trial can truly be used to compare microsurgery and radiosurgery. In the ab-

4.

5.

sence of such a study, we need a classification system for basal meningiomas to allow reasonable comparison. Such a system does not exist currently, although we are working on it. The authors have used very liberal criteria for “tumor shrinkage.” Many other radiosurgeons use a computer program to extract the tumor volume, and then compare it with subsequent studies. Dr. Ladislau Steiner feels that there must be at least a 20% reduction in the volume to call it “tumor shrinkage,” to allow for imaging disparities [personal communication, 1997]. The conclusion that absence of tumor growth implies “tumor control” is flawed, given that the median follow-up in this series was only 17.1 months, and natural history studies cited here show minimal growth of asymptomatic lesions. It was not stated in the paper what types of tumors were treated, whether they were symptomatic, and whether their growth rate was studied. No microsurgical series with a median follow-up of 17.1 months would be publishable with the statement that “there was no recurrence during follow-up.” The petroclival and cerebellopontine angle meningiomas of the dimensions stated in this series would be amenable to surgical resection with a very low morbidity and excellent long-term results. The results of microsurgery for cavernous sinus meningiomas have improved dramatically since early experience. These factors must also be taken into account. Patients who have been irradiated by fractionated external beam therapy have a much greater mortality and morbidity during subsequent microsurgery. It is likely that this is also the case for patients who have had prior radiosurgery, although our experience with this group is small.

Notwithstanding these criticisms, I believe radiosurgery has a place in the present armamentarium for basal meningiomas. But it should be reserved for elderly patients, those who have a tumor remnant after extensive microsurgery, or who are unable to undergo microsurgery for other reasons. Patients who have been treated by radiosurgery require careful, long-term (more than 5 years) follow-up. Laligam Sekhar, M.D., FACS Department of Neurological Surgery George Washington University Washington, DC The article by Iwai et al posits that “low-dose” treatment with the gamma knife is effective in controlling

Radiosurgery for Cranial Base Meningiomas

skull base meningiomas. Using a median dose of 10.6 Gy with a range of 8 to 15 Gy, 24 patients were treated. The dose selected was based on tumor location and volume. The authors report a tumor control rate of 100%, with about half of the patients demonstrating regression of tumor and only one experiencing treatment-related cranial neuropathy. The treatment of skull base meningiomas is difficult for at least two reasons. First, the location of such tumors makes complete surgical removal difficult and fraught with a high likelihood of morbidity. Second, the use of single fraction radiosurgery with either the gamma knife or linear acceleratorbased techniques has the potential to deliver high doses of radiation to the surrounding normal brain tissue. Thus, for meningiomas in critical locations such as the cavernous sinus, there is the possibility of injury to critical structures such as the optic apparatus. Despite this concern, the complication rates in the so-called “high-dose” series have been relatively low. In 50 patients with skull base meningiomas treated with gamma knife radiosurgery to a mean dose of 18 Gy, Nicolato et al report an overall tumor growth control rate of 98%, with only a 6% neurologic and an 8% radiographic complication rate [6]. Similarly, Duma et al report a 100% control rate and a 6% complication rate for 34 cavernous sinus meningiomas treated with gamma knife radiosurgery with a dose range of between 10 and 20 Gy [1]. In this series, the tumors were all less than 35 mm and the dose selected was based on the wellestablished integrated logistic formula developed by Flickinger et al [2]. Thus, the central question raised in the series by Iwai et al is whether lower doses may be equally effective in obtaining the same tumor control with either the same or perhaps lower complication rates. Due to the small number of patients and short follow-up, more time and additional patients will be needed to answer this question. Finally, the point should be made that conventional external beam irradiation and stereotactic radiotherapy are two additional radiotherapeutic options for treating skull base meningiomas. The major advantage of these techniques over radiosurgery is that they are fractionated. It is a wellestablished principle in radiobiology that fractionation has the advantage of improving tumor control and sparing normal tissues compared with singlefraction treatments [5]. Goldsmith et al describe a 98% progression-free survival and a 3.6% morbidity

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for patients with meningiomas treated with conventional postoperative radiation (median dose, 54 Gy), using modern imaging-based treatment planning [4]. This series represents a much less selected group of patients than is found in the radiosurgery literature. Stereotactic radiotherapy combines the precision of radiosurgical treatment with the fractionation advantages of conventional external beam therapy. Gademann et al reported on 62 patients with meningiomas treated with fractionated stereotactically-guided radiotherapy to a median dose of 64 Gy (daily fraction size of 2 Gy). There was a 97% tumor control rate, including radiographic partial of complete response in 37% of the patients, and no reported complications. Although the median follow-up time of 22 months is relatively short, it is certainly worth noting that the total dose of 64 Gy is approximately 8% higher than conventional fractionated radiation, without any significant toxicity. Thus, techniques that combine stereotactic precision with fractionation may ultimately prove to be the most beneficial for this challenging group of patients. Patrick J. Sweeney, M.D. Department of Radiation and Cellular Oncology University of Chicago Chicago, Illinois REFERENCES 1. Duma CM, Lunsford LD, Kondziolka D, Harsh GR 4th, Flickinger JC. Stereotactic radiosurgery of cavernous sinus meningiomas as an addition or alternative to microsurgery. Neurosurgery 1993;32:699 –704. 2. Flickinger JC, Lunsford LD, Kondziolka D. Dose prescription and dose-volume effects in radiosurgery. Neurosurg Clin North Am 1992;3:51–9. 3. Gademann G, Schlegel W, Debus J, Schad L, Bortfeld T, Hover KH, Lorenz W, Wannenmacher M. Fractionated stereotactially guided radiotherapy of head and neck tumors: a report on clinical use of a new system in 195 cases. Radiother Oncol 1993;29:205–13. 4. Goldsmith BJ, Wara WM, Wilson CB, Larson DA. Postoperative irradiation for subtotally resected meningiomas. A retrospective analysis of 140 patients treated from 1967 to 1990. J Neurosurg 1994;80:195–201. 5. Hall EJ, Brenner DJ. The radiobiology of radiosurgery: rationale for different treatment regimes for AVMs and malignancies. Int J Radiation Oncology Biol Phys 1993; 25:381–5. 6. Nicolato A, Ferraresi P, Foroni R, Pasqualin A, Piovan E, Severi F, Masotto B, Gerosa M. Gamma knife radiosurgery in skull base meningiomas. Preliminary experience with 50 cases. Stereotact Funct Neurosurg 1996; 66(Suppl. 1):112–20.