Stereotactic radiosurgery providing long-term tumor control of cavernous sinus meningiomas

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Object. To evaluate long-term outcomes of patients who have undergone stereotactic radiosurgery for cavernous sinus meningiomas, the authors retrospectively reviewed their 14-year experience with these cases.

Methods. One hundred seventy-six patients harbored meningiomas centered within the cavernous sinus. Seventeen patients were lost to follow-up review, leaving 159 analyzable patients, in whom 164 procedures were performed. Seventy-six patients (48%) underwent adjuvant radiosurgery after one or more attempts at surgical resection. Eighty-three patients (52%) underwent primary radiosurgery. Two patients (1%) had previously received fractionated external-beam radiation therapy. Four patients (2%) harbored histologically verified atypical or malignant meningiomas. Conformal multiple isocenter gamma knife surgery was performed. The median dose applied to the tumor margin was 13 Gy.

Neurological status improved in 46 patients (29%), remained stable in 99 (62%), and eventually worsened in 14 (9%). Adverse effects of radiation occurred after 11 procedures (6.7%). Tumor volumes decreased in 54 patients (34%), remained stable in 96 (60%), and increased in nine (6%). The actuarial tumor control rate for patients with typical meningiomas was 93.1 ± 3.3% at both 5 and 10 years. For the 83 patients who underwent radiosurgery as their sole treatment, the actuarial tumor control rate at 5 years was 96.9 ± 3%.

Conclusions. Stereotactic radiosurgery provided safe and effective management of cavernous sinus meningiomas. We believe it is the preferred management strategy for tumors of suitable volume (average tumor diameter ≤ 3 cm or volume ≤ 15 cm3).

Abstract

Object. To evaluate long-term outcomes of patients who have undergone stereotactic radiosurgery for cavernous sinus meningiomas, the authors retrospectively reviewed their 14-year experience with these cases.

Methods. One hundred seventy-six patients harbored meningiomas centered within the cavernous sinus. Seventeen patients were lost to follow-up review, leaving 159 analyzable patients, in whom 164 procedures were performed. Seventy-six patients (48%) underwent adjuvant radiosurgery after one or more attempts at surgical resection. Eighty-three patients (52%) underwent primary radiosurgery. Two patients (1%) had previously received fractionated external-beam radiation therapy. Four patients (2%) harbored histologically verified atypical or malignant meningiomas. Conformal multiple isocenter gamma knife surgery was performed. The median dose applied to the tumor margin was 13 Gy.

Neurological status improved in 46 patients (29%), remained stable in 99 (62%), and eventually worsened in 14 (9%). Adverse effects of radiation occurred after 11 procedures (6.7%). Tumor volumes decreased in 54 patients (34%), remained stable in 96 (60%), and increased in nine (6%). The actuarial tumor control rate for patients with typical meningiomas was 93.1 ± 3.3% at both 5 and 10 years. For the 83 patients who underwent radiosurgery as their sole treatment, the actuarial tumor control rate at 5 years was 96.9 ± 3%.

Conclusions. Stereotactic radiosurgery provided safe and effective management of cavernous sinus meningiomas. We believe it is the preferred management strategy for tumors of suitable volume (average tumor diameter ≤ 3 cm or volume ≤ 15 cm3).

Ever since Cushing and Eisenhardt published their seminal treatise in 1922,7 surgeons have recognized the complexity and dangers of skull base meningiomas. As microsurgical techniques advanced, access to the skull base including the cavernous sinus region became feasible.11 Despite the achievements and published successes in the surgical resection of these formidable lesions,1,3,9,32,33 surgery within the cavernous sinus often resulted in serious disease or death.8,9,29 Meningiomas of the cavernous sinus are intimately associated with critical neurovascular structures and have been shown to invade cranial nerve fascicles, making complete or even aggressive subtotal resection impossible.19,36

Advocates of stereotactic radiosurgery for cavernous sinus meningiomas have published their initial results in the management of these tumors.13,21,30,31 In the present report we provide data from an expanded follow-up interval and we analyze the outcomes of cavernous sinus meningioma radiosurgery performed over a 14-year period.

Clinical Material and Methods
Patient Population

Between October 1987 and December 2000, 176 consecutive patients with symptomatic cavernous sinus meningiomas underwent stereotactic GKS. Cavernous sinus meningiomas were defined as tumors with a predominant cavernous sinus component. Included in this definition were both primary cavernous sinus meningiomas and remnants of petroclival and sphenoid wing meningiomas that had been previously resected, leaving behind the cavernous sinus component. Follow-up clinical and imaging data were available for 159 patients (median age 56 years, range 10–87 years). Five patients underwent radiosurgery twice, creating a total of 164 procedures. One hundred twelve patients (70%) were female. Included in this analysis were all patients initially reported by Duma, et al., in 1993.13

Seventy-six patients (48%) had undergone at least one attempted tumor resection before undergoing adjuvant radiosurgery. Twelve (16%) of these 76 patients had undergone more than one resection. Eighty-three patients (52%) underwent primary radiosurgery for cavernous sinus tumors presumed to be meningiomas according to neurodiagnostic criteria alone (location, contrast pattern, and presence of a dural tail along the tentorium).

In six patients the meningiomas were related to previous radiation exposure. Two patients had previously received fractionated radiation therapy for their meningiomas. Two additional patients had received chemotherapy or hormone-blocking therapy (RU-486) before undergoing radiosurgery.

The presenting neurological signs in the 159 analyzable patients are shown in Table 1. Oculomotor, trigeminal, and abducent nerve deficits were the most common neurological presentations at the time of radiosurgery. We retrospectively compared patients who underwent primary radiosurgery with those who underwent adjuvant radiosurgery (approximately 60% of whom exhibited new neurological deficits after surgery). On the basis of available data it was impossible to distinguish cranial nerve disease due to tumor infiltration from that caused by surgical morbidity. Hence, the deficits listed in Table 1 represent all cranial nerve deficits observed at the time of GKS, regardless of cause.

TABLE 1

Presenting neurological signs in 159 patients who underwent GKS for cavernous sinus meningiomas

No. of Patients (%)
Neurological DeficitAdjuvant Radiosurgery (76 patients)*Primary Radiosurgery (83 patients)
cranial nerve deficit  
 I1 (1) 0 (0) 
 II29 (38) 6 (7) 
 III36 (47) 38 (46) 
 IV25 (33) 10 (12) 
 V49 (64) 28 (34) 
 VI35 (46) 39 (47) 
 VII6 (8) 0 (0) 
 VIII7 (9) 2 (2) 
 IX2 (3) 1 (1) 
 X1(1) 0 (0) 
 XI0 (0) 1 (1) 
 XII1 (1) 0 (0) 
motor dysfunction  
 ataxia2 (3) 0 (0) 
 hemiparesis6 (8) 0 (0) 

Included previous resection.

Included no previous surgical procedure.

Radiosurgical Procedure

All patients underwent application of a stereotactic frame (Leksell model G; Elekta Instruments, Atlanta, GA) after injection of a local anesthetic agent. Supplemental intravenous sedation (50 mg fentanyl, 1 mg midazolam) was provided to some patients. After 1991, high-resolution, contrast-enhanced, multiplanar MR imaging replaced computerized tomography scanning in the planning of GKS. Since 1993, a specific volume-acquisition MR imaging protocol with 1- or 1.5-mm slices has provided detailed graphic, three-dimensional visualization of the tumor and adjacent critical structures. The images were transferred to a dose-planning computer in the radiosurgery center via a fiber-optic ethernet system. Computerized dose planning was performed on a workstation—initially, the Micro-VAX II workstation (Digital Equipment Corp., Westminster, MA) and later, a Hewlett-Packard Co. workstation (Palo Alto, CA)—by using appropriate software (GammaPlan; Elekta Instruments). The maximum radiation dose, isodose, and margin dose that were delivered were determined by consultation among the neurosurgeon, radiation oncologist, and medical physicist. Radiosurgery was performed using a 201-source 60Co gamma knife unit (Leksell gamma knife model U or model B; Elekta Instruments). At the time of completion of radiosurgery, each patient received a single intravenous 40-mg dose of methylprednisolone.

Radiation Dosimetry

The tumor volumes and radiation dosimetry planning are presented in Table 2. Tumor volumes varied from 0.5 to 52.4 cm3 (median volume 6.5 cm3). Multiple isocenters were used in all but one patient. Three-dimensional conformal radiosurgery was performed by placing the 50% or greater isodose at the irregular tumor margin (Fig. 1). The median maximum dose delivered to the tumor center was 26 Gy (range 16–50 Gy) and the median dose delivered to the margin was 13 Gy (range 8–25 Gy). Overall dose selection was adjusted, based on our evolving experience with meningiomas, specific tumor volumes and locations, the risk of radiation-induced complications predicted by the integrated logistic formula, and any history of previous fractionated radiation therapy. The prescription dose range has remained consistent for the past 9 years (12–14 Gy at the 50% isodose line).

TABLE 2

Dose planning for 164 procedures in 159 patients who underwent GKS for cavernous sinus meningiomas

FactorNo. of Procedures (%)
tumor volume (cm3) 
 <320 (12) 
 3–1094 (57) 
 >1050 (30) 
 median6.5 
dose at tumor margin (Gy) 
 8–117 (4) 
 12–16137 (84) 
 17–2520 (12) 
 median13 
isodose at tumor margin (%) 
 405 (3) 
 452 (1) 
 50153 (93) 
 602 (1) 
 701 (1) 
 801 (1) 

Fig. 1.
Fig. 1.

Axial gadolinium-enhanced MR image demonstrating a multiple-isocenter conformal Gamma Plan for a left-sided cavernous sinus meningioma. The black line corresponds to the 50% isodose line and the gray lines indicate the 40% and 30% isodose curves, respectively.

Comparison of Primary and Adjuvant Radiosurgery

Patients were divided into two groups, based on whether radiosurgery was used as a primary option (83 patients) or as a postresection adjuvant therapy (76 patients), as shown in Table 3. The average age of patients undergoing radiosurgery alone was 59 years, whereas the average age of those undergoing adjuvant radiosurgery was 52 years (p < 0.01). Neither the radiation dose to the tumor margin nor the volume of the tumor was statistically different between the two groups.

TABLE 3

Comparison of primary and adjuvant radiosurgery: patient and treatment characteristics*

FactorAdjuvant RadiosurgeryPrimary Radiosurgeryp Value
no. of patients76 83  
median patient age (yrs)52 ± 14.4 59 ± 14 <0.0004 
median dose at tumor margin14 ± 2.4 13 ± 2 <0.591 
 (Gy)   
median treated tumor volume6.6 ± 8 6.3 ± 5.13 <0.915 
 (cm3)   

— = not applicable.

Determined by the Student t-test for two samples, assuming equal variances (two-tailed).

Subset Analysis

To define the long-term results of patients within our series, we analyzed all patients treated consecutively from October 1987 to December 1995. The median age for this group was 56 years (range 12–87 years). Fifty-nine patients (73%) were female. The median tumor volume was 6.5 cm3, and the median marginal dose was 15 Gy. Using the Student t-test, we found patient age or tumor volume to be not statistically different from those of patients treated after 1995. Nevertheless, we did find the median radiation dose to the tumor margin to be statistically higher (by a factor of 2 Gy) in the group of patients treated after 1995 (p < 0.01).

Follow-Up Review of Patients

After radiosurgery, patients were instructed to undergo clinical evaluations and serial imaging at 6 months, 1 year, and 2, 4, 8, and 12 years. For patients residing a significant distance from Pittsburgh, clinical evaluation and imaging studies were performed locally by their referring physicians and submitted to our institution for review.

Statistical Analysis

Three types of statistical analyses were used in this study: the Student t-test for two samples, assuming equal variances (two-tailed; performed with the aid of Microsoft Excel software; Microsoft Corp., Redmond, WA), an actuarial Kaplan—Meier analysis, and a univariate Cox regression analysis (the latter two analyses were performed with the aid of SPSS statistical package; SPSS Inc., Chicago, IL).

Results
Perioperative Period

Each patient underwent stereotactic radiosurgery and was discharged home to resume normal activities within 24 hours following the procedure. Brief discomfort located at the pin sites was experienced by some patients.

Clinical Outcome

Neurological evaluations of the 159 analyzable patients were obtained by the referring physicians, treating neurosurgeons, or by direct telephone contact with patients (mean follow-up period 35 months, range 2–138 months). After radiosurgery, neurological status improved in 46 patients (29%), remained stable in 99 (62%), and eventually worsened in 14 (9%). Clinical improvement was defined as a resolution of neurological or cranial nerve deficit, or a reduction in preoperative symptoms. Fourteen patients in whom clinical deterioration was observed were divided into two categories: those with adverse effects of radiation and those who experienced tumor progression despite radiosurgery.

Neuroimaging Response

The mean duration of follow-up neuroimaging was 39 months (range 2–145 months). Overall, tumor volumes decreased in 54 patients (34%; Fig. 2), remained stable in 96 (60%), and increased in nine (6%; Fig. 3). The percentage of patients with measurable tumor volume reduction increased from 24% at 2 years to 34% at 5 years. All nine patients in whom MR imaging demonstrated evidence of increased tumor size were categorized as having undergone failed radiosurgery (Table 4).

Fig. 2.
Fig. 2.

Upper: Axial (left) and coronal (right) gadolinium-enhanced MR images obtained in a 44-year-old man, revealing a right-sided cavernous sinus meningioma. This lesion was treated using GKS during which 13 Gy was delivered to the tumor margin. Lower: Follow-up axial (left) and coronal (right) MR images obtained in the same patient 30 months after radiosurgery. Tumor regression is evident.

Fig. 3.
Fig. 3.

Left: Axial gadolinium-enhanced MR image obtained in a 53-year-old woman, revealing a meningioma in the right cavernous sinus region. This lesion was treated using GKS during which 13 Gy was delivered to the tumor margin. Right: Follow-up MR image obtained in the same patient 36 months after radiosurgery, demonstrating tumor enlargement.

TABLE 4

Tumor progression despite radiosurgery in nine patients who underwent GKS for cavernous sinus meningiomas*

FactorNo. of Patients
neurological deterioration
 none4
 facial pain1
 optic neuropathy1
 oculomotor neuropathy2
 other cranial neuropathies1
treatment after tumor progression
 fractionated radiation therapy1
 craniotomy & resection3
 repeated radiosurgery5

Includes four patients with malignant and atypical meningiomas.

Radiosurgery failed in three patients in whom progressive neurological symptoms developed. One patient in whom radiosurgery failed began to experience trigeminal neuralgia and was, ultimately, treated using external-beam radiotherapy. Another patient experienced a worsening oculomotor palsy 31 months after radiosurgery and underwent repeated radiosurgery; this patient was stable 14 months after retreatment without tumor growth or progression of clinical symptoms. Another patient experienced a sixth nerve palsy 5 years after having undergone radiosurgery. An MR image demonstrated growth of a previously resected meningioma outside the original radiosurgery volume. The referring neurosurgeon performed a craniotomy and debulking of the tumor, which extended into the hypothalamus. The patient experienced a postoperative hematoma and died.

If we exclude the four patients with histologically verified malignant or atypical meningiomas, evidence of tumor growth on MR images was demonstrated in only five patients. Tumor control rates were determined using Kaplan—Meier survival analysis. The actuarial tumor control rate for all patients without malignant or atypical meningiomas was 93.1 ± 3.3% at 5 years and remained the same at 10 years (Fig. 4). The mean time to treatment failure after stereotactic radiosurgery was 31.4 months. Using univariate Cox regression analysis, we found patient age, sex, prior surgery, or radiation dose to the tumor margin to be not statistically significant factors (p > 0.05). The mean time to tumor progression in the four patients with malignant or atypical meningiomas was 42 ± 11 months. The tumor control rate at 5 years was 25 ± 21.7% for patients in whom biopsy revealed the tumors to be malignant or atypical meningiomas (Table 5).

Fig. 4.
Fig. 4.

Graph showing Kaplan—Meier survival curve for patients with typical meningiomas. The actuarial tumor control rate is 93.1 ± 3.3% at both 5 and 10 years.

TABLE 5

Tumor control rates at different time intervals in patients who underwent GKS for cavernous sinus meningiomas

Tumor Control Rate (%)*
FactorNo. of Patients1 Yr Post-GKS3 Yrs Post-GKS5 Yrs Post-GKS
all patients15599.2 ± 0.8 97.0 ± 1.793.1 ± 3.3
primary radiosurgery83100 96.9 ± 3.096.9 ± 3.0
adjuvant radiosurgery7697.1 ± 2.0 93.6 ± 3.179.6 ± 7.1
 typical meningioma7298.5 ± 1.5 94.7 ± 3.090.4 ± 5.1
 malignant/atypical475.0 ± 21.7 75.0 ± 21.725.0 ± 21.7
  meningioma 

Results from Kaplan—Meier survival analysis.

Excluding those with malignant and atypical meningiomas.

Adverse Effects of Radiation

Adverse effects of radiation occurred in 11 patients. These effects were defined as the presence of clinical or neurological deterioration in the absence of tumor growth on several MR images (Table 6). The mean time to clinical deterioration was 24.8 months (range 5–98 months).

TABLE 6

Adverse effects of radiation in 11 patients who underwent GKS for cavernous sinus meningiomas*

No. of Patients (%)
Adverse EffectTransient AREPermanent ARE
visual
 loss of visual acuity0 (0)1 (0.6)
 field cut0 (0)2 (1.3)
trigeminal nerve deficit0 (0)
 neuralgia0 (0)2 (1.3)
 paresthesias1 (0.6)0 (0)
 keratitis0 (0)2 (1.3)
cognitive deficit0 (0)1 (0.6)
temporal lobe seizures2 (1.3)0 (0)
total3 (1.9)8 (5.0)

ARE = adverse radiation effect.

Percent of all 159 analyzable patients in study.

Three patients experienced visual deterioration. In the first patient progressive optic neuropathy developed 5 months after computerized tomography—based radiosurgery. The estimated 7-Gy dose to the optic nerve was recalculated to have been 12 Gy. This patient was treated with steroid medications and the symptoms stabilized over the next 2 years of follow up. In another patient a slowly progressive visual field defect developed 31 months after radiosurgery (estimated dose to the optic chiasm was 12 Gy), despite a slight decrease in the size of the tumor on imaging studies. This hemianopsia stabilized and demonstrated no progression over the next 4 years of clinical follow up. Finally, a third patient experienced a delayed visual field deficit 98 months after radiosurgery. The consulting neurosurgeon performed a craniotomy for optic nerve decompression. Postoperatively, the patient suffered a third and fourth cranial nerve palsy, but her visual deficit remained stable.

Five patients experienced new trigeminal nerve dysfunction. In one patient transient V2 and V3 paresthesias developed. Two patients experienced typical trigeminal neuralgia; the first patient's pain was controlled with medication, whereas the second patient ultimately received benefit from acupuncture. In two patients corneal ulcerations (neurotrophic keratitis) developed; in both of these patients, the complications were managed by local corneal care or tarsorrhaphy.

Two patients experienced partial complex seizures 16 months after radiosurgery and recovered in response to medical treatment. Both patients were treated before 1992. Although it is possible that the untoward adverse effects of radiation developed in the mesial temporal lobe, no such correlation was observed on MR images. Further, these two patients had both undergone prior craniotomies, and one of the patients had abruptly discontinued use of antiepileptic drugs.

One patient experienced cognitive deterioration 7 months after radiosurgery. The symptoms suggested normal-pressure hydrocephalus and the patient responded to implantation of a lumboperitoneal shunt. Overall, the incidence rate of presumed adverse effects of radiation was 6.7% (11 of 164 procedures).

Failed Radiosurgery

In five patients MR images exhibited evidence of progressive tumor growth. All these patients were defined as having undergone failed radiosurgery. Three of these patients, who displayed clinical symptoms associated with MR imaging evidence of tumor growth, have been discussed in Neuroimaging Response. There were two other patients who underwent failed radiosurgery, but displayed no signs of clinical deterioration. The first was a 13-year-old child who had undergone previous resection of a cerebellopontine angle clear-cell meningioma. Radiosurgery was performed on the cavernous sinus component, but serial imaging obtained 3 years later demonstrated increased tumor size and the patient was treated a second time. The second patient had undergone two resections for a large cavernous sinus meningioma. The second radiosurgery appears to have provided tumor control over the follow-up period, which totals 4 years since the first radiosurgery.

Comparison of Primary and Adjuvant Radiosurgery

Patients were divided into two categories: those who underwent primary radiosurgery (83 patients) and those who underwent adjuvant radiosurgery (76 patients). The actuarial tumor control rate at 5 years for patients who had undergone primary radiosurgery was 96.9 ± 3%, and the tumor control rate at 5 years for patients who had undergone adjuvant radiosurgery was 79.6 ± 7.1% (Fig. 5). This was a statistically significant difference. If patients with known atypical or malignant meningiomas are excluded from the analysis, the actuarial tumor control rate for patients who underwent adjuvant radiosurgery is 90.4 ± 5.1%. We identified no statistically significant variable such as patient age, radiation dose to the tumor margin, or tumor volume between these two groups.

Fig. 5.
Fig. 5.

Graph comparing Kaplan—Meier survival curves of actuarial tumor-control rates for meningiomas subjected to radiosurgery as primary treatment and as adjuvant therapy. The 5-year tumor-control rate for primary radiosurgery was 96.9 + 3% and that for adjuvant radiosurgery (including atypical and malignant meningiomas) was 79.6% + 7.1%. n = number of patients.

Subset Analysis of Patients in Whom There Was Extended Follow Up

To emphasize long-term outcomes, we separately analyzed all patients treated consecutively from October 1987 to December 1995. Follow-up data were available for 79 (98%) of the 81 patients treated during this period. Adverse effects of radiation were observed in eight patients (10%). Of note, only two patients who had undergone radiosurgery after 1995 experienced any adverse radiation effects. The median neuroimaging follow up for these patients was 59 months (range 2–145 months). In only one patient was there evidence of tumor progression. The actuarial tumor control rate at both 5 and 10 years was 97.5 ± 2.5% for these 79 patients, in whom the duration of follow up was a median of 5 years.

Discussion

Resection of a meningioma and its dural base (Simpson Grade I) is the preferred treatment for many patients.4,23,24,27 Complete resection of meningiomas of the cavernous sinus, however, is not feasible without causing serious disease or death. Overall, the estimated likelihood of obtaining a complete resection of a cavernous sinus tumor ranges from 22.9 to 100%.3,6,10,11,18,29,30,34,37 The mortality rate in modern microsurgical series ranges from 0 to 7%.10,29,35 Permanent cranial nerve deficits were noted in a significant percentage of patients (8–26%).10,16,29 In patients in our series who had undergone prior attempted resection, there was a higher incidence of cranial nerve dysfunction. For example, there was a 35% incidence of postoperative visual deficits in patients before they underwent adjuvant radiosurgery, compared to a 6% incidence of visual deficits in patients before they underwent primary radiosurgery.

To reduce morbidity and mortality rates, some surgeons have opted for a less aggressive resection. Incomplete meningioma resection usually fails to affect tumor progression rates.25 Kallio, et al.,17 studied 225 patients with meningiomas and determined that the recurrence rates after complete resection were 7%, 20%, and 32% at 5, 10, and 15 years, respectively. In contrast, the rates of tumor progression after subtotal resection were 37%, 55%, and 91%, respectively, at the same time intervals. Such data provide a compelling reason to use radiosurgery as the primary management tool for treating cavernous sinus meningiomas.

The role of fractionated external-beam radiation in the management of meningiomas has generally been limited to postoperative adjunctive treatment. Recent studies have demonstrated improved outcomes and increased survival rates in patients who underwent subtotal resection plus radiation therapy. Authors of several studies have determined 5-year progression-free survival rates to be between 89 and 100%, and 10-year progression-free survival rates to be between 81 and 92.8%.12,15,22,28,39 Thus, tumor control rates can be improved by the addition of adjunctive fractionated external-beam radiation therapy. Unfortunately, this therapy has been associated with a significant risk of morbidity. Al-Mefty and associates2 retrospectively analyzed 58 patients who underwent radiation therapy between 1958 and 1987. Thirty-eight percent of these patients experienced major complications including visual loss, pituitary dysfunction, and brain radiation necrosis. In contrast, Dufour, et al.,12 reported on a series of 31 patients with cavernous sinus meningiomas who were treated with more recent radiation therapy techniques. In their study, no patient experienced adverse effects from the radiation. Understandably, fractionated external-beam radiation therapy has become safer as the methods of conformal fractionated delivery have evolved. Of interest, in this same study by Dufour, et al., four times as many patients with cavernous sinus tumors were treated using radiosurgery rather than radiation therapy, suggesting that a selection bias existed even within that study.

Stereotactic radiosurgery provides conformal, highly focused, single-fraction irradiation of irregular tumor volumes with a steep dose gradient. Multiple isocenter dose planning, configured with small beam diameters, facilitates precise delivery of the radiation dose to the irregular margins of the tumor. The steep radiation falloff of radiosurgery significantly protects adjacent critical structures from delayed radiation-induced injury. This benefit is reduced as the tumor volume increases.

Patient Outcomes

We observed a 5-year actuarial tumor control rate of 93.1 ± 3.3% for typical meningiomas. Using Kaplan—Meier survival analysis, we determined that this control rate remained the same for up to 10 years. The actuarial freedom from progression is comparable to that demonstrated in other radiosurgical series (Table 7).13,20,21,26,30,31 Morita and colleagues26 and Roche and coworkers31 documented progression-free survival rates of 95% and 93%, respectively. In a recent study of 40 patients, Shin, et al.,38 reported a tumor control rate of 86.4% at 3 years and 82.3% at 10 years. No recurrence was observed when the entire tumor received a minimum of 14 Gy. In cases in which a portion of tumor received between 10 and 12 Gy, 20% of lesions recurred; in cases in which a portion of tumor was not treated, a 100% recurrence rate was observed.

TABLE 7

Summary of cavernous sinus meningiomas treated using GKS*

Tumor Size (%)
Authors & YearNo. of CasesDecreasedUnchangedSurvivalMedian FU (mos)
Duma, et al., 199334564424
Pendl, et al., 199841346339
Liscak, et al., 199967524819
Roche, et al., 20009931649330
present study
 overall15934609324
 subset§7937599859

FU = follow up; — = not given.

Actuarial 5-year progression-free survival.

This series is included in the present study.

Subset of 79 patients for whom long-term follow-up data are available, as described in Subset Analysis.

To emphasize the long-term rates of the success of radiosurgery, we focused on our initial 8 years of radiosurgery experience. The median follow-up time in patients treated during that period was 5 years. Our analysis of the first 79 analyzable patients revealed an actuarial tumor control rate of 97.5 ± 2.5% at 5 and 10 years. Kallio, et al.,17 studied the long-term survival of more than 900 patients with meningiomas during a 20-year period and found that the median postoperative time until recurrence was 7.5 years. Cavernous sinus meningiomas, however, tend to recur earlier postsurgery than calvarial meningiomas because gross-total removal is impossible.24,25 Based on the 5-year median follow-up data available in these 79 patients, we assert that GKS for cavernous sinus meningiomas provides tumor control rates that exceed those observed after surgery alone.

Our results indicate that outcomes may be better for patients who undergo primary radiosurgery rather than adjuvant radiosurgery after attempted resection. There should be no biological difference between tumors that have been subjected to previous resection and those that have not; however, previously resected tumors may be more difficult to define on radiosurgical imaging studies. For example, a fat signal or postoperative meningeal enhancement may be confused with tumor. This limitation may be avoided by obtaining additional imaging sequences and by waiting several weeks postresection before performing adjuvant radiosurgery.

Our analysis is clearly limited by the lack of a control group with which to compare. This study could have been improved with the use of internal controls. For example, had we documented within the adjuvant radiosurgery group, the time from initial surgery to the time of tumor progression by analyzing imaging results or clinical symptoms, we could have used these data as an internal control. Unfortunately, these data are unavailable. Obviously, a prospective trial could also address this concern.

Adverse Effects of Radiation

Adverse effects of radiation after radiosurgery of the cavernous sinus manifested primarily as delayed cranial neuropathies. The motor nerves of the cavernous sinus (the third, fourth, and sixth cranial nerves) appear to be relatively resistant to radiosurgery. In our series there was no evidence of deterioration of the oculomotor nerves after radiosurgery in the absence of tumor progression. Many nerves remained functionally preserved, and in 25 patients, oculomotor function actually improved. This result is compatible with those of other previously published radiosurgical series. Leber, et al.,20 studied 50 benign tumors of the middle fossa. Six patients (12%) with oculomotor neuropathy attained significant recovery. Morita and colleagues26 reported the effects of GKS in 88 cases of skull base meningiomas and observed improvement in 11 oculomotor nerves.

In contrast to the motor nerves of the cavernous sinus, the trigeminal nerve appears to be more susceptible to adverse effects of radiation. In our series, trigeminal nerve dysfunction developed in five patients (Table 6) and four of these deficits were permanent. Three of these patients exhibited preexisting trigeminal dysfunction before radiosurgery. The relatively higher incidence of trigeminal deterioration after radiosurgery (compared with that at other cranial nerves) has been observed in other studies. Chang, et al.,5 reported their experience with secondary facial pain and skull base tumors in 27 patients. Although 86% of their patients initially received pain relief, half of the patients experienced recurrences of pain during the follow-up period. Morita and colleagues26 observed nine radiation-induced permanent trigeminal neuropathies (10.5% of the nerves at risk) after a latent interval of 2 to 7 months. Roche, et al.,31 found no significant incidence of cranial nerve dysfunction; in their study of 80 patients, no case of radiation-induced trigeminal dysfunction was observed.

The special sensitivity of the visual pathways to radiation injury is well known.14 In our series, we found three cases (2%) of visual deterioration after radiosurgery. Two of these patients had been treated with higher than average doses to the tumor margin: 17.5 Gy and 20 Gy delivered to the margin during the era before MR imaging was available. Although these deficits were progressive during the initial period, they eventually stabilized with residual loss of either visual acuity or field deficit. In one patient a permanent optic neuropathy developed 5 months after the tumor was treated using a radiosurgical dose of 12 Gy to the tumor margin. The cause of this patient's deterioration remains unclear, especially given that her tumor appears stable on imaging studies and that the optic nerve and chiasm received less than 8 Gy of radiation.

Our cumulative experience supports the concept that the single-fraction optic nerve tolerance is 8 to 10 Gy, depending on the volume of the nerve involved. Leber, et al.,20 found that when the maximum radiation dose to the visual pathways was less than 10 Gy, no signs of radiation-induced optic neuropathy were observed. When the dose ranged from 10 to less than 15 Gy, however, the incidence of radiation-induced optic neuropathy was 26.7%, and when the dose was 15 Gy or more, the incidence was 77.8%. Morita and colleagues26 adopted a policy of allowing for short segments of visual pathways to tolerate 12 to 16 Gy.

The occurrence of cognitive deficits after radiosurgery is rare. One patient who experienced cognitive worsening was suspected to have normal pressure hydrocephalus and responded to placement of a lumboperitoneal shunt.

In a previous report,13 we described two patients in whom partial complex seizures developed at an average of 16 months after radiosurgery for cavernous sinus meningiomas. Both patients had undergone prior craniotomies and partial tumor removal. There was no imaging evidence of temporal lobe necrosis or temporal lobe edema in either of these patients.

Conclusions

The results of the present study support the long-term benefit of radiosurgery in the management of cavernous sinus meningiomas. With the aid of radiation doses of 13 Gy to the tumor margin, we achieved long-term control of tumor growth and preserved neurological function in most patients. In our experience previous microsurgical resection of cavernous sinus meningiomas was associated with significant risks and all patients had undergone incomplete resection. In contrast, primary radiosurgery provided an actuarial tumor control rate of 96.9 ± 3% at both 5 and 10 years. The overall actuarial tumor control rate, excluding malignant or atypical meningiomas, was 93.1 ± 3.3% at 5 and 10 years. By keeping the radiation dose to the optic nerve lower than 8 Gy and by using a radiation dose of 13 Gy at the tumor margin, we kept the risk of adverse radiation effects to 6.7%. In the past 5 years only one (1.3%) of 78 patients has experienced optic neuropathy. We attribute this to better conformal planning, selecting a tumor margin dose of 13 Gy, and restricting the dose to the optic nerve to 8 Gy. Stereotactic radiosurgery should be the primary treatment tool for patients with small or medium-sized cavernous sinus meningiomas (volume ≤ 15 cm3 or diameter < 3 cm). Patients with larger tumors should undergo subtotal extracavernous resection, followed by stereotactic radiosurgery for the residual cavernous sinus component.

References

  • 1.

    Al-Mefty O: Management of the cavernous sinus and carotid siphon. Otolaryngol Clin North Am 24:152315331991Al-Mefty O: Management of the cavernous sinus and carotid siphon. Otolaryngol Clin North Am 24:

  • 2.

    Al-Mefty OKersh JERouth Aet al: The long-term side effects of radiation therapy for benign brain tumors in adults. J Neurosurg 73:5025121990J Neurosurg 73:

  • 3.

    Al-Mefty OSmith RR: Surgery of tumors invading the cavernous sinus. Surg Neurol 30:3703811988Surg Neurol 30:

  • 4.

    Borovich BDoron Y: Recurrence of intracranial meningiomas: the role played by regional multicentricity. J Neurosurg 64:58631986J Neurosurg 64:

  • 5.

    Chang SDAdler JR JrMartin DP: LINAC radiosurgery for cavernous sinus meningiomas. Stereotact Funct Neurosurg 71:43501998Stereotact Funct Neurosurg 71:

  • 6.

    Cioffi FBernini FPPunzo Aet al: Cavernous sinus meningiomas. Neurochirurgia 30:40471987Neurochirurgia 30:

  • 7.

    Cushing HEisenhardt L: Springfield, IL: Charles C Thomas1938

  • 8.

    Cusimano MDSekhar LNSen CNet al: The results of surgery for benign tumors of the cavernous sinus. Neurosurgery 37:1101995Neurosurgery 37:

  • 9.

    De Jesus OSekhar LNParikh HKet al: Long-term follow-up of patients with meningiomas involving the cavernous sinus: recurrence, progression, and quality of life. Neurosurgery 39:9159201996Neurosurgery 39:

  • 10.

    DeMonte FSmith HKAl-Mefty O: Outcome of aggressive removal of cavernous sinus meningiomas. J Neurosurg 81:2452511994J Neurosurg 81:

  • 11.

    Dolenc VV: Anatomy and Surgery of the Cavernous Sinus. New York: Springer-Verlag1989Dolenc VV: Anatomy and Surgery of the Cavernous Sinus.

  • 12.

    Dufour HMuracciole XMetellus Pet al: Long-term tumor control and functional outcome in patients with cavernous sinus meningiomas treated by radiotherapy with or without previous surgery: is there an alternative to aggressive tumor removal? Neurosurgery 48:2852962001Neurosurgery 48:

  • 13.

    Duma CMLunsford LDKondziolka Det al: Stereotactic radiosurgery of cavernous sinus meningiomas as an addition or alternative to microsurgery. Neurosurgery 32:6997051993Neurosurgery 32:

  • 14.

    Girkin CAComey CHLunsford LDet al: Radiation optic neuropathy after stereotactic radiosurgery. Ophthalmology 104:163416431997Ophthalmology 104:

  • 15.

    Goldsmith BJWara WMWilson CBet al: Postoperative irradiation for subtotally resected meningiomas. A retrospective analysis of 140 patients treated from 1967 to 1990. J Neurosurg 80:1952011994J Neurosurg 80:

  • 16.

    Hirsch WLSekhar LNLanzino Get al: Meningiomas involving the cavernous sinus: value of imaging for predicting surgical complications. AJR 160:108310881993AJR 160:

  • 17.

    Kallio MSankila RHakulinen Tet al: Factors affecting operative and excess long-term mortality in 935 patients with intracranial meningioma. Neurosurgery 31:2121992Neurosurgery 31:

  • 18.

    Lanzino GHirsch WLPomonis Set al: Cavernous sinus tumors: neuroradiologic and neurosurgical considerations on 150 operated cases. J Neurosurg Sci 36:1831961992J Neurosurg Sci 36:

  • 19.

    Larson JJvan Loveren HRBalko MGet al: Evidence of meningioma infiltration into cranial nerves: clinical implications for cavernous sinus meningiomas. J Neurosurg 83:5965991995J Neurosurg 83:

  • 20.

    Leber KABergloff JPendl G: Dose-response tolerance of the visual pathways and cranial nerves of the cavernous sinus to stereotactic radiosurgery. J Neurosurg 88:43501998J Neurosurg 88:

  • 21.

    Liscak RSimonova GVymazal Jet al: Gamma knife radiosurgery of meningiomas in the cavernous sinus region. Acta Neurochir 141:4734801999Acta Neurochir 141:

  • 22.

    Maguire PDClough RFriedman AHet al: Fractionated external-beam radiation therapy for meningiomas of the cavernous sinus. Int J Radiat Oncol Biol Phys 44:75791999Int J Radiat Oncol Biol Phys 44:

  • 23.

    Mahmood AQureshi NHMalik GM: Intracranial meningiomas: analysis of recurrence after surgical treatment. Acta Neurochir 126:53581994Acta Neurochir 126:

  • 24.

    Mathiesen TLindquist CKihlstrom Let al: Recurrence of cranial base meningiomas. Neurosurgery 39:291996Neurosurgery 39:

  • 25.

    Mirimanoff RODosoretz DELinggood RMet al: Meningioma: analysis of recurrence and progression following neurosurgical resection. J Neurosurg 62:18241985J Neurosurg 62:

  • 26.

    Morita ACoffey RJFoote RLet al: Risk of injury to cranial nerves after gamma knife radiosurgery for skull base meningiomas: experience in 88 patients. J Neurosurg 90:42491999J Neurosurg 90:

  • 27.

    Naumann MMeixensberger J: Factors influencing meningioma recurrence rate. Acta Neurochir 107:1081111990Acta Neurochir 107:

  • 28.

    Nutting CBrada MBrazil Let al: Radiotherapy in the treatment of benign meningioma of the skull base. J Neurosurg 90:8238271999J Neurosurg 90:

  • 29.

    O'Sullivan MGvan Loveren HRTew JM Jr: The surgical resectability of meningiomas of the cavernous sinus. Neurosurgery 40:2382471997Neurosurgery 40:

  • 30.

    Pendl GSchrottner OEustacchio Set al: Cavernous sinus meningiomas—what is the strategy: upfront or adjuvant gamma knife surgery? Stereotact Funct Neurosurg 70 (Suppl 1):33401998Stereotact Funct Neurosurg 70 (Suppl 1):

  • 31.

    Roche PHRegis JDufour Het al: Gamma knife radiosurgery in the management of cavernous sinus meningiomas. J Neurosurg 93 (Suppl 3):68732000J Neurosurg 93 (Suppl 3):

  • 32.

    Sekhar LNLanzino GSen CNet al: Reconstruction of the third through sixth cranial nerves during cavernous sinus surgery. J Neurosurg 76:9359431992J Neurosurg 76:

  • 33.

    Sekhar LNPatel SCusimano Met al: Surgical treatment of meningiomas involving the cavernous sinus: evolving ideas based on a ten year experience. Acta Neurochir Suppl 65:58621996Acta Neurochir Suppl 65:

  • 34.

    Sekhar LNPomeranz SSen CN: Management of tumours involving the cavernous sinus. Acta Neurochir Suppl 53:1011121991Acta Neurochir Suppl 53:

  • 35.

    Sekhar LNRoss DASen C: Cavernous sinus and sphenocavernous neoplasms: anatomy and surgerySekhar LNJanecka IP (eds): Surgery of Cranial Base Tumors. New York: Raven Press1993521659Surgery of Cranial Base Tumors.

  • 36.

    Sen CHague K: Meningiomas involving the cavernous sinus: histological factors affecting the degree of resection. J Neurosurg 87:5355431997J Neurosurg 87:

  • 37.

    Sepehrnia ASamii MTatagiba M: Management of intracavernous tumors: an 11-year experience. Acta Neurochir Suppl 53:1221261991Acta Neurochir Suppl 53:

  • 38.

    Shin MKurita HSasaki Tet al: Analysis of treatment outcome after stereotactic radiosurgery for cavernous sinus meningiomas. J Neurosurg 95:4354392001J Neurosurg 95:

  • 39.

    Taylor BW JrMarcus RB JrFriedman WAet al: The meningioma controversy: postoperative radiation therapy. Int J Radiat Oncol Biol Phys 15:2993041988Int J Radiat Oncol Biol Phys 15:

Article Information

Address reprint requests to: L. Dade Lunsford, M.D., Department of Neurological Surgery, University of Pittsburgh Medical Center, 200 Lothrop Street, Suite B-400, Pittsburgh, Pennsylvania 15213. email: lunsford@neuronet.pitt.edu.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Axial gadolinium-enhanced MR image demonstrating a multiple-isocenter conformal Gamma Plan for a left-sided cavernous sinus meningioma. The black line corresponds to the 50% isodose line and the gray lines indicate the 40% and 30% isodose curves, respectively.

  • View in gallery

    Upper: Axial (left) and coronal (right) gadolinium-enhanced MR images obtained in a 44-year-old man, revealing a right-sided cavernous sinus meningioma. This lesion was treated using GKS during which 13 Gy was delivered to the tumor margin. Lower: Follow-up axial (left) and coronal (right) MR images obtained in the same patient 30 months after radiosurgery. Tumor regression is evident.

  • View in gallery

    Left: Axial gadolinium-enhanced MR image obtained in a 53-year-old woman, revealing a meningioma in the right cavernous sinus region. This lesion was treated using GKS during which 13 Gy was delivered to the tumor margin. Right: Follow-up MR image obtained in the same patient 36 months after radiosurgery, demonstrating tumor enlargement.

  • View in gallery

    Graph showing Kaplan—Meier survival curve for patients with typical meningiomas. The actuarial tumor control rate is 93.1 ± 3.3% at both 5 and 10 years.

  • View in gallery

    Graph comparing Kaplan—Meier survival curves of actuarial tumor-control rates for meningiomas subjected to radiosurgery as primary treatment and as adjuvant therapy. The 5-year tumor-control rate for primary radiosurgery was 96.9 + 3% and that for adjuvant radiosurgery (including atypical and malignant meningiomas) was 79.6% + 7.1%. n = number of patients.

References

1.

Al-Mefty O: Management of the cavernous sinus and carotid siphon. Otolaryngol Clin North Am 24:152315331991Al-Mefty O: Management of the cavernous sinus and carotid siphon. Otolaryngol Clin North Am 24:

2.

Al-Mefty OKersh JERouth Aet al: The long-term side effects of radiation therapy for benign brain tumors in adults. J Neurosurg 73:5025121990J Neurosurg 73:

3.

Al-Mefty OSmith RR: Surgery of tumors invading the cavernous sinus. Surg Neurol 30:3703811988Surg Neurol 30:

4.

Borovich BDoron Y: Recurrence of intracranial meningiomas: the role played by regional multicentricity. J Neurosurg 64:58631986J Neurosurg 64:

5.

Chang SDAdler JR JrMartin DP: LINAC radiosurgery for cavernous sinus meningiomas. Stereotact Funct Neurosurg 71:43501998Stereotact Funct Neurosurg 71:

6.

Cioffi FBernini FPPunzo Aet al: Cavernous sinus meningiomas. Neurochirurgia 30:40471987Neurochirurgia 30:

7.

Cushing HEisenhardt L: Springfield, IL: Charles C Thomas1938

8.

Cusimano MDSekhar LNSen CNet al: The results of surgery for benign tumors of the cavernous sinus. Neurosurgery 37:1101995Neurosurgery 37:

9.

De Jesus OSekhar LNParikh HKet al: Long-term follow-up of patients with meningiomas involving the cavernous sinus: recurrence, progression, and quality of life. Neurosurgery 39:9159201996Neurosurgery 39:

10.

DeMonte FSmith HKAl-Mefty O: Outcome of aggressive removal of cavernous sinus meningiomas. J Neurosurg 81:2452511994J Neurosurg 81:

11.

Dolenc VV: Anatomy and Surgery of the Cavernous Sinus. New York: Springer-Verlag1989Dolenc VV: Anatomy and Surgery of the Cavernous Sinus.

12.

Dufour HMuracciole XMetellus Pet al: Long-term tumor control and functional outcome in patients with cavernous sinus meningiomas treated by radiotherapy with or without previous surgery: is there an alternative to aggressive tumor removal? Neurosurgery 48:2852962001Neurosurgery 48:

13.

Duma CMLunsford LDKondziolka Det al: Stereotactic radiosurgery of cavernous sinus meningiomas as an addition or alternative to microsurgery. Neurosurgery 32:6997051993Neurosurgery 32:

14.

Girkin CAComey CHLunsford LDet al: Radiation optic neuropathy after stereotactic radiosurgery. Ophthalmology 104:163416431997Ophthalmology 104:

15.

Goldsmith BJWara WMWilson CBet al: Postoperative irradiation for subtotally resected meningiomas. A retrospective analysis of 140 patients treated from 1967 to 1990. J Neurosurg 80:1952011994J Neurosurg 80:

16.

Hirsch WLSekhar LNLanzino Get al: Meningiomas involving the cavernous sinus: value of imaging for predicting surgical complications. AJR 160:108310881993AJR 160:

17.

Kallio MSankila RHakulinen Tet al: Factors affecting operative and excess long-term mortality in 935 patients with intracranial meningioma. Neurosurgery 31:2121992Neurosurgery 31:

18.

Lanzino GHirsch WLPomonis Set al: Cavernous sinus tumors: neuroradiologic and neurosurgical considerations on 150 operated cases. J Neurosurg Sci 36:1831961992J Neurosurg Sci 36:

19.

Larson JJvan Loveren HRBalko MGet al: Evidence of meningioma infiltration into cranial nerves: clinical implications for cavernous sinus meningiomas. J Neurosurg 83:5965991995J Neurosurg 83:

20.

Leber KABergloff JPendl G: Dose-response tolerance of the visual pathways and cranial nerves of the cavernous sinus to stereotactic radiosurgery. J Neurosurg 88:43501998J Neurosurg 88:

21.

Liscak RSimonova GVymazal Jet al: Gamma knife radiosurgery of meningiomas in the cavernous sinus region. Acta Neurochir 141:4734801999Acta Neurochir 141:

22.

Maguire PDClough RFriedman AHet al: Fractionated external-beam radiation therapy for meningiomas of the cavernous sinus. Int J Radiat Oncol Biol Phys 44:75791999Int J Radiat Oncol Biol Phys 44:

23.

Mahmood AQureshi NHMalik GM: Intracranial meningiomas: analysis of recurrence after surgical treatment. Acta Neurochir 126:53581994Acta Neurochir 126:

24.

Mathiesen TLindquist CKihlstrom Let al: Recurrence of cranial base meningiomas. Neurosurgery 39:291996Neurosurgery 39:

25.

Mirimanoff RODosoretz DELinggood RMet al: Meningioma: analysis of recurrence and progression following neurosurgical resection. J Neurosurg 62:18241985J Neurosurg 62:

26.

Morita ACoffey RJFoote RLet al: Risk of injury to cranial nerves after gamma knife radiosurgery for skull base meningiomas: experience in 88 patients. J Neurosurg 90:42491999J Neurosurg 90:

27.

Naumann MMeixensberger J: Factors influencing meningioma recurrence rate. Acta Neurochir 107:1081111990Acta Neurochir 107:

28.

Nutting CBrada MBrazil Let al: Radiotherapy in the treatment of benign meningioma of the skull base. J Neurosurg 90:8238271999J Neurosurg 90:

29.

O'Sullivan MGvan Loveren HRTew JM Jr: The surgical resectability of meningiomas of the cavernous sinus. Neurosurgery 40:2382471997Neurosurgery 40:

30.

Pendl GSchrottner OEustacchio Set al: Cavernous sinus meningiomas—what is the strategy: upfront or adjuvant gamma knife surgery? Stereotact Funct Neurosurg 70 (Suppl 1):33401998Stereotact Funct Neurosurg 70 (Suppl 1):

31.

Roche PHRegis JDufour Het al: Gamma knife radiosurgery in the management of cavernous sinus meningiomas. J Neurosurg 93 (Suppl 3):68732000J Neurosurg 93 (Suppl 3):

32.

Sekhar LNLanzino GSen CNet al: Reconstruction of the third through sixth cranial nerves during cavernous sinus surgery. J Neurosurg 76:9359431992J Neurosurg 76:

33.

Sekhar LNPatel SCusimano Met al: Surgical treatment of meningiomas involving the cavernous sinus: evolving ideas based on a ten year experience. Acta Neurochir Suppl 65:58621996Acta Neurochir Suppl 65:

34.

Sekhar LNPomeranz SSen CN: Management of tumours involving the cavernous sinus. Acta Neurochir Suppl 53:1011121991Acta Neurochir Suppl 53:

35.

Sekhar LNRoss DASen C: Cavernous sinus and sphenocavernous neoplasms: anatomy and surgerySekhar LNJanecka IP (eds): Surgery of Cranial Base Tumors. New York: Raven Press1993521659Surgery of Cranial Base Tumors.

36.

Sen CHague K: Meningiomas involving the cavernous sinus: histological factors affecting the degree of resection. J Neurosurg 87:5355431997J Neurosurg 87:

37.

Sepehrnia ASamii MTatagiba M: Management of intracavernous tumors: an 11-year experience. Acta Neurochir Suppl 53:1221261991Acta Neurochir Suppl 53:

38.

Shin MKurita HSasaki Tet al: Analysis of treatment outcome after stereotactic radiosurgery for cavernous sinus meningiomas. J Neurosurg 95:4354392001J Neurosurg 95:

39.

Taylor BW JrMarcus RB JrFriedman WAet al: The meningioma controversy: postoperative radiation therapy. Int J Radiat Oncol Biol Phys 15:2993041988Int J Radiat Oncol Biol Phys 15:

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