www.surgicalneurology-online.com

Surgical Neurology

Changing treatment strategy of cavernous sinus meningiomas:

experience of a single institution

M. Necmettin Pamir, MD, Tqrker KVlVc, MD, PhDT, Fatih BayraklV, MD, Selcuk Peker, MDInstitute of Neurological Sciences, Marmara University, PK 53 Maltepe, Istanbul 81532, Turkey

Abstract Background: Oncological treatment of a neoplasm is more than surgical removal of the tumor.

0090-3019/$ – see fro

doi:10.1016/j.surneu.2

Abbreviations: GK

artery; KPS, Karnof

imaging; PFS, progre

T Corresponding

5249, +90 216 305 79

E-mail address: tu

Probably, this truth is the reason for the ongoing discussion on cavernous sinus meningiomas in the last

decade. Debate on optimal management of cavernous sinus meningiomas aims to compare the different

treatment strategies: (a) radical surgical resection and (b) conservative surgical resection comple-

mented with radiosurgical treatment.

Materials and Methods: Natural history of the change in the management strategy of cavernous

sinus meningiomas in our department before and after GK facility became available in 1997 allowed

us to compare the 2 aforementioned strategies. Before installation of a Leksell GK unit at the

hospital in 1997, the neurosurgical team at Marmara University Institute of Neurological Sciences

and Faculty of Medicine (Istanbul, Turkey) treated patients with cavernous sinus meningioma using

radical resection (radical strategy, group A, 10 patients). After 1997, the same neurosurgical team

used understanding of surgical removal of the extracavernous sinus tumor component with GK

irradiation of the intracavernous part (conservative strategy, group B, 12 patients). Another group of

patients, who were treated with GK as a first-step treatment, was analyzed (GK group, group C,

26 patients).

Results: At the end of the third year, more stable tumor volume control was achieved in groups B

and C; after the second year, an incline in the tumor volume-time graph was detected. Group B

resulted in less cranial nerverelated complications; a certain degree of improvement in cranial nerve

deficits was observed.

Conclusion: Comparing 2 different management strategies for cavernous sinus meningiomas in the

same hospital setting using the same neurosurgical group, we conclude that extracavernous resection

followed by GK is as effective as radical surgery. Considering cranial nerve complications and third-

year tumor volume control achievement, conservative approach yielded better results. Longer

follow-up with larger series is necessary.

D 2005 Elsevier Inc. All rights reserved.

Keywords: Meningioma; Radical resection; Gamma Knife irradiation

1. Introduction

Basic skull-base approaches, which are now adapted into

most residency education curricula, have enabled us to sur-

gically treat previously so-called unresectable intracranial

nt matter D 2005 Elsevier Inc. All rights reserved.

005.07.053

, Gamma Knife radiosurgery; ICA, internal carotid

sky performance scale; MRI, magnetic resonance

ssion-free survival.

author. Tel.: +90 532 514 14 98; fax: +90 216 327

61.

rkilic@tnn.net (T. KVlVc).

lesions. Cavernous sinus lesions are among the most

important of these diseases [3,5,8,14,18,28,41,43,44]. How-

ever, oncological treatment of a neoplasm is different from

surgical removal of the tumor [9,19,20,22,34]. Probably,

this fact is the reason for the ongoing discussion on

cavernous sinus meningiomas in the last decade.

Debate on optimal management of cavernous sinus

meningiomas aims to compare the different treatment

strategies: (a) radical surgical resection, which is the total

removal of the tumor including the intracavernous sinus

component, and (b) conservative surgical resection with

64 (2005) S2:58–S2:66

Table 1

Demographic data of the patients

Patient

groups

Age range

(y)

Mean age

(y)

No. of patients,

sex (F/M)

Mean

follow-up (y)

A 10-62 42.4 10, 8:2 9.8

B 28-65 38.1 12, 10:2 5.2

C 29-74 51.9 26, 19:7 3.3

F indicates female; M, male.

M.N. Pamir et al. / Surgical Neurology 64 (2005) S2:58–S2:66 S2:59

radiosurgical treatment, which is the resection of the

extracavernous sinus component followed by radio-

surgical treatment of the intracavernous sinus part. Micro-

surgery and radiosurgery are complementary for managing

patients with cavernous sinus meningiomas yet are often

presented as competitive, with most of the reports favoring

the results of one homogenous treatment modality. Few data

exist with a direct comparison of the outcomes achievable

with both approaches used at a single institution.

The history of themanagement strategy of cavernous sinus

meningiomas in our department before and after GK facility

became available in 1997 allowed us to compare the

2 aforementioned strategies. This analysis contributes to the

debate on cavernous sinus meningiomas, which uniquely

compared the 2 strategies in the same hospital setting.

2. Materials and methods

2.1. Patients and surgical data

Before the installation of Leksell GK unit at the hospital

in 1997, the neurosurgical team at Marmara University

Table 2

Cranial nerve morbidities are examined separately for each group

Group A

Cranial nerves Preoperative deficit Early postoperative function

Improved Unchanged

II 3 (30) 1 (10) 2 (20)

III 5 (50) – 3 (30)

IV 2 (20) – 2 (20)

V – – 1 (10)

VI 2 (20) – 2 (20)

Group B

Cranial nerves Preoperative deficit Postoperative function

Improved Unchanged

II 1 (8.3) – 1 (8.3)

III 2 (16.6) – 1 (8.3)

IV 1 (8.3) – 1 (8.3)

VI 3 (25) – –

Group C

Cranial nerves Pre–GK surgery Post–GK surgery (third year)

Improved Unchanged

II 2 (7.6) – 2 (7.6)

III 6 (23) 3 (11.5) 3 (11.5)

IV – – –

V 2 (7.6) 1 (3.8) 1 (3.8)

VI 5 (19.2) 2 (19.2) 3 (11.5)

Cranial nerve morbidities are significantly higher ( P b .05) in group A than in g

Institute of Neurological Sciences and Faculty of Medicine

(Istanbul, Turkey) treated patients with cavernous sinus

meningioma using radical resection (radical strategy,

group A). After 1997, the same neurosurgical team per-

formed surgical removal of the extracavernous sinus tumor

component with GK irradiation of the intracavernous part

(conservative strategy, group B). Another group of patients

who were treated with GK as a first-step treatment were

analyzed within group C (GK group) (Table 1).

Three subgroups of cavernous sinus meningioma cases

treated at Marmara University are included into this

retrospective clinical study. Group A consists of all of the

10 patients who were treated with radical surgical strategy

between the dates of 1992 and 1997 January. Group B

consists of all of the 12 patients who were managed with the

strategy of extracavernous surgical removal and intra-

cavernous GK irradiation between the dates of January

1997 and December 2001. Group C consists of all of the

26 patients who were managed with only GK irradiation as

the primary modality in the management between the dates

of January 1997 and December 2001.

Cavernous sinus meningioma cases treated after Decem-

ber 2001, and all cases that had been operated elsewhere and

referred to our GK unit for treatment were excluded from

the study. Radical surgical resection was done in all group

A patients (n = 10), and Dolenc’s approach for cavernous

sinus exploration was used. For group B patients (n = 12),

classic pterional craniotomy was applied. None of the

patients had undergone previous surgery or radiation

therapy. Before surgical resection, none of the patients

Third year

Worsened Improved Unchanged Worsened

– 1 (10) 2 (20) –

1 (10) – 3 (30) 1 (10)

1 (10) – 2 (20) 1 (10)

1 (10) – – 1 (10)

4 (40) – – 4 (40)

Post–GK surgery (third year)

Worsened Improved Unchanged Worsened

– – 1 (8.3) –

4 (33.3) 3 (25) 2 (16.6) –

5 (41.6) 3 (25) 4 (33.3) –

9 (75) 5 (41.6) 4 (33.3) –

Worsened

–

–

–

–

–

roups B and C. Values in parentheses are percentages.

Fig. 1. Time-dependent KPS scores are presented as line graph analyses.

M.N. Pamir et al. / Surgical Neurology 64 (2005) S2:58–S2:66S2:60

underwent transarterial embolization of tumor-feeding

arteries from the external carotid artery. Complete medical,

neurological, neurophysiological, ophthalmologic, and neu-

roradiological assessments were performed before and after

each operation. The histological diagnoses were meningo-

thelial meningioma in 16 patients and fibrous meningioma in

8 patients. Mean follow-up times for group A, B, and C

patients are 9.8, 5.2, and 4.3 years, respectively; however,

patients with at least 3 years of follow-up are included in

the study.

2.2. Radiosurgical treatment

Patients were immobilized in a Leksell stereotactic

coordinating frame and underwent MRI with contrast media

to obtain precise information on the shape, volume, and 3D

coordinates of the tumors. Radiosurgery was performed

with a GK. Neurosurgeons and radiation oncologists jointly

determined dose planning using commercially available

software (GammaPlan; Elekta Instruments, Stockholm,

Sweden). In principle, the dose to the tumor margin was

designed to be greater than 15 Gy within the 50% isodose

line. If the tumor was sufficiently distant from the optic

apparatus and the brainstem, the dose was increased

occasionally according to the tumor volume to enhance

long-term tumor control (Table 1).

2.3. Radiological investigations

All patients underwent T1- (with and without gadolinium

enhancement) and T2-weighted MRI as well as computed

tomography with bone density studies that included 3D

skull-base constructions. The adequacy of the vascular

collateral circulation was evaluated by digital subtraction

angiography and transcranial Doppler ultrasonography

examinations. Postoperative control MRI was performed

at 24 hours, every 3 months in the first year, and every

6 months thereafter.

The extent of surgical resection was determined from the

magnetic resonance images obtained 24 hours postsurgery

and was classified as radical (no residual tumor or a small

questionable area), subtotal (clear presence of residual

tumor), or partial (b90% of mass resected). All occurrences

of clinical deterioration during a patient’s hospital stay

postsurgery were considered boperative complications.Q

2.4. Cranial nerve function and KPS evaluation

Cranial nerve morbidities and pretreatment, posttreat-

ment, and latest KPS scores for each group of patients were

evaluated and compared. Neurological examination and

evaluation of the KPS score were performed at the routine

clinical visits at 3rd, 6th, 9th, 12th, 18th, 24th, and 36thmonths

after completion of the treatment.

2.5. Graphics and data analysis

Tumor volume was measured on an Image Analyzer

(Image Inc, Montreal, Canada) or by measuring the radius

of the lesion on MRI scans done in 3 planes (r1-r3) and

using the formula V = 4/3 p � r1 � r2 � r3 [9]. Tumor

volumes of the patients who underwent GK treatment were

calculated by GammaPlan. The Statview software package

(Version 4.5; Abacus Concepts, Berkeley, CA) was used to

determine mean values and statistical analysis and cell-line

Fig. 2. Time-dependent tumor volume (milliliters) changes are presented as cell-line graph analyses for group A (radical surgery group) with an illustrative case.

M.N. Pamir et al. / Surgical Neurology 64 (2005) S2:58–S2:66 S2:61

graphs of tumor volume changes and KPS scores (F1 SD

were used for error bars). Student t test was used to

statistically analyze the 3 groups with respect to cranial

nerve morbidities.

3. Results

No disease-related mortality occurred during the follow-

up period; 1 patient in group A died because of myocardial

infarction 8 months after meningioma treatment. As to

surgery-related complications, 1 patient in group A who

had a postoperative hemorrhage in the tumoral site

immediately underwent evacuation of the hematoma,

resulting in no neurological sequelae. Diabetes insipidus

was observed transiently after surgery in 1 patient in group

A, pneumonia in 2 other patients, 1 in group A and 1 in

group B. None of these complications affected the

patients’ final status. Outcome of KPS scores and cranial

nerve complications are studied separately in Table 2

and Fig. 1.

3.1. Group A patients

Fig. 2 presents the graph of the volumetric analysis of

group A. After a remarkable volumetric decrease in the

early postoperative period after surgery, a slow incline is

detected in the volumetric statistics, which becomes more

notable after 2 years. Table 2 presents the status of cranial

nerve function, and Fig. 1 displays the outcome of KPS

scores of group A patients.

3.2. Group B patients

Fig. 3 presents the graph of the volumetric analysis of

group B. After a remarkable volumetric decrease in the

early postoperative period, in contrast to group A, a slow

M.N. Pamir et al. / Surgical Neurology 64 (2005) S2:58–S2:66S2:62

decline was detected in the volumetric statistics after GK.

Table 2 presents the status of cranial nerve function,

and Fig. 1 displays the outcome of KPS score of group

B patients.

3.3. Group C patients

Fig. 4 presents the graph of the volumetric analysis of

group C. A slow decline is detected in the volumetric

statistics, which becomes more notable after 2 years. Table 2

presents the status of cranial nerve function, and Fig. 1

displays the outcome of KPS scores of group C patients.

4. Discussion

4.1. Current debate topics on the management of cavernous

sinus meningiomas

Skull-base approaches such as Dolenc’s pretemporal

cavernous sinus exploration or orbitozygomatic approaches

enabled neurosurgeons to resect cavernous sinus meningi-

omas [2,10,15,16,23,24,36,38,43]. The 1990s was the era

of reports informing of high rate of gross total resection.

However, in the second half of this decade, it has been

understood that oncological cure of a neoplasm is different

from surgical resection of the tumor [20,22]. Consequently,

other management modalities aiming for biological treat-

ment of the meningioma have been used in a linearly

increasing pattern. One of these biological treatment

modalities for these tumors is radiosurgery [7,11,13,17,27,

29-31,37,42,45]. Nevertheless, because radiosurgery is not a

totally immune modality to complications, its use is some-

what limited [4,40,45]. Answers to current debate topics on

the management of cavernous sinus meningiomas can be

collected in the following subgroups.

4.1.1. Subgroup A

Surgery cannot provide oncological cure because of

anatomical localization and invasive nature of the cavernous

sinus meningiomas. Cavernous sinus meningiomas are

interdural tumors [1]. Because they are not originally

extradural and show a certain degree of infiltration to the

anatomical structures in the cavernous sinus and bone tissue,

according to grading system of De Monte et al [8], the

extent of cavernous sinus meningioma resection cannot be

better than grade 4a, which indicates intentional subtotal

removal to preserve cranial nerves or blood vessels and

complete microscopic removal of tumor dural attachment.

Degree of ICA involvement and the invasion of the vessel

wall by the meningioma encasing ICA is one other

determinant of impossible complete resection of the tumor

oncologically [6,26,40]. Resection of the ICA and its

cavernous branches partially devascularizes the cranial

nerves of the cavernous sinus and could result in an

infarction of these nerves, decreasing their rates of functional

recovery [39]. In our view, although opposite opinions have

been presented, sacrifice of the ICA to remove the remnants

of adherent tumor is not established as an acceptable risk

nor as a way to increase the long-term rate of cure. Another

anatomical reason for oncological eradication of these

tumors being impossible is absence of arachnoidal planes.

Considering arachnoidal anatomy, cavernous sinus menin-

giomas are similar to type I clinoidal meningiomas, which

have been reported to be impossible to resect completely

[2]. In addition, although we excluded all cases who

underwent radiation therapy or previous surgery, it has

been reported that previous fractionated radiation therapy

and surgery increase the difficulty of finding and using the

surgical planes [40]. Misimpression regarding the possibility

of oncological total resection by modern skull-base surgical

techniques may be partly due to the early surgical series in

which imaging of postoperative radiological control subjects

were performed by computed tomography instead of MRI.

Another original feature of this series is the use of 24-hour

postoperative MRI to assess residual meningioma volume

after surgery [33]. A recently published prospective study of

80 patients with pituitary adenoma at one clinic confirmed

the merit of this method [21]. The authors showed that

24-hour postoperative MRI allowed accurate determination

of residual tumor volume and concluded that this was a

valuable tool for deciding the next step in management. In

our surgical cases, 24-hour MRI enabled us to determine the

exact volume of the residual tumor and apply the next

treatment step promptly. This is extremely important

because residual meningiomas start to grow almost imme-

diately after the initial surgery. Again, to our knowledge,

this is the first published report to include brealQ residual

chordoma volumes as calculated from 24-hour postoperative

MRI scans.

4.1.2. Subgroup B

Surgery is the main step in the treatment of the

extracavernous part of these tumors and to establish the

tissue diagnosis. As evident in this study, the extent of

extracavernous involvement will determine the resectability

of the cavernous sinus meningioma. The result is often a

strategy of cytoreduction of extracavernous tumor to protect

the brain function and the containment of the tumor within

the cavernous sinus to preserve cranial nerve functions. In

our department, the evolution of the understanding of the

nature of surgical treatment of these tumors has taught us

that pursuing the aim of radical excision by using all the

surgical strengths that modern skull-base surgery enables

was usually an unnecessary effort that led us to complica-

tions and decrease in the quality of life (group A), which

could have been avoided with more conservative strategy

(group B). There was one disease-unrelated death (myocar-

dial infarction 8 months after treatment) in our group A;

other authors reported mortality in 1 of 70 patients, 3 of 41

patients, 1 of 15 patients, and 0 in 39 patients [3,6,8,32,41].

These results confirm the low mortality rates in experienced

hands. However, the major concern after surgical excision of

the intracavernous compartment of the tumor is cranial nerve

Fig. 3. Time-dependent tumor volume (milliliters) changes are presented as cell-line graph analyses for group B (extracavernous sinus surgery followed by GK)

with an illustrative case.

M.N. Pamir et al. / Surgical Neurology 64 (2005) S2:58–S2:66 S2:63

paralysis. Studies report permanent morbidity rates ranging

from 10% to 59% [8,24,27,32], with morbidities mostly

involving cranial nerves [24,32]. It is apparent in this study

that the rate of extraocular deterioration is mainly determined

by the aggressiveness of the surgical strategy. Our experi-

ence taught us that the worst complications, such as

hemiparesis, tend to relate to the extracavernous extension

of the tumor. The most common complication faced during

the management of these tumors is extraocular nerve palsy.

Although, usually, this neurological finding is reversible in

1 year, it is so common and so disturbing that it becomes the

main determining factor for the quality of life in the post-

operative period. The probability of improvement in preoper-

atively determined extraocular palsy is higher with the

GK treatment of the intracavernous compartment (group B).

Moreover, postoperative occurrence of extraocular nerve palsy

is more common in the radical resection group (group A),

so preoperative detection of extraocular palsy is not an

indication for radical surgery. However, the situation is

different with optic nerve; preoperative optic nerve dysfunc-

tion should be managed by surgical removal of the compress-

ing part of this extracavernous tumor. Consequently,

protection of normal optic nerve function or the reduction

of meningioma away from the optic system in preparation for

radiosurgery may be an indication for surgery.

4.1.3. Subgroup C

Although radiosurgery cannot eradicate the neoplasm, it

makes a favorable change in their natural history and helps

clinical healing or stabilization of the symptoms. Data from

the recent literature and our experience demonstrate that

radiosurgery is an effective therapeutic tool for the selected

Fig. 4. Time-dependent tumor volume (milliliters) changes are presented as cell-line graph analyses for group C (only radiosurgery) with an illustrative case.

M.N. Pamir et al. / Surgical Neurology 64 (2005) S2:58–S2:66S2:64

cavernous sinus meningioma cases. Reported tumor growth

control rate for cavernous sinus meningiomas after

radiosurgery is more than 90% [7,25,29,30,35]. Roche et al

[37] reported volume reduction in 31% of cases, and

Nicolato et al [30] reported same parameter as 61.5%. From

a clinical perspective, all published series indicate stable

or improved neurological status in more than 90% of

cases. Nicolato et al [30], reporting on the data generated

from 122 patients (62 of them primary treatment), indicate

that neurological improvement was much more frequent

when it was possible to use GK as a primary mode of

treatment (78.5%) rather than as a radiosurgical adjuvant

therapy (60.5%). The authors of the article conclude that

this significant difference could be attributable to the

potential postmicrosurgical insult to the nervous structures.

Radiosurgery makes a difference in PFS period. De Jesus

et al [6] reported 62% rate of PFS at 5 years after radical

microsurgical removal strategy. On the other hand, several

radiosurgical series, for example, Kurita et al [27], Roche

et al [37], and Nicolato et al [30], report PFS rates of

85.7%, 92.8%, and 95.5% (at fifth year), respectively.

Tumor volumes in most microsurgical series are usually

incomparably larger than radiosurgical series. In our

opinion, present data in literature and data presented in

our study should not be interpreted as radiosurgery being

the primary mode of treatment in the management of

cavernous sinus meningiomas but rather as radiosurgery

being an effective use for meningiomas having volumes

less than 20 mL. Radiation sensitivity of optic apparatus is

one of the radiosurgery-limiting issues in the management

of cavernous sinus meningiomas. Duma et al [11] reported

2 of 34 patients having radiation-induced neuropathy after

radiosurgery. In our practice, whatever the volume of the

tumor, we try to have at least a 3-mm difference between

the tumor margin and the closest optical anatomical struc-

ture. Otherwise, as noted earlier, initial reduction of the

meningioma away from the optic system is the principle.

4.2. Algorithm based on our experience on cavernous sinus

meningiomas

The differences of our algorithm from previously

published series to be determined by these subgroups.

Our algorithm is mainly based on volume of the cavernous

sinus meningioma. As long as patients’ systemic condition

favors a possible surgical intervention, age of the patient

is not regarded as a parameter in decision making.

O’Sullivan et al [32] consider surgery more as first-line

Fig. 5. An algorithm based on our experience on cavernous sinus meningiomas.

M.N. Pamir et al. / Surgical Neurology 64 (2005) S2:58–S2:66 S2:65

management as the age of the patient gets younger.

Similarly, extraocular nerve palsies are not regarded as

surgery-promoting parameters, in our understanding, be-

cause clinical decrease of the diplopia is also possible after

radiosurgery (Fig. 5).

One important determinant for decision making is

clinical or radiological findings of optic system compres-

sion. At least 3 mm of difference between tumor and

optic anatomical structures is required for safe and

effective radiosurgical treatment of cavernous sinus

meningiomas. Therefore, tumors having volume less than

20 mL but with no safety margin of 3 mm to optic

apparatus should therefore be surgically prepared for

radiosurgery; so anatomical preparation of the meningio-

ma for radiosurgery is a goal that should be accomplished

during surgery and can be achieved by simple surgical

volumetric reduction of meningioma and transposition of

optic system by using Gelfoam to gain a 3-mm distance

at the tumor border.

One different approach that is being used in this

algorithm is performing 24-hour MRI after the surgery

and completing the whole management of the patient by

making the radiosurgical treatment at the same hospital

stay, even 24 hours postsurgically. Our experience with

pituitary adenomas and chordomas published earlier

implies that early postoperative (24 hours) MRI reveals

anatomical details more clearly before anatomical dis-

turbances because postsurgical inflammation and hemato-

ma degradation disturb the radiological differential

diagnosis [12,21].

Acknowledgment

Scientific activities of Tqrker KVlVc, MD, PhD, have been

financially supported by Turkish Academy of Sciences.

References

[1] Abdel-Aziz KM, Froelich SC, Dagnew E, Jean W, Breneman JC,

Zuccarello M, van Loveren HR, Tew Jr JM. Large sphenoid wing

meningiomas involving the cavernous sinus: conservative surgical

strategies for better functional outcomes. Neurosurgery 2004;

54:1375-83 [discussion 1383-1374].

[2] Al-Mefty O. Clinoidal meningiomas. J Neurosurg 1990;73:840-9.

[3] Al-Mefty O, Smith RR. Surgery of tumors invading the cavernous

sinus. Surg Neurol 1988;30:370 -81.

[4] Blake PY, Miller NR, Long DM. Treatment of cavernous sinus

meningiomas. J Neurosurg 1995;82:702-3.

[5] Day JD. Cranial base surgical techniques for large sphenocavernous

meningiomas: technical note. Neurosurgery 2000;46:754-9 [discus-

sion 759-760].

[6] De Jesus O, Sekhar LN, Parikh HK, Wright DC, Wagner DP. Long-

term follow-up of patients with meningiomas involving the cavernous

sinus: recurrence, progression, and quality of life. Neurosurgery

1996;39:915-9 [discussion 919-920].

[7] De Salles AA, Frighetto L, Grande CV, Solberg TD, Cabatan-

Awang C, Selch MT, Wallace R, Ford J. Radiosurgery and

stereotactic radiation therapy of skull base meningiomas: proposal

of a grading system. Stereotact Funct Neurosurg 2001;76:218-29.

M.N. Pamir et al. / Surgical Neurology 64 (2005) S2:58–S2:66S2:66

[8] DeMonte F, Smith HK, al-Mefty O. Outcome of aggressive removal

of cavernous sinus meningiomas. J Neurosurg 1994;81:245-51.

[9] Deniz ML, Kilic T, Almaata I, Kurtkaya O, Sav A, Pamir MN.

Expression of growth factors and structural proteins in chordomas:

basic fibroblast growth factor, transforming growth factor alpha, and

fibronectin are correlated with recurrence. Neurosurgery 2002;51:

753 -60 [discussion 760].

[10] Dolenc V. Microsurgical removal of large sphenoidal bone meningi-

omas. Acta Neurochir Suppl (Wien) 1979;28:391-6.

[11] Duma CM, Lunsford LD, Kondziolka D, Harsh GRt, Flickinger JC.

Stereotactic radiosurgery of cavernous sinus meningiomas as an

addition or alternative to microsurgery. Neurosurgery 1993;32:699 -

704 [discussion 704-695].

[12] Ekinci G, Akpinar IN, Baltacioglu F, Erzen C, Kilic T, Elmaci I, Pamir

N. Early-postoperative magnetic resonance imaging in glial tumors:

prediction of tumor regrowth and recurrence. Eur J Radiol

2003;45:99-107.

[13] Friedman WA, Foote KD. Linear accelerator radiosurgery in the

management of brain tumours. Ann Med 2000;32:64-80.

[14] George B, Ferrario CA, Blanquet A, Kolb F. Cavernous sinus

exenteration for invasive cranial base tumors. Neurosurgery

2003;52:772 -80 [discussion 780-772].

[15] Goel A, Muzumdar DP, Nitta J. Surgery on lesions involving

cavernous sinus. J Clin Neurosci 2001;8(Suppl 1):71 -7.

[16] Heth JA, Al-Mefty O. Cavernous sinus meningiomas. Neurosurg

Focus 2003;14:e3.

[17] Iwai Y, Yamanaka K, Ishiguro T. Gamma knife radiosurgery for the

treatment of cavernous sinus meningiomas. Neurosurgery 2003;52:

517 -524 [discussion 523-514].

[18] Kawase T, Shiobara R, Ohira T, Toya S. Developmental patterns and

characteristic symptoms of petroclival meningiomas. Neurol Med Chir

(Tokyo) 1996;36:1 -6.

[19] Kilic T, Alberta JA, Zdunek PR, Acar M, Iannarelli P, O’Reilly T,

Buchdunger E, Black PM, Stiles CD. Intracranial inhibition of

platelet-derived growth factor–mediated glioblastoma cell growth by

an orally active kinase inhibitor of the 2-phenylaminopyrimidine

class. Cancer Res 2000;60:5143-50.

[20] Kilic T, Bayri Y, Ozduman K, Acar M, Diren S, Kurtkaya O, Ekinci

K, Bugra K, Sav A, Ozek MM, Pamir MN. Tenascin in meningioma:

expression is correlated with anaplasia, vascular endothelial growth

factor expression, and peritumoral edema but not with tumor border

shape. Neurosurgery 2002;51:183-92 [discussion 192-183].

[21] Kilic T, Ekinci G, Seker A, Elmaci I, Erzen C, Pamir MN.

Determining optimal MRI follow-up after transsphenoidal surgery

for pituitary adenoma: scan at 24 hours postsurgery provides reliable

information. Acta Neurochir (Wien) 2001;143:1103-26.

[22] Kilic T, Ozduman K, Elmaci I, Sav A, Necmettin Pamir M. Effect of

surgery on tumor progression and malignant degeneration in

hemispheric diffuse low-grade astrocytomas. J Clin Neurosci

2002;9:549.

[23] Kleinpeter G, Bock F. Invasion of the cavernous sinus by medial

sphenoid meningioma—bradicalQ surgery and recurrence. Acta Neuro-chir (Wien) 1990;103:87 -91.

[24] Knosp E, Perneczky A, Koos WT, Fries G, Matula C. Meningiomas of

the space of the cavernous sinus. Neurosurgery 1996;38:434-42

[discussion 442-434].

[25] Kobayashi T, Kida Y, Mori Y. Long-term results of stereotactic

gamma radiosurgery of meningiomas. Surg Neurol 2001;55:325-31.

[26] Kotapka MJ, Kalia KK, Martinez AJ, Sekhar LN. Infiltration of the

carotid artery by cavernous sinus meningioma. J Neurosurg 1994;

81:252-5.

[27] Kurita H, Sasaki T, Kawamoto S, Taniguchi M, Terahara A, Tago M,

Kirino T. Role of radiosurgery in the management of cavernous sinus

meningiomas. Acta Neurol Scand 1997;96:297-304.

[28] Lesoin F, Jomin M, Bouchez B, Duret MH, Clarisse J, Arnott G,

Pellerin P, Francois P. Management of cavernous sinus meningiomas.

Neurochirurgia (Stuttg) 1985;28:195 -8.

[29] Maruyama K, Shin M, Kurita H, Kawahara N, Morita A, Kirino MDT.

Proposed treatment strategy for cavernous sinus meningiomas: a

prospective study. Neurosurgery 2004;55:1068-75.

[30] Nicolato A, Foroni R, Alessandrini F, Bricolo A, Gerosa M.

Radiosurgical treatment of cavernous sinus meningiomas: experience

with 122 treated patients. Neurosurgery 2002;51:1153-9 [discussion

1159-1161].

[31] Nicolato A, Foroni R, Alessandrini F, Maluta S, Bricolo A, Gerosa M.

The role of Gamma Knife radiosurgery in the management of

cavernous sinus meningiomas. Int J Radiat Oncol Biol Phys 2002;

53:992-1000.

[32] O’Sullivan MG, van Loveren HR, Tew Jr JM. The surgical

resectability of meningiomas of the cavernous sinus. Neurosurgery

1997;40:238-44 [discussion 245-237].

[33] Pamir M, Kilic T, Ozek M, Sav A, Erzen C. Surgical approach to

cavernous sinus tumors. North American Skull Base Society 8th

Annual Meeting. Little Rock, Arkansas, USA; 1997.

[34] Pamir MN, Kilic T, Ture U, Ozek MM. Multimodality manage-

ment of 26 skull-base chordomas with 4-year mean follow-up:

experience at a single institution. Acta Neurochir (Wien) 2004;146:

343 -54.

[35] Pendl G, Schrottner O, Eustacchio S, Ganz JC, Feichtinger K.

Cavernous sinus meningiomas—what is the strategy: upfront or

adjuvant gamma knife surgery? Stereotact Funct Neurosurg 1998;

70(Suppl 1):33 -40.

[36] Risi P, Uske A, de Tribolet N. Meningiomas involving the anterior

clinoid process. Br J Neurosurg 1994;8:295 -305.

[37] Roche PH, Regis J, Dufour H, Fournier HD, Delsanti C, Pellet W,

Grisoli F, Peragut JC. Gamma knife radiosurgery in the manage-

ment of cavernous sinus meningiomas. J Neurosurg 2000;93(Suppl 3):

68 -73.

[38] Sekhar LN, Babu RP, Wright DC. Surgical resection of cranial base

meningiomas. Neurosurg Clin N Am 1994;5:299-330.

[39] Sekhar LN, Lanzino G, Sen CN, Pomonis S. Reconstruction of the

third through sixth cranial nerves during cavernous sinus surgery.

J Neurosurg 1992;76:935 -43.

[40] Sekhar LN, Levine ZT, Sarma S. Grading of meningiomas. J Clin

Neurosci 2001;8(Suppl 1):1 -7.

[41] Sekhar LN, Patel S, Cusimano M, Wright DC, Sen CN, Bank WO.

Surgical treatment of meningiomas involving the cavernous sinus:

evolving ideas based on a ten year experience. Acta Neurochir Suppl

1996;65:58 -62.

[42] Selch MT, Ahn E, Laskari A, Lee SP, Agazaryan N, Solberg TD,

Cabatan-Awang C, Frighetto L, Desalles AA. Stereotactic radiother-

apy for treatment of cavernous sinus meningiomas. Int J Radiat Oncol

Biol Phys 2004;59:101-11.

[43] Sen C, Hague K. Meningiomas involving the cavernous sinus:

histological factors affecting the degree of resection. J Neurosurg

1997;87:535-43.

[44] Wilson CB. Cavernous sinus meningiomas. Surg Neurol 1996;

46:191-2.

[45] Ziyal IM, Sekhar LN, Salas E. Radiosurgery: an effective treatment for

cavernous sinus meningiomas? Crit Rev Neurosurg 1999;9:107-15.