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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.
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