J Neurosurg 74:552-559, 1991
Stereotactic radiosurgery of meningiomas DOUGLAS KONDZIOLKA, M.D., L. DADE LUNSFORD, M.D., ROBERT J. COFFEY, M.D., AND JOHN" C. FLICK1NGER, M.D.
Departments of Neurological Surgery, Radiation Oncology, and Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania ~" Stereotactic radiosurgery has an expanding role in the management of selected intracranial tumors. In an initial 30-month experience using the 201-source cobalt-60 gamma knife at the University of Pittsburgh, 50 patients with meningiomas were treated. The most frequent site of origin was the skull base. Previously, 36 patients (72%) had undergone at least one craniotomy and four patients (8%) had received fractionated external beam radiation therapy. Stereotactic radiosurgery was the primary treatment modality in 16 patients (32%) with symptomatic tumors demonstrated by neuroimaging. Computer imaging-generated isodose plans (with one to five irradiation isocenters) for singje-treatment irradiation gave optimal (_> 50% isodose line) coverage in 44 patients (88%). The proximity of cranial nerves or vascular, pituitary, and brain-stem structures to the often convoluted tumor mass was crucial to dose selection. Serial imaging studies were evaluated in all 50 patients. Twenty-four patients were examined between 12 and 36 months after treatment; 13 (54%) showed a reduction in tumor volume while nine (38%) showed no change. Of 26 patients evaluated between 6 and 12 months after treatment, four showed a decrease in tumor size while 22 showed no change. Two patients (both with large tumors that received suboptimal irradiation) had delayed tumor growth outside the radiosurgical treatment volume. The actuarial 2-year tumor growth control rate was 96%. Between 3 and 12 months after radiosurgery, three patients developed delayed neurological deficits that gradually improved, compatible with delayed radiation injury. Although extended follow-up monitoring over many years will be necessary to fully evaluate treatment, to date stereotactic radiosurgery has proved to be a relatively safe and effective therapy for selected patients with symptomatic meningiomas, including those who failed surgical resection. Radiosurgery was an effective primary treatment alternative for those patients whose advanced age, medical condition, or high-risk tumor location mitigated against surgical resection. KEY WORDS cavernous sinus '
stereotactic radiosurgery skull base
URGERY is the preferred treatment of meningiomas, and long-term disease-free survival can be achieved with surgical resection of the tumor and its associated dural base) 5'78'~~ Despite recent advances in microsurgical techniques, some meningiomas recur. Although many basal meningiomas can be resected completely from their dural attachment, such surgery frequently is associated with the undesirable development of new neurological deficits. 17,31.38As a result, in order to preserve neurological function, surgeons often perform incomplete resections. Some patients with meningiomas are considered unsuitable for surgery if they are elderly or are "medically unit. ''2'13 Single-fraction precisely guided multiple photon-beam irradiation (stereotactic radiosurgery) offers treatment to such patients: those with tumors in highrisk locations; those with residual meningiomas after surgical resection; and those whose advanced age or
S
552
.
meningioma
9 brain tumor
associated medical illness pose unacceptable risks for surgical removal. This report is the first comprehensive clinical analysis of stereotactic radiosurgery performed in patients with meningiomas. We present our management strategies and initial results, and conclude that radiosurgery is an effective primary and important adjuvant treatment in the management of selected meningiomas. Clinical Material and Methods Between August, 1987, and January, 1990, 50 patients (36 women and 14 men) underwent treatment of their meningiomas with the 201-source cobalt-60 gamma knife.* All patients selected for radiosurgery
* Gamma knife manufactured by Elekta instruments, Tucker, Georgia. J. Neurosurg. / Volume 74/April, 1991
Stereotactic radiosurgery of meningiomas had a well-circumscribed intracranial tumor with imaging findings characteristic of a meningioma. Contrastenhanced computerized tomography (CT) or magnetic resonance (MR) imaging revealed a well-demarcated dura-based mass. Diagnostic angiography in selected patients showed a blood supply typically associated with meningiomas. Thirty-six patients (72%) had undergone at least one prior surgical procedure; in two patients, craniotomy was performed but the tumor was neither resected nor biopsied because of its location in the cavernous sinus. One patient previously underwent resection of a meningioma in another location. Sixteen patients had received radiosurgery for a tumor defined by clinical and imaging criteria as a meningioma. Four patients previously received fractionated external beam radiation therapy (46 to 50 Gy) after subtotal surgical resections. Patients were not accepted for radiosurgery if the lesion was too large (> 35 m m in average diameter), was within 5 m m of the optic chiasm, or was amenable to open microsurgical resection with acceptable risk. The clinical characteristics of the 50 patients appear in Table 1. The mean age of our 36 female patients was 56.6 years (range 37 to 82 years) and of our 14 male patients was 50.5 years (range 14 to 71 years). The median Karnofsky Performance Scale score was 90 (range 60 to 100). In all patients the Leksell Model G stereotactic coordinate framer was applied and all underwent imaging and treatment under local anesthesia supplemented by intravenous sedation. Stereotactic CT scans were performed in order to define tumor boundaries and obtain target coordinates. In selected cases, stereotactic M R imaging was used in addition to CT, especially for small lesions or those located near the optic pathways. Computer-dose planning was performed on a high-speed Microvax system.:~ The treatment isodose, central dose, and dose to the margin were determined by the neurosurgeon, the radiation oncologist, and the radiation physicist. Selection of dose was based on prior experience in the radiosurgical treatment of arteriovenous malformations and other brain tumors and on the location and size of the lesion. ~5~626 Patients received a single dose of methylprednisolone (40 mg intravenously) immediately after radiosurgery. In the preoperative period, therapeutic anti-convulsant levels were achieved in patients with supratentorial brain tumors. All patients were discharged from the hospital on the day after treatment. Follow-up imaging studies (CT or M R imaging) were scheduled at 3, 6, and 12 months after radiosurgery, and at 6-month intervals thereafter. For patients who lived a long distance from Pittsburgh, clinical and ira-
t Stereotactic coordinate frame, Model G, manufactured by Elekta Instruments, Tucker, Georgia. Microvax manufactured by Digital Equipment Corp., Westminster, Massachusetts.
J. Neurosurg. / Volume 74/April, 1991
TABLE 1 Clinical characteristics of 50 palients with meningiomas Characteristic
No. of Cases
sex (F:M) location cavernous sinus parasellarregion petrous apex tentorium cerebellopontineangle tuberculum sellae confluence of falx & tentorium
36:14 13 6 6 5 5 3 3
clivus
2
parasagittalregion lateral ventricle jugular foramen olfactorygroove sphenoid ridge torcular herophili
2 1 1 1 1 1
aging follow-up monitoring was sometimes provided by the referring physicians. Results
Radiation Dosimetry The radiation dosimetry in this series of 50 patients is presented in Table 2. The meningiomas were treated
TABLE 2 Radiosurgical dosimetry in 50 patients RadiosurgicalDosimetry No. of Cases tumor volume(cu ram)* < 1000 8 1000-5000 19 5000-10,000 16 10,000-20,000 4 > 20,000 3 marginal treatment isodose(%) 20t I 40 5 50 38 60 3 70 2 80 1 radiation dose to tumor margin (Gy) 10 2 12 1 13 4 14 4 15 6 16 4 17 5 18 7 20 16 25 1 * Tumor volume is estimated using 4/3rr 3, where r = radius (estimatedas 89 the tumor mean diameter (d), where d = ~Yx.y.z (x, y, z = maximum tumor dimensionsin three planes)). "~Tumor volume = 25,594 cu mm (consideredsuboptimal treatment) in a patient who was resistant to blood transfusion due to religiousbeliefs. 553
D. Kondziolka, el al.
FIG. 2. Scattergram of marginal dose (Gy) versus volume (cu ram) for 50 patients, with complications indicated by triangles. A secondary y axis indicates the diameter (mm) for a sphere of equivalent volume. The solid line represents a relatively linear portion of an isoeffect curve derived from the integrated logistic equation ~5 for a 3% risk of permanent symptomatic brain injury from gamma knife radiosurgery. FIG. 1. Magnetic resonance (T~-weighted spin-echo) image with gadolinium-DTPA enhancement showing a left cavernous sinus meningioma at radiosurgcry. Three isocenters of irradiation were used to construct the isodosc plan (maximum dose 30 Gy).
TABLE 3 Imaging evaluation after radiosurgery in 50 patients* Tumor Size
with single irradiation isocenters in nine cases and multiple irradiation isocenters in 41 (Fig. 1). Five isocenters of irradiation were used in four patients, and four isocenters were used in another four. Forty-four patients (88%) were treated at the 50% isodose line or greater, to take advantage of the sharp fall-off of the radiation field outside the target volume. 4~ The mean dose delivered to the tumor margin was 16.98 Gy (range 10 to 25 Gy). A scatterplot of tumor volume versus dose to the margin for all 50 tumors is presented in Fig. 2. Selection of treatment dose was based on tumor size and location (especially proximity to crucial vascular, cranial nerve, brain-stem, and pituitary structures) and on previously administered fractioned conventional irradiation dose (if any). For tumors in the region of the optic apparatus, we kept the dose to the chiasm below 9 Gy.
Imaging Evaluation All 50 patients were evaluated between 6 and 34 months after radiosurgery (Table 3). The actuarial 2year tumor growth control rate was 96%, according to the calculation method of Berkson and Gage. 6 In the group of 24 patients who were followed for 12 to 36 months after treatment, 13 patients (54%) showed a decrease in tumor size; eight showed loss of central contrast enhancement on CT or M R imaging consistent with intratumor necrosis. Nine patients (38%) showed 554
Time Posttreatment(mos)
6-12 12-24 24-36 decreased 4 (2) 7 (5) 6 (3) no change 22 (2) 6 (1) 3 increased 0 2t 0 * Imaging evaluation was with contrast-enhanced computerized tomography or magneticresonance imaging. Number in parentheses represents the number of patients with loss of central contrast enhancement. t Both patients had suboptimal treatment because of tumor size and/or local tumor invasion.
no change in tumor size and only one showed loss of central contrast enhancement. Two patients had growth of the tumor outside the radiosurgical treatment volume: both of these patients had tumors that we believe were treated subtotally. The first patient had a recurrent invasive malignant torcular meningioma and had undergone three prior operations and conventional radiation therapy. The second patient had a large upper clivus and cavernous sinus region tumor that had recurred after multiple craniotomies. Both patients were treated ineffectively by radiosurgery because of the excessive size and lack of well-demarcated borders of their tumors. Twenty-six patients had follow-up imaging studies 6 to 12 months after radiosurgery; four showed a decrease in tumor size (Fig. 3). Two of these four patients had loss of central contrast enhancement that was recognized as early as 3 months after treatment. Twenty-two patients showed no change in tumor size, with two
J. Neurosurg. / Volume 74/April, I991
Stereotactic radiosurgery of meningiornas
FIG. 3. Magnetic resonance (Trweighted spin-echo) images with gadolinium-DPTA enhancement. A: A large falx meningioma is seen prior to radiosurgery. B: At I month postradiosurgery, the tumor is slightly smaller. C: At 6 months postradiosurgery, the tumor is markedly smaller and the surrounding brain structures appear normal.
TABLE 4 Clinical evaluation after radiosurgep3' in 50 patients Neurological
Time Posttreatment(mos)
Findings
6-12
12-24
24-36
unchanged improved new deficit died*
21 1 l 1
l0 4 1 l
9 0 l 0
* One patient died due to glomerulonephritisand one due to seizure (see text).
showing loss of central contrast enhancement. No patient had evidence of tumor growth during this interval. Clinical Outcome Clinical follow-up evaluation was available for all 50 patients (Table 4). Twenty-six patients were evaluated 12 to 36 months after radiosurgery; 19 remained clinically stable without evidence of any new neurological deficit, and four patients improved. Of the 24 patients evaluated between 6 and 12 months after treatment, 21 remained in stable neurological condition after radiosurgery; one additional patient had neurological improvement. Two patients died during the follow-up period. A 72-year-old man with a parasellar meningioma died 6 months after radiosurgery due to lung carcinoma and glomerulonephritis. He had remained in stable neurological condition. The second patient was a 66-year-old woman who had growth of a recurrent cavernous sinus tumor after treatment. She died of respiratory, complications after a seizure. Complications No immediate postoperative complications or perioperative seizures occurred. Mild headache associated with application of the stereotactic frame was relieved by oral analgesics. Since all patients left the hospital within 24 hours after radiosurgery, the duration of J. Neurosurg. / Volume 74/April, 1991
hospitalization in these patients was only 36 to 48 hours. Three patients developed temporary new neurological deficits 389 12, and 12 months after radiosurgery (actuarial risk 6.9% at 1 and 2 years). ~ The first patient was a 47-year-old woman with a petrous apex meningioma (tumor size 19 x 20 x 28 mm; 20 Gy was administered to the 50% isodose line). She developed trigeminal hypesthesia and contralateral weakness 12 months after radiosurgery and improved over the next 7 months. An MR image obtained 12 months after treatment showed a rim of gadolinium enhancement in the lateral brain stem adjacent to the tumor. This subsequently resolved over 6 months (Fig. 4). However, 24 months after radiosurgery, she developed a sixth nerve palsy, which had fully resolved at 36 months posttreatment. The second patient was an 80-year-old woman with a tentorial meningioma (tumor size 17 x 35 x 23 ram; 18 Gy was administered to the 50% isodose line, Fig. 5). Tumor shrinkage and loss of contrast enhancement were seen on a CT scan 6 months after treatment; however, 12 months after radiosurgery, she developed contralateral hemiparesis that responded to a brief course of oral corticosteroids. The third patient, who had a large (20 x 42 x 24-ram) residual petroclival meningioma, with multiple cranial neuropathies and hemiparesis, developed a fight third nerve palsy 389 months after treatment. A C T scan showed areas of low attenuation surrounding the tumor, consistent with edema. The tumor had not changed in size; his condition remains unchanged 7 months after treatment.
Discussion Surgical Resection as Primary Therapy Surgical excision of meningiomas along with their dural base provides long-term tumor control in many patients. ~,5."~,3~ Simpson 43 analyzed the results of surgery in 242 meningioma patients followed over a 16-year period. He reported a 9% recurrence rate for fififi
D. Kondziolka, et al.
FIG. 4. a: Computerized tomography scan with contrast enhancement obtained at the time of radiosurgery showing the left petrous apex meningioma, treated at the 50% isodose margin (arr(mg. Three isocenters of irradiation were used with a marginal dose of 20 Gy. b and c: Magnetic resonance (Trweighted spin-echo) images with gadolinium-DTPA enhancement. At 14 months after surgery (b), the tumor remains unchanged in size and there is an area of enhancement within the ventrolateral brain stem (arrows) adjacent to the tumor. This region was included in the 20% isodose margin (calculated dose 8 Gy). At 20 months posttreatment (c), the region of brain-stem enhancement has resolved and the tumor remains unchanged in size.
FIG. 5. Left: Computerized tomography scan with contrast enhancement showing a left tentorial meningioma treated at the 50% isodose line (two isocenters of irradiation; marginal dose 18 Gy). Right; Magnetic resonance (TIweighted spin-echo) image with gadolinium-DTPA enhancement showing a marked decrease in tumor size at 10 months after radiosurgery.
tumors completely resected along with their dural attachment; a 19% recurrence rate was calculated if the tumor was resected completely and the adjacent dura was cauterized. A recurrence rate of 40% was noted in patients having partially resected tumors. These recurrence rates have remained remarkably consistent in more recent reports. 10.33 Recent surgical series reported the successful removal of basal meningiomas, using extensive surgical exposures and advances in microsurgical techniques. '73~' 32,38-42Complete tumor resection was achieved in 26% to 81% of patients in some reports. 3~,3~39,4~,42 In such patients, the occurrence of new postoperative cranial neuropathies has varied between 23% and 46%. 31'~s-4~ Encouraging results with new skull-base surgical techniques have enabled increasing numbers of patients with difficult tumors to be treated with less morbidity. 556
Perioperative morbidity has been especially high in elderly patients and in those with large tumors. Awad, et al., 2 and Djindjian, et al., j3 recently reported the results of meningioma surgery, in elderly patients (aged > 60 years and > 70 years, respectively). Djindjian, et al., reported a 23% surgical mortality, while Awad, et a{, reported a morbidity rate of 52% in a subgroup of patients over the age of 70 years. The worst surgical outcomes occurred in patients with basal and infratentorial tumors. Thus, for patients whose advanced age or medical condition might mitigate against craniotomy, we believe that radiosurgery offers a promising treatment alternative. Fractionated Radiation Therapy as A d j u v a n t Treatment
The management of patients with residual or recurrent meningiomas has remained problematic. One option was to conduct close clinical observation and serial imaging studies until tumor growth made surgery necessary. Another option was to administer fractionated external beam radiation therapy in an attempt to control tumor growth. Although the role of fractionated radiotherapy in the treatment of meningiomas has been controversial, several recent series have reported its benefit in s o m e p a t i e n t s . 4'9"18'37"45"4vCarella, et al., 9 reported 68 patients with recurrent tumor, 43 of whom were treated with surgery plus fractionated radiotherapy (dose 5000 to 7459 cGy). Those authors concluded that radiotherapy had an established role for incompletely excised, recurrent or malignant meningiomas and, in some cases, in the initial management. Barbaro, et aL, 4 reported a recurrence rate for subtotally excised tumors of 60% (without radiotherapy) and 32% (with radiotherapy). The mean time to recurrence was extended from 66 to 125 months with radiotherapy. These results sharply contrast with other reports that failed to show J. Neurosurg. / Volume 74/April, 1991
Stereotactic radiosurgery of meningiomas any benefit from fractionated radiotherapy eilher in preventing or controlling recurrence, t ~
Stereotactic radiosurgery of meningiomas DOUGLAS KONDZIOLKA, M.D., L. DADE LUNSFORD, M.D., ROBERT J. COFFEY, M.D., AND JOHN" C. FLICK1NGER, M.D.
Departments of Neurological Surgery, Radiation Oncology, and Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania ~" Stereotactic radiosurgery has an expanding role in the management of selected intracranial tumors. In an initial 30-month experience using the 201-source cobalt-60 gamma knife at the University of Pittsburgh, 50 patients with meningiomas were treated. The most frequent site of origin was the skull base. Previously, 36 patients (72%) had undergone at least one craniotomy and four patients (8%) had received fractionated external beam radiation therapy. Stereotactic radiosurgery was the primary treatment modality in 16 patients (32%) with symptomatic tumors demonstrated by neuroimaging. Computer imaging-generated isodose plans (with one to five irradiation isocenters) for singje-treatment irradiation gave optimal (_> 50% isodose line) coverage in 44 patients (88%). The proximity of cranial nerves or vascular, pituitary, and brain-stem structures to the often convoluted tumor mass was crucial to dose selection. Serial imaging studies were evaluated in all 50 patients. Twenty-four patients were examined between 12 and 36 months after treatment; 13 (54%) showed a reduction in tumor volume while nine (38%) showed no change. Of 26 patients evaluated between 6 and 12 months after treatment, four showed a decrease in tumor size while 22 showed no change. Two patients (both with large tumors that received suboptimal irradiation) had delayed tumor growth outside the radiosurgical treatment volume. The actuarial 2-year tumor growth control rate was 96%. Between 3 and 12 months after radiosurgery, three patients developed delayed neurological deficits that gradually improved, compatible with delayed radiation injury. Although extended follow-up monitoring over many years will be necessary to fully evaluate treatment, to date stereotactic radiosurgery has proved to be a relatively safe and effective therapy for selected patients with symptomatic meningiomas, including those who failed surgical resection. Radiosurgery was an effective primary treatment alternative for those patients whose advanced age, medical condition, or high-risk tumor location mitigated against surgical resection. KEY WORDS cavernous sinus '
stereotactic radiosurgery skull base
URGERY is the preferred treatment of meningiomas, and long-term disease-free survival can be achieved with surgical resection of the tumor and its associated dural base) 5'78'~~ Despite recent advances in microsurgical techniques, some meningiomas recur. Although many basal meningiomas can be resected completely from their dural attachment, such surgery frequently is associated with the undesirable development of new neurological deficits. 17,31.38As a result, in order to preserve neurological function, surgeons often perform incomplete resections. Some patients with meningiomas are considered unsuitable for surgery if they are elderly or are "medically unit. ''2'13 Single-fraction precisely guided multiple photon-beam irradiation (stereotactic radiosurgery) offers treatment to such patients: those with tumors in highrisk locations; those with residual meningiomas after surgical resection; and those whose advanced age or
S
552
.
meningioma
9 brain tumor
associated medical illness pose unacceptable risks for surgical removal. This report is the first comprehensive clinical analysis of stereotactic radiosurgery performed in patients with meningiomas. We present our management strategies and initial results, and conclude that radiosurgery is an effective primary and important adjuvant treatment in the management of selected meningiomas. Clinical Material and Methods Between August, 1987, and January, 1990, 50 patients (36 women and 14 men) underwent treatment of their meningiomas with the 201-source cobalt-60 gamma knife.* All patients selected for radiosurgery
* Gamma knife manufactured by Elekta instruments, Tucker, Georgia. J. Neurosurg. / Volume 74/April, 1991
Stereotactic radiosurgery of meningiomas had a well-circumscribed intracranial tumor with imaging findings characteristic of a meningioma. Contrastenhanced computerized tomography (CT) or magnetic resonance (MR) imaging revealed a well-demarcated dura-based mass. Diagnostic angiography in selected patients showed a blood supply typically associated with meningiomas. Thirty-six patients (72%) had undergone at least one prior surgical procedure; in two patients, craniotomy was performed but the tumor was neither resected nor biopsied because of its location in the cavernous sinus. One patient previously underwent resection of a meningioma in another location. Sixteen patients had received radiosurgery for a tumor defined by clinical and imaging criteria as a meningioma. Four patients previously received fractionated external beam radiation therapy (46 to 50 Gy) after subtotal surgical resections. Patients were not accepted for radiosurgery if the lesion was too large (> 35 m m in average diameter), was within 5 m m of the optic chiasm, or was amenable to open microsurgical resection with acceptable risk. The clinical characteristics of the 50 patients appear in Table 1. The mean age of our 36 female patients was 56.6 years (range 37 to 82 years) and of our 14 male patients was 50.5 years (range 14 to 71 years). The median Karnofsky Performance Scale score was 90 (range 60 to 100). In all patients the Leksell Model G stereotactic coordinate framer was applied and all underwent imaging and treatment under local anesthesia supplemented by intravenous sedation. Stereotactic CT scans were performed in order to define tumor boundaries and obtain target coordinates. In selected cases, stereotactic M R imaging was used in addition to CT, especially for small lesions or those located near the optic pathways. Computer-dose planning was performed on a high-speed Microvax system.:~ The treatment isodose, central dose, and dose to the margin were determined by the neurosurgeon, the radiation oncologist, and the radiation physicist. Selection of dose was based on prior experience in the radiosurgical treatment of arteriovenous malformations and other brain tumors and on the location and size of the lesion. ~5~626 Patients received a single dose of methylprednisolone (40 mg intravenously) immediately after radiosurgery. In the preoperative period, therapeutic anti-convulsant levels were achieved in patients with supratentorial brain tumors. All patients were discharged from the hospital on the day after treatment. Follow-up imaging studies (CT or M R imaging) were scheduled at 3, 6, and 12 months after radiosurgery, and at 6-month intervals thereafter. For patients who lived a long distance from Pittsburgh, clinical and ira-
t Stereotactic coordinate frame, Model G, manufactured by Elekta Instruments, Tucker, Georgia. Microvax manufactured by Digital Equipment Corp., Westminster, Massachusetts.
J. Neurosurg. / Volume 74/April, 1991
TABLE 1 Clinical characteristics of 50 palients with meningiomas Characteristic
No. of Cases
sex (F:M) location cavernous sinus parasellarregion petrous apex tentorium cerebellopontineangle tuberculum sellae confluence of falx & tentorium
36:14 13 6 6 5 5 3 3
clivus
2
parasagittalregion lateral ventricle jugular foramen olfactorygroove sphenoid ridge torcular herophili
2 1 1 1 1 1
aging follow-up monitoring was sometimes provided by the referring physicians. Results
Radiation Dosimetry The radiation dosimetry in this series of 50 patients is presented in Table 2. The meningiomas were treated
TABLE 2 Radiosurgical dosimetry in 50 patients RadiosurgicalDosimetry No. of Cases tumor volume(cu ram)* < 1000 8 1000-5000 19 5000-10,000 16 10,000-20,000 4 > 20,000 3 marginal treatment isodose(%) 20t I 40 5 50 38 60 3 70 2 80 1 radiation dose to tumor margin (Gy) 10 2 12 1 13 4 14 4 15 6 16 4 17 5 18 7 20 16 25 1 * Tumor volume is estimated using 4/3rr 3, where r = radius (estimatedas 89 the tumor mean diameter (d), where d = ~Yx.y.z (x, y, z = maximum tumor dimensionsin three planes)). "~Tumor volume = 25,594 cu mm (consideredsuboptimal treatment) in a patient who was resistant to blood transfusion due to religiousbeliefs. 553
D. Kondziolka, el al.
FIG. 2. Scattergram of marginal dose (Gy) versus volume (cu ram) for 50 patients, with complications indicated by triangles. A secondary y axis indicates the diameter (mm) for a sphere of equivalent volume. The solid line represents a relatively linear portion of an isoeffect curve derived from the integrated logistic equation ~5 for a 3% risk of permanent symptomatic brain injury from gamma knife radiosurgery. FIG. 1. Magnetic resonance (T~-weighted spin-echo) image with gadolinium-DTPA enhancement showing a left cavernous sinus meningioma at radiosurgcry. Three isocenters of irradiation were used to construct the isodosc plan (maximum dose 30 Gy).
TABLE 3 Imaging evaluation after radiosurgery in 50 patients* Tumor Size
with single irradiation isocenters in nine cases and multiple irradiation isocenters in 41 (Fig. 1). Five isocenters of irradiation were used in four patients, and four isocenters were used in another four. Forty-four patients (88%) were treated at the 50% isodose line or greater, to take advantage of the sharp fall-off of the radiation field outside the target volume. 4~ The mean dose delivered to the tumor margin was 16.98 Gy (range 10 to 25 Gy). A scatterplot of tumor volume versus dose to the margin for all 50 tumors is presented in Fig. 2. Selection of treatment dose was based on tumor size and location (especially proximity to crucial vascular, cranial nerve, brain-stem, and pituitary structures) and on previously administered fractioned conventional irradiation dose (if any). For tumors in the region of the optic apparatus, we kept the dose to the chiasm below 9 Gy.
Imaging Evaluation All 50 patients were evaluated between 6 and 34 months after radiosurgery (Table 3). The actuarial 2year tumor growth control rate was 96%, according to the calculation method of Berkson and Gage. 6 In the group of 24 patients who were followed for 12 to 36 months after treatment, 13 patients (54%) showed a decrease in tumor size; eight showed loss of central contrast enhancement on CT or M R imaging consistent with intratumor necrosis. Nine patients (38%) showed 554
Time Posttreatment(mos)
6-12 12-24 24-36 decreased 4 (2) 7 (5) 6 (3) no change 22 (2) 6 (1) 3 increased 0 2t 0 * Imaging evaluation was with contrast-enhanced computerized tomography or magneticresonance imaging. Number in parentheses represents the number of patients with loss of central contrast enhancement. t Both patients had suboptimal treatment because of tumor size and/or local tumor invasion.
no change in tumor size and only one showed loss of central contrast enhancement. Two patients had growth of the tumor outside the radiosurgical treatment volume: both of these patients had tumors that we believe were treated subtotally. The first patient had a recurrent invasive malignant torcular meningioma and had undergone three prior operations and conventional radiation therapy. The second patient had a large upper clivus and cavernous sinus region tumor that had recurred after multiple craniotomies. Both patients were treated ineffectively by radiosurgery because of the excessive size and lack of well-demarcated borders of their tumors. Twenty-six patients had follow-up imaging studies 6 to 12 months after radiosurgery; four showed a decrease in tumor size (Fig. 3). Two of these four patients had loss of central contrast enhancement that was recognized as early as 3 months after treatment. Twenty-two patients showed no change in tumor size, with two
J. Neurosurg. / Volume 74/April, I991
Stereotactic radiosurgery of meningiornas
FIG. 3. Magnetic resonance (Trweighted spin-echo) images with gadolinium-DPTA enhancement. A: A large falx meningioma is seen prior to radiosurgery. B: At I month postradiosurgery, the tumor is slightly smaller. C: At 6 months postradiosurgery, the tumor is markedly smaller and the surrounding brain structures appear normal.
TABLE 4 Clinical evaluation after radiosurgep3' in 50 patients Neurological
Time Posttreatment(mos)
Findings
6-12
12-24
24-36
unchanged improved new deficit died*
21 1 l 1
l0 4 1 l
9 0 l 0
* One patient died due to glomerulonephritisand one due to seizure (see text).
showing loss of central contrast enhancement. No patient had evidence of tumor growth during this interval. Clinical Outcome Clinical follow-up evaluation was available for all 50 patients (Table 4). Twenty-six patients were evaluated 12 to 36 months after radiosurgery; 19 remained clinically stable without evidence of any new neurological deficit, and four patients improved. Of the 24 patients evaluated between 6 and 12 months after treatment, 21 remained in stable neurological condition after radiosurgery; one additional patient had neurological improvement. Two patients died during the follow-up period. A 72-year-old man with a parasellar meningioma died 6 months after radiosurgery due to lung carcinoma and glomerulonephritis. He had remained in stable neurological condition. The second patient was a 66-year-old woman who had growth of a recurrent cavernous sinus tumor after treatment. She died of respiratory, complications after a seizure. Complications No immediate postoperative complications or perioperative seizures occurred. Mild headache associated with application of the stereotactic frame was relieved by oral analgesics. Since all patients left the hospital within 24 hours after radiosurgery, the duration of J. Neurosurg. / Volume 74/April, 1991
hospitalization in these patients was only 36 to 48 hours. Three patients developed temporary new neurological deficits 389 12, and 12 months after radiosurgery (actuarial risk 6.9% at 1 and 2 years). ~ The first patient was a 47-year-old woman with a petrous apex meningioma (tumor size 19 x 20 x 28 mm; 20 Gy was administered to the 50% isodose line). She developed trigeminal hypesthesia and contralateral weakness 12 months after radiosurgery and improved over the next 7 months. An MR image obtained 12 months after treatment showed a rim of gadolinium enhancement in the lateral brain stem adjacent to the tumor. This subsequently resolved over 6 months (Fig. 4). However, 24 months after radiosurgery, she developed a sixth nerve palsy, which had fully resolved at 36 months posttreatment. The second patient was an 80-year-old woman with a tentorial meningioma (tumor size 17 x 35 x 23 ram; 18 Gy was administered to the 50% isodose line, Fig. 5). Tumor shrinkage and loss of contrast enhancement were seen on a CT scan 6 months after treatment; however, 12 months after radiosurgery, she developed contralateral hemiparesis that responded to a brief course of oral corticosteroids. The third patient, who had a large (20 x 42 x 24-ram) residual petroclival meningioma, with multiple cranial neuropathies and hemiparesis, developed a fight third nerve palsy 389 months after treatment. A C T scan showed areas of low attenuation surrounding the tumor, consistent with edema. The tumor had not changed in size; his condition remains unchanged 7 months after treatment.
Discussion Surgical Resection as Primary Therapy Surgical excision of meningiomas along with their dural base provides long-term tumor control in many patients. ~,5."~,3~ Simpson 43 analyzed the results of surgery in 242 meningioma patients followed over a 16-year period. He reported a 9% recurrence rate for fififi
D. Kondziolka, et al.
FIG. 4. a: Computerized tomography scan with contrast enhancement obtained at the time of radiosurgery showing the left petrous apex meningioma, treated at the 50% isodose margin (arr(mg. Three isocenters of irradiation were used with a marginal dose of 20 Gy. b and c: Magnetic resonance (Trweighted spin-echo) images with gadolinium-DTPA enhancement. At 14 months after surgery (b), the tumor remains unchanged in size and there is an area of enhancement within the ventrolateral brain stem (arrows) adjacent to the tumor. This region was included in the 20% isodose margin (calculated dose 8 Gy). At 20 months posttreatment (c), the region of brain-stem enhancement has resolved and the tumor remains unchanged in size.
FIG. 5. Left: Computerized tomography scan with contrast enhancement showing a left tentorial meningioma treated at the 50% isodose line (two isocenters of irradiation; marginal dose 18 Gy). Right; Magnetic resonance (TIweighted spin-echo) image with gadolinium-DTPA enhancement showing a marked decrease in tumor size at 10 months after radiosurgery.
tumors completely resected along with their dural attachment; a 19% recurrence rate was calculated if the tumor was resected completely and the adjacent dura was cauterized. A recurrence rate of 40% was noted in patients having partially resected tumors. These recurrence rates have remained remarkably consistent in more recent reports. 10.33 Recent surgical series reported the successful removal of basal meningiomas, using extensive surgical exposures and advances in microsurgical techniques. '73~' 32,38-42Complete tumor resection was achieved in 26% to 81% of patients in some reports. 3~,3~39,4~,42 In such patients, the occurrence of new postoperative cranial neuropathies has varied between 23% and 46%. 31'~s-4~ Encouraging results with new skull-base surgical techniques have enabled increasing numbers of patients with difficult tumors to be treated with less morbidity. 556
Perioperative morbidity has been especially high in elderly patients and in those with large tumors. Awad, et al., 2 and Djindjian, et al., j3 recently reported the results of meningioma surgery, in elderly patients (aged > 60 years and > 70 years, respectively). Djindjian, et al., reported a 23% surgical mortality, while Awad, et a{, reported a morbidity rate of 52% in a subgroup of patients over the age of 70 years. The worst surgical outcomes occurred in patients with basal and infratentorial tumors. Thus, for patients whose advanced age or medical condition might mitigate against craniotomy, we believe that radiosurgery offers a promising treatment alternative. Fractionated Radiation Therapy as A d j u v a n t Treatment
The management of patients with residual or recurrent meningiomas has remained problematic. One option was to conduct close clinical observation and serial imaging studies until tumor growth made surgery necessary. Another option was to administer fractionated external beam radiation therapy in an attempt to control tumor growth. Although the role of fractionated radiotherapy in the treatment of meningiomas has been controversial, several recent series have reported its benefit in s o m e p a t i e n t s . 4'9"18'37"45"4vCarella, et al., 9 reported 68 patients with recurrent tumor, 43 of whom were treated with surgery plus fractionated radiotherapy (dose 5000 to 7459 cGy). Those authors concluded that radiotherapy had an established role for incompletely excised, recurrent or malignant meningiomas and, in some cases, in the initial management. Barbaro, et aL, 4 reported a recurrence rate for subtotally excised tumors of 60% (without radiotherapy) and 32% (with radiotherapy). The mean time to recurrence was extended from 66 to 125 months with radiotherapy. These results sharply contrast with other reports that failed to show J. Neurosurg. / Volume 74/April, 1991
Stereotactic radiosurgery of meningiomas any benefit from fractionated radiotherapy eilher in preventing or controlling recurrence, t ~
