INTRODUCTION

Meningiomas account for approximately 20% of all intracranial tumors in males and 38% in females.¹ Although the primary treatment for intracranial meningioma is surgical removal when feasible, not all tumors are managed best by attempted resection. Increasingly, small, even asymptomatic meningiomas are detected incidentally in critical areas of the brain during an imaging evaluation. Observation with follow-up imaging may be an appropriate initial management for these patients. If tumor growth is documented by serial imaging or symptoms develop, many meningiomas can be treated effectively by radiosurgery, a minimally invasive option. In our experience, tumor growth can be documented in more than 80% of patients by the time ten years have passed in an observation strategy.

Surgical resection is the preferred treatment whenever total removal can be proposed with acceptable morbidity.² The ideal resection (Simpson grade 1) includes the entire tumor and all involved and hyperostotic bone. The remaining dural rim must be free of tumor. Large meningioma surgery series document that gross total resection was possible in 38% to 80% of patients, depending primarily on tumor location.^3–8 However, the intimate relationship between some meningiomas and critical neurovascular structures makes complete resection (with acceptable risk) impossible.^9,10 The challenges of operating on intracranial meningiomas include tumor location (critical sites), close association with important neurovascular structures, and infiltration of adjacent cranial nerves.

Progression or recurrence after initial resection is a concern with all types of intracranial meningiomas regardless of extent of resection. Even after gross total resection, tumor recurrence rates at 5 and 10 years have varied from 4% to 14% and from 18% to 25%, respectively.^3–8 The recurrence rate after total resection varies with histologic grade (12% for benign grade I,^11–14 52% for atypical grade II,¹⁵ and 84% for malignant grade III meningiomas^15,16). Studies have identified numerous factors associated with meningioma recurrence: tumor location, incomplete surgical resection, dissemination of tumor fragments, histologic classification as atypical or malignant, prominent nucleoli, more than two mitotic figures per 10 high-power fields, and heterogeneous contrast enhancement on computed tomography (CT).^8,17

The extent of surgical removal is very important. In 1957, Simpson² published a landmark paper that documented the direct correlation between the extent of meningioma resection and later clinical tumor recurrence (in an era without CT or magnetic resonance imaging [MRI]). With a follow-up interval extending more than 20 years, the rate of symptomatic clinical tumor recurrence was 9%, 19%, and 29% for patients with grade 1, 2, and 3 resection, respectively. Radical extirpation (Simpson grade 1) was strongly linked with prolonged survival. For patients with atypical or malignant meningiomas that are incompletely excised (Simpson grades 2–3), the prognosis is poor.¹⁵ In addition to factors related to tumor location, the molecular genetics, pathology, and cell kinetics of meningiomas may also influence recurrence. Cytogenetic studies have suggested that deletions of chromosomes 10, 14, 18, and 22 are associated with more atypical features and more aggressive clinical behavior in meningiomas.⁸ In addition to cytogenetic investigation, quantitative MIB-1 proliferation index labeling is useful for routine diagnostic assessment of meningiomas. This testing also provides information about prognosis, and therefore, helps in planning the most suitable treatment. High levels of MIB-1 (an indicator of Ki-67 expression) are thought to be strongly associated with tumor recurrence.^18–20

STEREOTACTIC RADIOSURGERY

Stereotactic radiosurgery (SRS) is now performed for an increasing number of patients with small to moderate-size meningiomas as an alternative to surgical excision.^21–32 Gamma Knife® radiosurgery is used as a first-line management or for postoperative adjuvant management. By 2006, 49,558 meningioma patients worldwide had undergone Gamma Knife radiosurgery management. Frequent indications include patients with skull-base meningiomas, especially those in the posterior fossa or cavernous sinus. Such tumors are not eligible for Simpson grade 1 resections.³³ The combination of microsurgery and SRS extends the therapeutic spectrum for meningioma patients. Small, sharply demarcated tumors are the best candidates for radiosurgery. SRS can be performed even after surgery and radiation therapy have failed.³⁴ Gamma Knife radiosurgery (GKRS) has proven an effective strategy for many patients with recurrent meningiomas.³⁵

In general, the biological nature of the meningioma is the main factor that determines how effectively radiosurgery will control tumor growth. Studies have shown that cases of atypical or malignant meningioma exhibit high rates of recurrence despite surgery, radiation therapy, and radiosurgery.^31,36 Younger age and smaller tumor size are associated with better tumor control after SRS.^37,38 In addition to being an attractive adjuvant treatment for some meningiomas, high tumor control rates and low morbidity indicated that SRS may provide better outcome than microsurgery.³⁹ To reduce morbidity, some surgeons recommend the combination of subtotal resection and subsequent SRS.^38,40

UNIVERSITY OF PITTSBURGH EXPERIENCE

Over a 20-year period, 972 patients with 1045 intracranial meningioma underwent Gamma Knife SRS at our institution. Six-hundred and ninety-one patients underwent radiosurgery for skull base meningiomas (Table 52-1). Detailed outcome analysis was performed for 982 available tumors. The mean patient age was 57 years. Five hundred and forty patients had no prior treatment. Patients who underwent prior surgeries usually had subtotal tumor removals. Multiple tumors were present in 161 patients and solitary tumors in 818 patients. Neurofibromatosis type 2 was diagnosed in 26 patients. There were 299 men (30%) and 683 women (70%). Men had a higher rate of atypical and malignant meningiomas. At the time of initial craniotomy 49 of 317 tumors in male patients (15.5%) were found to have World Health Organization (WHO) grade II or III. The incidence of atypical and malignant meningiomas in women was 5.2%. Other prior treatments included radiation therapy (54 patients), radiosurgery at another institution (2 patients), and chemotherapy (8 patients).

TABLE 52-1 Locations of 1045 intracranial meningiomas managed with Gamma Knife radiosurgery at the University of Pittsburgh

STEREOTACTIC IMAGING

Radiosurgery was performed using the Gamma Knife® (models U, B, C, 4C or Perfexion, Elekta Instruments, Atlanta, GA). Gamma Knife SRS is an outpatient surgical procedure performed in a single day. The procedure began with rigid fixation of an imaging (CT, MRI) compatible Leksell stereotactic frame (model G, Elekta Instruments, Atlanta, GA) to the patient’s head. Local anesthetic scalp infiltration (5% Marcaine and 1% Xylocaine) was supplemented by mild intravenous sedation. A 3-D volume acquisition MRI using a gradient pulse sequence (divided into 1 or 1.5 mm thick 28–36 axial slices) was performed to cover the entire lesion and surrounding critical structures. Stereotactic images were transferred via a fiberoptic ethernet to the GammaPlan® dose planning computer where images are first checked for any distortion or inaccuracy. Planning was performed on narrow slice thickness axial MR images with coronal and sagittal reconstructions.

DOSE PLANNING

Dose planning is one of the most critical aspects of radiosurgery. A 3-D conformal radiosurgery plan is necessary to reduce radiation fall off in adjacent critical structures (selectivity). Highlights of Gamma Knife meningioma radiosurgery planning include accurate 3-D delineation of tumor volume, use of multiple isocenters, beam weighting, and use of beam blocking patterns when appropriate to achieve selectivity (Figs. 52-1 and 52-2). Precise three-dimensional conformality between planned isodose volume and tumor volumes is needed to avoid radiation related complications.⁴¹ This degree of conformality can be achieved through complex multiisocenter planning. Meningioma dose planning at our center was usually performed using a combination of small beam diameters (4- and 8-mm) collimators. For large tumors, 14-mm collimators were also used. A series of 4 mm isocenters were used to create a tapered isodose plan to conform to the dural tail portion of the tumor. The mean tumor volume in our series was 7.4 cc. A mean of 7 isocenters were used to provide a conformal and selective radiosurgery.

FIGURE 52-1 A 74-year-old woman diagnosed with left petroclival meningioma. A, Her axial T1-weighted contrast-enhanced MR images showing radiosurgery target at the time of SRS. B, Axial T1-weighted contrast-enhanced MR images obtained 4 years after SRS showing regression of the enhancing lesion.

FIGURE 52-2 A 52-year-old woman diagnosed with right cavernous sinus meningioma. A, Her axial T1-weighted contrast-enhanced MR images showing radiosurgery target at the time of SRS. B, Axial T1-weighted contrast-enhanced MR images obtained 2 years after SRS showing regression of the enhancing lesion.

DOSE PRESCRIPTION