Meningiomas are among the most common intracranial tumors in adults. The mainstay of treatment has been extirpation. Stereotactic radiosurgery (SRS) is an important option in the management of inaccessible, recurrent, or residual benign meningiomas. Image guidance and a steep dose fall off are critical features. SRS offers durable tumor control for grade I meningiomas with a low incidence of complications or neurologic deficits. Neurologic function is generally preserved or improved. Complications are relatively rare. For many, the risk to benefit ratio seems favorable compared with treatment alternatives. We present a short review of the literature on SRS for intracranial meningiomas.
Key points
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Stereotactic radiosurgery (SRS) is an important treatment option in the management meningiomas and can be used as upfront or adjuvant treatment modality.
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SRS seems to afford a high and durable rate of tumor control with a very low complication rate and a high safety profile.
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Complications resulting from radiosurgery are relatively rare, and they are typically manageable and temporary.
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For many patients with meningiomas, the risk to benefit ratio profile seems favorable compared with the treatment alternatives of radical resection or tumor progression.
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Multicenter-driven, evidence-based, objective outcome evaluations and international consortium efforts promise to continue improving and advance better patients care.
Introduction
Meningioma Classification and Epidemiology
Meningiomas are among the most common intracranial tumors in adults. These tumors are thought to originate from the arachnoidal cap cells, forming the outer layer of the arachnoid membrane villi (the latter facilitates cerebrospinal fluid drainage into the dural sinuses and veins). Intracranial meningiomas account for 24% to 33% of primary brain tumors and have an incidence of approximately 6 in 100,000, but they can be discovered incidentally on neuroimaging for other concerns, or at autopsy. In the absence of genetic or environmental risk factors, the incidence of meningiomas increases with age, occurring primarily in the sixth to eighth decades of life. Meningiomas are histologically characterized as benign, atypical, or malignant (also known as anaplastic) by the 3-tiered World Health Organization (WHO) classification scheme. Most meningiomas are benign (ie, WHO grade I), slow-growing tumors. WHO grade I meningiomas are discussed much more frequently in the literature owing to their high incidence and the long-term patient survival associated with contemporary management strategies.
The WHO scheme has been revised dramatically in recent years, including a major revision in 2000. The latest update from 2007 resulted in the redistribution of many meningiomas into different classes. According to previous classification schemes, approximately 90% of meningiomas were classified as benign, 5% to 7% as atypical, and 3% to 5% as malignant. In the current pathologic classification, approximately 35% of all meningiomas are atypical (WHO grade II) or malignant (WHO grade III). WHO grade II and III meningiomas behave very differently and quite often exhibit an aggressive course accompanied by recurrence, invasion, and even distant metastasis. The 5- and 10-year overall survival rates for all meningioma patients are high at 82% and 64%, respectively, but the prognosis for aggressive, higher grade meningiomas is much worse. The 5- and 10-year survival rates for patients with aggressive meningiomas are 65% and 51%, respectively. Grades II and III tumors are more likely to recur and are associated with worse overall survival ( Tables 1 and 2 ).
| Location | Author, Year | No. of Patients | Median Tumor Volume (mL) | Median Follow-Up | Patients with >10 y Assessment, n (%) | Actuarial Local Control (%) | Actuarial PFS, n (%) | Morbidity/Complications (%) | |
|---|---|---|---|---|---|---|---|---|---|
| 5 y | 10 y | ||||||||
| All | Kondziolka et al, 2014 | 290 | 5.5 | 56 | 29 (10) | — | 87.7 | 80.3 | 17.9 |
| Santacroce et al, 2012 | 4565 | 4.8 | 63 | 8.4 | 92.6 | 82 | 95.2 (5 y), 88.6 (10 y) | 6.6 | |
| Pollock et al, 2012 | 416 | 7.3 | 60 | 17 | 96 | 89 | 97 (5 y), 94 (10 y) | 11 | |
| Zada et al, 2010 | 116 | 3.4 | 75 | — | 98.9 | 84 | 94 (10 y) | 8 | |
| Kondziolka et al, 2008 | 972 | 7.4 mean | 48 mean | 7.7 | — | 91, 95 | — | 7.7 | |
| Kollova et al, 2007 | 325 | 4.4 | 60 | NR | 97.9 | 90 | — | 5.7 | |
| Dibiase et al, 2004 | 121 | 4.5 | 54 | NR | 86.2 | — | 86.2 (5 y) | 8.3 | |
| Stafford et al, 2001 | 168 | — | 40 | NR | 93 | — | — | 13 | |
| Convexity | Kondziolka et al, 2009 | 115 | 7 | 31 | NR | 95.3 | — | — | 9.6 |
| Pamir et al, 2007 | 43 | — | 46 | NR | 89 | — | — | — | |
| Kim et al, 2005 | 26 | 4.7 | 33 mean | NR | 96 | — | — | — | |
| Skull base | Cohen-Inbar et al, 2015 | 135 | 4.7 | 102.5 | 37 | 100 | 88.1 | 95.4 (10 y) | 14.8 |
| Iwai et al, 2008 | 108 | 8.1 | 86.1 | 23 | — | 83 | 83 (10 y) | 6 | |
| Kreil et al, 2005 | 200 | 6.5 | 95 | — | 98.5 | 97 | 97.2 (10 y) | 2.5 | |
| Parasellar | Williams et al, 2011 | 138 | 7.5 | 76 | 16 | 95.4 | — | 69 (10 y) | 10 |
| Skeie et al, 2010 | 100 | — | 82 mean | 20 | 94.2 | 91.6 | — | 6 | |
| Hasegawa et al, 2007 | 115 | 14 | 62 | 9 | 94 | 92 | 73.5 (10 y) | 12 | |
| Nicolato et al, 2001 | 122 | 8.3 | 49 | — | 96.5 | — | 96.5 (5 y) | 4 | |
| Lee et al, 2002 | 159 | 6.45 mean | 39 | — | 96.9 | 93 | 93.1 (10 y) | 6.9 | |
| FM | Starke et al, 2010 | 5 | 6.8 | 72 | — | 80 | — | — | 0 |
| Author, Year | WHO Grade | Patient Number | Control Rate | PFS | Overall Survival |
|---|---|---|---|---|---|
| Ojemann et al, 2000 | 3 | 19 (31) | — | 26% at 5 y | 40% at 5 y |
| Stafford et al, 2001 | 2 | 13 | 68% at 5 y | — | 76% at 5 y a |
| 3 | 9 | 0% at 5 y | 0% at 5 y a | ||
| Harris et al, 2003 | 2 | 18 | — | 83% at 5 y | 59% at 5, 10 y |
| 3 | 12 | 72% at 5 y | 59% at 5 y, 0% at 10 y | ||
| Huffmann et al, 2005 | 2 | 15 (21) | 93% at 6 mo | — | 100% at 35 mo |
| Kondziolka et al, 2008 | 2 | 54 | 50% at 2 y | — | — |
| 3 | 29 | 17% at 15 mo | |||
| Attia et al, 2012 | 2 | 24 | 75% at 1 y 51% at 2 y 44% at 5 y | 40% at 2 y, 25% at 5 y | 92% at 1 y, 67% at 2 y, 52% at 5 y |
| Mori et al, 2013 | 2 | 19 (22) | 74% at 1 y | — | — |
| 3 | 4 | 54% at 2 y 34% at 3 y | |||
| Tamura et al, 2013 | 2 | 9 | 29% at 40.5 mo | — | — |
| 3 | 7 | ||||
| Ferraro et al, 2014 | 2 | 31 | — | 95.7% at 1 y, 70.1% at 3 y | 92.4% at 1 y, 83.4% at 3 y |
| 3 | 4 | 0% at 1, 3 y | 33% at 1, 3 y |
Brief Overview of Resection
Microsurgical resection has traditionally been regarded as the treatment of choice for meningiomas, still playing a significant role in the management of many patients. Resection offers several advantages, including a histologic confirmation of the tumor features, relief of compression and mass effect imposed on neurovascular structures, and, in the instance of gross total resection, the chance of a cure. Control rates after resection vary depending on the extent of resection; this observation was first described by Simpson in 1957. Simpson reported that after a complete resection (ie, excision of tumor, its dural attachment and any abnormal bone, later defined as Simpson grade I), tumor recurrences at 5, 10, and 15 years are 5%, 10%, and 30%, respectively. Since this landmark report, more recent studies reported a wide range of tumor control, progression-free survival, and recurrence rates, mirroring at least in part the evolving technology and surgical skills. A literature review of major surgical resection series for meningiomas is presented in Tables 1 and 2 .
Despite tremendous advances in neurosurgical technique and equipment, postoperative morbidity continues to taint open complete removal of many cranial base tumors, with an incidence of temporary and permanent postoperative cranial nerve deficits as high as 44% and 56%, respectively. Operative mortality rates in some series was reported to be as high as 9% (median, 3.6%). Thus, the advantage of a radical tumor resection must be weighed against the associated surgical morbidity. Subtotal resections may be required for meningiomas that involve major draining veins or cranial nerves. Lesions adjacent to critical neurovascular structures, especially skull base meningiomas, often do not allow for a safe complete resection, which can lead to lower local control and increased risk of tumor progression or recurrence. Resection carries the added risk of surgery-related morbidity. In such instances, where a complete resection is not prudent or feasible, a cytoreductive or “near total” resection may be advantageous to relieve mass effect and decrease the remaining target volume for radiosurgery (later termed the adaptive hybrid surgery approach).
The need for a Simpson grade I/II resection has been repeatedly called into question in modern times for patients with WHO grade I meningiomas. Some reports state no significant difference in recurrence-free survival between patients undergoing a Simpson grade I, II, III, or IV resection. Given the option of adjuvant treatment (eg, stereotactic radiosurgery [SRS]) for small residual or recurrent WHO grade I meningiomas, a gross total or near total resection may not be as important to progression-free survival as when Simpson’s work was published in 1957.
The Evolution of Radiosurgery
Since its inception more than 60 years ago, SRS techniques and technology have evolved significantly, but its fundamental principles remain unchanged. In 2006, the American College of Radiology and the American Society for Radiation Oncology published practice guidelines for the performance of SRS. A multidisciplinary, collaborative effort among neurosurgeons, radiation oncologists, and medical physicists was recommended to optimize the quality and operational efficiency of successful SRS. A subsequent publication put forth in 2007 by the SRS Task Force (a joint committee of the American Association of Neurologic Surgeons and the Congress of Neurologic Surgeons), in conjunction with the American Society for Radiation Oncology, distinguished between SRS and fractionated stereotactic radiotherapy. This same joint task force, further defined SRS to be “typically performed in a single session, using a rigidly attached stereotactic guiding device, other immobilization technology and/or a stereotactic imaging guidance system, but can be performed in a limited number of sessions, up to a maximum of five.’’
The ionizing radiation used in SRS is most commonly either gamma radiation (usually emitted by the radioactive Cobalt [Co] isotope 60) or accelerated electrons from linear accelerators (LINAC). Modern SRS systems include the gamma knife (Elekta AB, Stockholm, Sweden), Cyberknife (Accuray, Sunnyvale, CA), Edge (Varian Medical Systems, Palo Alto, CA), Novalis (Brainlab AG, Feldkirchen, Germany), and Infini (MASEP, City of Industry, CA) to name a few.
Introduction
Meningioma Classification and Epidemiology
Meningiomas are among the most common intracranial tumors in adults. These tumors are thought to originate from the arachnoidal cap cells, forming the outer layer of the arachnoid membrane villi (the latter facilitates cerebrospinal fluid drainage into the dural sinuses and veins). Intracranial meningiomas account for 24% to 33% of primary brain tumors and have an incidence of approximately 6 in 100,000, but they can be discovered incidentally on neuroimaging for other concerns, or at autopsy. In the absence of genetic or environmental risk factors, the incidence of meningiomas increases with age, occurring primarily in the sixth to eighth decades of life. Meningiomas are histologically characterized as benign, atypical, or malignant (also known as anaplastic) by the 3-tiered World Health Organization (WHO) classification scheme. Most meningiomas are benign (ie, WHO grade I), slow-growing tumors. WHO grade I meningiomas are discussed much more frequently in the literature owing to their high incidence and the long-term patient survival associated with contemporary management strategies.
The WHO scheme has been revised dramatically in recent years, including a major revision in 2000. The latest update from 2007 resulted in the redistribution of many meningiomas into different classes. According to previous classification schemes, approximately 90% of meningiomas were classified as benign, 5% to 7% as atypical, and 3% to 5% as malignant. In the current pathologic classification, approximately 35% of all meningiomas are atypical (WHO grade II) or malignant (WHO grade III). WHO grade II and III meningiomas behave very differently and quite often exhibit an aggressive course accompanied by recurrence, invasion, and even distant metastasis. The 5- and 10-year overall survival rates for all meningioma patients are high at 82% and 64%, respectively, but the prognosis for aggressive, higher grade meningiomas is much worse. The 5- and 10-year survival rates for patients with aggressive meningiomas are 65% and 51%, respectively. Grades II and III tumors are more likely to recur and are associated with worse overall survival ( Tables 1 and 2 ).
| Location | Author, Year | No. of Patients | Median Tumor Volume (mL) | Median Follow-Up | Patients with >10 y Assessment, n (%) | Actuarial Local Control (%) | Actuarial PFS, n (%) | Morbidity/Complications (%) | |
|---|---|---|---|---|---|---|---|---|---|
| 5 y | 10 y | ||||||||
| All | Kondziolka et al, 2014 | 290 | 5.5 | 56 | 29 (10) | — | 87.7 | 80.3 | 17.9 |
| Santacroce et al, 2012 | 4565 | 4.8 | 63 | 8.4 | 92.6 | 82 | 95.2 (5 y), 88.6 (10 y) | 6.6 | |
| Pollock et al, 2012 | 416 | 7.3 | 60 | 17 | 96 | 89 | 97 (5 y), 94 (10 y) | 11 | |
| Zada et al, 2010 | 116 | 3.4 | 75 | — | 98.9 | 84 | 94 (10 y) | 8 | |
| Kondziolka et al, 2008 | 972 | 7.4 mean | 48 mean | 7.7 | — | 91, 95 | — | 7.7 | |
| Kollova et al, 2007 | 325 | 4.4 | 60 | NR | 97.9 | 90 | — | 5.7 | |
| Dibiase et al, 2004 | 121 | 4.5 | 54 | NR | 86.2 | — | 86.2 (5 y) | 8.3 | |
| Stafford et al, 2001 | 168 | — | 40 | NR | 93 | — | — | 13 | |
| Convexity | Kondziolka et al, 2009 | 115 | 7 | 31 | NR | 95.3 | — | — | 9.6 |
| Pamir et al, 2007 | 43 | — | 46 | NR | 89 | — | — | — | |
| Kim et al, 2005 | 26 | 4.7 | 33 mean | NR | 96 | — | — | — | |
| Skull base | Cohen-Inbar et al, 2015 | 135 | 4.7 | 102.5 | 37 | 100 | 88.1 | 95.4 (10 y) | 14.8 |
| Iwai et al, 2008 | 108 | 8.1 | 86.1 | 23 | — | 83 | 83 (10 y) | 6 | |
| Kreil et al, 2005 | 200 | 6.5 | 95 | — | 98.5 | 97 | 97.2 (10 y) | 2.5 | |
| Parasellar | Williams et al, 2011 | 138 | 7.5 | 76 | 16 | 95.4 | — | 69 (10 y) | 10 |
| Skeie et al, 2010 | 100 | — | 82 mean | 20 | 94.2 | 91.6 | — | 6 | |
| Hasegawa et al, 2007 | 115 | 14 | 62 | 9 | 94 | 92 | 73.5 (10 y) | 12 | |
| Nicolato et al, 2001 | 122 | 8.3 | 49 | — | 96.5 | — | 96.5 (5 y) | 4 | |
| Lee et al, 2002 | 159 | 6.45 mean | 39 | — | 96.9 | 93 | 93.1 (10 y) | 6.9 | |
| FM | Starke et al, 2010 | 5 | 6.8 | 72 | — | 80 | — | — | 0 |
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