Ofall intracranial meningiomas, approximately 7%–12% are located in the posterior fossa.13,16,56Resection represents the upfront treatment for many patients with symptomatic or progressive posterior fossa meningiomas.50However, the extent of resection can be limited by the meningioma's proximity to critical vascular and neural structures. Gross-total resection rates reported in the literature for posterior fossa meningiomas vary significantly, from 40% to 96%, and resections are often associated with significant morbidity, mortality, and recurrence.1–5,7,9–12,15–17,20–22,24,27,28,31–33,36,38,41–43,45–48,51,54,56Extent of resection and morbidity rates vary by location of the tumor in the posterior fossa. For instance, in a recent study, morbidity following resection of petroclival meningiomas and cerebellopontine angle (CPA) meningiomas varied from 20.3% to 47% and 10.4% to 35.7%, respectively.14In that same study, extent of complete resection for petroclival meningiomas and CPA meningiomas was 0–48% and 82%–86.1%, respectively.14
Some neurosurgeons have recommended radical resection for recurrent meningiomas to prolong life in neurologically stable patients.5Others have advocated for aggressive maximal resection of meningiomas at first presentation with the use of radiosurgery to treat recurrent or residual meningiomas.8,11,26,60Stereotactic radiosurgery (SRS) has become an acceptable treatment option for recurrent/residual meningiomas as well as an upfront option.6,29,30
The use of Gamma Knife radiosurgery (GKRS; Elekta AB) for intracranial meningiomas had been previously described in the literature. However, there are few large series for which meaningful statistical analysis can be performed. The posterior fossa has unique anatomical concerns in terms of mass effect, and radiosurgical constraints that differ from supratentorial meningiomas. In the current study, we evaluated the outcomes of patients with posterior fossa meningiomas treated with GKRS across a multiinstitutional experience spanning more than two decades.
开云体育世界杯赔率
Patient Population
七个医疗中心参与朝鲜merican Gamma Knife Consortium obtained individual institutional review board approvals to participate in this study. A total of 675 patients were identified with posterior fossa meningiomas managed at least in part by GKRS (Table 1）.At each center, retrospective clinical outcome analysis of patients with posterior fossa meningiomas who underwent GKRS was performed. The following centers contributed data for this study: the University of Pittsburgh (271 patients), Yale University (9 patients), Cleveland Clinic (12 patients), University of Sherbrooke (64 patients), Barrow Neurological Institute (118 patients), University of Pennsylvania (44 patients), and the University of Virginia (157 patients).
Characteristics of 675 patients with posterior fossa meningiomas treated with GKRS
| Characteristic | Total |
|---|---|
| Female sex (%) | 535 (79.3) |
| Age (yrs) | |
| Median | 57.6 ± 13.4 |
| Range | 12–89 |
| Previous resection (%) | 292 (43.3) |
| Prior radiotherapy (%) | 11 (1.6) |
| Time from presentation to GKRS (mos) | |
| Mean ± SD | 28.8 ± 47.0 |
| Range | 0–324 |
| Initial presentation (%) | |
| Headache | 227 (33.6) |
| Subjective dizziness | 236 (35.0) |
| Subjective cognitive alteration | 41 (6.1) |
| CN III/IV/VI | 83 (13.1) |
| CN V | 224 (33.3) |
| CN VII | 54 (8.0) |
| CN VIII | 193 (28.6) |
| CN IX/X | 31 (4.6) |
| CN XI | 3 (2.4) |
| CN XII | 16 (2.4) |
| Cerebellar alteration/deficit | 27 (4.0) |
| Body weakness | 43 (6.4) |
| Change in body sensation | 53 (7.9) |
| Location (%) | |
| Clival | 48 (7.1) |
| Petroclival | 254 (37.6) |
| Petrous | 33 (4.9) |
| Tentorial | 145 (21.5) |
| Cerebellopontine angle | 177 (26.2) |
| Foramen magnum | 18 (2.7) |
| Tumor volume (cm3) | |
| Mean ± SD | 6.5 ± 6.2 |
| Range | 0.15–41.8 |
| Follow-up (mos) | |
| Mean ± SD | 60.1 ± 45.4 |
| Range | 6–252 |
The records of patients with meningioma who underwent GKRS between 1988 and 2012 were evaluated by clinicians at each center for study inclusion. A database with selected variables was created and sent to all participating centers. Participating centers reviewed the medical records of their patients, entered the data in the spreadsheet, and removed all patient identifiers from the database. Pooled and de-identified data were screened by an independent third party for errors. Any uncertainties or ambiguities in the data were addressed to the contributing center. Afterward, data were transmitted to the first author, who along with his coauthors developed this report.
患者纳入研究如果他们histologically diagnosed WHO Grade I meningioma located within the posterior fossa. In addition, patients were included in this study if they had clinical and neuroimaging features consistent with a benign meningioma of this neuroanatomical region. Clinical features would include a medical history absent of prior cancer and an intracranial tumor located in the posterior fossa with MRI and/or CT features most consistent with a meningioma. The neuroimaging features included an extraaxial location, contrast enhancement, dural attachment, and for some patients, tumor calcification. For inclusion, patients were required to have a minimum of 6 months of neuroimaging and clinical follow-up after GKRS.
Radiosurgical Technique
The Gamma Knife Models U, B, C, 4C, or Perfexion were used depending on the technology available at the time of treatment for the participating centers. The radiosurgery began with the application of the Leksell Model G stereotactic frame (Elekta AB) using local anesthetic supplemented by additional sedation as needed. After stereotactic frame placement, high-resolution stereotactic MRI was performed. In rare cases in which MRI was not feasible or when MRI distortion was a concern, a stereotactic CT scan was obtained. Thin-slice axial and/or coronal plane images were obtained after intravenous contrast administration. Radiosurgical dose planning was then performed by the neurosurgeon in conjunction with a radiation oncologist and medical physicist.
The mean volume of the posterior fossa meningiomas was 6.5 cm3(range 0.15–41.8 cm3;Table 1）.The median prescription dose delivered to the tumor margin was 13.6 Gy (range 8–40 Gy). The mean prescription isodose line was 48.5% (range 25%–65%;Table 2）.Most of the dose plans involved a multiisocentric approach; a mean of 11 isocenters (range 1–59) were used. Dose selection was based on an empirical algorithm that included considerations related to tumor volume, proximity to critical structures such as the brainstem, preexisting neurological deficits, and history of previous treatment with fractionated radiation therapy.
Gamma Knife radiosurgery parameters
| Characteristic | Value ± SD | Range |
|---|---|---|
| Median margin dose (Gy) | 13.6 ± 2.2 | 8–40 |
| Mean maximum dose (Gy) | 28.6 ± 5.6 | 12–80 |
| Mean isodose line (%) | 48.5 ± 5.3 | 25–65 |
| Mean no. of isocenters | 11.0 ± 7.4 | 1–59 |
Clinical and Neuroimaging Follow-Up
临床和神经影像学评估ly performed at follow-up intervals of 6 months for the first 2 years after radiosurgery. In patients who demonstrated no evidence of tumor growth and absence of new neurological findings, follow-up intervals were later increased to every 1–2 years. Whenever feasible, patients underwent follow-up neurological examination and neuroimaging at the respective treating center. However, because participating institutions represent tertiary referral centers, some patients underwent follow-up evaluations by their local physicians. For such patients, clinical notes and actual neuroimaging studies (i.e., not just the radiological reports) were received and reviewed by the treating clinicians who performed the GKRS. The follow-up images were compared with the images obtained at the time of GKRS. Tumor dimensions were assessed in the axial, sagittal, and coronal planes and compared with the comparable measurements on the Gamma Knife neuroimaging studies. Tumor growth, as defined by an increase in 1 of these measurements beyond the tomographic margin of uncertainty within the planned treatment volume or adjacent to it, was considered tumor progression.
Statistical Analysis
提出了数据值或均值和范围continuous variables, and as frequency and percentage for categorical variables. Calculations of normality were performed by ladder of powers and assessed graphically. Statistical analyses of categorical variables were performed using chi-square, Fisher's exact, and Mantel-Haenszel tests for linear association as appropriate. Statistics of means were conducted using the unpaired Student t-test, both with and without equal variance (Levene's test) as necessary and Wilcoxon rank-sum tests when variables were not normally distributed. The following dependent variables were assessed in univariate and multivariate analysis: tumor-free progression, worsening or new decline in neurological function, and favorable outcome (no tumor progression or worsening or new decline in neurological function). Kaplan-Meier risk of tumor progression was calculated. Factors predictive of tumor progression (p < 0.15) were entered into multivariate Cox regression analyses to assess hazard ratios (HRs). Clinical covariates predicting new or worsening neurological function with a univariate p value < 0.15 were included in multivariable logistic regression analyses. Additionally, clinical covariates predicting unfavorable outcome with a univariate p value < 0.15 were included in multivariable logistic regression analyses. Clinically significant variables and interaction expansion covariates were further assessed in both Cox and logistic multivariable analyses as deemed relevant. Those p values ≤ 0.05 were considered statistically significant.
Results
Patient and Tumor Attributes
Of the 675 patients, the median patient age was 57.6 years (range 12–89 years;Table 1）.There was a clear sex predilection in the series, with 535 (79.3%) female patients and only 140 (20.7%) male patients. Two hundred and ninety-two patients (43.3%) had previously undergone resection with histologically confirmed WHO Grade I meningiomas. The remaining patients displayed neuroimaging and clinical features consistent with a benign meningioma. Prior fractionated radiation therapy had been used in 1.6% of patients. The most common presenting symptoms were headaches and dizziness in 33.6% and 35% of patients, respectively. Deficits were observed most frequently in cranial nerves (CNs) V (33.3%) and VIII (28.6%).
Meningioma location was classified by the participating centers based upon the location of the majority (i.e., maximum volume) of the tumor. Locations were categorized based upon commonly used neuroanatomical regions of the skull base.2,3,5,27,55,59Meningioma locations included 7.1% clival, 37.6% petroclival, 4.9% petrous, 21.5% tentorial, 26.2% CPA, and 2.7% foramen magnum. Mean tumor volume was 6.5 cm3．Mean follow up was 60.1 months (range 6–252 months). Preradiosurgical patient characteristics, presentations, and tumor characteristics are detailed inTable 1．
Radiological Outcome
The mean follow-up duration was 60.1 ± 45.4 months (range 6–252 months). Following radiosurgery, tumor volume decreased by a mean of 1.6 cm3to a mean posttreatment volume of 4.9 ± 5.9 cm3(range 0–33 cm3;Table 3）.At the last follow-up evaluation, 59 patients (8.8%) had an increase in tumor size, 275 (41.0%) had a decrease in tumor size, and 336 (50.2%) displayed no change in tumor size. Thus, the overall rate of tumor control (i.e., stable or decreased tumor) was 91.2%.
Overall clinical and tumor outcomes
| Characteristic | Outcome |
|---|---|
| Pre-GKRS tumor volume (cm3) | |
| Mean ± SD | 6.5 ± 6.2 |
| Range | 0.15–41.8 |
| Post-GKRS tumor volume (cm3) | |
| Mean ± SD | 4.9 ± 5.9 |
| Range | 0–33 |
| Tumor volume (%) | |
| Decrease | 336 (50.2) |
| No change | 275 (41.0) |
| Increase | 59 (8.8) |
| Clinical outcome (%) | |
| No change | 424 (64.9) |
| Improvement | 179 (27.4) |
| New or worsening neurological function | 50 (7.7) |
| Overall outcome (%) | |
| Favorable | 557 (85.8) |
| Unfavorable | 92 (14.2) |
| Post-GKRS (%) | |
| 脑积水 | 14 (2.1) |
| Ventriculoperitoneal shunt placement | 11 (1.7) |
| Radiotherapy | 10 (1.5) |
| Resection | 24 (3.6) |
Kaplan-Meier analysis demonstrated radiological progression-free survival at 3, 5, 10, and 12 years to be 95%, 92%, 81%, and 77% respectively (Fig. 1）.Factors predictive of tumor progression in univariate analysis are displayed inTable 4．Patients with a history of prior resection were not more likely to have tumor progression (HR 1.10, 95% CI 0.65–1.85, p = 0.719;Fig. 2upper). Progression-free tumor survival according to mean volume is presented inFig. 2lower. There was no statistically significant difference in progression-free survival according to tumor location (Fig. 3）.
Kaplan-Meier plot of progression-free survival after SRS for all 675 patients with posterior fossa meningiomas. Numbers in parentheses represent the number of patients reaching each significant timeline milestone.
Kaplan-Meier plot of progression-free survival after SRS for patients with and without a prior resection(upper), and for patients with tumors < 6.5 cm3versus those with tumors ≥ 6.5 cm3(lower)．Numbers in parentheses represent the number of patients reaching each significant timeline milestone.
Kaplan-Meier plot of progression-free survival after SRS for meningiomas in a specific location in the posterior fossa. Figure is available in color online only.
Factors predictive of tumor progression in univariate and multivariate analyses*
| Analysis | Pre-GKRS Variables | HR (95% CI) | p Value |
|---|---|---|---|
| Univariate | |||
| Age >65 years | 1.95 (1.13–3.34) | 0.016 | |
| Increasing time from symptom onset | 1.01 (1.00–1.01) | 0.011 | |
| Prior radiotherapy | 6.87 (3.22–14.67) | <0.001 | |
| Increasing tumor volume | 1.04 (1.01–1.08) | 0.010 | |
| Multivariate | |||
| Age >65 years | 2.36 (1.30–4.29) | 0.005 | |
| Increasing tumor volume | 1.05 (1.01–1.08) | 0.005 | |
| Prior radiotherapy | 5.19 (1.69–15.94) | 0.004 |
肿瘤复发的预测因素(p < 0.15)。There was a trend toward increased tumor progression with increasing time from symptom onset in multivariate analysis (HR 1.01, 95% CI 1.00–1.01, p = 0.065).
In Cox multivariate analysis, pre-GKRS covariates predictive of tumor progression included age greater than 65 years (HR 2.36, 95% CI 1.30–4.29, p = 0.005), prior history of conventional radiotherapy (HR 5.19, 95% CI 1.69–15.94, p = 0.004), and increasing tumor volume (HR 1.05, 95% CI 1.01–1.08, p = 0.005;Table 4）.There was a trend toward tumor progression with increasing time from symptom onset to GKRS in multivariate analysis (HR 1.01, 95% CI 1.00–1.01, p = 0.065). An absence of pre-GKRS resection was not predictive of tumor progression in multivariate analysis when controlling for other covariates or when assessing for interaction between potential relevant covariates. Patients with tumor progression after radiosurgery were 5.16 times more likely to have new or worsening neurological function (95% CI 2.58–10.31, p < 0.001)
Clinical Outcomes
At last clinical follow-up, 424 patients (64.9%) demonstrated no change in clinical outcome, 179 (27.4%) had improvement in clinical outcome, and 50 (7.7%) had new or worsening neurological function (Table 3）.Specific alterations in clinical signs and symptoms following GKRS are detailed inTable 5．GKRS后,新的或恶化CN功能障碍was observed most commonly in CN V followed by aggregate dysfunction of CNs III/IV/VI and least commonly in lower cranial nerves including CN IX through XII (Table 5）.放射治疗后,24 patients (3.6%) required resection and 10 (1.5%) underwent radiation therapy to treat tumor progression. Of the 653 patients with reliable clinical follow-up information, 14 patients (2.1%) developed hydrocephalus apparent on radiological imaging, and 11 (1.7%) required ventriculoperitoneal shunt placement.
Specific alterations in clinical signs and symptoms following GKRS
| Characteristic | Presentation (%) | New or Worsening Function (%) |
|---|---|---|
| Subjective dizziness | 236 (35.0) | 34 (5.1) |
| Subjective cognitive alteration | 41 (6.1) | 15 (2.2) |
| CN III/IV/VI | 83 (13.1) | 21 (3.3) |
| CN V | 224 (33.3) | 28 (4.2) |
| CN VII | 54 (8.0) | 8 (1.2) |
| CN VIII | 193 (28.6) | 12 (1.8) |
| CN IX/X | 31 (4.6) | 6 (0.9) |
| CN XI | 3 (2.4) | 1 (0.2) |
| CN XII | 16 (2.4) | 3 (0.5) |
| Ataxia | 4 (12.4) | 14 (2.1) |
| Other cerebellar alteration/deficit | 27 (4.0) | 27 (4.0) |
| Body weakness | 43 (6.4) | 10 (1.5) |
| Change body sensation | 53 (7.9) | 8 (1.2) |
Univariate predictors of new or worsening neurological function after GKRS are displayed inTable 6．These predictors of new or worsening neurological function after GKRS within the univariate analysis were male sex; clival, petrous, and CPA location; prior conventional radiotherapy; symptomatic presentation other than headache; peripheral and maximal dose; and increasing tumor volume (Table 6）.In multivariate analysis, increasing tumor volume (OR 1.06, 95% CI 1.01–1.10, p = 0.009) and clival, petrous, or CPA location versus petroclival, tentorial, and foramen magnum location (OR 1.95, 95% CI 1.05–3.65, p = 0.036) were predictive of new or worsening neurological function after radiosurgery.
Factors predictive of new or worsening symptoms following radiosurgery in univariate and multivariate analyses*
| Analysis | Pre-GKRS Variables | OR (95% CI) | p Value |
|---|---|---|---|
| Univariate | |||
| Male sex | 2.62 (0.84–3.09) | 0.148 | |
| Location | |||
| Clival, petrous, CPA | 1.61 (0.90–2.87) | 0.106 | |
| Petroclival, tentorium, foramen magnum | 1 | ||
| Prior radiotherapy | 5.43 (1.36–21.67) | 0.017 | |
| Symptomatic presentation other than headache | 2.35 (0.92–6.05) | 0.076 | |
| Increasing peripheral dose | 0.83 (0.69–0.99) | 0.034 | |
| Increasing maximal dose | 0.95 (0.89–1.01) | 0.147 | |
| Isodose volume | 1.06 (1.01–1.10) | 0.008 | |
| Increasing volume | 1.05 (1.01–1.09) | 0.024 | |
| Multivariate | |||
| Location | |||
| Clival, petrous, CPA | 1.95 (1.05–3.65) | 0.036 | |
| Petroclival, tentorium, foramen magnum | 1 | ||
| Increasing tumor volume | 1.06 (1.01–1.10) | 0.009 |
肿瘤复发的预测因素(p < 0.15)。
Favorable Outcome After SRS
A favorable outcome, defined as tumor control along with neurological stability or improvement, was achieved in 557 (85.8%) of 649 patients. An unfavorable outcome (i.e., tumor progression and/or new or worsening neurological function) was found in 92 patients (14.2%). Univariate predictors of overall outcome are demonstrated inTable 7．Multivariate predictors of an unfavorable outcome included increasing tumor volume (OR 3.24, 95% CI 1.12–9.37, p = 0.001) and a history of prior conventional radiotherapy (OR 13.46, 95% CI 2.4–75.22, p = 0.003).
Factors predictive of an unfavorable outcome in univariate and multivariate analyses*
| Analysis | Variables | OR (95% CI) | p Value |
|---|---|---|---|
| Univariate | |||
| Increasing tumor volume | 1.06 (1.02–1.09) | 0.001 | |
| Symptomatic other than headache | 1.79 (0.95–3.40) | 0.074 | |
| Prior radiotherapy | 26.38 (5.50–126.35) | <0.001 | |
| Increasing time from symptom onset | 1.01 (1.0–1.01) | 0.046 | |
| Margin dose | 0.88 (0.77–1.00) | 0.051 | |
| Isodose line | 0.96 (0.92–0.99) | 0.013 | |
| Multivariate | |||
| Increasing tumor volume | 3.24 (1.12–9.37) | 0.001 | |
| Prior radiotherapy | 13.46 (2.4–75.22) | 0.003 |
Favorable outcome defined as no tumor progression or new or worsening neurological function. Factors predictive of tumor recurrence (p < 0.15).
Other Serious Adverse Effects
In the current study, there was no evidence of radiation-induced tumor formation or malignant transformation of an existing meningioma.
Discussion
Posterior Fossa Location and Resection
Meningiomas involving the posterior fossa comprise approximately 7%–12% of all meningiomas.13,16,56Posterior fossa meningiomas present a unique set of challenges as compared with those involving the supratentorial region. Posterior fossa meningiomas are often closely associated with critical arteries, venous sinuses, cranial nerves, and the brainstem, and such proximity to critical structures makes resection more challenging. Also, their resulting growth can lead to mass effect that is less tolerated than their supratentorial counterparts. In instances of appreciable mass effect, hydrocephalus, or significant histological uncertainty, resection remains a valuable approach. Nevertheless, complete resection rates for posterior fossa meningiomas vary substantially, with rates ranging from 40% to 96%.1–5,7,9–12,15–17,20–22,24,27,28,31–33,36,38,41–43,45–48,51,54,56
Although some continue to advocate for aggressive resection, others have instead proposed a more conservative approach involving subtotal resection that is guided by relief of mass effect and preservation of neurological function.6,9,34,60In published series, this contemporary approach has led to morbidity and mortality rates of 0%–13% and 13%–40%, respectively. Recurrence rates after an initial resection vary from 12% to 91%.1–5,7,9–12,15–17,20–22,24,27,28,31–33,36,38,41–43,45–48,51,54,56Such recurrences depend upon the length of follow-up, characteristics of the tumor, and the extent of the initial resection. Although repeat resection is feasible, repeat resection is associated with increased morbidity and mortality due to difficult resection planes.5,7,22,24,60
Radiation Therapy
放射治疗已被用于一些病人with intracranial meningiomas, including ones involving the posterior fossa. Progression-free survival rates at 5 and 10 years after conventional radiotherapy range from 73% to 92% and 61% to 83%, respectively.23,25,26,35,40,57More contemporary techniques such as intensity-modulated radiation therapy and proton therapy offer increased conformality and more sparing of critical structures compared with conventional techniques.44,58The lower integral dose and higher conformality that are touted as the advantages of intensity-modulated radiation therapy and proton beam over conventional radiotherapy techniques for meningiomas have been longstanding features of radiosurgery. While radiotherapy has been used for large volume or poorly delineated posterior fossa meningiomas, its role for smaller to moderately sized and well-demarcated meningiomas involving the posterior fossa has largely been displaced by SRS.
Stereotactic Radiosurgery
Radiosurgery has proven to be an important tool in the treatment of meningiomas, with most large radiosurgical series demonstrating tumor control rates of 85% or higher for patients with Grade I meningiomas.49放射治疗后,tumor control has generally been accompanied by neurological preservation or improvement in the majority of patients.49However, most radiosurgical series have looked broadly at meningiomas of various locations, and few have focused on the challenges associated with meningiomas of the posterior fossa.
In the published literature, there are only a few radiosurgical series that focus exclusively on posterior fossa meningiomas (Table 8）.In an earlier series by the University of Pittsburgh team, Subach and colleagues reported on their experience with 62 patients exhibiting petroclival meningiomas. Of these 62 patients, 39 (63%) had at least 1 prior resection. With a median follow-up of 37 months, tumor control was achieved in 92% of patients, and neurological status improved in 21% and remained stable in 66% of patients.55In a later series by that same group, tumor control and neurological preservation were achieved in 90% and 85%, respectively, of 168 patients with petroclival meningiomas who underwent GKRS.18In another study by the group in Verona, Italy, Nicolato and colleagues39used GKRS to treat 57 patients with 62 posterior fossa meningiomas. With a median follow-up of 28.7 months, tumor regression was observed in 55% of cases and stability in another 40%.39Transient side effects due to radiosurgically induced edema were noted in 6.5%, but there were no instances of permanent morbidity associated with GKRS in this series.39More recently from the University of Virginia, a series of 152 patients with posterior fossa meningiomas were evaluated after GKRS. With a median follow-up of 84 months, tumor control and neurological preservation were achieved in 87% and 91% of patients, respectively.52Smaller radiosurgical series confirm the efficacy and safety of radiosurgery for patients with posterior fossa meningiomas, even of the foramen magnum.53,61
Major radiosurgical series for posterior fossa meningiomas
| Authors & Year | No. of Patients | Median or Mean Follow-Up (mos) | Tumor Control (%) | Neurological Preservation (%) | Complications (%) |
|---|---|---|---|---|---|
| Subach et al., 1998 | 62 | 37 | 92 | 87 | 8 |
| Nicolato et al., 2001 | 57 | 28.7 | 95 | 100 | 6.5 |
| Flannery et al., 2010 | 168 | 72 | 90 | 85 | 8 |
| Starke et al., 2010 | 5 | 60 | 100 | 100 | 0 |
| Starke et al., 2011 | 152 | 84 | 87 | 91 | 9 |
| Zenonos et al., 2012 | 24 | 47 | 100 | 100 | 0 |
| Current series | 675 | 60 | 91 | 92.3 | 7.7 |
The current series represents the largest one to date for posterior fossa meningiomas treated with radiosurgery (Table 8）.This series has sufficient statistical power to permit subgroup analysis to evaluate the effect of tumor location, and the study also gives a broader assessment of neurological complications associated with GKRS. In the current series, tumor control was achieved in 91.2% of patients at last follow-up. Just if not more importantly, neurological preservation was accomplished in 92.3% of patients. Thus, based upon the high chance of tumor control and neurological preservation observed in the current series, those with small to moderately sized posterior fossa meningiomas for whom relief of mass effect is not required would appear well served by GKRS. Those with a smaller tumor volume and no prior radiation therapy were more likely to achieve both tumor control and a favorable neurological outcome after radiosurgery of their posterior fossa meningiomas. The benefit of a smaller tumor volume at the time of radiosurgery does underscore the benefits of a cytoreductive but neurologically preserving surgery for those patients who have larger tumors at initial presentation. In terms of prior radiotherapy, patients in whom radiation therapy was unsuccessful likely exhibit a more aggressive tumor. Also, prior radiotherapy can require a reduction in the radiosurgical dose below that which might be optimal. Thus, the radiosurgical cohort that had unsuccessful prior radiotherapy is an inherently more challenging one to manage, and the prescription dose lower than what would likely have been given in the absence of prior ionizing radiation makes tumor control less likely.
Cranial nerve dysfunction after GKRS varied depending upon the nerve. Cranial nerve V and aggregate CN III, IV, and VI dysfunction were most common whereas lower CN dysfunction was exceedingly rare (Table 4）.The risk factors for CN palsy after GKRS are likely multifactorial. Variability of the CNs to ionizing radiation may be due in part to the functionality (e.g., special sensory, visceral sensory, visceral motor, and somatic motor), relative radioresistance, vascular supply to the nerve, and irradiated length of a particular nerve. In particular, CN V can routinely tolerate a maximum dose of 80 Gy in cases of trigeminal neuralgia when such a dose is delivered to a small volume of the nerve. While the doses used in this series to treat meningiomas were substantially lower than 80 Gy, the length of nerve irradiated and the integrated dose to the nerve have been shown to be related to and affect the probability of trigeminal nerve dysfunction after GKRS, and these parameters were likely responsible for some of the CN V dysfunction.34肿瘤的位置(例如,坚硬的、岩斜)affected the likelihood of new or worsening neurological symptoms following radiosurgery. In cases in which the tumor may have a broader interface with the brainstem or traversing cranial nerves, neurological dysfunction may occur with a higher probability after radiosurgery.
Similarly to patients undergoing resection, radiation therapy, or no treatment, longitudinal follow-up of patients after radiosurgery is required. In the current series, 2.1% of patients with posterior fossa meningiomas developed hydrocephalus following radiosurgery. The incidence of postradiosurgical hydrocephalus compares favorably with the 16% incidence noted in a recent surgical series of posterior fossa meningiomas by Nanda et al.37Cerebrospinal fluid malabsorption from a high protein level has been postulated to be the cause of postradiosurgical hydrocephalus.19Such patients require CSF diversion, typically with a shunt as was the case in 1.6% of patients in the current series. Tumor progression in the current series was rare, but 5.1% of patients in the current series required additional intervention for their meningioma. Close surveillance with neuroimaging and clinical assessments will allow detection of problems and timely intervention when necessary for radiosurgical patients.
Study Limitations
The current study represents the largest radiosurgical one to date on this particular indication. Nevertheless, the study has limitations worth noting. The participating centers use a common radiosurgical platform and dose planning software. The outcomes, both favorable and unfavorable, may not be representative of other commercially available systems. Also, radiosurgery comprises a significant portion of the practice of the contributing clinicians in this study. We did not examine the learning curve for this indication nor did we examine the number of cases required to maintain proficiency. In addition, the radiosurgical techniques for planning, treatment, and delivery have evolved over the time span of this study. We do not account for the evolution of the field in assessing outcomes with posterior fossa meningiomas.
The study suffers from inherent biases of a retrospective study. These include selection bias and a lack of a control arm to the study. In particular, selection criteria varied from center to center and as a function of time as the field of radiosurgery has evolved over the past two decades. Also, not all of the tumors were histologically confirmed to be a meningioma. Thus, it is possible that some other benign skull-based lesions were included in this study. However, any patient with histology inconsistent with a WHO Grade I meningioma was excluded from the study. This is true of preradiosurgical histology and histology obtained at the time of resection following failed radiosurgery.
Conclusions
Gamma Knife radiosurgery affords tumor control and neurological preservation in the vast majority of patients with posterior fossa meningiomas. While resection continues to be of value for relief of mass effect and histological confirmation in ambiguous cases, radiosurgery either as an upfront treatment or an adjuvant one after prior resection represents a valuable neurosurgical tool for treatment of patients with posterior fossa meningiomas.
Acknowledgment
We appreciate the assistance of Ms. Sharon DeCesare with coordination of data for the North American Gamma Knife Consortium.
Author Contributions
Conception and design: Sheehan. Acquisition of data: Kano, Barnett, Mathieu, Chiang, Yu, Hess, McBride, Honea, Nakaji, Lee, Rahmathaulla, Evanoff, Alonso-Basanta, Lunsford. Analysis and interpretation of data: Starke, Lunsford. Drafting the article: Sheehan. Critically revising the article: Sheehan, Starke, Kano, Barnett, Mathieu, Chiang, Yu, McBride, Nakaji, Lee, Alonso-Basanta, Lunsford.
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1
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3 ↑
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4
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5 ↑
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6 ↑
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7 ↑
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8 ↑
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9 ↑
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10
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11 ↑
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12
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14 ↑
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15
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16 ↑
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17
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18 ↑
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19 ↑
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20
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21
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22 ↑
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23 ↑
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24 ↑
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25 ↑
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26 ↑
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28 ↑
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29 ↑
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30 ↑
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31
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32
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33
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34 ↑
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35 ↑
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37 ↑
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38 ↑
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39 ↑
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40 ↑
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41
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42
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43
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44 ↑
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45
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46
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47
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48
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49 ↑
希恩JP,,WilliamsBJ,&YenCP:Stereotactic radiosurgery for WHO grade I meningiomas．J Neurooncol99:407–416,2010
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50 ↑
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51 ↑
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52 ↑
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53 ↑
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54 ↑
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55 ↑
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56 ↑
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57 ↑
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58 ↑
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59 ↑
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60 ↑
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61 ↑
ZenonosG,,KondziolkaD,,FlickingerJC,,GardnerP,&LunsfordLD:Gamma Knife surgery in the treatment paradigm for foramen magnum meningiomas．J Neurosurg117:864–873,2012
