Stereotactic Radiosurgery for Intracranial Noncavernous Sinus Benign Meningioma: International Stereotactic Radiosurgery Society Systematic Review, Meta-Analysis and Practice Guideline

 [bib_ref] Treatment and survival of patients with nonmalignant intracranial meningioma: results from the..., Cahill [/bib_ref] [bib_ref] Effects of using combined transpetrosal surgical approaches to treat petroclival meningiomas, Mathiesen [/bib_ref] [bib_ref] Effects of using combined transpetrosal surgical approaches to treat petroclival meningiomas, Mathiesen [/bib_ref] [bib_ref] Della Rocca R. Sphenoorbital meningiomas: surgical limitations and lessons learned in their..., Shrivastava [/bib_ref] [bib_ref] The contemporary role of stereotactic radiosurgery in the treatment of meningiomas, Cohen-Inbar [/bib_ref] [bib_ref] Fractionated radiotherapy and radiosurgery of intracranial meningiomas, Biau [/bib_ref] [bib_ref] Radiosurgery for intracranial meningiomas: a systematic review and meta-analysis, Pinzi [/bib_ref] [bib_ref] Stereotactic radiosurgery for benign (World Health Organization grade I) cavernous sinus meningiomas-International..., Lee [/bib_ref] 

# Methods

## Article selection
The ISRS clinical practice guideline taskforce conducted a systematic review of the literature specific to the management of intracranial meningioma with SRS, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (2009) and the Cochrane guidelines for systematic reviews of interventions.Articles were included when inclusion criteria were met.

## Inclusion criteria
Retrospective and prospective studies reporting outcomes on adult patients with a radiological and/or pathological diagnosis of intracranial WHO grade I meningioma were included. In those series that included other grades of meningioma (WHO grade II and III), only those studies that segregated outcomes for the WHO grade I population were included. Similarly, those studies including CS meningioma were excluded, unless outcomes were segregated for non-CS meningioma. For series reporting outcomes without segregating the study population to non-CS patients and CS patients, an exception was made, provided that the proportion of CS patients included did not exceed 30% to 40% of the overall population. A minimum follow-up period of 3 yr was deemed mandatory for the analysis of LC and progression-free-survival (PFS); series with a mean/median follow-up period lower than 36 mo have been considered if specified the number of patients for which a longer than 3 yr follow-up is available.
Studies which included re-irradiated patients, or whose population amounted to less than 10 patients, were also excluded. SRS and HSRT, delivered over 2 to 5 fractions, were permitted. Lastly, patients who had been treated with primary or adjuvant/salvage SRS were included.

## Objectives
The primary objective of the study was to define the efficacy of SRS in the treatment of intracranial WHO grade I meningioma (excluding CS lesions). The primary outcomes analyzed were rates of LC, PFS, and overall survival.
Secondary objectives included analyses of symptoms-control, radiation-induced toxicity, and prognostic factors.

## Search strategy
The Medline, Embase, and Cochrane database were searched for English abstracts and keywords of relevant studies published until June 6, 2018. The details of the search strategy are listed in Supplemental Digital Content 1.
Exclusion criteria have been recorded and listed in [fig_ref] FIGURE 1: Flowchart of search process [/fig_ref].

## Data extraction
The extracted data include information on study design, follow-up interval, patient's demographic features, tumor characteristics, treatment parameters (including primary adjuvant and salvage setting), outcomes, and prognostic factors.

## Risk-of-bias assessment
There is no single recommended instrument to assess the risk of bias for systematic reviews that includes both prospective and retrospective observational studies. We chose to evaluate the risk of bias by using a previously published system based on a 10-item assessment (see Supplemental Digital Content 2). [bib_ref] Radiosurgery for intracranial meningiomas: a systematic review and meta-analysis, Pinzi [/bib_ref] The system was developed to evaluate the kind of bias and the completeness of information. Particularly, items 1 and 2 assess the selection bias, items 3 to 5 the reporting bias, item 6 the attrition bias, and items 7 to 10 assess the extensiveness of information on treatments and outcomes. Specifically, an affirmative answer, "yes," indicates a low risk of bias, while a negative answer, "no," a high risk. Unclear or unknown risks are indicated by the definition "unclear."

## Ranking the evidence quality
The evidence quality was ranked by applying an evidence hierarchy developed by the ISRS Guidelines Committee for a number of studies: diagnostic, prognostic, therapeutic, and decision modeling. The method used to assess the quality of the evidence is exemplified in this link: https://www.cns.org/guidelines/guideline-development-methodology.

## Strength of recommendation rating scheme
Recommendation level I: high degree of clinical certainty (class I evidence or overwhelming class II evidence). Recommendation level II: clinical certainty (class II evidence or a strong consensus of class III evidence).
Recommendation level III: clinical uncertainty (inconclusive or conflicting evidence or opinion).

# Statistical methods
The 3-yr, 5-yr, and 10-yr rates and the respective CI and/or standard errors (SE) for efficacy end points were extracted and reported from each study, where available or deducible.
The percentage of patients with symptom control and the percentage of patients suffering at least from one toxicity (together with the 95% CI) were also extracted or calculated. The Freemen-Tukey double arcsine transformation was performed to obtain the overall estimates, and the DerSimonian-Laird random effect model has been applied to calculate the weighted pooled estimate. The overall estimate was backtransformed.
The STATA software, version 14.3 (StataCorp), has been used to analyze the data.

# Results

## Selection of the studies
The PubMed, Embase, and Cochran searches identified 2844 studies. After the removal of duplicates, 2233 papers remained, out of which 1927 were excluded upon title and abstract evaluation. Following a full text scrutiny of the remaining 305 studies, 27 studies 10-36 were deemed to have met the inclusion criteria and selected for this review and summarized in [fig_ref] FIGURE 1: Flowchart of search process [/fig_ref]. One study was prospective, [bib_ref] Volumetric follow-up of meningiomas: a quantitative method to evaluate treatment outcome of..., Feigl [/bib_ref] in 4 studies the study design was unclear, [bib_ref] Linear accelerator-based stereotactic radiosurgery of intracranial meningiomas: results of the first 5..., Abdelaziz [/bib_ref] [bib_ref] Gamma Knife surgery for convexity, parasagittal, and falcine meningiomas: clinical article, Hasegawa [/bib_ref] [bib_ref] Longterm follow-up confirms the efficacy of LINAC radiosurgery for acoustic neuroma and..., Kalogeridi [/bib_ref] [bib_ref] Long-term tumor control of benign intracranial tumors after Gamma Knife radiosurgery in..., Massager [/bib_ref] and the remaining studies were retrospective. Two studies were multicenter, [bib_ref] Volumetric follow-up of meningiomas: a quantitative method to evaluate treatment outcome of..., Feigl [/bib_ref] [bib_ref] Gamma knife radiosurgery for sellar and parasellar meningiomas: a multicenter study, Sheehan [/bib_ref] while the remaining were single-center institutional series.

## Risk-of-bias assessment
Based on the established risk-of-bias assessment method, none of the analyzed studies fulfill the criteria for low risk of bias, according to the defined 4 sections (selection bias, reporting bias, attrition bias, extensiveness of information on intervention analyzed). Four studies could be considered at low risk for selection bias, as they enrolled patients in a consecutive manner and reported the reasons to exclude some patients from the study. [bib_ref] Volumetric follow-up of meningiomas: a quantitative method to evaluate treatment outcome of..., Feigl [/bib_ref] [bib_ref] Longterm follow-up confirms the efficacy of LINAC radiosurgery for acoustic neuroma and..., Kalogeridi [/bib_ref] [bib_ref] Gamma knife radiosurgery for petroclival meningioma: long-term outcome and failure pattern, Kim [/bib_ref] [bib_ref] Long-term outcomes following Gamma Knife radiosurgery for small, newly diagnosed meningiomas, Lee [/bib_ref] Five studies were considered at low risk for reporting bias. [bib_ref] Postoperative Gamma Knife surgery for benign meningiomas of the cranial base, Davidson [/bib_ref] [bib_ref] Predictors of response to Gamma Knife radiosurgery for intracranial meningiomas, Mansouri [/bib_ref] [bib_ref] Multisession radiosurgery for sellar and parasellar benign meningiomas: long-term tumor growth control..., Marchetti [/bib_ref] [bib_ref] Single-fraction radiosurgery of benign intracranial meningiomas, Pollock [/bib_ref] [bib_ref] Long-term outcomes and patterns of tumor progression after Gamma Knife radiosurgery for..., Zada [/bib_ref] A total of 14 studies should be considered at low risk of attrition bias. [bib_ref] Linear accelerator-based stereotactic radiosurgery of intracranial meningiomas: results of the first 5..., Abdelaziz [/bib_ref] [bib_ref] Gamma Knife radiosurgery of skull base meningiomas, Aichholzer [/bib_ref] [bib_ref] Outcomes and complications of Gamma Knife radiosurgery for skull base meningiomas, Bir [/bib_ref] [bib_ref] Development of dose-volume relation model for Gamma Knife surgery of non-skull base..., Chung [/bib_ref] [bib_ref] Postoperative Gamma Knife surgery for benign meningiomas of the cranial base, Davidson [/bib_ref] [bib_ref] Factors predicting local tumor control after Gamma Knife stereotactic radiosurgery for benign..., Dibiase [/bib_ref] [bib_ref] Volumetric follow-up of meningiomas: a quantitative method to evaluate treatment outcome of..., Feigl [/bib_ref] [bib_ref] Gamma Knife surgery for convexity, parasagittal, and falcine meningiomas: clinical article, Hasegawa [/bib_ref] [bib_ref] Treatment modalities and outcomes for asymptomatic meningiomas, Jo [/bib_ref] [bib_ref] Longterm follow-up confirms the efficacy of LINAC radiosurgery for acoustic neuroma and..., Kalogeridi [/bib_ref] [bib_ref] Gamma knife radiosurgery for petroclival meningioma: long-term outcome and failure pattern, Kim [/bib_ref] [bib_ref] Long term experience of Gamma Knife radiosurgery for benign skull base meningiomas, Kreil [/bib_ref] [bib_ref] Long-term outcomes following Gamma Knife radiosurgery for small, newly diagnosed meningiomas, Lee [/bib_ref] All but one 35 of the series included was at risk of bias with respect to the reporting of the results. Details about the Risk-of-Bias evaluation are reported in Supplemental Digital Content 3.

## Patient and tumor characteristics
From the reviewed literature summarized in [fig_ref] TABLE 1: Studies, Tumors, and Treatments Features [/fig_ref] , a total of 3654 patients (3750 tumors) were included. The median followup was 60 mo. The mean patient age at the time of treatment ranged from 40 to 71 (median, 57 yr). The percentage of male patients across studies ranged from 11% to 41% (median, 26%). The analysis includes WHO grade I meningiomas treated with SRS and HSRT; the grade was based on pathological confirmation or based on radiological assessment. A single study included grade II and II meningiomas; however, WHO grade I tumors were reported separately and, as a result, they have been than included in this analysis. [bib_ref] Volumetric follow-up of meningiomas: a quantitative method to evaluate treatment outcome of..., Feigl [/bib_ref] The tumor site distribution is represented in [fig_ref] TABLE 2: The Meningiomas Sites Are Here Described [/fig_ref]. The overall tumor volume ranged from 0.5 to 26 cc (median, 6.4 cc), and ranged from 0.5 to 15.2 cc (median, 5.6 cc) in the SRS series and from 7.6 to 26 cc (median, 16.2 cc) in the HSRT series.

## Tumor control and pfs rates
A total of 16 studies provide data specific to LC, 5 of which, evaluating 662 patients, reported a 10-yr LC rate ranging from 71% to 100% (median, 94.2%). [bib_ref] Postoperative Gamma Knife surgery for benign meningiomas of the cranial base, Davidson [/bib_ref] [bib_ref] Gamma Knife surgery for convexity, parasagittal, and falcine meningiomas: clinical article, Hasegawa [/bib_ref] [bib_ref] Treatment modalities and outcomes for asymptomatic meningiomas, Jo [/bib_ref] [bib_ref] Radiosurgery as definitive management of intracranial meningiomas, Kondziolka [/bib_ref] [bib_ref] Single-fraction radiosurgery of benign intracranial meningiomas, Pollock [/bib_ref] Eight studies, including more than 783 patients, reported a 5-yr posttreatment LC rate ranging from 85% the 100% (median, 93.8%). [bib_ref] Development of dose-volume relation model for Gamma Knife surgery of non-skull base..., Chung [/bib_ref] [bib_ref] Postoperative Gamma Knife surgery for benign meningiomas of the cranial base, Davidson [/bib_ref] [bib_ref] Gamma Knife surgery for convexity, parasagittal, and falcine meningiomas: clinical article, Hasegawa [/bib_ref] [bib_ref] Treatment modalities and outcomes for asymptomatic meningiomas, Jo [/bib_ref] [bib_ref] Longterm follow-up confirms the efficacy of LINAC radiosurgery for acoustic neuroma and..., Kalogeridi [/bib_ref] [bib_ref] Radiosurgery as definitive management of intracranial meningiomas, Kondziolka [/bib_ref] [bib_ref] Cyber Knife stereotactic radiosurgery and hypofractionated stereotactic radiotherapy as first-line treatments for..., Manabe [/bib_ref] [bib_ref] Single-fraction radiosurgery of benign intracranial meningiomas, Pollock [/bib_ref] Ten studies, evaluating more than 750 patients, reported LC rates ranging from 52% to 100% based on the last follow-up. [bib_ref] Linear accelerator-based stereotactic radiosurgery of intracranial meningiomas: results of the first 5..., Abdelaziz [/bib_ref] [bib_ref] Gamma Knife radiosurgery of skull base meningiomas, Aichholzer [/bib_ref] [bib_ref] Hypofractionated stereotactic radiotherapy (HFSRT) for who grade I anterior clinoid meningiomas (ACM), Demiral [/bib_ref] [bib_ref] Gamma knife radiosurgery for petroclival meningioma: long-term outcome and failure pattern, Kim [/bib_ref] [bib_ref] Radiosurgery as definitive management of intracranial meningiomas, Kondziolka [/bib_ref] [bib_ref] Long-term outcomes following Gamma Knife radiosurgery for small, newly diagnosed meningiomas, Lee [/bib_ref] [bib_ref] Predictors of response to Gamma Knife radiosurgery for intracranial meningiomas, Mansouri [/bib_ref] [bib_ref] Long-term tumor control of benign intracranial tumors after Gamma Knife radiosurgery in..., Massager [/bib_ref] [bib_ref] Long-term evaluation of the effect of hypofractionated high-energy proton treatment of benign..., Ryttlefors [/bib_ref] PFS was reported in 15 studies. The longest reported observation period was 15 yr in one study with a PFS of 89%. [bib_ref] Stereotactic LINAC radiosurgery for the treatment of typical intracranial meningiomas. Efficacy and..., El-Khatib [/bib_ref] Eight-to ten-year PFS rates were reported in 10 studies [bib_ref] Gamma Knife radiosurgery in sphenopetroclival meningiomas: preliminary experience at the Iran Gamma..., Azar [/bib_ref] [bib_ref] Outcomes and complications of Gamma Knife radiosurgery for skull base meningiomas, Bir [/bib_ref] [bib_ref] Stereotactic LINAC radiosurgery for the treatment of typical intracranial meningiomas. Efficacy and..., El-Khatib [/bib_ref] [bib_ref] Gamma Knife surgery for convexity, parasagittal, and falcine meningiomas: clinical article, Hasegawa [/bib_ref] [bib_ref] Single-fractionated stereotactic radiosurgery for intracranial meningioma in elderly patients: 25-year experience at..., Hasegawa [/bib_ref] [bib_ref] Gamma knife radiosurgery for petroclival meningioma: long-term outcome and failure pattern, Kim [/bib_ref] [bib_ref] Long term experience of Gamma Knife radiosurgery for benign skull base meningiomas, Kreil [/bib_ref] [bib_ref] Multisession radiosurgery for sellar and parasellar benign meningiomas: long-term tumor growth control..., Marchetti [/bib_ref] [bib_ref] Gamma knife radiosurgery for sellar and parasellar meningiomas: a multicenter study, Sheehan [/bib_ref] [bib_ref] Long-term outcomes and patterns of tumor progression after Gamma Knife radiosurgery for..., Zada [/bib_ref] that evaluated more than 1146 patients, with a PFS rate ranging from 55% to 97% (median, 85.0%). Four-to five-year PFS rates ranged from 74% to 99% (median, 89.4%) in 14 studies, based on more than 1057 patients. [bib_ref] Gamma Knife radiosurgery in sphenopetroclival meningiomas: preliminary experience at the Iran Gamma..., Azar [/bib_ref] [bib_ref] Outcomes and complications of Gamma Knife radiosurgery for skull base meningiomas, Bir [/bib_ref] [bib_ref] Hypofractionated stereotactic radiotherapy (HFSRT) for who grade I anterior clinoid meningiomas (ACM), Demiral [/bib_ref] [bib_ref] Factors predicting local tumor control after Gamma Knife stereotactic radiosurgery for benign..., Dibiase [/bib_ref] [bib_ref] Stereotactic LINAC radiosurgery for the treatment of typical intracranial meningiomas. Efficacy and..., El-Khatib [/bib_ref] [bib_ref] Volumetric follow-up of meningiomas: a quantitative method to evaluate treatment outcome of..., Feigl [/bib_ref] [bib_ref] Gamma Knife surgery for convexity, parasagittal, and falcine meningiomas: clinical article, Hasegawa [/bib_ref] [bib_ref] Single-fractionated stereotactic radiosurgery for intracranial meningioma in elderly patients: 25-year experience at..., Hasegawa [/bib_ref] [bib_ref] Gamma knife radiosurgery for petroclival meningioma: long-term outcome and failure pattern, Kim [/bib_ref] [bib_ref] Long term experience of Gamma Knife radiosurgery for benign skull base meningiomas, Kreil [/bib_ref] [bib_ref] Cyber Knife stereotactic radiosurgery and hypofractionated stereotactic radiotherapy as first-line treatments for..., Manabe [/bib_ref] [bib_ref] Multisession radiosurgery for sellar and parasellar benign meningiomas: long-term tumor growth control..., Marchetti [/bib_ref] [bib_ref] Long-term outcomes and patterns of tumor progression after Gamma Knife radiosurgery for..., Zada [/bib_ref] Amongst those reporting predictive factors, the most common factors associated with tumor control were smaller tumor volume 12,18,26,33 and patient age (lower than 65). [bib_ref] Gamma Knife radiosurgery in sphenopetroclival meningiomas: preliminary experience at the Iran Gamma..., Azar [/bib_ref] [bib_ref] Gamma Knife surgery for convexity, parasagittal, and falcine meningiomas: clinical article, Hasegawa [/bib_ref] [bib_ref] Long-term outcomes and patterns of tumor progression after Gamma Knife radiosurgery for..., Zada [/bib_ref] The impact of tumor location on the tumor control was investigated by 4 studies. [bib_ref] Stereotactic LINAC radiosurgery for the treatment of typical intracranial meningiomas. Efficacy and..., El-Khatib [/bib_ref] [bib_ref] Single-fractionated stereotactic radiosurgery for intracranial meningioma in elderly patients: 25-year experience at..., Hasegawa [/bib_ref] [bib_ref] Single-fraction radiosurgery of benign intracranial meningiomas, Pollock [/bib_ref] Two out of these studies [bib_ref] Single-fractionated stereotactic radiosurgery for intracranial meningioma in elderly patients: 25-year experience at..., Hasegawa [/bib_ref] [bib_ref] Single-fraction radiosurgery of benign intracranial meningiomas, Pollock [/bib_ref] suggest that parafalcine, parasagittal, and convexity locations are significant negative prognostic factors in terms of tumor control, while other 2 studies 18,20 did not observe statistical significance.
Tumor-control rates and the PFS are summarized in [fig_ref] TABLE 3: Local Control and Progression-Free-Survival Rates [/fig_ref].

## Treatment features and dose
A total of 22 papers reported specifically on single-fraction SRS (3458 tumors have been included), [bib_ref] Linear accelerator-based stereotactic radiosurgery of intracranial meningiomas: results of the first 5..., Abdelaziz [/bib_ref] [bib_ref] Gamma Knife radiosurgery of skull base meningiomas, Aichholzer [/bib_ref] [bib_ref] Gamma Knife radiosurgery in sphenopetroclival meningiomas: preliminary experience at the Iran Gamma..., Azar [/bib_ref] [bib_ref] Outcomes and complications of Gamma Knife radiosurgery for skull base meningiomas, Bir [/bib_ref] [bib_ref] Development of dose-volume relation model for Gamma Knife surgery of non-skull base..., Chung [/bib_ref] [bib_ref] Postoperative Gamma Knife surgery for benign meningiomas of the cranial base, Davidson [/bib_ref] [bib_ref] Factors predicting local tumor control after Gamma Knife stereotactic radiosurgery for benign..., Dibiase [/bib_ref] [bib_ref] Stereotactic LINAC radiosurgery for the treatment of typical intracranial meningiomas. Efficacy and..., El-Khatib [/bib_ref] [bib_ref] Volumetric follow-up of meningiomas: a quantitative method to evaluate treatment outcome of..., Feigl [/bib_ref] [bib_ref] Gamma Knife surgery for convexity, parasagittal, and falcine meningiomas: clinical article, Hasegawa [/bib_ref] [bib_ref] Single-fractionated stereotactic radiosurgery for intracranial meningioma in elderly patients: 25-year experience at..., Hasegawa [/bib_ref] [bib_ref] Treatment modalities and outcomes for asymptomatic meningiomas, Jo [/bib_ref] [bib_ref] Longterm follow-up confirms the efficacy of LINAC radiosurgery for acoustic neuroma and..., Kalogeridi [/bib_ref] [bib_ref] Gamma knife radiosurgery for petroclival meningioma: long-term outcome and failure pattern, Kim [/bib_ref] [bib_ref] Radiosurgery as definitive management of intracranial meningiomas, Kondziolka [/bib_ref] [bib_ref] Long term experience of Gamma Knife radiosurgery for benign skull base meningiomas, Kreil [/bib_ref] [bib_ref] Long-term outcomes following Gamma Knife radiosurgery for small, newly diagnosed meningiomas, Lee [/bib_ref] [bib_ref] Predictors of response to Gamma Knife radiosurgery for intracranial meningiomas, Mansouri [/bib_ref] [bib_ref] Long-term tumor control of benign intracranial tumors after Gamma Knife radiosurgery in..., Massager [/bib_ref] [bib_ref] Single-fraction radiosurgery of benign intracranial meningiomas, Pollock [/bib_ref] [bib_ref] Gamma knife radiosurgery for sellar and parasellar meningiomas: a multicenter study, Sheehan [/bib_ref] [bib_ref] Long-term outcomes and patterns of tumor progression after Gamma Knife radiosurgery for..., Zada [/bib_ref] one of which included staged SRS (8/200 total treatments). [bib_ref] Long term experience of Gamma Knife radiosurgery for benign skull base meningiomas, Kreil [/bib_ref] Three studies (based on 181 tumors) reported outcomes specific to HSRT. [bib_ref] Hypofractionated stereotactic radiotherapy (HFSRT) for who grade I anterior clinoid meningiomas (ACM), Demiral [/bib_ref] [bib_ref] Multisession radiosurgery for sellar and parasellar benign meningiomas: long-term tumor growth control..., Marchetti [/bib_ref] [bib_ref] Long-term evaluation of the effect of hypofractionated high-energy proton treatment of benign..., Ryttlefors [/bib_ref] Two studies included both SRS and HSRT treatments; in these studies, 51 tumors had SRS and 60 tumors had HSRT. [bib_ref] Cyber Knife stereotactic radiosurgery and hypofractionated stereotactic radiotherapy as first-line treatments for..., Manabe [/bib_ref] The Gamma Knife (Elekta AB) was the reference device in 20 studies (3316 tumors), [bib_ref] Gamma Knife radiosurgery of skull base meningiomas, Aichholzer [/bib_ref] [bib_ref] Gamma Knife radiosurgery in sphenopetroclival meningiomas: preliminary experience at the Iran Gamma..., Azar [/bib_ref] [bib_ref] Outcomes and complications of Gamma Knife radiosurgery for skull base meningiomas, Bir [/bib_ref] [bib_ref] Development of dose-volume relation model for Gamma Knife surgery of non-skull base..., Chung [/bib_ref] [bib_ref] Postoperative Gamma Knife surgery for benign meningiomas of the cranial base, Davidson [/bib_ref] [bib_ref] Factors predicting local tumor control after Gamma Knife stereotactic radiosurgery for benign..., Dibiase [/bib_ref] [bib_ref] Volumetric follow-up of meningiomas: a quantitative method to evaluate treatment outcome of..., Feigl [/bib_ref] [bib_ref] Gamma Knife surgery for convexity, parasagittal, and falcine meningiomas: clinical article, Hasegawa [/bib_ref] [bib_ref] Single-fractionated stereotactic radiosurgery for intracranial meningioma in elderly patients: 25-year experience at..., Hasegawa [/bib_ref] [bib_ref] Treatment modalities and outcomes for asymptomatic meningiomas, Jo [/bib_ref] [bib_ref] Gamma knife radiosurgery for petroclival meningioma: long-term outcome and failure pattern, Kim [/bib_ref] [bib_ref] Radiosurgery as definitive management of intracranial meningiomas, Kondziolka [/bib_ref] [bib_ref] Long term experience of Gamma Knife radiosurgery for benign skull base meningiomas, Kreil [/bib_ref] [bib_ref] Long-term outcomes following Gamma Knife radiosurgery for small, newly diagnosed meningiomas, Lee [/bib_ref] [bib_ref] Predictors of response to Gamma Knife radiosurgery for intracranial meningiomas, Mansouri [/bib_ref] [bib_ref] Long-term tumor control of benign intracranial tumors after Gamma Knife radiosurgery in..., Massager [/bib_ref] [bib_ref] Single-fraction radiosurgery of benign intracranial meningiomas, Pollock [/bib_ref] [bib_ref] Gamma knife radiosurgery for sellar and parasellar meningiomas: a multicenter study, Sheehan [/bib_ref] [bib_ref] Long-term outcomes and patterns of tumor progression after Gamma Knife radiosurgery for..., Zada [/bib_ref] the LINAC in 4 (231 tumors), [bib_ref] Linear accelerator-based stereotactic radiosurgery of intracranial meningiomas: results of the first 5..., Abdelaziz [/bib_ref] [bib_ref] Hypofractionated stereotactic radiotherapy (HFSRT) for who grade I anterior clinoid meningiomas (ACM), Demiral [/bib_ref] [bib_ref] Stereotactic LINAC radiosurgery for the treatment of typical intracranial meningiomas. Efficacy and..., El-Khatib [/bib_ref] [bib_ref] Longterm follow-up confirms the efficacy of LINAC radiosurgery for acoustic neuroma and..., Kalogeridi [/bib_ref] the CyberKnife (Accuray) in 2 (184 tumors), [bib_ref] Cyber Knife stereotactic radiosurgery and hypofractionated stereotactic radiotherapy as first-line treatments for..., Manabe [/bib_ref] [bib_ref] Multisession radiosurgery for sellar and parasellar benign meningiomas: long-term tumor growth control..., Marchetti [/bib_ref] and proton SRS in 1 study . [bib_ref] Long-term evaluation of the effect of hypofractionated high-energy proton treatment of benign..., Ryttlefors [/bib_ref] The SRS prescription dose ranged from 11 to 17 Gy (median, 14 Gy), and the prescription isodose line ranged from 20% to 90% (median, 50%). The maximum point dose ranged from 15 to 32 Gy (median, 27 Gy). Doses varied widely across all analyzed papers; older series generally included treatments whose total dose was higher than in more recent series (15 to 12 Gy, marginal).
The most common schedule for HSRT was 25 Gy in 5 fractions. [bib_ref] Hypofractionated stereotactic radiotherapy (HFSRT) for who grade I anterior clinoid meningiomas (ACM), Demiral [/bib_ref] [bib_ref] Cyber Knife stereotactic radiosurgery and hypofractionated stereotactic radiotherapy as first-line treatments for..., Manabe [/bib_ref] [bib_ref] Multisession radiosurgery for sellar and parasellar benign meningiomas: long-term tumor growth control..., Marchetti [/bib_ref] The observed HSRT schedules ranged from 14 to 30 Gy delivered in 2 to 5 fractions. The prescription isodose line ranged from 44% to the 95% isodose line.

## Primary, adjuvant, or salvage therapy
Approximately half of the study population in this analysis underwent SRS as primary treatment. Two studies found that previous surgery was associated with worse tumor LC. [bib_ref] Gamma Knife surgery for convexity, parasagittal, and falcine meningiomas: clinical article, Hasegawa [/bib_ref] [bib_ref] Single-fractionated stereotactic radiosurgery for intracranial meningioma in elderly patients: 25-year experience at..., Hasegawa [/bib_ref] Similarly, El-Khatib et al [bib_ref] Stereotactic LINAC radiosurgery for the treatment of typical intracranial meningiomas. Efficacy and..., El-Khatib [/bib_ref] reported better PFS at 5, 10, and 15 yr when SRS was performed as a primary treatment as opposed to an adjuvant or salvage indication. From the Mayo clinic, Pollock et al 33 also reported prior surgery (hazard ratio: 6.9, P = .002) to be a negative risk factor in terms of local tumor control, as did Sheehan et al, [bib_ref] Gamma knife radiosurgery for sellar and parasellar meningiomas: a multicenter study, Sheehan [/bib_ref] who concluded that more than one prior surgery significantly increased the likelihood of tumor progression after SRS. However, a recent series by Kim et al 25 failed to detect any relationship with prior surgery and LC following SRS.

## Single-session or fractionated treatments
Single-session SRS was considered the reference treatment (level II recommendation) as an established practice, with consistent reports of LC with mature followup. [bib_ref] Linear accelerator-based stereotactic radiosurgery of intracranial meningiomas: results of the first 5..., Abdelaziz [/bib_ref] [bib_ref] Gamma Knife radiosurgery of skull base meningiomas, Aichholzer [/bib_ref] [bib_ref] Gamma Knife radiosurgery in sphenopetroclival meningiomas: preliminary experience at the Iran Gamma..., Azar [/bib_ref] [bib_ref] Outcomes and complications of Gamma Knife radiosurgery for skull base meningiomas, Bir [/bib_ref] [bib_ref] Development of dose-volume relation model for Gamma Knife surgery of non-skull base..., Chung [/bib_ref] [bib_ref] Postoperative Gamma Knife surgery for benign meningiomas of the cranial base, Davidson [/bib_ref] [bib_ref] Factors predicting local tumor control after Gamma Knife stereotactic radiosurgery for benign..., Dibiase [/bib_ref] [bib_ref] Stereotactic LINAC radiosurgery for the treatment of typical intracranial meningiomas. Efficacy and..., El-Khatib [/bib_ref] [bib_ref] Volumetric follow-up of meningiomas: a quantitative method to evaluate treatment outcome of..., Feigl [/bib_ref] [bib_ref] Gamma Knife surgery for convexity, parasagittal, and falcine meningiomas: clinical article, Hasegawa [/bib_ref] [bib_ref] Single-fractionated stereotactic radiosurgery for intracranial meningioma in elderly patients: 25-year experience at..., Hasegawa [/bib_ref] [bib_ref] Treatment modalities and outcomes for asymptomatic meningiomas, Jo [/bib_ref] [bib_ref] Longterm follow-up confirms the efficacy of LINAC radiosurgery for acoustic neuroma and..., Kalogeridi [/bib_ref] [bib_ref] Gamma knife radiosurgery for petroclival meningioma: long-term outcome and failure pattern, Kim [/bib_ref] [bib_ref] Radiosurgery as definitive management of intracranial meningiomas, Kondziolka [/bib_ref] [bib_ref] Long term experience of Gamma Knife radiosurgery for benign skull base meningiomas, Kreil [/bib_ref] [bib_ref] Long-term outcomes following Gamma Knife radiosurgery for small, newly diagnosed meningiomas, Lee [/bib_ref] [bib_ref] Predictors of response to Gamma Knife radiosurgery for intracranial meningiomas, Mansouri [/bib_ref] [bib_ref] Long-term tumor control of benign intracranial tumors after Gamma Knife radiosurgery in..., Massager [/bib_ref] [bib_ref] Single-fraction radiosurgery of benign intracranial meningiomas, Pollock [/bib_ref] [bib_ref] Gamma knife radiosurgery for sellar and parasellar meningiomas: a multicenter study, Sheehan [/bib_ref] [bib_ref] Long-term outcomes and patterns of tumor progression after Gamma Knife radiosurgery for..., Zada [/bib_ref] Five series evaluated HSRT and, although the data are limited, similar results were observed. [bib_ref] Hypofractionated stereotactic radiotherapy (HFSRT) for who grade I anterior clinoid meningiomas (ACM), Demiral [/bib_ref] [bib_ref] Cyber Knife stereotactic radiosurgery and hypofractionated stereotactic radiotherapy as first-line treatments for..., Manabe [/bib_ref] [bib_ref] Multisession radiosurgery for sellar and parasellar benign meningiomas: long-term tumor growth control..., Marchetti [/bib_ref] [bib_ref] Long-term evaluation of the effect of hypofractionated high-energy proton treatment of benign..., Ryttlefors [/bib_ref] Despite the limited number of the analyzed patients, 2 studies comparing SRS with HSRT would suggest a potential role of HSRT for large lesions. [bib_ref] Cyber Knife stereotactic radiosurgery and hypofractionated stereotactic radiotherapy as first-line treatments for..., Manabe [/bib_ref] Four studies, all analyzing SRS, found that a higher tumor volume is a negative prognostic factor in terms of tumor control. [bib_ref] Gamma Knife radiosurgery in sphenopetroclival meningiomas: preliminary experience at the Iran Gamma..., Azar [/bib_ref] [bib_ref] Stereotactic LINAC radiosurgery for the treatment of typical intracranial meningiomas. Efficacy and..., El-Khatib [/bib_ref] [bib_ref] Radiosurgery as definitive management of intracranial meningiomas, Kondziolka [/bib_ref] [bib_ref] Single-fraction radiosurgery of benign intracranial meningiomas, Pollock [/bib_ref] One of the few studies on HSRT (120 patients with follow-up longer than 3 yr) did not show any correlation between tumor volume and PFS. 31

## Imaging and contouring techniques
The oldest series included treatments based on computed tomography (CT) images. In more modern series, the target and the critical structures are additionally defined using magnetic resonance imaging (MRI) scans. Specific to the MRI protocol, the T1 axial contrast-enhanced MRI was the most used sequence to define the target volume (TV). The TV was contoured according to the contrast enhancement without any further margin in most of the series. A T2 fast spin echo with a slice thickness of 1 to 1.5 mm could be recommended for inner-ear and/or cranial nerve definition. Two studies specifically debated the inclusion of the dural tail and concluded that it should be included in the TV, although without any specific analysis to support such practice. [bib_ref] Gamma Knife radiosurgery of skull base meningiomas, Aichholzer [/bib_ref] [bib_ref] Factors predicting local tumor control after Gamma Knife stereotactic radiosurgery for benign..., Dibiase [/bib_ref] 

## Neurological outcomes and adverse events
Eight studies suggest a post-SRS neurological deterioration rate ranging from 0% to 13.3% (median, 7.4%). [bib_ref] Gamma Knife radiosurgery of skull base meningiomas, Aichholzer [/bib_ref] [bib_ref] Gamma Knife radiosurgery in sphenopetroclival meningiomas: preliminary experience at the Iran Gamma..., Azar [/bib_ref] [bib_ref] Postoperative Gamma Knife surgery for benign meningiomas of the cranial base, Davidson [/bib_ref] [bib_ref] Hypofractionated stereotactic radiotherapy (HFSRT) for who grade I anterior clinoid meningiomas (ACM), Demiral [/bib_ref] [bib_ref] Stereotactic LINAC radiosurgery for the treatment of typical intracranial meningiomas. Efficacy and..., El-Khatib [/bib_ref] [bib_ref] Gamma knife radiosurgery for petroclival meningioma: long-term outcome and failure pattern, Kim [/bib_ref] [bib_ref] Long term experience of Gamma Knife radiosurgery for benign skull base meningiomas, Kreil [/bib_ref] [bib_ref] Multisession radiosurgery for sellar and parasellar benign meningiomas: long-term tumor growth control..., Marchetti [/bib_ref] The meta-analysis, possible for 6 out of these studies, [bib_ref] Gamma Knife radiosurgery of skull base meningiomas, Aichholzer [/bib_ref] [bib_ref] Gamma Knife radiosurgery in sphenopetroclival meningiomas: preliminary experience at the Iran Gamma..., Azar [/bib_ref] [bib_ref] Postoperative Gamma Knife surgery for benign meningiomas of the cranial base, Davidson [/bib_ref] [bib_ref] Hypofractionated stereotactic radiotherapy (HFSRT) for who grade I anterior clinoid meningiomas (ACM), Demiral [/bib_ref] [bib_ref] Stereotactic LINAC radiosurgery for the treatment of typical intracranial meningiomas. Efficacy and..., El-Khatib [/bib_ref] [bib_ref] Gamma knife radiosurgery for petroclival meningioma: long-term outcome and failure pattern, Kim [/bib_ref] [bib_ref] Long term experience of Gamma Knife radiosurgery for benign skull base meningiomas, Kreil [/bib_ref] suggests an overall symptoms control rate of 95.1% (95% CI: 92.1%-97.5%); an estimate for the relative frequency of patients with symptom control was obtained, with high heterogeneity among studies (I2 = 53.8%) (see [fig_ref] FIGURE 2: Proportion of patients with symptom control [/fig_ref].
In general, toxicity rates ranged from 2.5% to 34.6% (median, 8.0%) in 13 papers. [bib_ref] Gamma Knife radiosurgery of skull base meningiomas, Aichholzer [/bib_ref] [bib_ref] Outcomes and complications of Gamma Knife radiosurgery for skull base meningiomas, Bir [/bib_ref] [bib_ref] Development of dose-volume relation model for Gamma Knife surgery of non-skull base..., Chung [/bib_ref] [bib_ref] Postoperative Gamma Knife surgery for benign meningiomas of the cranial base, Davidson [/bib_ref] [bib_ref] Hypofractionated stereotactic radiotherapy (HFSRT) for who grade I anterior clinoid meningiomas (ACM), Demiral [/bib_ref] [bib_ref] Factors predicting local tumor control after Gamma Knife stereotactic radiosurgery for benign..., Dibiase [/bib_ref] [bib_ref] Volumetric follow-up of meningiomas: a quantitative method to evaluate treatment outcome of..., Feigl [/bib_ref] [bib_ref] Gamma Knife surgery for convexity, parasagittal, and falcine meningiomas: clinical article, Hasegawa [/bib_ref] [bib_ref] Single-fractionated stereotactic radiosurgery for intracranial meningioma in elderly patients: 25-year experience at..., Hasegawa [/bib_ref] [bib_ref] Long term experience of Gamma Knife radiosurgery for benign skull base meningiomas, Kreil [/bib_ref] [bib_ref] Predictors of response to Gamma Knife radiosurgery for intracranial meningiomas, Mansouri [/bib_ref] [bib_ref] Single-fraction radiosurgery of benign intracranial meningiomas, Pollock [/bib_ref] A single study reported 2 cases of grade 4 toxicity (system of reporting not mentioned). [bib_ref] Cyber Knife stereotactic radiosurgery and hypofractionated stereotactic radiotherapy as first-line treatments for..., Manabe [/bib_ref] The meta-analysis was possible for 11 out of these studies [bib_ref] Gamma Knife radiosurgery of skull base meningiomas, Aichholzer [/bib_ref] [bib_ref] Outcomes and complications of Gamma Knife radiosurgery for skull base meningiomas, Bir [/bib_ref] [bib_ref] Development of dose-volume relation model for Gamma Knife surgery of non-skull base..., Chung [/bib_ref] [bib_ref] Postoperative Gamma Knife surgery for benign meningiomas of the cranial base, Davidson [/bib_ref] [bib_ref] Factors predicting local tumor control after Gamma Knife stereotactic radiosurgery for benign..., Dibiase [/bib_ref] [bib_ref] Volumetric follow-up of meningiomas: a quantitative method to evaluate treatment outcome of..., Feigl [/bib_ref] [bib_ref] Gamma Knife surgery for convexity, parasagittal, and falcine meningiomas: clinical article, Hasegawa [/bib_ref] [bib_ref] Long term experience of Gamma Knife radiosurgery for benign skull base meningiomas, Kreil [/bib_ref] [bib_ref] Predictors of response to Gamma Knife radiosurgery for intracranial meningiomas, Mansouri [/bib_ref] [bib_ref] Single-fraction radiosurgery of benign intracranial meningiomas, Pollock [/bib_ref] [bib_ref] Long-term outcomes and patterns of tumor progression after Gamma Knife radiosurgery for..., Zada [/bib_ref] ; the data showed an overall relative frequency of patients with toxicity of 11.0% (95% CI: 6.4%-16.5%) with a high heterogeneity (I2 = 88.1%) among studies [fig_ref] FIGURE 3: Proportion of patients with at least one toxicity event [/fig_ref].
Possible prognostic factors for a negative clinical outcome were higher marginal dose [bib_ref] Single-fractionated stereotactic radiosurgery for intracranial meningioma in elderly patients: 25-year experience at..., Hasegawa [/bib_ref] and larger volumes. [bib_ref] Single-fraction radiosurgery of benign intracranial meningiomas, Pollock [/bib_ref] Two studies [bib_ref] Single-fraction radiosurgery of benign intracranial meningiomas, Pollock [/bib_ref] suggest that the postradiosurgery edema rate may be related to the parafalcine, parasagittal, and convexity locations, while 2 studies 28,30 failed to observe a correlation between tumor location and clinical or radiological toxicity.
The clinical and toxicity data are summarized in [fig_ref] TABLE 4: Treatment Response in Terms of Symptom Control [/fig_ref].

# Discussion
The results of this systematic review support the effectiveness of SRS with respect to LC for WHO grade I meningioma. The 5-yr PFS ranged from 85% to 100% (median, 89%) and the 10-yr PFS ranged from 53% to 100% (median, 85%). These data are consistent with what we observe in the surgical literature [bib_ref] EANO guidelines for the diagnosis and treatment of meningiomas, Goldbrunner [/bib_ref] and may further explain the reason why SRS is being increasingly used as the primary therapeutic modality for meningioma.
Regarding the dose, the most recent data show that a marginal dose ranging from 15 to 12 Gy is generally sufficient with respect to durable LC. [bib_ref] Long term experience of Gamma Knife radiosurgery for benign skull base meningiomas, Kreil [/bib_ref] [bib_ref] Stereotactic radiosurgery of intracranial meningiomas, Pollock [/bib_ref] With regards to HSRT, the literature lacks the mature longterm outcomes to draw any firm conclusions; however, the preliminary data summarized in this review suggest a potential role of such a technique in selected cases, and the most common fractionation schedule is 25 Gy in 5 fractions.
Whether SRS as a primary treatment is preferable to adjuvant SRS remains to be confirmed. However, the evidence suggests that previous surgery may adversely affect tumor control. [bib_ref] Stereotactic LINAC radiosurgery for the treatment of typical intracranial meningiomas. Efficacy and..., El-Khatib [/bib_ref] [bib_ref] Gamma Knife surgery for convexity, parasagittal, and falcine meningiomas: clinical article, Hasegawa [/bib_ref] [bib_ref] Single-fractionated stereotactic radiosurgery for intracranial meningioma in elderly patients: 25-year experience at..., Hasegawa [/bib_ref] [bib_ref] Single-fraction radiosurgery of benign intracranial meningiomas, Pollock [/bib_ref] [bib_ref] Gamma knife radiosurgery for sellar and parasellar meningiomas: a multicenter study, Sheehan [/bib_ref] This could be related to a more complex definition of the target volume due to the complexity of the postoperative radiological images and/or to a potentially more aggressive inherent biology, given that patients required surgery as upfront treatment without a GTR possible. There is no evidence that adjuvant SRS may yield better results than salvage SRS, or vice versa. The choice has been largely been based on the clinician's or institution's preference and by taking into account a variety of factors such as tumor volume and location, previous surgery, clinical condition, age, etc. The specifics with respect to decision making were not stipulated in the relevant series and are beyond the scope of this review.
The issue regarding optimal imaging has not been defined yet; it is very important to establish a common strategy to delineate the TV and critical structures. Most studies define the TV as the contrast-enhanced tumor without margins. The role of biological imaging (CT/MRI positron emission tomography) requires a more in-depth investigation as well. Finally, regarding clinical outcome and toxicity, it is well known that specific treatment-related risks are often closely linked to the tumor location. For example, skull base meningioma often involves cranial nerves, and sparing them becomes challenging both in terms of surgery and SRS. Parasagittal meningiomas are also associated with an increased risk of post-SRS edema, and there is a lack of outcome data co-relating the risk of edema with dose fractionation and volume. The results on neurological toxicity from this review suggest a low risk of neurological deterioration (median 7.4%) and a low rate of serious adverse events (median 8.0%).
The role of the tumor location in term of both tumor control and clinical outcome is also of importance and requires further investigation.
Cognitive status and quality-of-life were not analyzed in the literature reviewed and are an active area of investigation. A summary of recommendations based on this review of the evidence as endorsed by the ISRS are provided in [fig_ref] TABLE 6: Summary of the ISRS Recommendations for SRS and Meningioma [/fig_ref].
Key Areas for Future Investigation -Although SRS in the treatment of intracranial benign meningioma is being increasingly used, the literature lacks class I and II evidence. Higher-level evidence is needed, particularly in regards to comparative analysis of SRS, HSRT, intensity modulated radiation therapy, charged particle radiation, and the various surgical techniques, in order to help clinicians make optimal therapeutic decisions. -The timing of SRS (primary, adjuvant, or as salvage treatment) requires further investigation.

## Recommendations level
Recommendation level II. SRS may be proposed as a primary treatment modality for an asymptomatic or mildly symptomatic meningioma, and should be considered when a complete surgical excision cannot be achieved or is not amenable Recommendation level II. After surgery, when a residual tumor is not evident or is minimal, a wait-and-scan approach appears to be reasonable with a regular radiological follow-up. At the time of recurrence or progression, SRS should be taken into consideration as a treatment modality. Some studies suggest that the recurrence/progression rate is lower when SRS is delivered as the primary treatment as compared to an adjuvant treatment and this remains to be confirmed. Recommendation level III. Single-fraction SRS with a dose of 12 to 15 Gy appears to be sufficient to manage benign intracranial meningioma. A prescription dose of at least 14 Gy would be advisable. Recommendation level III. HSRT may be considered for the treatment of large or/and critically located meningioma. Optimal practice has yet to be defined; however, 25 Gy in 5 fractions is a common approach. Recommendation level III. SRS generally entails a low risk of neurological deterioration. Patients may experience a clinical improvement without tumor shrinkage.
-Before HSRT can be recommended as a standard of care, mature follow-up of existing series is needed and ideally comparative clinical trials, especially for large or meningioma located in critical locations where SRS is limited by dose tolerances. -Further research as to the ideal MR sequence to define the TV, including the dural tail, and the incorporation of multimodal imaging, including biological imaging, is needed. -While there is consensus on the prescription dose for SRS, the best treatment schedule, dose-per-fraction, and total dose for HSRT require further investigations.

# Study limitations
The main limitations with respect to the conclusions from this systematic review lie in the lack of strong evidence and, in general, the lack of a common terminology with respect to endpoints, as pointed out by the risk-of-bias assessment.
The limited number of studies reporting the CI and/or the number of patients at risk at any given time limited the possibility of a meta-analysis about the efficacy.
Randomized controlled trials would be recommended; on the other hand, such studies are unlikely to be performed given current practice patterns, funding constraints, and clinical equipoise.

# Conclusion
SRS has traditionally been considered to be an adjuvant treatment modality in case of remnants or recurrent tumors, or as primary treatment for patients who are not surgically amenable. Regardless of the indication, SRS represents an important treatment option for most benign intracranial meningiomas.
Given the strong consensus of class III evidence studies with favorable outcomes, today SRS can be considered a primary treatment in many cases (recommendation level II). Tumor control rates are generally high, with rare events of post-SRS deterioration. However, due to the lack of class level I and II evidence, further investigation with longer periods of observation and larger, multiinstitutional series are needed. Finally, the development of common terminology criteria and reporting methodology is desirable to ensure consistency in the interpretation of the evidence.

# Disclosures
This evidence-based clinical practice guideline was supported by the International Stereotactic Radiosurgery Society. Dr Sahgal is an advisor/consultant with Elekta (Gamma Knife Icon); belongs to the Elekta MR Linac Research Consortium, Elekta Spine, Oligometastases, and Linac Based SRS Consortia; had past educational seminars with Elekta AB, Accuray Inc, Varian (CNS Teaching Faculty), and BrainLAB; and had a Medtronic Kyphon Research grant with Elekta AB Travel accommodations/expenses by Elekta, Varian, and BrainLAB. Dr Marchetti and Dr Fariselli have grants from Accuray Europe for unrelated research. Mr Paddick is a consultant for and has received a research grant from Elekta AB. Dr Regis is a consultant for and has received research grants from Medtronic and Elekta AB. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. Dr Sahgal is an advisor/consultant with Abbvie, Merck, Roche, Varian (Medical Advisory Group), BrainLAB, and VieCure (Medical Advisory Board). Dr Suh is consultant for Abbvie.

## Disclaimer
These consensus reviews should not be considered inclusive of all methods of care or exclusive of other methods or care reasonably directed to obtain similar results. The physician must make the ultimate judgment depending on characteristics and circumstances of individual patients. Adherence to this guideline will not ensure successful treatment in every situation. The authors of this guideline and the International Stereotactic Radiosurgery Society assume no liability for the information, conclusions, and recommendations contained in this report.
[fig] FIGURE 1: Flowchart of search process. [/fig]
[fig] 4: yr rate; b = 8 yr rate. [/fig]
[fig] FIGURE 2: Proportion of patients with symptom control. ES = estimate; I2 = heterogeneity Higgins index; p = P-value. [/fig]
[fig] FIGURE 3: Proportion of patients with at least one toxicity event. ES = estimate; I2 = heterogeneity Higgins index; p = P-value. [/fig]
[table] TABLE 1: Studies, Tumors, and Treatments Features [/table]
[table] TABLE 2: The Meningiomas Sites Are Here Described [/table]
[table] TABLE 3: Local Control and Progression-Free-Survival Rates [/table]
[table] TABLE 6: Summary of the ISRS Recommendations for SRS and Meningioma [/table]