Outcomes following stereotactic radiosurgery for foramen magnum meningiomas: a single-center experience and systematic review of the literature

Constantine L. KarrasDepartment of Neurological Surgery, Northwestern University, Chicago;

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Pavlos TexakalidisDepartment of Neurological Surgery, Northwestern University, Chicago;

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Jeffrey Z. NieSchool of Medicine, Southern Illinois University, Springfield; and

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S. Joy TrybulaDepartment of Neurological Surgery, Northwestern University, Chicago;

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Mark W. YoungbloodDepartment of Neurological Surgery, Northwestern University, Chicago;

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Sean SachdevDepartment of Radiation Oncology, Northwestern University, Chicago, Illinois

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Tarita O. ThomasDepartment of Radiation Oncology, Northwestern University, Chicago, Illinois

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John KalapurakalDepartment of Radiation Oncology, Northwestern University, Chicago, Illinois

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James P. ChandlerDepartment of Neurological Surgery, Northwestern University, Chicago;

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Stephen T. MagillDepartment of Neurological Surgery, Northwestern University, Chicago;

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OBJECTIVE

Foramen magnum meningiomas (FMMs) pose a unique challenge given their intimate anatomical relationship with the craniovertebral junction. While resection has been studied extensively, much less has been reported about the use of stereotactic radiosurgery (SRS) for FMMs. This study includes what is to the authors’ knowledge the first systematic review in the literature that summarizes patient and treatment characteristics and synthesizes outcomes following SRS for FMMs.

METHODS

A retrospective chart review was conducted at a single major academic institution, and a systematic review was performed according to PRISMA guidelines. The initial search on the PubMed and Scopus databases yielded 530 results. Key data extracted from both databases included Karnofsky Performance Status (KPS) score and neurological deficits at presentation, tumor location, treatment indication, target volume, single versus multiple fractions, marginal and maximum doses, isodose line, clinical and radiographic follow-up times, and primary (clinical stability and local control at last follow-up) and secondary (mortality, adverse radiation events, time to regression, progression-free survival) outcomes.

RESULTS

The study patients included 9 patients from the authors’ institution and 165 patients across 4 studies who received SRS for FMMs. The weighted median age at treatment was 60.2 years, and 73.9% of patients were female. Common presenting symptoms included headache (33.9%), dizziness/ataxia (29.7%), cranial nerve deficit(s) (27.9%), numbness (22.4%), weakness (15.2%), and hydrocephalus (4.2%). Lateral/ventrolateral (64.2%) was the most common tumor location. SRS was utilized as the primary therapy in 63.6% of patients and as salvage (21.8%) or adjuvant (14.5%) therapy for the rest of the patients. Most patients (91.5%) were treated with a single fraction. A tumor with a weighted median target volume of 2.9 cm3 was treated with a weighted median marginal dose, maximum dose, and isodose line of 12.9 Gy, 22.8 Gy, and 58%, respectively. Clinical stability and local control at last follow-up were achieved in 98.8% and 97.0% of patients, respectively. Only one possible adverse radiation event occurred, and no mortality directly related to the tumor or SRS was reported.

CONCLUSIONS

In this retrospective analysis and systematic review, the authors demonstrate SRS to be an effective and safe treatment option for carefully selected patients with FMMs.

ABBREVIATIONS

ARE = adverse radiation event; CN = cranial nerve; FMM = foramen magnum meningioma; KPS = Karnofsky Performance Status; LC = local control; PFS = progression-free survival; SRS = stereotactic radiosurgery.

OBJECTIVE

Foramen magnum meningiomas (FMMs) pose a unique challenge given their intimate anatomical relationship with the craniovertebral junction. While resection has been studied extensively, much less has been reported about the use of stereotactic radiosurgery (SRS) for FMMs. This study includes what is to the authors’ knowledge the first systematic review in the literature that summarizes patient and treatment characteristics and synthesizes outcomes following SRS for FMMs.

METHODS

A retrospective chart review was conducted at a single major academic institution, and a systematic review was performed according to PRISMA guidelines. The initial search on the PubMed and Scopus databases yielded 530 results. Key data extracted from both databases included Karnofsky Performance Status (KPS) score and neurological deficits at presentation, tumor location, treatment indication, target volume, single versus multiple fractions, marginal and maximum doses, isodose line, clinical and radiographic follow-up times, and primary (clinical stability and local control at last follow-up) and secondary (mortality, adverse radiation events, time to regression, progression-free survival) outcomes.

RESULTS

The study patients included 9 patients from the authors’ institution and 165 patients across 4 studies who received SRS for FMMs. The weighted median age at treatment was 60.2 years, and 73.9% of patients were female. Common presenting symptoms included headache (33.9%), dizziness/ataxia (29.7%), cranial nerve deficit(s) (27.9%), numbness (22.4%), weakness (15.2%), and hydrocephalus (4.2%). Lateral/ventrolateral (64.2%) was the most common tumor location. SRS was utilized as the primary therapy in 63.6% of patients and as salvage (21.8%) or adjuvant (14.5%) therapy for the rest of the patients. Most patients (91.5%) were treated with a single fraction. A tumor with a weighted median target volume of 2.9 cm3 was treated with a weighted median marginal dose, maximum dose, and isodose line of 12.9 Gy, 22.8 Gy, and 58%, respectively. Clinical stability and local control at last follow-up were achieved in 98.8% and 97.0% of patients, respectively. Only one possible adverse radiation event occurred, and no mortality directly related to the tumor or SRS was reported.

CONCLUSIONS

In this retrospective analysis and systematic review, the authors demonstrate SRS to be an effective and safe treatment option for carefully selected patients with FMMs.

Although 35%–50% of intracranial meningiomas arise from a skull base location,1 foramen magnum meningiomas (FMMs) are quite rare, comprising only 2%–3% of meningiomas.2,3 Meningiomas do, however, account for 75% of all extramedullary lesions at the foramen magnum.3 In symptomatic patients, FMMs typically present with lower cranial neuropathies, myelopathy, and/or ataxia. Given their intimate anatomical relationship with the brainstem, critical neurovascular structures, and the craniovertebral junction, FMMs pose a unique challenge when considering treatment options.4

While surveillance and conservative management are warranted for small and asymptomatic tumors, growing or symptomatic lesions are commonly treated with resection, stereotactic radiosurgery (SRS), or a combination of both.5 Maximal safe resection, ideally gross-total resection, is the goal for surgically treated meningiomas and provides excellent long-term tumor control,6 but may be difficult to achieve for FMMs. Surgical risks inherent to the approach, as well as to patient age and comorbidities, can be particularly high for FMMs and must be accounted for when weighing treatment options. Rates of permanent morbidity and peri- or postoperative mortality can be as high as 15%–50% and 0%–25%, respectively.79 Morbidity can be significant, including dysphagia requiring a permanent feeding tube or difficulty handling secretions requiring tracheostomy. Greater tumor volume, vertebral artery encasement, subtotal resection, pathological mitoses, and ventral/ventrolateral location have been previously identified as risk factors for postoperative complications following resection of FMMs.4,10 Thus, SRS is an important primary or adjuvant treatment for appropriately selected FMMs, for which reducing mass effect is not required.11,12

SRS is an essential tool in the management of intracranial meningiomas and provides durable long-term tumor control with a favorable safety profile.13 The treatment of FMMs with SRS was first documented in the 1990s for patients who were medically unable to tolerate surgery.14 Since that time, SRS has been selectively used in the management of FMMs. However, due to the rarity of these tumors and because many FMMs present with mass effects requiring surgical decompression, the largest studies of SRS for FMMs are limited by study size. In comparison to meningiomas in other skull base locations, much less has been studied and reported about the use of SRS for FMMs. This institutional case series and review is to our knowledge the first systematic review in the literature that summarizes patient and treatment characteristics and synthesizes outcomes following SRS for FMMs.

Methods

This systematic review was performed according to the PRISMA guidelines.15 Additionally, a retrospective chart review was conducted at a single major academic medical center for patients with FMMs treated with SRS from January 2000 through March 2022. The Northwestern University IRB approved this study. For the retrospective chart review, the same inclusion and exclusion criteria were used as described below for the systematic review, except that 6 months of radiographic and clinical follow-up time was required for inclusion. Additionally, the same characteristics and variables, as well as primary and secondary outcomes, were extracted from the retrospective chart review as described below for the systematic review. Ultimately, the data from the retrospective chart review were analyzed and described separately, then synthesized and included with the data from the systematic review of the literature.

Search Strategy and Selection Criteria

The PubMed and Scopus databases were queried for published articles through March 2022. The search algorithm was the following: ((foramen magnum) OR FMM OR FM OR (posterior fossa)) AND meningioma AND (radiosurgery OR radiotherapy OR radiation OR gamma OR cyber). The search was conducted by two independent investigators (C.L.K. and P.T.).

After the initial search, duplicate articles were removed. The remaining abstracts and titles were screened for relevance. The studies progressing to a full-text review were screened using prespecified inclusion and exclusion criteria. Inclusion criteria included the following: 1) articles published in English; 2) tumor type: meningiomas (based on radiographic appearance or pathology if adjuvant/salvage therapy); 3) location classified as foramen magnum; 4) meningiomas undergoing primary or adjuvant/salvage therapy with SRS (single fraction or hypofractionated); 5) patient and radiosurgery treatment characteristics clearly described; and 6) clinical and radiographic outcomes of interest reported. Exclusion criteria included 1) case reports or case series of fewer than 5 patients; 2) conference abstracts; 3) animal or biomechanical studies; 4) articles not in English; 5) clear overlap of patients from another study, determined via screening of authors, institutions, and publication dates; 6) meningiomas grouped with other tumor types and outcomes not clearly delineated; 7) foramen magnum location grouped with other locations (such as posterior fossa) and outcomes not clearly delineated; 8) no clear description of patient/treatment characteristics; and 9) no clear description of clinical and radiographic outcomes. The articles that met the criteria were included in the study. The references of the included studies were also manually reviewed to identify further eligible articles.

Data Extraction and Outcomes

All studies were reviewed, and the data extracted included first author, title, year of publication, years analyzed, study type, level of evidence, type of SRS used, total patients, median age, patient sex, Karnofsky Performance Status (KPS) score at presentation, symptoms at presentation (including asymptomatic, headache, cranial nerve [CN] deficit[s], weakness, numbness, dizziness/ataxia, hydrocephalus), foramen magnum location (ventral, lateral/ventrolateral, dorsal/dorsolateral), treatment indication (primary, adjuvant, salvage), median target volume, single fraction versus hypofractionated, median marginal dose, median maximum dose, median isodose line, number of isocenters, median clinical follow-up, median radiographic follow-up, definition of radiographic progression versus regression, and outcomes of interest.

The primary outcomes assessed were clinical stability (stable or improved neurologically at last follow-up) and local control (LC; tumor volume stable or regressed at last follow-up). Secondary outcomes assessed included mortality, adverse radiation events (AREs), median time to regression, and progression-free survival (PFS).

Risk of Bias Assessment

A level of evidence was designated for each study using the criteria adapted from the American Society of Plastic Surgeons levels of evidence for therapeutic studies.16 The ROBINS-I (Risk of Bias in Non-Randomised Studies of Interventions) tool was used to delineate a risk of bias for all included studies.17 The risk of bias for our systematic review was determined by considering the risk of bias for all the included studies.

Results

Use of the search strategy described above led to the identification of 389 articles after duplicates were removed. After irrelevant studies were excluded based on title and abstract, 24 articles underwent full-text evaluation. Three studies12,14,18 met all inclusion criteria but were excluded due to overlap of patients from included studies based on a review of the authors and institutions. Ultimately, 3 studies3,9,19 fulfilled our selection criteria and were included in this review, as presented in the PRISMA flow diagram (Fig. 1). The study designs included a single-center retrospective study and 2 multicenter retrospective studies, all of which were classified as level III evidence with a moderate risk of bias (Supplementary Table 1), predisposing our review to an overall moderate risk of bias.

FIG. 1.
FIG. 1.

PRISMA search flow diagram. Data added to the PRISMA template (from Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med. 2009;6[7]:e1000097) under the terms of the Creative Commons Attribution License.

After applying the same inclusion and exclusion criteria, we identified 9 patients from our single-center retrospective chart review. The patient demographics, tumor and treatment characteristics, and primary outcomes from the retrospective chart review are listed in Table 1. The data were then synthesized and pooled with the data extracted from the systematic review, as described below and shown in subsequent tables.

TABLE 1.

Patient demographic, tumor, and SRS treatment characteristics, and primary outcomes from a single center

Patient No.Age (yrs)/SexTx Date (mo/day/yr)Pre-Tx KPS/SxTumor LocationTx IndicationTarget Vol (cm3)Margin Dose (Gy)Max Dose (Gy)Tumor Control*/Radiographic FU (mos)Clinical Stability/FU (mos)Time to Regression (mos)
168/M5/7/0990/noneL/VLPT4.716.033.3Regression/133Stable/1336
244/M10/21/0990/mild CN X–XII palsies (postop)L/VLST2.012.024.0Regression/145Improved/14540
356/F11/18/09100/NoneL/VLPT10.712.024.0Stable/149Stable/149
435/F11/23/09 100/NoneL/VLPT1.616.032.0Stable/144Stable/144
557/F4/7/1090/mild CN X palsyL/VLST5.513.5Stable/130Improved/130
658/M2/23/12100/HAL/VLAT3.612.023.9Regression/57Improved/433
758/F1/15/1590/HAL/VLST2.512.024.4Regression/65Improved/6529
856/F1/27/16100/noneL/VLST3.714.028.2Stable/65Stable/65
974/F10/19/1790/noneVPT2.212.024.0Stable/28Stable/29

AT = adjuvant therapy; FU = follow-up; HA = headache; L/VL = lateral/ventrolateral; PT = primary therapy; ST = salvage therapy; Sx = symptoms; Tx = treatment; V = ventral; — = data unavailable.

Determined by absolute change in tumor volume after treatment. Regression = 10% decrease; progression = 10% increase; stable = unchanged by more than 10%.

Characteristics of Included Studies and Patients

Overall, 4 studies, including 165 total patients treated with SRS for FMMs, were included (Table 2). The weighted median age of the cohort was 60.2 years (range 57.0–64.0 years), and the majority of patients were female (73.9%, n = 122). The weighted median pretreatment KPS score was 94, with an overall range of 40 to 100. In studies with available data, only 29.7% (n = 38/137) of patients were asymptomatic at the time of treatment.

TABLE 2.

Patient demographic and pretreatment characteristics from each included study

Authors & YearNo. of Patients (% F)Age (yrs)*Pre-Tx KPS Score*Tumor LocationAsymptomatic Dizziness/AtaxiaHACN Deficit(s)NumbnessWeaknessHydrocephalus
Mehta et al., 20181957 (68.4%)64.0 (30–83)90 (40–100)V (17.5%), L/VL (68.4%), D/DL (14.0%)15 (26.3%)1720 (35.1%)22 (38.6%)18 (31.6%)12 (21.1%)6 (10.5%)
Akyoldaş et al., 2021337 (89.2%)58.0 (23–74)90 (40–90)V (21.6%), L/VL (64.9%), D/DL (13.5%)2024 (64.9%)10 (27.0%)11 (29.7%)5 (13.5%)1 (2.7%)
Ehret et al., 2022962 (71.0%)58.5 (33.7–89.6)100 (50–100)V (22.6%), L/VL (56.5%), D/DL (21.0%)18 (29.0%)1210 (16.1%)12 (19.4%)8 (12.9%)8 (12.9%)0
Present study9 (66.6%)57.0 (35–74)90 (90–100)V (11.1%), L/VL (88.8%), D/DL (0%)5 (55.5%)02 (22.2%)2 (22.2%)00 0
Total165 (73.9%)60.2 (57–64)94 (90–100)V (20.0%), L/VL (64.2%), D/DL (15.8%)38 (29.7%)49 (29.7%)56 (33.9%)46 (27.9%)37 (22.4%)25 (15.2%)7 (4.2%)

D/DL = dorsal/dorsolateral. All percentages are proportions of the total number of patients unless otherwise specified. Total values are computed across all studies with available data and are either sums (percentage of total) or medians weighted by the study sample size (range of medians across studies).

Reported as median (range).

Can exceed the total number of patients since some patients presented with both dizziness and ataxia.

The most common symptoms at presentation were headache (33.9%, n = 56) and dizziness/ataxia (28.3%, n = 49). Other presenting symptoms included CN deficit(s) (27.9%, n = 46), numbness (22.4%, n = 37), weakness (15.2%, n = 25), and hydrocephalus (4.2%, n = 7). Lateral/ventrolateral was the most common tumor location (64.2%, n = 106), followed by ventral (20.0%, n = 33) and dorsal/dorsolateral (15.8%, n = 26).

Summary and Description of Treatment (SRS) Characteristics

SRS was utilized as the primary therapy in most patients (63.6%, n = 105) (Table 3). Radiosurgery was indicated for salvage therapy (following recurrence or progression) after resection and as adjuvant therapy for residual disease in 21.8% (n = 36) and 14.5% (n = 24) of patients, respectively. Three of 4 studies utilized the Gamma Knife system, while 1 study9 utilized the CyberKnife robotic radiosurgery system. SRS was administered as a single fraction in 91.5% (n = 151) of cases and as multiple fractions in 8.5% (n = 14) of cases.

TABLE 3.

Radiosurgery treatment parameters and characteristics from each included study

Authors & YearTx StrategyRadiotherapy TypeHF: No. of FractionsTarget Vol (ml)*Marginal Dose (Gy)*Max Dose (Gy)*Isodose Line (%)*
Mehta et al., 201819PT (68.4%), AT (12.3%), ST (19.3%)SF (100%), HF (0%)2.9 (0.4–17.0)12.5 (10.0–16.0)25.0 (14.0–43.0)50 (30–80)
Akyoldaş et al., 20213PT (62.2%), AT (8.1%), ST (29.7%)SF (94.5%), HF (5.4%)53.3 (0.6–17.6)SF: 12.0 (8.0–14.0), HF: 20.0SF: 24.0 (16.0–30.0), HF: 45.0 (40.0–50.0)SF: 50 (40–50), HF: 45 (40–50)
Ehret et al., 20229PT (62.9%), AT (21.0%), ST (16.1%)SF (80.6%), HF (19.4%)3–52.6 (0.2–13.7)SF: 14.0 (12.0–17.0), HF: 21.0 (19.5–26.0)20.0 (15.0–37.8)70 (61–80)
Present studyPT (44.4%), AT (11.1%), ST (44.4%)SF (100%), HF (0%)3.6 (1.6–10.7)12.0 (12.0–16.0)24.0 (24.0–33.0)50 (50–50)
TotalPT (63.6%), AT (14.5%), ST (21.8%)SF (91.5%), HF (8.5%)2.9 (2.6–3.6)12.9 (12.0–14.0)22.8 (20.0–25.0)58 (50–70)

HF = hypofractionated; SF = single fraction.

All percentages are proportions of the total number of patients unless otherwise specified. Total values are computed across all studies with available data and are either sums (percent of total) or medians weighted by the study sample size (range of medians across studies).

Reported as median (range) and include patients treated with SF and HF radiotherapy unless otherwise specified.

The weighted median target volume was 2.9 (range 2.6–3.6) cm3. In single-fraction treatments, the weighted median values (range) for marginal dose, maximum dose, and isodose line were 12.9 (12.0–14.0) Gy, 22.8 (20.0–25.0) Gy, and 58% (50%–70%), respectively. The median maximum dose to the brainstem was reported in 1 study9 as 13.5 (range 6.7–26.5) Gy, while another study3 reported that the brainstem dose was "kept below 12 Gy when possible."

A subgroup of patients (n = 14) across 2 studies underwent hypofractionated SRS. The indication for hypofractionated SRS seemed to be larger tumor volume. In one study,3 these patients were administered a median marginal dose of 20.0 Gy in 5 sessions and a median maximum dose of 45.0 Gy, at a median isodose line of 45%. In the other study,9 these patients were administered a median marginal dose of 21.0 Gy in 3–5 sessions, and tumor volumes were significantly larger (median volume 5.3 vs 2.1 cm3; p < 0.01) than those in patients undergoing single-fraction treatment.

Primary Outcomes: Clinical Stability and LC

Patients were followed clinically for a weighted median period of 54 (range 29–130) months (Table 4). Clinical stability (stable or improved neurologically through last follow-up) was reported in 98.8% (n = 163) of patients. Overall, 58.8% (n = 97) of patients remained stable neurologically, 40.0% (n = 66) experienced some degree of neurological improvement, and 1.2% (n = 2) worsened neurologically.

TABLE 4.

Radiosurgery outcomes from each included study

Authors & YearClinical FU (mos)*Clinical StabilityRadiographic FU (mos)*Regression/Progression ThresholdLocal Control§Tumor Regression Time to Regression (mos)*AREPFS
Mehta et al., 20181953 (6–196)57 (100%)36 (6–196)10%53 (93.0%)25 (43.9%) 16 (6–55)1 (1.8%)5- & 10-yr: 92%
Akyoldaş et al., 2021380 (18–151)37 (100%)84 (18–144)20%36 (97.3%)13 (35.1%)22 (17–34)05- & 10-yr: 100%
Ehret et al., 2022929 (6–132)60 (96.8%)29 (6–132)10%62 (100%)43 (69.4%)05-yr: 93%
Present study130 (29–149)9 (100%)130 (29–149)10%9 (100%)4 (44.4%)18 (3–40)0
Total54 (29–130)163 (98.8%)49 (29–130)160 (97.0%)85 (51.5%)18 (16–22)1 (0.6%)5-yr: 94.3% (92–100%), 10-yr: 95.1% (92–100%)

All percentages are proportions of the total number of patients. Total values are computed across all studies with available data and are either sums (percent of total) or medians weighted by the study sample size (range of medians across studies).

Reported as median (range).

Defined as stable or improved neurological symptoms at last clinical follow-up.

Refers to the threshold at which the absolute percent change in tumor volume after treatment is considered regression (decrease) or progression (increase).

Defined as tumor stability or regression at radiographic follow-up.

The weighted median radiographic follow-up period was 49 months (range 29–130) months. Definitions of radiographic progression and regression varied across studies based on percentage increase (progression) or decrease (regression) from the pretreatment volume: 3 studies9,19 (including ours) utilized a 10% threshold, while the other study3 utilized a 20% threshold. Tumors were characterized as stable if they did not meet the above criteria for progression or regression. LC (defined as stability or regression) at last follow-up was achieved in 97.0% (n = 160) of patients. Overall, 51.5% (n = 85) of tumors regressed, 45.5% (n = 75) were stable, and 3.0% (n = 5) progressed in volume by last follow-up after treatment with SRS.

Secondary Outcomes

No mortalities were attributed to the disease (FMM) or treatment (SRS). A total of 7 (4.2%) mortalities were reported, all due to unrelated factors or comorbidities in the cited articles. No mortalities occurred in our retrospective institutional series either. Radiation toxicity was extremely rare, with only 1 (0.6%) reported possible ARE across all studies. This patient developed delayed hearing loss and new numbness without radiographic changes,19 which was classified as a potential ARE. The weighted median time to regression was 18 months from 3 studies3,19 (including ours) with available data. The 3 largest studies calculated PFS rates and reported 5-year PFS rates of 100%,3 93%,9 and 92%.19 PFS at 10 years remained at 100%3 and 92%19 in the 2 studies with available data.

Discussion

Key Results

This case series and systematic review of SRS for FMM demonstrates that SRS is very effective at providing long-term tumor control, with 5- and 10-year actuarial PFS rates over 94% with a very low rate of adverse events. These data highlight the importance of considering SRS as a primary or adjuvant option for appropriate selected FMMs in order to reduce treatment-related morbidity.

Surgery for FMMs

Despite being relatively rare,2,3 much has been reported about the surgical management of FMMs given their unique and difficult location and relationship with the brainstem, lower CNs, and critical vascular structures. The surgical approach and strategy are often dictated by the tumor and its location within the foramen magnum. Some groups have reported success with the endoscopic endonasal approach to the craniovertebral junction for strictly anterior FMMs.2022 More traditionally, the extreme lateral or far lateral approach (with or without some degree of condylectomy)23 has been used for anterior, anterolateral, or lateral tumors within the foramen magnum.8 Midline suboccipital craniotomies can be employed for posterior or posterolateral tumors of the foramen magnum, which are the least common locations for these tumors.4,10

Multiple large series reporting outcomes following resection of FMMs have been published,4,8,10,2429 including a useful classification system by Bruneau and George.26 Although some of the surgical outcomes are impressive, it is critical to respect the risk of neurological injuries at the craniovertebral junction when considering treatment strategies. In some of the larger series, transient or permanent morbidity rates have been reported to be as high as 40%–50%.4,10 Frequently identified complications included CSF leak or hydrocephalus, new weakness/numbness/gait disturbance, pneumonia, and new or worsened lower cranial neuropathies. These complications can have serious implications, resulting in reoperations, aspiration events, significant deteriorations in quality of life, and need for tracheostomy or percutaneous endoscopic gastrostomy (PEG) feeding. In the largest single-center surgical series of 185 patients,10 rates of nasal feeding and tracheostomy placement were 41.1% and 29.2%, respectively, highlighting the unforgiving nature of this anatomical region despite technical excellence (GTR rate 83.2%) and relatively high patient volume. While a maximal safe resection certainly plays a key role in the management of growing, symptomatic FMMs, SRS represents an important tool in the treatment paradigm.

Role of SRS in Treatment of FMMs

Our systematic review revealed extremely high rates of clinical/neurological stability (98.8%) and LC (97.0%) after SRS, signifying that it is a safe and effective treatment option in well-selected patients with FMMs. Indications for SRS treatment varied (primary therapy 63.6%, salvage therapy 21.8%, adjuvant therapy 14.5%), highlighting the versatility of SRS application and its effectiveness across all indications.

Reasonable treatment algorithms have been proposed by two groups for FMMs.4,12 Generally, SRS can be considered as a primary treatment option in asymptomatic or minimally symptomatic FMMs that demonstrate growth during surveillance. In higher-risk surgical patients (with older age, multiple comorbidities, lower KPS score at presentation), it may even be a viable primary option for symptomatic lesions without significant brainstem compression. Patients at our institution who underwent primary SRS therapy all met this criterion. Patients with larger tumors (> 35 mm in diameter),12 particularly if symptomatic with significant brainstem compression, should undergo maximal safe resection in medically optimized patients after thorough risk/benefit analysis and counseling. SRS should be strongly considered for adjuvant therapy after subtotal resection (especially if pathology is grade 2 or 3, or if high-risk features are present) or salvage therapy after recurrence or progression. The efficacy and safety profile of SRS, and its usefulness as an adjuvant, may offer surgeons the opportunity to avoid surgical morbidity, knowing that small residual tumors can be treated effectively with SRS.

Until 2018, relatively little had been documented about the application and outcomes following SRS for FMMs aside from 1 study12 of 21 patients at a single institution, case reports, and small series of fewer than 10 patients.14,18 Since 2018, 3 larger-cohort studies3,9,19 have been published regarding outcomes following SRS for FMMs. These recent publications may suggest that although SRS treatment for FMMs has been historically underutilized, it is more recently gaining traction and recognition as an important treatment option. Notably, other studies1,30,31 have reviewed outcomes following SRS for posterior fossa or skull base tumors that may have included, but did not clearly delineate, FMMs specifically. Location-specific studies are essential, particularly for FMMs in the posterior fossa where the morbidity of treatment can vary by tumor location. Given the rarity of FMMs, a systematic review is useful to synthesize data regarding these location-specific outcomes and inform therapeutic decision-making.

The historic success of SRS for such lesions can be attributed to highly accurate positioning and localization—the Gamma Knife platform is able to deliver treatment with submillimeter accuracy.32 However, such dedicated intracranial treatment systems have to be used with care when approaching more inferior lesions around the craniocervical junction. Even if the treatment is technically feasible (i.e., enough latitude for the treatment isocenter to coincide with the target), cranium-based immobilization may not be reliable in ensuring correct patient position throughout the treatment. At our institution, the decision to proceed with such treatment is undertaken only after careful consultation with colleagues in medical physics as well as consensus between the neurosurgeon and treating radiation oncologist. Fortunately, if there is concern that the lesion is "too inferior," advancement in modern sophisticated image-guided linear accelerator systems can still make radiosurgical treatment feasible. These systems, which are also available at our institution, allow larger immobilization devices that can minimize motion of the craniocervical junction and on-demand image guidance to verify positioning at the time of treatment.

Biases, Shortcomings, and Future Directions

Certain limitations and biases should be noted when considering the data presented in this review. Selection bias is present in all the studies we reviewed, including our institutional series, as the treating investigators deemed the patients SRS candidates, and there are no randomized or matched comparisons that can be made with surgically treated meningiomas. There is a low number of included studies and patients due to the inherently rare prevalence of FMMs, as well as the potential underutilization of SRS for FMMs historically. We did exclude one of the larger and more significant studies12 because patients later overlapped in the included multi-institutional study.19 The overall follow-up time was relatively short in the context of the natural history of meningiomas, although of the included studies our cohort had the longest median follow-up time of 130 months. While out of the scope of this review, fractionated external beam radiotherapy is another potentially effective modality—especially for large lesions that may be difficult to treat with SRS. Additionally, SRS application to this anatomical location is constrained by the brainstem dose (generally up to 12 Gy is tolerated) and inability to treat below the foramen magnum for lesions that extend into the cervical spine.3,9 Last, there were no control cohorts in any of these studies, although it would have been useful to compare the rates of clinical stability and LC to those for patients undergoing resection or surveillance.

Conclusions

Although FMMs comprise a small minority of skull base tumors, they frequently mandate intervention and represent a formidable challenge. While GTR represents the gold standard of management for these tumors, surgical risks and morbidity can be high in this location. The risk of serious morbidity may be unacceptably elevated in certain patients and tumor types, making SRS an important option for primary treatment or adjuvant/salvage therapy. In this single-center retrospective chart review and systematic review of outcomes following SRS for FMMs, we have shown that SRS is an effective and safe treatment option that should be considered in appropriate and carefully selected patients.

Acknowledgments

This work was supported by funding from the Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Cancer Center to S.T.M.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: all authors. Acquisition of data: Karras, Texakalidis, Nie, Trybula, Youngblood. Analysis and interpretation of data: Karras, Texakalidis, Nie, Sachdev, Thomas, Kalapurakal, Chandler. Drafting the article: Karras, Texakalidis, Nie, Trybula, Youngblood, Sachdev, Magill. Critically revising the article: Karras, Texakalidis, Nie, Youngblood, Sachdev, Thomas, Kalapurakal, Chandler, Magill. Reviewed submitted version of manuscript: Karras, Texakalidis, Nie, Trybula, Sachdev, Thomas, Kalapurakal, Chandler, Magill. Approved the final version of the manuscript on behalf of all authors: Karras. Statistical analysis: Karras, Nie. Study supervision: Karras, Chandler, Magill.

Supplemental Information

Online-Only Content

Supplemental material is available online.

References

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    Aichholzer M, Bertalanffy A, Dietrich W, et al. Gamma knife radiosurgery of skull base meningiomas. Acta Neurochir (Wien). 2000;142(6):647653.

  • 2

    Arnautović KI, Al-Mefty O, Husain M. Ventral foramen magnum meninigiomas. J Neurosurg. 2000;92(1 suppl):7180.

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    Akyoldaş G, Samancı Y, Yılmaz M, Şengöz M, Peker S. Long-term results of gamma knife radiosurgery for foramen magnum meningiomas. Neurosurg Rev. 2021;44(5):26672673.

    • Crossref
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    Magill ST, Shahin MN, Lucas CG, et al. Surgical outcomes, complications, and management strategies for foramen magnum meningiomas. J Neurol Surg B Skull Base. 2019;80(1):19.

    • Crossref
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    Jumah F, Narayan V, Samara A, et al. Efficacy and safety of gamma knife radiosurgery for posterior cranial fossa meningioma: a systematic review. Neurosurg Rev. 2020;43(4):10891099.

    • Crossref
    • Search Google Scholar
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  • 6

    Javalkar V, Banerjee AD, Nanda A. Posterior cranial fossa meningiomas. J Neurol Surg B Skull Base. 2012;73(1):110.

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    Bir SC, Maiti TK, Nanda A. Foramen magnum meningiomas. Handb Clin Neurol. 2020;170:167174.

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    Bruneau M, George B. Foramen magnum meningiomas: detailed surgical approaches and technical aspects at Lariboisière Hospital and review of the literature. Neurosurg Rev. 2008;31(1):1933.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Ehret F, Kufeld M, Fürweger C, et al. The role of stereotactic radiosurgery in the management of foramen magnum meningiomas—a multicenter analysis and review of the literature. Cancers (Basel). 2022;14(2):341.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    Li D, Wu Z, Ren C, et al. Foramen magnum meningiomas: surgical results and risks predicting poor outcomes based on a modified classification. J Neurosurg. 2017;126(3):661676.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Cheshier SH, Hanft SJ, Adler JR, Chang SD. CyberKnife radiosurgery for lesions of the foramen magnum. Technol Cancer Res Treat. 2007;6(4):329336.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    Zenonos G, Kondziolka D, Flickinger JC, Gardner P, Lunsford LD. Gamma Knife surgery in the treatment paradigm for foramen magnum meningiomas. J Neurosurg. 2012;117(5):864873.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13

    Cohen-Inbar O, Lee CC, Sheehan JP. The contemporary role of stereotactic radiosurgery in the treatment of meningiomas. Neurosurg Clin N Am. 2016;27(2):215228.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Muthukumar N, Kondziolka D, Lunsford LD, Flickinger JC. Stereotactic radiosurgery for anterior foramen magnum meningiomas. Surg Neurol. 1999;51(3):268273.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    Page MJ, McKenzie JE, Bossuyt PM, et al. Updating guidance for reporting systematic reviews: development of the PRISMA 2020 statement. J Clin Epidemiol. 2021;134:103112.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16

    Burns PB, Rohrich RJ, Chung KC. The levels of evidence and their role in evidence-based medicine. Plast Reconstr Surg. 2011;128(1):305310.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Sterne JA, Hernán MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919.

  • 18

    Starke RM, Nguyen JH, Reames DL, Rainey J, Sheehan JP. Gamma knife radiosurgery of meningiomas involving the foramen magnum. J Craniovertebr Junction Spine. 2010;1(1):2328.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19

    Mehta GU, Zenonos G, Patibandla MR, et al. Outcomes of stereotactic radiosurgery for foramen magnum meningiomas: an international multicenter study. J Neurosurg. 2018;129(2):383389.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20

    Khattar N, Koutourousiou M, Chabot JD, et al. Endoscopic endonasal and transcranial surgery for microsurgical resection of ventral foramen magnum meningiomas: a preliminary experience. Oper Neurosurg (Hagerstown). 2018;14(5):503514.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Mansilla R, Serrat Prevedello DM, de Lima L, Carrau RL, Landeiro JA. Endoscopic endonasal approach to foramen magnum meningioma: two-dimensional surgical video. World Neurosurg. 2020;137:362.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22

    Revuelta Barbero JM, Montaser AS, Shahein M, et al. Endoscopic endonasal focal transclival-medial condylectomy approach for resection of a foramen magnum meningioma: 2-dimensional operative video. Oper Neurosurg (Hagerstown). 2019;16(2):271.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23

    Kawashima M, Tanriover N, Rhoton AL Jr, Ulm AJ, Matsushima T. Comparison of the far lateral and extreme lateral variants of the atlanto-occipital transarticular approach to anterior extradural lesions of the craniovertebral junction. Neurosurgery. 2003;53(3):662675.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24

    Akalan N, Seçkin H, Kiliç C, Ozgen T. Benign extramedullary tumors in the foramen magnum region. Clin Neurol Neurosurg. 1994;96(4):284289.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25

    Bertalanffy H, Gilsbach JM, Mayfrank L, Klein HM, Kawase T, Seeger W. Microsurgical management of ventral and ventrolateral foramen magnum meningiomas. Acta Neurochir Suppl. 1996;65:82-85.

    • Search Google Scholar
    • Export Citation
  • 26

    Bruneau M, George B. Classification system of foramen magnum meningiomas. J Craniovertebr Junction Spine. 2010;1(1):1017.

  • 27

    Goel A, Desai K, Muzumdar D. Surgery on anterior foramen magnum meningiomas using a conventional posterior suboccipital approach: a report on an experience with 17 cases. Neurosurgery. 2001;49(1):102107.

    • Search Google Scholar
    • Export Citation
  • 28

    Nanda A, Vincent DA, Vannemreddy PS, Baskaya MK, Chanda A. Far-lateral approach to intradural lesions of the foramen magnum without resection of the occipital condyle. J Neurosurg. 2002;96(2):302309.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    Samii M, Klekamp J, Carvalho G. Surgical results for meningiomas of the craniocervical junction. Neurosurgery. 1996;39(6):10861095.

  • 30

    Starke RM, Nguyen JH, Rainey J, et al. Gamma Knife surgery of meningiomas located in the posterior fossa: factors predictive of outcome and remission. J Neurosurg. 2011;114(5):13991409.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31

    Nicolato A, Foroni R, Pellegrino M, et al. Gamma knife radiosurgery in meningiomas of the posterior fossa. Experience with 62 treated lesions. Minim Invasive Neurosurg. 2001;44(4):211217.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32

    Heck B, Jess-Hempen A, Kreiner HJ, Schöpgens H, Mack A. Accuracy and stability of positioning in radiosurgery: long-term results of the Gamma Knife system. Med Phys. 2007;34(4):14871495.

    • Crossref
    • Search Google Scholar
    • Export Citation

Supplementary Materials

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    FIG. 1.

    PRISMA search flow diagram. Data added to the PRISMA template (from Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med. 2009;6[7]:e1000097) under the terms of the Creative Commons Attribution License.

  • 1

    Aichholzer M, Bertalanffy A, Dietrich W, et al. Gamma knife radiosurgery of skull base meningiomas. Acta Neurochir (Wien). 2000;142(6):647653.

  • 2

    Arnautović KI, Al-Mefty O, Husain M. Ventral foramen magnum meninigiomas. J Neurosurg. 2000;92(1 suppl):7180.

  • 3

    Akyoldaş G, Samancı Y, Yılmaz M, Şengöz M, Peker S. Long-term results of gamma knife radiosurgery for foramen magnum meningiomas. Neurosurg Rev. 2021;44(5):26672673.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4

    Magill ST, Shahin MN, Lucas CG, et al. Surgical outcomes, complications, and management strategies for foramen magnum meningiomas. J Neurol Surg B Skull Base. 2019;80(1):19.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5

    Jumah F, Narayan V, Samara A, et al. Efficacy and safety of gamma knife radiosurgery for posterior cranial fossa meningioma: a systematic review. Neurosurg Rev. 2020;43(4):10891099.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6

    Javalkar V, Banerjee AD, Nanda A. Posterior cranial fossa meningiomas. J Neurol Surg B Skull Base. 2012;73(1):110.

  • 7

    Bir SC, Maiti TK, Nanda A. Foramen magnum meningiomas. Handb Clin Neurol. 2020;170:167174.

  • 8

    Bruneau M, George B. Foramen magnum meningiomas: detailed surgical approaches and technical aspects at Lariboisière Hospital and review of the literature. Neurosurg Rev. 2008;31(1):1933.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Ehret F, Kufeld M, Fürweger C, et al. The role of stereotactic radiosurgery in the management of foramen magnum meningiomas—a multicenter analysis and review of the literature. Cancers (Basel). 2022;14(2):341.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    Li D, Wu Z, Ren C, et al. Foramen magnum meningiomas: surgical results and risks predicting poor outcomes based on a modified classification. J Neurosurg. 2017;126(3):661676.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Cheshier SH, Hanft SJ, Adler JR, Chang SD. CyberKnife radiosurgery for lesions of the foramen magnum. Technol Cancer Res Treat. 2007;6(4):329336.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    Zenonos G, Kondziolka D, Flickinger JC, Gardner P, Lunsford LD. Gamma Knife surgery in the treatment paradigm for foramen magnum meningiomas. J Neurosurg. 2012;117(5):864873.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13

    Cohen-Inbar O, Lee CC, Sheehan JP. The contemporary role of stereotactic radiosurgery in the treatment of meningiomas. Neurosurg Clin N Am. 2016;27(2):215228.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Muthukumar N, Kondziolka D, Lunsford LD, Flickinger JC. Stereotactic radiosurgery for anterior foramen magnum meningiomas. Surg Neurol. 1999;51(3):268273.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    Page MJ, McKenzie JE, Bossuyt PM, et al. Updating guidance for reporting systematic reviews: development of the PRISMA 2020 statement. J Clin Epidemiol. 2021;134:103112.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16

    Burns PB, Rohrich RJ, Chung KC. The levels of evidence and their role in evidence-based medicine. Plast Reconstr Surg. 2011;128(1):305310.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Sterne JA, Hernán MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919.

  • 18

    Starke RM, Nguyen JH, Reames DL, Rainey J, Sheehan JP. Gamma knife radiosurgery of meningiomas involving the foramen magnum. J Craniovertebr Junction Spine. 2010;1(1):2328.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19

    Mehta GU, Zenonos G, Patibandla MR, et al. Outcomes of stereotactic radiosurgery for foramen magnum meningiomas: an international multicenter study. J Neurosurg. 2018;129(2):383389.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20

    Khattar N, Koutourousiou M, Chabot JD, et al. Endoscopic endonasal and transcranial surgery for microsurgical resection of ventral foramen magnum meningiomas: a preliminary experience. Oper Neurosurg (Hagerstown). 2018;14(5):503514.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Mansilla R, Serrat Prevedello DM, de Lima L, Carrau RL, Landeiro JA. Endoscopic endonasal approach to foramen magnum meningioma: two-dimensional surgical video. World Neurosurg. 2020;137:362.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22

    Revuelta Barbero JM, Montaser AS, Shahein M, et al. Endoscopic endonasal focal transclival-medial condylectomy approach for resection of a foramen magnum meningioma: 2-dimensional operative video. Oper Neurosurg (Hagerstown). 2019;16(2):271.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23

    Kawashima M, Tanriover N, Rhoton AL Jr, Ulm AJ, Matsushima T. Comparison of the far lateral and extreme lateral variants of the atlanto-occipital transarticular approach to anterior extradural lesions of the craniovertebral junction. Neurosurgery. 2003;53(3):662675.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24

    Akalan N, Seçkin H, Kiliç C, Ozgen T. Benign extramedullary tumors in the foramen magnum region. Clin Neurol Neurosurg. 1994;96(4):284289.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25

    Bertalanffy H, Gilsbach JM, Mayfrank L, Klein HM, Kawase T, Seeger W. Microsurgical management of ventral and ventrolateral foramen magnum meningiomas. Acta Neurochir Suppl. 1996;65:82-85.

    • Search Google Scholar
    • Export Citation
  • 26

    Bruneau M, George B. Classification system of foramen magnum meningiomas. J Craniovertebr Junction Spine. 2010;1(1):1017.

  • 27

    Goel A, Desai K, Muzumdar D. Surgery on anterior foramen magnum meningiomas using a conventional posterior suboccipital approach: a report on an experience with 17 cases. Neurosurgery. 2001;49(1):102107.

    • Search Google Scholar
    • Export Citation
  • 28

    Nanda A, Vincent DA, Vannemreddy PS, Baskaya MK, Chanda A. Far-lateral approach to intradural lesions of the foramen magnum without resection of the occipital condyle. J Neurosurg. 2002;96(2):302309.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    Samii M, Klekamp J, Carvalho G. Surgical results for meningiomas of the craniocervical junction. Neurosurgery. 1996;39(6):10861095.

  • 30

    Starke RM, Nguyen JH, Rainey J, et al. Gamma Knife surgery of meningiomas located in the posterior fossa: factors predictive of outcome and remission. J Neurosurg. 2011;114(5):13991409.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31

    Nicolato A, Foroni R, Pellegrino M, et al. Gamma knife radiosurgery in meningiomas of the posterior fossa. Experience with 62 treated lesions. Minim Invasive Neurosurg. 2001;44(4):211217.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32

    Heck B, Jess-Hempen A, Kreiner HJ, Schöpgens H, Mack A. Accuracy and stability of positioning in radiosurgery: long-term results of the Gamma Knife system. Med Phys. 2007;34(4):14871495.

    • Crossref
    • Search Google Scholar
    • Export Citation

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