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Purpose: Gamma knife radiosurgery (GKRS) for orbital cavernous hemangioma (OCH) has emerged as a promising method due to its significant clinical improvement and low incidence of complications. This study aimed to evaluate the safety and efficacy of GKRS for the treatment of OCH., Methods: In accordance with the PRISMA framework, we searched PubMed, Cochrane Central, and Embase for studies reporting outcomes of GKRS for OCH. Studies reporting complications, visual improvement, proptosis, tumor reduction rate, and tumor progression rate for OCH following GKRS were included., Results: Six studies, out of 1856 search results, with 100 patients were included. Among them, only 5 minor complications were related to GKRS, including 3 with orbital pain and 2 with periorbital chemosis. Thus, the complication rate was 13% (95% CI, 7-25%). Visual acuity and visual field improvement rates after GKRS were 80% (95% CI, 63-96%) and 71% (95% CI, 47-95%) respectively. Proptosis improved in 94% of cases (95% CI, 83-100%). The tumor reduction rate was 77% after GKRS (95% CI, 69-85%)., Conclusion: GKRS for OCH appears to be a safe technique, as evidenced by the rate of clinical improvement and radiological improvement. However, studies are limited by an absence of a control group. Additional studies are needed to evaluate the relative efficacy of GKRS as compared with alternative surgical modalities for OCH., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The aim of the study was to investigate whether morphology (i.e. compact/diffuse) of brain arteriovenous malformations (bAVMs) correlates with the incidence of hemorrhagic events in patients receiving Stereotactic Radiosurgery (SRS) for unruptured bAVMs. This retrospective study included 262 adult patients with unruptured bAVMs who underwent upfront SRS. Hemorrhagic events were defined as evidence of blood on CT or MRI. The morphology of bAVMs was evaluated using automated segmentation which calculated the proportion of vessel, brain tissue, and cerebrospinal fluid in bAVMs on T2-weighted MRI. Compactness index, defined as the ratio of vessel to brain tissue, categorized bAVMs into compact and diffuse types based on the optimal cutoff. Cox proportional hazard model was used to identify the independent factors for post-SRS hemorrhage. The median clinical follow-ups was 62.1 months. Post-SRS hemorrhage occurred in 13 (5.0%) patients and one of them had two bleeds, resulting in an annual bleeding rate of 0.8%. Multivariable analysis revealed bAVM morphology (compact versus diffuse), bAVM volume, and prescribed margin dose were significant predictors. The post-SRS hemorrhage rate increased with larger bAVM volume only among the diffuse nidi (1.7 versus 14.9 versus 30.6 hemorrhage per 1000 person-years in bAVM volume < 20 cm 3 versus 20-40 cm 3 versus > 40 cm 3 ; p = 0.022). The significantly higher post-SRS hemorrhage rate of Spetzler-Martin grade IV-V compared with grade I-III bAVMs (20.0 versus 3.3 hemorrhages per 1000 person-years; p = 0.001) mainly originated from the diffuse bAVMs rather than the compact subgroup (30.9 versus 4.8 hemorrhages per 1000 person-years; p = 0.035). Compact and smaller bAVMs, with higher prescribed margin dose harbor lower risks of post-SRS hemorrhage. The post-SRS hemorrhage rate exceeded 2.2% annually within the diffuse and large (> 40 cm 3 ) bAVMs and the diffuse Spetzler-Martin IV-V bAVMs. These findings may help guide patient selection of SRS for the unruptured bAVMs., (© 2024. The Author(s).)

Background and Objectives: The pathophysiology of vestibular schwannoma (VS) pseudoprogression after Gamma Knife radiosurgery (GKRS) remains unclear. Radiological features in pretreatment magnetic resonance images may help predict VS pseudoprogression. This study used VS radiological features quantified using an automated segmentation algorithm to predict pseudoprogression after GKRS treatment., Methods: This is a retrospective study comprising 330 patients with VS who received GKRS. After image preprocessing and T2W/contrast-enhanced T1-weighted image (CET1W) image generation, with fuzzy C-means clustering, VSs were segmented into solid and cystic components and classified as solid and cystic. Relevant radiological features were then extracted. The response to GKRS was classified into "nonpseudoprogression" and "pseudoprogression/fluctuation". The Z test for two proportions was used to compare solid and cystic VS for the likelihood of pseudoprogression/fluctuation. Logistic regression was used to assess the correlation between clinical variables and radiological features and response to GKRS., Results: The likelihood of pseudoprogression/fluctuation after GKRS was significantly higher for solid VS compared with cystic VS (55% vs 31%, P < .001). For the entire VS cohort, multivariable logistic regression revealed that a lower mean tumor signal intensity (SI) in T2W/CET1W images was associated with pseudoprogression/fluctuation after GKRS ( P = .001). For the solid VS subgroup, a lower mean tumor SI in T2W/CET1W images ( P = .035) was associated with pseudoprogression/fluctuation after GKRS. For the cystic VS subgroup, a lower mean SI of the cystic component in T2W/CET1W images ( P = .040) was associated with pseudoprogression/fluctuation after GKRS., Conclusion: Pseudoprogression is more likely to occur in solid VS compared with cystic VS. Quantitative radiological features in pretreatment magnetic resonance images were associated with pseudoprogression after GKRS. In T2W/CET1W images, solid VS with a lower mean tumor SI and cystic VS with a lower mean SI of cystic component were more likely to have pseudoprogression after GKRS. These radiological features can help predict the likelihood of pseudoprogression after GKRS., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Purpose: To examine the differential effects of SRS and TKI on EGFR-mutated NSCLC patients with brain metastases (BMs) and outcomes following continuation of the same TKI agent in case of new BMs., Methods: This study included 608 NSCLC patients (2,274 BMs) while meta-analyses included 1,651 NSCLC patients (> 3,944 BMs). Overall survival (OS) and intracranial progression free survival (iPFS) were estimated using Kaplan-Meier methods. Hazard ratios (95% CI) of prognostic factors were estimated using Cox regression models., Results: The median OS/iPFS (95% CI) (months) for patients with wildtype EGFR/ALK, EGFR mutations, and ALK rearrangements were 17.7 (12.9-23.6)/12.1 (9.8-15.6), 28.9 (23.8-33.3)/17.7 (14.8-21.2), and 118.0 (not reached)/71.7 (15.1-not reached), respectively. In EGFR-mutated patients, meta-analyses combining our data showed significantly improved OS and iPFS of patients who received SRS and TKI (OS:35.1 months, iPFS:20.0 months) when compared to those who have SRS alone (OS:20.8 months, iPFS:11.8 months) or TKI alone (OS:24.3 months, iPFS:13.8 months). Having SRS for newly diagnosed BMs while keeping the existing TKI agent yielded OS (30.0 vs. 32.1 months, p = 0.200) non-inferior to patients who started combined SRS and TKI therapy for their newly diagnosed NSCLC with BMs. Multivariable analyses showed that good performance score and TKI therapy were associated with improved outcomes., Conclusions: Combined SRS and TKI resulted in favorable outcomes in EGFR-mutated NSCLC patients with newly diagnosed BMs. Continuation of the same TKI agent plus SRS in case of new brain metastases yielded good clinical outcomes and may be considered a standard-of-care treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Whole brain radiation therapy (WBRT) for brain metastases (BMs) is a common cause of radiation-induced leukoencephalopathy; however the safety of alternative stereotactic radiosurgery (SRS) remains unclear. This study examined the incidence of leukoencephalopathy in patients treated with SRS alone versus WBRT plus SRS for BMs with a focus on the relationship between prognostic factors and leukoencephalopathy., Methods: Analysis was performed between 2002 and 2021. The total enrollment was 993 patients with the distribution: WBRT plus SRS (n = 291) and SRS only (n = 702). Leukoencephalopathy was graded from 0 to 3 for changes in white matter indicated by the MRI after WBRT or SRS. Patient characteristics and SRS dosimetric parameters were reviewed to identify factors that contributed to the incidence of leukoencephalopathy or overall survival., Results: The incidence of leukoencephalopathy was consistently higher in WBRT plus SRS group than in SRS alone group (p < 0.001). Leukoencephalopathy was also associated with a larger total tumor volume (≧28cm 3 ; p = 0.028) and age (> 77 years; p = 0.025). Nonetheless, the SRS integral dose to skull in the subgroup of WBRT plus SRS treatment was not demonstrated significance in development of leukoencephalopathy (p = 0.986 for integral dose 1-2 J, p = 0.776 for integral dose > 2 J)., Conclusions: This study revealed that SRS is safe for oligo-BMs in terms of leukoencephalopathy development. Patient age and total tumor volume were identified as important factors in assessing the development of leukoencephalopathy. The additional of SRS (even at an integral dose > 2 J) did not increase the incidence of leukoencephalopathy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Metastases extending to the pituitary gland and cavernous sinus are extremely rare; however, advances in neuroimaging have increased the reported incidence. Stereotactic radiosurgery (SRS) affords the precise delivery of focused radiation to minimize adverse radiation effects. This study assessed the efficacy and safety of SRS in the treatment of pituitary and cavernous sinus metastases., Methods: Analysis was performed on 23 patients with pituitary and cavernous sinus metastases who underwent treatment using SRS between 1996 and 2021. The cohort was categorized into 2 groups in terms of metastasis location: pituitary involvement (Group 1, n = 11) and cavernous sinus involvement (Group 2, n = 12). Overall survival, local tumor control, and distal tumor control rates were compared between the two groups using Kaplan-Meier analysis., Results: The median age of the cohort was 52.2 years and the median tumor volume was 4.5 mL. Overall survival rates were as follows: 1 year (72.9%), 2 years (51.8%), and 3 years (45.3%). Local tumor control rates were as follows: 1 year (82.3%), 2 years (82.3%), and 3 years (65.9%). Visual deficit and hypopituitarism were the most common presentations in Group 1, whereas cranial nerve deficit was the most common presentation in Group 2., Conclusions: SRS appears to be a safe and effective therapy for the treatment of pituitary and cavernous sinus metastases. GKRS is a relatively simple procedure, which places minimal stress on the patient, thereby facilitating further anti-cancer treatment. Considering the limited survival duration in cases of metastasis, it is very likely that post-GKRS complications (e.g., new onset cranial nerve deficit and hypopituitarism) would not become an issue before patient passes away., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Stereotactic radiosurgery (SRS) is an effective treatment for brain metastases (BMs) in patients with non-small cell lung cancer (NSCLC). However, factors associated with the development of post-SRS leptomeningeal metastasis (LM) remain unclear. The authors analyzed the incidence and risk factors of LM development in patients with NSCLC and BMs after SRS and examined the survival outcomes and prognostic factors after LM development., Methods: This retrospective study included patients with NSCLC treated with SRS for MRI-diagnosed BM from 2002 to 2021. The authors recorded various clinical and demographic data, including age, sex, tumor histology, molecular profile of tumors, extracranial disease status, previous craniotomy, Karnofsky Performance Status, systemic treatments, tumor volume, and number of BMs. The management and survival outcomes after LM diagnosis were also recorded., Results: LM developed in 13.7% of patients with NSCLC and BMs after SRS treatment. Large initial tumor volume and more than 5 BM lesions, but not EGFR mutation status and post-SRS treatment, were associated with LM development after SRS. Multivariate analysis revealed that chemotherapy and targeted therapy after LM were associated with better survival in patients with LM after SRS., Conclusions: This study is the first to evaluate the risk factors for LM in a relatively large cohort of patients with NSCLC after SRS. In patients with BMs harboring risk factors for subsequent LM, such as initial tumor volume and number of metastatic lesions, aggressive therapies with high CNS penetrating ability should be considered.

Objective: The goal of this study was to assess the safety and efficacy of single-session Gamma Knife radiosurgery (GKRS) for orbital cavernous hemangiomas (OCHs)., Methods: Patients who presented with an OCH between September 1999 and May 2022 and were treated with single-session GKRS were included in this single-center cohort study., Results: There were 23 patients (7 males and 16 females) in this study. The median margin dose was 12 Gy (range 11-13 Gy). The median clinical and radiological follow-ups were 45 months (range 5-190 months) and 45 months (range 6-190 months), respectively. Nine (69.2%) of 13 patients with visual acuity impairment had improvement in best corrected visual acuity. Of the 8 patients with visual field defects, 5 patients (62.5%) had complete resolution. Tumor regression was observed in 22 patients (95.7%). The mean relative reduction in tumor volume was 82.6% ± 23.7%. The relative reductions in tumor volume were 33%, 49%, 72%, 84%, and 89% at 6, 12, 24, 36, and 48 months, respectively. Adverse effects of radiation were not observed., Conclusions: GKRS appears to be safe and efficacious for treating OCHs over long-term follow-up. The treatment is associated with a high rate of regression in OCHs and remarkable improvement in both visual acuity and visual field deficits.

Objective: Tyrosine kinase inhibitors (TKIs) is the first-line treatment for EGFR-positive non-small cell lung cancer (NSCLC); however, its applicability to patients with wild-type NSCLC remains an issue of contention. This study compared the effects of gamma knife radiosurgery (GKRS) alone versus combining GKRS and TKIs in treating two genetic forms of NSCLC., Methods: This retrospective study examined 479 NSCLC patients with 1982 brain metastases who underwent GKRS and for whom imaging follow-up data or death records were available. All our patients were consecutive. All gene mutations were confirmed by lung biopsy. The three main endpoints in this study were overall survival (OS), local intracranial tumor control (LC), and distal intracranial tumor control (DC)., Results: There were 296 NSCLC patients with EGFR positive: TKI treatment (n = 262) and without TKI treatment (n = 34). GKRS + TKIs was more effective than GKRS alone in terms of OS (HR 0.53, p = 0.085) and DC (HR 0.51, p < 0.001). There were 150 NSCLC patients with wild-type EGFR: TKI treatment (n = 50) and without TKI treatment (n = 100). GKRS + TKIs was less effective than GKRS alone in terms of OS (HR 1.82, p = 0.049) and DC (HR: 1.40, p = 0.011). We observed no difference in terms of LC in both genetic groups., Conclusions: Combining GKRS with TKIs proved effective in EGFR positive NSCLC patients; however, we do not observe the similar results when combining GKRS with TKIs for patients with wild-type NSCLC., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The goal of the study was to define and quantify brain arteriovenous malformation (bAVM) compactness and to assess its effect on outcomes after Gamma Knife radiosurgery (GKRS) for unruptured bAVMs., Methods: Unsupervised machine learning with fuzzy c-means clustering was used to differentiate the tissue constituents of bAVMs on T2-weighted MR images. The percentages of vessel, brain, and CSF were quantified. The proposed compactness index, defined as the ratio of vasculature tissue to brain tissue, categorized bAVM morphology into compact, intermediate, and diffuse types according to the tertiles of this index. The outcomes of interest were complete obliteration and radiation-induced changes (RICs)., Results: A total of 209 unruptured bAVMs treated with GKRS were retrospectively included. The median imaging and clinical follow-up periods were 49.2 and 72.3 months, respectively. One hundred seventy-three bAVMs (82.8%) achieved complete obliteration after a median latency period of 43.3 months. The rates of RIC and permanent RIC were 76.1% and 3.8%, respectively. Post-GKRS hemorrhage occurred in 14 patients (6.7%), resulting in an annual bleeding risk of 1.0%. Compact bAVM, smaller bAVM volume, and exclusively superficial venous drainage were independent predictors of complete obliteration. Diffuse bAVM morphology, larger bAVM volume, and higher margin dose were independently associated with RICs., Conclusions: The compactness index quantitatively describes the compactness of unruptured bAVMs. Moreover, compact bAVMs may have a higher obliteration rate and a smaller risk of RICs than diffuse bAVMs. This finding could help guide decision-making regarding GKRS treatment for patients with unruptured bAVMs.

Purpose: Our purpose was to determine whether the coverage of brain parenchyma within the 12 Gy radiosurgical volume (V12) correlates with the development of radiation-induced changes (RICs) in patients with unruptured cerebral arteriovenous malformations (AVM) after undergoing stereotactic radiosurgery (SRS)., Methods and Materials: This study conducted regular follow-up examinations of 165 patients with unruptured AVMs who had previously undergone SRS. The RICs identified in T2-weighted magnetic resonance imaging (MRI) scans at any time point in the first 3 years after SRS were labeled "early RICs." The RICs identified in T2-weighted MRI scans at 5-year follow-up brain images were labeled "late RICs." Fully automated segmentation was used to analyze the MRI scans from these patients, whereupon the volume and proportion of brain parenchyma within the V12 was calculated. Logistic regression analysis was used to characterize the factors affecting the incidence of early and late RICs of any grade after SRS., Results: The median duration of follow-up was 70 months (range, 36-222). Early RICs were identified in 124 of the 165 patients with the highest grades as followed: grade 1 (103 patients), grade 2 (19 patients), and grade 3 (2 patients). Only 103 patients had more than 5 years follow-up, and late RICs were identified in 70 of 103 patients. Seventeen of 70 patients with late RICs were symptomatic. The median volume and proportion of brain parenchyma within the V12 was 22.4 cm 3 (range, 0.6-63.9) and 58.7% (range, 18.4-76.8). Univariate analysis revealed that AVM volume and the brain volume within the V12 were correlated with the incidence of both early and late RICs after SRS. Multivariable analysis revealed that only the brain volume within the V12 was significantly associated with the incidence of early and late RICs after SRS., Conclusions: In patients with unruptured AVM, the volume of brain parenchyma within the V12 was an important factor associated with the incidence of early and late RICs after SRS. Before SRS, meticulous radiosurgical planning to reduce brain parenchyma coverage within the V12 could reduce the risk of complications., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Although rare, orbital cavernous hemangioma (OCH) is the most common benign orbital neoplasm in adults and may cause vision disturbance or loss due to optic nerve compression. The conventional treatment is surgical excision, which carries a risk of intraoperative nerve damage, whereas gamma knife radiosurgery (GKRS) can be a safe and effective alternative. Herein, we report the results of four patients with OCH treated with GKRS, and describe the method of treatment including the optic nerve protection., Methods: This retrospective study included four consecutive patients (three women, one man; mean age: 50 ± 14.7 years) with OCH treated with single-session GKRS between 2014 and 2020. Three patients had decreased visual acuity. During GKRS, the prescription dose delivered to the tumor margin was 12 Gy at the 55-58% isodose line. The dose to the optic nerve margin was < 12 Gy. Follow-up included sequential magnetic resonance imaging (MRI) and ophthalmological examinations at 6-month intervals., Results: The median follow-up period was 29.5 ± 23 months (range, 12-63 months). After GKRS, three patients with visual dysfunction had substantial vision improvement; the fourth patient continued to have normal vision without deterioration. Radiological outcomes after GKRS indicated an average tumor shrinkage of 70% ± 10.6% at the 6-month follow-up and 83% ± 2.64% at the 1-year follow-up. No adverse radiation effects were observed., Conclusions: GKRS for OCH achieved favorable clinical outcomes, with substantial tumor volume reduction. OCH can be diagnosed based on characteristic MRI findings. GKRS may be considered a treatment option for OCH in selected cases.

Background: We proposed an algorithm to automate the components within the identification of components within the nidus of cerebral arteriovenous malformations (AVMs) which may be used to analyze the relationship between its diffuseness and treatment outcomes following stereotactic radiosurgery (SRS)., Objectives: to determine the impact of the diffuseness of the AVM nidus on SRS outcomes., Methods: This study conducted regular follow-ups of 209 patients with unruptured AVMs who underwent SRS. The diffuseness of the AVM nidus was estimated by quantifying the proportions of vascular nidal component, brain parenchyma, and cerebrospinal fluid in T2-weighted MRIs. We used Cox regression analysis to characterize the association between nidal diffuseness and treatment outcomes in terms of obliteration rate and radiation-induced change (RICs) rate following SRS., Results: The median AVM volume was 20.7 cm3. The median duration of imaging follow-up was 51 months after SRS. The overall AVM obliteration rate was 68.4%. RICs were identified in 156 of the 209 patients (74.6%). The median proportions of the nidus of AVM and brain parenchyma components within the prescription isodose range were 30.2 and 52.2%, respectively. Cox regression multivariate analysis revealed that the only factor associated with AVM obliteration rate after SRS was AVM volume. However, a larger AVM volume (>20 mL) and a larger proportion of brain parenchyma (>50%) within the prescription isodose range were both correlated with a higher RIC rate following SRS., Conclusions: The diffuseness of the nidus indeed appears to affect the RIC rate following SRS in patients with unruptured AVMs., (© 2020 S. Karger AG, Basel.)

Purpose: Stereotactic radiosurgery (SRS) is a potential re-irradiation treatment for recurrent intracranial ependymoma after prior radiation therapy. The purpose of this study was to examine the efficacy and safety of repeated SRS in the treatment of recurrent intracranial ependymomas., Methods: This is a retrospective study of consecutive patients with residual or recurrent intracranial ependymomas who were treated with SRS between 1993 and 2018. Tumor progression was defined as a ≥ 10% increase in tumor volume. Tumor regression was defined as a ≥ 10% reduction in tumor volume. A tumor that remained within 10% of its original volume was defined as stable. Tumor control comprised tumor regression and stability. Time-dependent analyses were performed using two treatment failure endpoint definitions: (1) evidence of local tumor progression or distant metastasis (single SRS analysis), and (2) lack of tumor response to SRS (repeated SRS analysis). These analyses were adjusted for the competing risk of death., Results: The study comprised 37 patients (65 intracranial ependymomas) who underwent multiple SRS sessions (range: 1-7). Median age was 10.2 years (range: 0.8-53.8 years), and median tumor volume was 1.5 mL (range: 0.01-22.5 mL). The median radiation dose was 13.3 Gy (range: 7.9-22.0 Gy) at a median isodose line of 57% (range: 50-90%). Overall tumor control rates in the single SRS analysis adjusting for the competing risk of death were 53.6%, 30.5%, and 23.6% at 1, 3, and 5 years, respectively. Overall tumor control rates in the repeated SRS analysis adjusting for the competing risk of death were 70.6%, 50.4%, and 43.1% at 1, 3, and 5 years, respectively. Prior gross total resection was the only independent predictor of overall tumor control after SRS (aHR = 25.62 (1.55-422.1), p = 0.02)., Conclusions: Repeated GKRS appeared to be an effective treatment strategy for recurrent or residual intracranial ependymomas, with acceptable complication rates.

Purpose: Gamma Knife radiosurgery (GKRS) is a non-invasive procedure for the treatment of brain metastases. This study sought to determine whether radiomic features of brain metastases derived from pre-GKRS magnetic resonance imaging (MRI) could be used in conjunction with clinical variables to predict the effectiveness of GKRS in achieving local tumor control., Methods: We retrospectively analyzed 161 patients with non-small cell lung cancer (576 brain metastases) who underwent GKRS for brain metastases. The database included clinical data and pre-GKRS MRI. Brain metastases were demarcated by experienced neurosurgeons, and radiomic features of each brain metastasis were extracted. Consensus clustering was used for feature selection. Cox proportional hazards models and cause-specific proportional hazards models were used to correlate clinical variables and radiomic features with local control of brain metastases after GKRS., Results: Multivariate Cox proportional hazards model revealed that higher zone percentage (hazard ratio, HR 0.712; P = .022) was independently associated with superior local tumor control. Similarly, multivariate cause-specific proportional hazards model revealed that higher zone percentage (HR 0.699; P = .014) was independently associated with superior local tumor control., Conclusions: The zone percentage of brain metastases, a radiomic feature derived from pre-GKRS contrast-enhanced T1-weighted MRIs, was found to be an independent prognostic factor of local tumor control following GKRS in patients with non-small cell lung cancer and brain metastases. Radiomic features indicate the biological basis and characteristics of tumors and could potentially be used as surrogate biomarkers for predicting tumor prognosis following GKRS.

Background: Remission rate is associated with higher dose of Gamma Knife Radiosurgery (GKRS; Gamma Knife: Elekta AB, Stockholm, Sweden) for acromegaly, but the dose ≥25 Gy is not always feasible when the functioning adenoma is close to optic apparatus., Objective: To evaluate the efficacy and safety of low-dose (<25 Gy) GKRS in the treatment of patients with acromegaly., Methods: Single-center retrospective review of acromegaly cases treated with GKRS between June 1994 and December 2016. A total of 76 patients with the diagnosis of acromegaly who were treated with low-dose GKRS were selected for inclusion. Patients were treated with a median margin dose, isodose line, and treatment volume of 15.8 Gy, 57.5%, and 4.8 mL, respectively. Any identifiable portion of the optic apparatus was limited to a radiation dose of 10 Gy. All patients underwent full endocrine, ophthalmological, and imaging evaluation prior to and after GKRS treatments, and results of these were analyzed., Results: Biochemical remission was achieved in 33 (43.4%) patients. Actuarial remission rates were 20.3%, 49.9%, and 76.3% at 4, 8, and 12 yr, respectively. Absence of cavernous sinus invasion (P = .042) and lower baseline insulin-like growth factor-1 levels (P = .019) were significant predictors of remission. New hormone deficiencies were found in 9 (11.8%) patients. Actuarial hormone deficiency rates were 3%, 14%, and 22.2% at 4, 8, and 10 yr, respectively. Two (2.6%) patients who achieved initial remission experienced recurrence. No optic complications were encountered., Conclusion: Reasonable remission and new hormone deficiency rates can be achieved with low-dose GKRS for acromegaly. These rates may be comparable to those with standard GKRS margin doses., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Purpose: To evaluate the outcomes of patients who underwent Gamma Knife radiosurgery (GKRS) for the treatment of cavernous sinus (CS) meningiomas., Methods: We retrospectively reviewed the clinical and radiological outcomes of 95 patients with CS meningiomas at Taipei Veterans General Hospital between 1993 and 2011. The study cohort comprised 27 men and 68 women with a median age of 50 years (range 29-79 years). The median pre-GKRS tumor volume was 6.6 ml (range 0.9-35.7 ml). The median margin dose was 12 Gy (range 11-21 Gy). The clinical factors related to favorable outcomes were assessed., Results: The median follow-up period was 59 (range 12-209) months. At the final follow-up, the tumor volume regressed in 70 patients (74%) and progressed in eight (8%). Kaplan-Meier analysis revealed that the progression-free survival rates at 5 and 10 years were 92.7% and 81.2%, respectively. Three patients (3.2%) experienced exacerbated cranial nerve dysfunction following radiosurgery. Confined tumors were found to be an independent prognostic factor for tumor control and shorter times to regression in the multivariable analyses. No risk factor for tumor progression was identified in either the univariate or multivariate analyses., Conclusions: GKRS provides good long-term tumor control and is associated with low cranial nerve-related morbidity development rates in patients with small- to medium-sized CS meningiomas. Confined tumor could be an independent prognostic factor for tumor control and shorter times to regression in multivariate analysis. Life-long follow-up is mandatory in such settings, even for outpatients with shrunken or stabilized tumors.

Objective: There is a lack of consensus regarding whether if residual non-functional macroadenomas (NFM) should undergo empirical stereotactic radiosurgery (SRS) or be monitored until tumor progression before SRS treatment. The aim of this study is to compare the risks and benefits of empirical versus progression-guided SRS for NFM after subtotal resection., Methods: This is a retrospective study of consecutive NFM patients who subtotal surgical resection followed by SRS between 1999 and 2014. Patients were dichotomized into two groups: empirical SRS (SRS without evidence of tumor progression) and progression-guided SRS (SRS after demonstration of tumor progression) groups. Tumor response was categorized into: (1) regression, ≥ 10% decrease in tumor volume; (2) stable, < 10% increase or decrease in tumor volume; and (3) progression, ≥ 10% increase in tumor volume. Tumor control comprised stable tumor response and tumor regression., Results: Of the 112 patients who underwent SRS for NFM, 106 patients were treated for residual NFM after surgical resection, and included in the final analysis. The empirical SRS and progression-guided SRS groups comprised 46 and 60 patients, respectively. Overall tumor control rate was 88.7%. Higher rate of tumor control was achieved in the empirical SRS group compared to the progression-guided SRS group (95.65% vs. 83.33%, p = 0.047). Rates of new visual field deficit, cranial neuropathy and endocrinopathy were comparable between the two groups. Empirical SRS group had higher rates of progression-free survival compared to progression-guided SRS group (p = 0.015). Actuarial progression-free survival rates for the empirical SRS group were 93.2%, 93.2%, and 81.5% at 3, 5, and 10 years after SRS. Actuarial progression-free survival rates for the progression-guided SRS were 86.4%, 82.1%, and 68.4% at 3, 5, and 10 years after SRS., Conclusion: Empirical SRS offers higher rates of tumor control and progression-free survival compared to progression-guided SRS in patients with residual NFM after surgical resection. Rates of new hypopituitarism and cranial neuropathies were comparable between the two groups.

Background: Gamma knife radiosurgery (GKRS) is a common treatment for cerebral arterio-venous malformations (AVMs), particularly in cases where the malformation is deep-seated, large, or in eloquent areas of the brain. Unfortunately, these procedures can result in radiation injury to brain parenchyma. The fact that every AVM is unique in its vascular morphology makes it nearly impossible to exclude brain parenchyma from isodose radiation exposure during the formulation of a GKRS plan. Calculating the percentages of the various forms of tissue exposed to specific doses of radiation is crucial to understanding the clinical responses and causes of brain parenchyma injury following GKRS for AVM., Methods: In this study, we developed a fully automated algorithm using unsupervised classification via fuzzy c-means clustering for the analysis of T2 weighted images used in a Gamma knife plan. This algorithm is able to calculate the percentages of nidus, brain tissue, and cerebrospinal fluid (CSF) within the prescription isodose radiation exposure region., Results: The proposed algorithm was used to assess the treatment plan of 25 patients with AVM who had undergone GKRS. The Dice similarity index (SI) was used to determine the degree of agreement between the results obtained using the algorithm and a visually guided manual method (the gold standard) performed by an experienced neurosurgeon. In the nidus, the SI was (74.86 ± 1.30%) (mean ± standard deviation), the sensitivity was (83.05 ± 11.91)%, and the specificity was (86.73 ± 10.31)%. In brain tissue, the SI was (79.50 ± 6.01)%, the sensitivity was (73.05 ± 9.77)%, and the specificity was (85.53 ± 7.13)%. In the CSF, the SI was (69.57 ± 15.26)%, the sensitivity was (89.86 ± 5.87)%, and the specificity was (92.36 ± 4.35)%., Conclusions: The proposed clustering algorithm provides precise percentages of the various types of tissue within the prescription isodose region in the T2 weighted images used in the GKRS plan for AVM. Our results shed light on the causes of brain radiation injury after GKRS for AVM. In the future, this system could be used to improve outcomes and avoid complications associated with GKRS treatment., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the safety and efficacy of SRS treatment of central neurocytomas (CNCs), cavernous sinus hemangiomas (CSHs), and glomus tumors (GTs); and to compare upfront stereotactic radiosurgery (SRS) and adjuvant SRS in the treatment of these hypervascular tumors., Methods: This was a retrospective review of consecutive CNCs, CSHs, and GTs treated with SRS between 1993 and 2017. Tumor response was categorized based on volumetric analysis on magnetic resonance imaging: (1) tumor regression [> 10% decrease in tumor volume (TV)]; (2) stable tumor (≤ 10% change in TV); or (3) tumor progression (> 10% increase in TV)., Results: Sixty hypervascular tumors (CNC: 28; CSH: 16; GT: 16) underwent SRS between 1993 and 2017. Margin doses were 13 Gy, 12 Gy, and 14 Gy for CNCs, CSHs, and GTs, respectively. Tumor regression was observed in 54 tumors (90%) with initial SRS after a median follow-up of 82 months. Relative reductions in TVs for CNCs were 38%, 52%, and 73% at 12, 24, and 48 months, respectively. Relative reductions in TVs for CSHs were 51%, 68%, and 88% at 12, 24, and 48 months, respectively. Relative reductions in TVs for GTs were 22%, 31%, and 47% at 12, 24, and 48 months, respectively. Upfront SRS was performed in 26 patients (43%). No difference in relative TV reductions were found between upfront and adjuvant SRS. Adverse radiation effects were observed in five patients. No mortality was encountered., Conclusion: SRS for hypervascular tumors is associated with high rates of tumor regression with low risk of complications. No significant difference in rates of relative TV reduction were found between upfront and adjuvant SRS. Hence, upfront SRS may be considered in select patients.

Background: Diffusion tensor imaging (DTI) is a novel MRI technique that enables noninvasive evaluation of microstructural alterations in white matter of brain. Initially, DTI was used in intra- or inter-hemispheric association bundles. Recent technical advances are overcoming the challenges of imaging small white matter bundles, such as the cranial nerves. In this study, we use DTI to shed more light on the microstructure changes in long-standing trigeminal neuralgia. We also utilize DTI to study the effect of early stereotactic radiosurgery (SRS) on the microstructures of the trigeminal nerve and to predict the effectiveness of early SRS in the treatment of medically refractory trigeminal neuralgia (TN)., Methods: To analyze the presentation of trigeminal nerve, the DTI was reconstructed in 21 cases pre- and post-SRS. DTI parameters recorded include fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), linear anisotropy coefficient (Cl), planar anisotropy coefficient (Cp), and spherical anisotropy coefficient (Cs). Comparisons between ipsilateral (symptomatic) and contralateral (asymptomatic) trigeminal nerves and symptom durations of < 5 and ≧ 5 years were performed., Results: The study cohort comprised 21 patients with TN with a median age of 66 years. Initial adequate facial pain relief (Barrow Neurological Institute facial pain scores I-IIIb) was achieved in 16 (76%) patients. For the pre-SRS DTI findings, ipsilateral trigeminal nerve was associated with higher baseline root entry zone (REZ) Cs compared to contralateral nerve (0.774 vs. 0.743, p = 0.04). Ipsilateral trigeminal nerve with symptoms of < 5 years was associated with higher baseline FA compared to trigeminal nerve with symptoms of ≧ 5 years (0.314 vs. 0.244, p = 0.02). For the post-SRS DTI findings, ipsilateral trigeminal nerves with symptoms of <5 years demonstrated decrease in Cl, while those with symptoms ≧ 5 years demonstrated increase in Cl after SRS at the ipsilateral REZ (- 0.025 vs. 0.018, p = 0.04). At the cisternal segment of ipsilateral trigeminal nerve, symptoms of < 5 years were associated with decreased FA and increased λ 2 , while symptoms of ≧ 5 years were associated with increased FA and decreased λ 2 after SRS (FA - 0.068 vs. 0.031, p = 0.04, λ 2 0.0003 vs. - 0.0002, p = 0.02)., Conclusions: SRS provides high rates of initial pain relief with moderate rates of facial hypoesthesia. Ipsilateral trigeminal nerve was associated with higher baseline REZ Cs, and baseline FA was associated with duration of symptoms. There were significant associations between duration of symptoms and changes in ipsilateral REZ Cl, cisternal segment FA, and cisternal segment λ 2 after SRS. These preliminary findings serve as comparisons for future studies investigating the use of DTI in radiosurgical planning for patients with TN.

In Gamma Knife forward treatment planning, normalization effect may be observed when multiple shots are used for treating large lesions. This effect can reduce the proportion of coverage of high-value isodose lines within targets. The aim of this study was to evaluate the performance of forward treatment planning techniques using the Leksell Gamma Knife for the normalization effect reduction. We adjusted the shot positions and weightings to optimize the dose distribution and reduce the overlap of high-value isodose lines from each shot, thereby mitigating the normalization effect during treatment planning. The new collimation system, Leksell Gamma Knife Perfexion, which contains eight movable sectors, provides an additional means to reduce the normalization effect by using composite shots. We propose different techniques in forward treatment planning that can reduce the normalization effect. Reducing the normalization effect increases the coverage proportion of higher isodose lines within targets, making the high-dose region within targets more uniform and increasing the mean dose to targets. Because of the increase in the mean dose to the target after reducing the normalization effect, we can set the prescribed marginal dose at a higher isodose level and reduce the maximum dose, thereby lowering the risk of complications., (© 2017 Shuang Ho Hospital-Taipei Medical University. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Background: Atypical and anaplastic meningiomas have much higher recurrence rates after surgical resection compared with benign meningiomas, but the role of adjuvant radiosurgery remains unclear. This study was undertaken to evaluate the outcomes of gamma knife radiosurgery for patients with atypical and anaplastic meningiomas., Methods: In this retrospective analysis of a prospectively maintained database, 46 patients with histologically proven atypical or anaplastic meningiomas by current World Health Organization (WHO) criteria underwent postoperative Gamma Knife radiosurgery between 1993 and 2013. The median follow-up period was 32.6 months. The median tumor volume and margin dose were 11.7 mL (range, 2-53 mL) and 13.1 Gy (range, 12.0-16.5 Gy), respectively., Results: Local control at 3 and 5 years was 50.6% and 32.1%, respectively. Gender (P = 0.013) and marginal dose less than or equal to 13 Gy (P = 0.049) were associated with the local control. The 3- and 5-year overall survival for patients with WHO grade II was 97.1% and 88.3%, respectively, compared with 66.7% and 66.7% for patients with WHO grade III meningiomas. Radiation therapy before Gamma Knife radiosurgery (GKRS; P = 0.018) and tumor grade (P = 0.019) were the factors associated with a worse overall survival rate. Fourteen patients (30.4%) developed adverse radiation effects after GKRS treatment, and all were Radiation Therapy Oncology Group grade I., Conclusions: Postoperative GKRS treatment for patients with atypical and anaplastic meningioma is challenging. More aggressive treatment, including of safely maximizing the extent of surgical resection and using a higher margin dose (>13Gy), should be applied to achieve better local control., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Gamma-knife radiosurgery (GKS) for vestibular schwannomas (VSs) has become popular during the last two decades, and a promising tumor control rate has been reported. Therefore, the evaluation and preservation of auditory-vestibular nerve function after GKS have become more and more important in these patients with long-term survival. We have traditionally used pure-tone audiometry (PTA) for evaluation of auditory nerve function, and the caloric test for superior vestibular nerve function. Vestibular-evoked myogenic potential (VEMP) has recently emerged from various neurophysiological examinations for assessment of the integrity of the inferior vestibular nerve function. This novel tool has been established to represent a sacculo-collic reflex. By using these three tools, the auditory-vestibular nerve function of VS patients can be evaluated and monitored before and after GKS., Methods: Fourteen patients with unilateral VS that underwent GKS were prospectively recruited. All of them received a battery of auditory-vestibular function tests including PTA, caloric, and cVEMP tests before and after GKS at each time point (1, 6, and 12 months). Our data also included the tumor volumes and their relationship with the PTA, caloric, and cVEMP test results., Results: The PTA, caloric, and cVEMP tests showed abnormal results before GKS in 85.7%, 78.6% and 78.6% of our VS patients, respectively. The PTA, caloric, and cVEMP results did not show strong correlations between each other. However, there was a tendency that when the tumor grew larger, the auditory-vestibular function deficits became more severe. The PTA and cVEMP test results remained stable during the 1-year follow-up after GKS. However, the caloric test showed transient deterioration at the 6th month follow-up, which then recovered by the 1-year follow-up., Conclusion: The combination of these three tests can help us diagnose VS and assess the change in auditory-vestibular nerve function during the post-GKS follow-up period. The results of these three tests were independent for smaller tumors, but all tests may show abnormal findings with larger tumors. Although the study is still ongoing, the preliminary data showed that GKS treatment would not affect the auditory-vestibular nerve function within a 1-year follow-up period., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Object: The goal of this study was to evaluate the obliteration rate of intracranial dural arteriovenous fistulas (DAVFs) in patients treated with stereotactic radiosurgery (SRS), and to compare obliteration rates between cavernous sinus (CS) and noncavernous sinus (NCS) DAVFs, and between DAVFs with and without cortical venous drainage (CVD)., Methods: A systematic literature review was performed using PubMed. The CS DAVFs and the NCS DAVFs were categorized using the Barrow and Borden classification systems, respectively. The DAVFs were also categorized by location and by the presence of CVD. Statistical analyses of pooled data were conducted to assess complete obliteration rates in CS and NCS DAVFs, and in DAVFs with and without CVD., Results: Nineteen studies were included, comprising 729 patients harboring 743 DAVFs treated with SRS. The mean obliteration rate was 63% (95% CI 52.4%-73.6%). Complete obliteration for CS and NCS DAVFs was achieved in 73% and 58% of patients, respectively. No significant difference in obliteration rates between CS and NCS DAVFs was found (OR 1.72, 95% CI 0.66-4.46; p=0.27). Complete obliteration in DAVFs with and without CVD was observed in 56% and 75% of patients, respectively. A significantly higher obliteration rate was observed in DAVFs without CVD compared with DAVFs with CVD (OR 2.37, 95% CI 1.07-5.28; p=0.03)., Conclusions: Treatment with SRS offers favorable rates of DAVF obliteration with low complication rates. Patients harboring DAVFs that are refractory or not amenable to endovascular or surgical therapy may be safely and effectively treated using SRS.

This article elucidates the role of stereotactic radiosurgery for the management of central neurocytoma. This rare intraventricular tumor is usually benign and is best treated with surgical excision if the tumor is large and symptomatic. However, some distinctive neuroimaging features are found in this tumor that help to identify the tumor based on detailed MRI and computed tomography examinations. The cumulative experience shows that single-session radiosurgery using Gamma Knife radiosurgery is an effective and safe alternative treatment of incidental central neurocytoma. After radiosurgery, a serial MRI examination performed every 6 months for long-term follow-up is necessary to monitor radiosurgical response of the tumor., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Object: Resection of vestibular schwannoma (VS) after Gamma Knife surgery (GKS) is infrequently performed. The goals of this study were to analyze and discuss the neurological outcomes and technical challenges of VS resection and to explore strategies for treating tumors that progress after GKS., Methods: In total, 708 patients with VS underwent GKS between 1993 and 2012 at Taipei Veterans General Hospital. The post-GKS clinical courses, neurological presentations, and radiological changes in these patients were analyzed. Six hundred patients with imaging follow-up of at least 1 year after GKS treatment were included in this study., Results: Thirteen patients (2.2%) underwent microsurgery on average 36.8 months (range 3-107 months) after GKS. The indications for the surgery included symptomatic adverse radiation effects (in 4 patients), tumor progression (in 6), and cyst development (in 3). No morbidity or death as a result of the surgery was observed. At the last follow-up evaluation, all patients, except 1 patient with a malignant tumor, had stable or near-normal facial function., Conclusions: For the few VS cases that require resection after radiosurgery, maximal tumor resection can be achieved with modern skull-based techniques and refined neuromonitoring without affecting facial nerve function.

Object: The authors evaluated individual anatomical variations in the trigeminal nerves of patients with medically intractable trigeminal neuralgia and clarified the relationships among the variations, radiosurgical target locations, and the clinical outcomes after high-dose Gamma Knife surgery (GKS)., Methods: From 2006 through 2011, the authors conducted a retrospective review of 106 cases of primary or secondary trigeminal neuralgia consecutively treated with GKS targeting the dorsal root entry zone (DREZ) for which a maximal dose of 90 Gy and a 20% isodose line to the brainstem were used. A questionnaire was used to evaluate patients' pre- and post-GKS clinical conditions. To evaluate individual anatomical variations among trigeminal nerves, the authors used 3 parameters: the length of the trigeminal nerve in the cistern (nerve length), the length of the target between the radiation shot and the brainstem (targeting length), and the ratio between nerve length and targeting length (targeting ratio)., Results: The median length of the trigeminal nerves in the 106 patients was 9.6 mm (range 6.04-20.74 mm), the median targeting length was 3.8 mm (range 1.81-10.84 mm), and the median targeting ratio was 38% (range 13%- 80%). No statistically significant differences in pain relief and pain recurrence were detected among patients with these various nerve characteristics. However, radiation-induced facial hypesthesia correlated with nerve length and targeting ratio (p < 0.05) but not with absolute distance from the brainstem (targeting length)., Conclusions: In trigeminal neuralgia patients who received DREZ-targeted GKS, the rate of pain relief did not differ according to anatomical nerve variations. However, the frequency of facial hypesthesia was higher among patients in whom the nerve was longer (> 11 mm) or the targeting ratio was lower (< 36%). Adjusting the target according to the targeting ratio, especially for patients with longer nerves, can reduce facial hypesthesia and enable maintenance of effective pain control.

Object: Although craniopharyngiomas are benign intracranial tumors, their high recurrence rates and intimate associations with surrounding neurovascular structures make gross tumor resection challenging. Stereotactic radiosurgery has been introduced as a valuable adjuvant therapy for recurrent or residual craniopharyngiomas. However, studies with large patient populations documenting long-term survival and progression-free survival rates are rare in the literature. The current study aims to report the long-term radiosurgical results and to define the prognostic factors in a large cohort of patients with a craniopharyngioma., Methods: A total of 137 consecutive patients who underwent 162 sessions of Gamma Knife surgery (GKS) treatments at the Taipei Veterans General Hospital between 1993 and 2012 were analyzed. The patients' median age was 30.1 years (range 1.5-84.9 years), and the median tumor volume was 5.5 ml (range 0.2-28.4 ml). There were 23 solid (16.8%), 23 cystic (16.8%), and 91 mixed solid and cystic (66.4%) craniopharyngiomas. GKS was indicated for residual or recurrent craniopharyngiomas. The median radiation dose was 12 Gy (range 9.5-16.0 Gy) at a median isodose line of 55% (range 50%-78%)., Results: At a median imaging follow-up of 45.7 months after GKS, the rates of tumor control were 72.7%, 73.9%, and 66.3% for the solid, cystic, and mixed tumors, respectively. The actuarial progression-free survival rates plotted by the Kaplan-Meier method were 70.0% and 43.8% at 5 and 10 years after radiosurgery, respectively. After repeated GKS, the actuarial progression-free survival rates were increased to 77.3% and 61.2% at 5 and 10 years, respectively. The overall survival rates were 91.5% and 83.9% at the 5- and 10-year follow-ups, respectively. Successful GKS treatment can be predicted by tumor volume (p = 0.011). Among the 137 patients who had clinical follow-up, new-onset or worsened pituitary deficiencies were detected in 11 patients (8.0%). Two patients without tumor growth had a worsened visual field, and 1 patient had a new onset of third cranial nerve palsy., Conclusions: The current study suggests that GKS is a relatively safe modality for the treatment of recurrent or residual craniopharyngiomas, and it is associated with improved tumor control and reduced in-field recurrence rates. Acceptable rates of complications occurred.

Object: Nonfunctioning pituitary adenomas (NFAs) are the most common type of pituitary adenoma and, when symptomatic, typically require surgical removal as an initial means of management. Gamma Knife radiosurgery (GKRS) is an alternative therapeutic strategy for patients whose comorbidities substantially increase the risks of resection. In this report, the authors evaluated the efficacy and safety of initial GKRS for NFAs., Methods: An international group of three academic Gamma Knife centers retrospectively reviewed outcome data in 569 patients with NFAs., Results: Forty-one patients (7.2%) underwent GKRS as primary management for their NFAs because of an advanced age, multiple comorbidities, or patient preference. The median age at the time of radiosurgery was 69 years. Thirty-seven percent of the patients had hypopituitarism before GKRS. Patients received a median tumor margin dose of 12 Gy (range 6.2-25.0 Gy) at a median isodose of 50%. The overall tumor control rate was 92.7%, and the actuarial tumor control rate was 94% and 85% at 5 and 10 years postradiosurgery, respectively. Three patients with tumor growth or symptom progression underwent resection at 3, 3, and 96 months after GKRS, respectively. New or worsened hypopituitarism developed in 10 patients (24%) at a median interval of 37 months after GKRS. One patient suffered new-onset cranial nerve palsy. No other radiosurgical complications were noted. Delayed hypopituitarism was observed more often in patients who had received a tumor margin dose > 18 Gy (p = 0.038) and a maximum dose > 36 Gy (p = 0.025)., Conclusions: In this study, GKRS resulted in long-term control of NFAs in 85% of patients at 10 years. This experience suggests that GKRS provides long-term tumor control with an acceptable risk profile. This approach may be especially valuable in older patients, those with multiple comorbidities, and those who have endocrine-inactive tumors without visual compromise due to mass effect of the adenoma.

Background: This report presents our 15-year experience with Gamma Knife radiosurgery (GKS) for the treatment of 321 patients with dural arteriovenous fistulas (DAVFs) in different locations., Methods: The most common locations of DAVFs were the cavernous sinus (206 cases) and transverse-sigmoid sinus (72 cases), which together accounted for 86.6 % of cases. In all, 54 patients had undergone embolization or surgery prior to radiosurgery, and the other patients underwent GKS as the primary treatment. During GKS, radiation was confined to the involved sinus wall, which was considered the true nidus of the DAVF. Target volume ranged from 0.8 to 52 cm(3). Marginal and maximum doses to the nidus ranged from 14 to 25 Gy and from 25 to 36 Gy, respectively., Results: The mean follow-up time was 28 months (range 2-149 months). In 264 of 321 patients (82 %) available for follow-up study, 173 (66 %) showed complete obliteration of DAVFs with symptomatic resolution, 87 (33 %) had partial obliteration, 2 (0.8 %) had stationary status, 1 (0.4 %) had progression, and 1 (0.4 %) died from a new hemorrhagic episode. Complications were found in only two (0.8 %) patients, one with venous hemorrhage and one with focal brain edema after GKS., Conclusions: GKS is a safe, effective treatment for DAVFs. It provides a minimally invasive therapeutic option for patients who harbor less-aggressive DAVFs but who suffer from intolerable clinical symptoms. For some aggressive DAVFs with extensive venous hypertension or hemorrhage, multimodal treatment with combined embolization or surgery is necessary.

Dural arteriovenous fistulas (DAVFs) are abnormal arteriovenous communications within the dura. The symptoms depend on their location and the pattern of the venous drainage. Patients with cavernous sinus DAVFs often present with ocular manifestations such as exophthalmos, chemosis and diplopia. Patients with transverse or sigmoid sinus DAVFs frequently experience headache and tinnitus on the affected side. DAVFs with anterograde sinus or cortical venous drainage (CVD) have been clinically regarded as benign, whereas DAVFs with retrograde CVD are considered aggressive in behavior. Similar to other cerebral arteriovenous malformations, DAVFs can hemorrhage, with an estimated annual risk of approximately 1.8%. The recommended therapeutic intervention for a DAVF is dependent on the anticipated natural history of the lesion. Management options include surgical resection, embolization and radiosurgery. Radiosurgical treatment has been used for DAVFs in various locations including the anterior cranial fossa, cavernous sinus, transverse/sigmoid sinus, superior sagittal sinus and tentorium. We present an update on 321 DAVF patients treated at the Taipei Veterans General Hospital using Gamma Knife radiosurgery. The prescribed mean margin dose was 17.2 Gy. In our series, 98% of patients had a stable or improved clinical condition after radiosurgery. Stereotactic radiosurgery using the Gamma Knife is a safe and effective alternative for the treatment of DAVFs., (Copyright © 2013 S. Karger AG, Basel.)

Object: The authors retrospectively reviewed the efficacy and safety of Gamma Knife surgery (GKS) in patients with brainstem cavernous malformations (CMs). The CMs had bled repeatedly and placed the patients at high risk with respect to surgical intervention., Methods: Between 1993 and 2010, 49 patients with symptomatic CMs were treated by GKS. The mean age in these patients was 37.8 years, and the predominant sex was female (59.2%). All 49 patients experienced at least 2 instances of repeated bleeding before GKS; these hemorrhages caused neurological deficits including cranial nerve deficits, hemiparesis, hemisensory deficits, spasticity, chorea or athetosis, and consciousness disturbance., Results: The mean size of the CMs at the time of GKS was 3.2 cm(3) (range 0.1-14.6 cm(3)). The mean radiation dose directed to the lesion was 11 Gy with an isodose level at 60.0%. The mean clinical and imaging follow-up time was 40.6 months (range 1.0-150.7 months). Forty-five patients participated in regularly scheduled follow-up. Twenty-nine patients (59.2%) were followed up for > 2 years, and 16 (32.7%) were followed up for < 2 years. The pre-GKS annual hemorrhage rate was 31.3% (69 symptomatic hemorrhages during a total of 220.3 patient-years). After GKS, 3 episodes of symptomatic hemorrhage were observed within the first 2 years of follow-up (4.29% [corrected] annual hemorrhage rate), and 3 episodes of symptomatic hemorrhage were observed after the first 2 years of follow-up (3.64% [corrected] annual hemorrhage rate). In this study of 49 patients, symptomatic radiation-induced complications developed in only 2 patients (4.1%; cyst formation in 1 patient and perifocal edema with neurological deficits in the other patient). There were no deaths in this group., Conclusions: Gamma Knife surgery is effective in reducing the rate of recurrent hemorrhage. In the authors' experience, it was possible to control bleeding using a low-dose treatment. In addition, there were few symptomatic radiation-induced complications. As a result, the authors believe that GKS is a good alternative treatment for brainstem CMs.

Object: The optimal management of central neurocytoma (CN) remnants and recurrences is still not clear. To date no large series of patients treated with Gamma Knife surgery (GKS) for CNs has been published. For that reason the authors decided to combine data from 5 different centers so that they could analyze the largest population of patients treated with GKS for CN currently available., Methods: Data obtained in 42 patients who were treated for CN with GKS before July 1, 2010, were retrospectively collected and analyzed. The median prescribed dose was 13 Gy (range 11-25 Gy). The follow-up time in these patients ranged from 0.5 to 14.7 years (mean 6.1 years, median 4.9 years). Eleven patients were followed up for 5-10 years and 9 patients for more than 10 years. All patients were alive and well at the closing of the study except 1 patient, who died of injuries sustained in a traffic accident., Results: Two cases of local tumor progression and 2 cases of distant tumor recurrence occurred among the patient population, yielding 5- and 10-year tumor control rates of 91% and 81%, respectively. No permanent complications occurred. The findings were in line with results reported in earlier publications. Despite the high tumor control rate, enlargement of part of or the whole ventricular system was seen in 45% of patients., Conclusions: The high tumor control rate and the low complication rate following GKS indicate that GKS is the preferred treatment for CN tumor remnants or recurrences following microsurgery. However, data from longer follow-up times in more patients are needed before this conclusion can be validated. The patients need to be closely monitored and potential hydrocephalus managed despite tumor control.

Object: Central neurocytoma (CN) is considered to be a benign neuronal tumor with possible atypical behavior. Microsurgery, radiation therapy (RT) and radiosurgery all have been used in treating this rare disease during the past decade. In this study, the authors present the experience with gamma knife radiosurgery (GKRS) on 14 patients with CN during a median follow-up period of 65 months and document the safety and efficacy of GKRS in the treatment of CN., Methods: Between November 1997 and December 2009, 14 patients pathologically diagnosed with CN were treated with GKRS. Follow-up magnetic resonance imaging (MRI) was performed at 6-month intervals. Tumor volume and adverse radiation effects (ARE) were documented to evaluate tumor response to GKRS. The Karnofsky Performance Scale (KPS) and neurological status were used to assess clinical outcome. The mean radiation dose prescribed to the tumor margin was 12.1 Gy (ranging from 11 to 13 Gy). The mean tumor volume was 19.6 ml (ranging from 3.5 to 48.9 ml). The mean follow-up period was 70 months (ranging from 30 to 140 months), and the median follow-up period was 65 months., Results: Tumor shrinkage was found in all patients at the final MRI follow-up. The mean volume reduction was 69% (ranging from 47 to 87%). No tumor progression, ARE or radiation-related toxicity developed in any of the cases. The KPS scores of all patients were the same or had increased, and the neurological functions were all stable without deterioration at the final follow-up., Conclusion: In our observations, GKRS was found to be an effective and safe alternative as adjuvant therapy for pathology-confirmed CN. The tumor volume and functional outcome can be controlled with a favorable result in long-term observation. Compared with RT and microsurgery, GKRS plays an important role in the treatment of CN as a minimally invasive technique with low morbidity. Regular long-term MRI follow-up should be mandatory to document the tumor response and possible recurrence. Multicenter consortia should be considered for further investigation and evaluation of GKRS for such a rare tumor., (Copyright © 2011 S. Karger AG, Basel.)

Objective: To establish the role of gamma knife radiosurgery (GKS) as a treatment strategy for glomus jugulare and tympanicum., Method: A retrospective review of 14 glomus tumors, including 11 glomus jugulare and 3 glomus tympanicum tumors, which were treated by GKS in Taipei Veterans General Hospital from 1993 to 2009, was conducted. Two of these cases had undergone prior surgery with partial tumor resection, and the other 12 cases received primary treatment with GKS after a thorough neuroimaging and cerebral angiography. The tumor volume ranged from 6.5 to 22.1 ml. The maximum dose at the tumor center ranged from 21.6 to 26.3 Gy. All 14 patients were regularly followed up by clinical and radiological evaluations. The median follow-up time was 40.3 months., Results: All 14 patients had significant tumor regression after radiosurgery. The median tumor volume reduction was 34.0% (range 3-79%). Only 1 patient had temporary tumor volume progression (24% increment 6 months post-treatment), accompanied with unilateral facial palsy (from grade III to grade IV) and hearing impairment (from grade I to grade II). The tumor volume of this patient had regressed by 12 months, but facial palsy persisted. The tumor control rate in the series was 100% (n = 14/14), and the preservation rate of cranial nerve function was 92.8% (13/14). There was no complication of lower cranial nerve damage after radiosurgery., Conclusion: GKS appeared to be a good alternative or adjuvant to microsurgical resection in patients who are not amenable to complete surgical eradication, with an excellent tumor control rate and little morbidity after long-term follow-up., (Copyright © 2011 S. Karger AG, Basel.)

Object: Although radiosurgery has been well accepted as a treatment for small- to medium-sized vestibular schwannomas (VSs), its application in the treatment of large VSs remains controversial because of unfavorable effects such as tumor swelling and potential compression of the brainstem. The authors present a retrospective study spanning 17 years, during which 21 patients underwent Gamma Knife surgery (GKS) for large VSs. Long-term outcomes are reported, and possible factors affecting tumor responses to GKS are analyzed., Methods: Five hundred thirteen patients harboring VSs underwent GKS between March 1993 and October 2009. A large VS was defined as a tumor whose diameter was > 3 cm. This paper focuses on 21 patients who harbored large VSs ranging in volume from 12.7 to 25.2 cm(3) (mean 17.3 cm(3)) and were treated by GKS. Fourteen of these patients had undergone 1 or more craniotomies previously to remove the tumor. Seven patients underwent GKS alone because of patient preference or a poor clinical condition that precluded microsurgery with general anesthesia. The mean radiation dose directed to the tumor ranged from 15 to 17.5 Gy. The mean radiation dose prescribed to the tumor margin was 11.9 Gy (range 11-14 Gy). The mean follow-up period was 66 months (range 12-155 months), and the median follow-up period was 53 months., Results: The tumor control rate was 90.5% (19 of 21 lesions). No deterioration in facial nerve or trigeminal nerve function was noted. Disturbances in balance (some temporary) occurred in 5 patients. Three of the 21 patients developed initial tumor swelling, which required minor surgical interventions, including aspiration using an Ommaya reservoir or placement of a ventriculoperitoneal shunt. All 3 patients recovered satisfactorily after aspiration of an enlarging cyst or ventriculoperitoneal shunt placement. There was no significant correlation between tumor control and the following factors: patient age or sex, tumor volume, radiation dose, previous operation, presence of brainstem compression, petrous bone invasion, T2 signal ratio between tumor and brainstem, and presence of a cyst. However, there was a significant correlation between the T2 signal ratio between tumor and brainstem and the duration of tumor swelling (p = 0.003)., Conclusions: Treatment of large VSs remains a challenge to neurosurgeons regardless of whether they perform microsurgery or radiosurgery. Control of tumor growth and preservation of neurological function are the main goals of treatment. Although delayed microsurgery was required in 2 patients (9.5%), the satisfactory tumor control rate and excellent preservation of facial and trigeminal nerve function are the great advantages of radiosurgery. Radiosurgery is not only a practical treatment for patients with small- to medium-sized VSs, but it is also an excellent tool for treating larger tumors up to 25 cm(3). In selected cases, radiosurgery plays an important role in treating large VSs with satisfactory results.

Background: Cavernous hemangioma in the cavernous sinus (CS) is a rare vascular tumor. Direct microsurgical approach usually results in massive hemorrhage. Radiosurgery has emerged as a treatment alternative to microsurgery., Objective: To further investigate the role of Gamma Knife surgery (GKS) in treating CS hemangiomas., Methods: This was a retrospective analysis of 7 patients with CS hemangiomas treated by GKS between 1993 and 2008. Data from 84 CS meningiomas treated during the same period were also analyzed for comparison. The patients underwent follow-up magnetic resonance imaging at 6-month intervals. Data on clinical and imaging changes after radiosurgery were analyzed., Results: Six months after GKS, magnetic resonance imaging revealed an average of 72% tumor volume reduction (range, 56%-83%). After 1 year, tumor volume decreased 80% (range, 69%-90%) compared with the pre-GKS volume. Three patients had > 5 years of follow-up, which showed the tumor volume further decreased by 90% of the original size. The average tumor volume reduction was 82%. In contrast, tumor volume reduction of the 84 cavernous sinus meningiomas after GKS was only 29% (P < .001 by Mann-Whitney U test). Before treatment, 6 patients had various degrees of ophthalmoplegia. After GKS, 5 improved markedly within 6 months. Two patients who suffered from poor vision improved after radiosurgery., Conclusion: GKS is an effective and safe treatment modality for CS hemangiomas with long-term treatment effect. Considering the high risks involved in microsurgery, GKS may serve as the primary treatment choice for CS hemangiomas.

Stereotactic radiosurgery for vestibular schwannomas (VSs) has become popular during the last decade with promising clinical results after long-term follow-up. However, on rare occasions, some cases have needed traditional microsurgery to remove the tumor several months or years after radiosurgery. We present a retrospective analysis of data acquired during a 16-year period in delayed microsurgery of seven patients with VSs who underwent gamma knife surgery (GKS). A total of 444 with VS underwent GKS between March 1993 and December 2008, and 7 (1.57%) underwent delayed microsurgery at a median of 26 months (range from 3 months to 6 years) after GKS. The mean size of the tumor during GKS was 10.4 ml (range 2.3-23.5 ml). These seven patients were younger, and female predominant. The indications of microsurgery included adverse radiation effect with peri-focal edema, tumor enlargement, and cyst enlargement. Although the perifocal edema could lead to more difficulty in surgery than in typically performed operations for schwannoma, subtotal resection was achieved in all patients. There was no surgery-related morbidity or mortality. The histology showed benign tumor in five patients, malignant peripheral nerve sheath tumor in one, and necrotic tissue in one. The need of microsurgery for further treatment of VS after radiosurgery is rare, but can be a challenge to neurosurgeons in terms of surgical indication, timing, and techniques. The authors concluded the incidence of delayed microsurgery was 1.57% in a series of 444 patients over a 16-year period. We concluded some experience from operative indications, timing, approach, and outcome.

To evaluate the efficacy and safety of gamma knife radiosurgery (GKS) in treating temporal lobe epilepsy, GKS was performed in four adult patients with recurrent complex partial seizures who underwent incomplete anterior temporal lobectomy (ATL) but were reluctant to undergo a second resective surgery. A marginal dose of 24.5-25Gy, corresponding to 65-70% isodose curve, was delivered to the treatment target that included the residual amygdala and the head and anterior body of the hippocampus. None of the patients had severe acute side effects but three patients had radiation-induced MRI signal changes around the target volume 13, 20, and 24 months after GKS, respectively. All four patients had significant seizure reduction during the first 6-month period and clinical efficacy persisted throughout the 2-year follow-up period. All of the patients also had improved neuropsychological profiles, including memory function and quality-of-life, compared to their pre-GKS conditions. In conclusion, the safety and clinical efficacy of GKS make it a reasonable and suitable therapeutic alternative for patients with recurrent seizures after incomplete ATL. A higher marginal dose of >25Gy and wider coverage may be more clinically beneficial but warrant further investigation.

Object: The effectiveness and safety of radiosurgery for small- to medium-sized cerebral arteriovenous malformations (AVMs) have been well established. However, the management for large cerebral AVMs remains a great challenge to neurosurgeons. In the past 5 years the authors performed preplanned staged radiosurgery to treat extra-large cerebral AVMs., Methods: An extra-large cerebral AVM is defined as one with nidus volume > 40 ml. The nidus volume of cerebral AVM is measured from the dose plan-that is, as being the volume contained within the best-fit prescription isodose. From January 2003 to December 2007, the authors treated 6 patients with extra-large AVMs by preplanned staged GKS. Staged radiosurgery is implemented by rigid transformation with translation and rotation of coordinates between 2 stages. The average radiation-targeted volume was 60 ml (range 47-72 ml). The presenting symptoms were seizure in 4 patients and a bleeding episode in 2. One patient had undergone a previous craniotomy and evacuation of hematoma. The mean interval between the 2 radiosurgical sessions was 6.9 months (range 4.5-9.1 months). The prescribed marginal dose given to the nidus volume in each stage ranged from 16 to 18.6 Gy. The expected marginal dose of total nidus was 17-19 Gy. Regular follow-up MR imaging was performed every 6 months. The mean follow-up period was 28 months (range 12-54 months)., Results: Most of the patients exhibited clinical improvement: relief of headache and reduced frequency of seizure attack. All patients had significant regression of nidus observed on MR imaging follow-up. Two patients had angiogram-confirmed complete obliteration of the nidus 45 and 60 months after the second-stage radiosurgical session. One patient experienced minor bleeding 8 months after the second-stage radiosurgery with mild headache. She had satisfactory recovery without clinical neurological deficit after conservative treatment., Conclusions: These preliminary results indicate that staged radiosurgery is a practical strategy to treat patients with extra-large cerebral AVMs. It takes longer to obliterate the AVMs. The observed high signal T2 changes after the radiosurgery appeared clinically insignificant in 6 patients followed up for an average of 28 months. Longer follow-up is necessary to confirm its long-term safety.

Object: Studies on the efficacy of arteriovenous malformation (AVM) radiosurgery have largely been conducted in the adult population. Clinically, the results may not always be applicable to pediatric patients. Moreover, studies involving the pediatric population have largely comprised small- (< 3 cm3) and medium-sized (3-10 cm3) AVMs. For large (> 10 cm3) AVMs in children, sparse radiosurgical results are available. The current study was conducted to further clarify the role of radiosurgery in the treatment of pediatric AVMs., Methods: A retrospective analysis was performed of data obtained in 105 pediatric patients (< 18 years of age) with cerebral AVMs treated by Gamma Knife surgery (GKS) between 1993 and 2006. For statistical comparison the authors studied data acquired in 458 adult patients with AVMs treated during the same period. The patients underwent follow-up magnetic resonance imaging at 6-month intervals. Cerebral angiography was used to confirm the obliteration of the AVM., Results: In pediatric patients, the AVM obliteration rate at 48 months after a primary GKS was 65%. Repeated GKS in those in whom primary treatments failed further ablated some AVMs, for an overall obliteration rate of 81%. The efficacy of GKS correlated with the size of the AVM: 91% for small, 86% for medium, and 64% for large AVMs. The treatments were associated with an 8% morbidity rate and < 1% mortality rate. Posttreatment hemorrhage occurred in 4 (4%) of 105 patients. Obliteration rates at 48 months of small and extremely large (> 20 cm3) AVMs were similar in the pediatric and adult groups, whereas AVMs between 3 and 10 cm3 responded less efficaciously in children (p = 0.042). The AVMs with volumes ranging from 10 to 20 cm3 were also associated with a lower obliteration rate in children at 48 months, but statistical significance was not reached (p = 0.279)., Conclusions: Gamma Knife surgery is an effective and safe treatment alternative for pediatric AVMs. The medium (3-10-cm3) and large (10-20-cm3) AVMs tend to respond less efficaciously than those of comparable size in adults.

Object: The purpose of this study was to assess the efficacy and safety of Gamma Knife surgery (GKS) for the treatment of cavernous sinus dural arteriovenous fistulas (CSDAVFs) and other intracranial dural arteriovenous fistulas (ODAVFs)., Methods: Among the 238 GKS procedures performed for intracranial DAVFs in the authors' institute, 227 cases (146 CSDAVFs and 81 OIDAVFs) with clinical follow up formed the database from which the authors determined clinical outcome and the incidence of untoward events. One hundred ninety-five cases (118 CSDAVFs and 77 ODAVFs) with imaging follow up formed the database from which the authors determined the imaging results. Older age, female sex, higher incidence of diabetes, and shorter duration of symptoms were noted more in cases of CSDAVF than in ODAVFs. Most patients had symptomatic improvement after GKS. A symptomatic cure was observed in one patient with CSDAVFs as early as 6 weeks. The cumulative cure rate based on follow-up angiography of CSDAVFs approached 75% at 24 months, which was much better than that of ODAVFs (approximately 50% at 24 months). A neuroimaging-based cure lagged behind that of the clinical symptoms. Overall, there were only two nonfatal intracerebral hemorrhages during the follow-up period, both occurring less than 1 week after GKS and both being Cognard Type IIa+b with initial aggressive symptoms. Transient deterioration of neurological status without hemorrhage was noted in six patients with ODAVFs. Thrombosis of the superior ophthalmic vein occurred in 11 patients with CSDAVFs, in two of whom there were unilateral visual impairments. There were three cranial nerve neuropathies: transient in one CSDAVF and one ODAVF involving the jugular foramen, and another one was a CSDAVF previously treated by conventional radiotherapy., Conclusions: Gamma Knife surgery provides a safe and effective option for treatment of intracranial DAVFs with a low risk of complications. In cases of DAVFs with benign clinical presentation, GKS can serve as a primary treatment. In some cases of aggressive DAVFs in which there is extensive retrograde cortical vein drainage, combined treatment with embolization or surgery is suggested.

Object: The authors report the long-term treatment results of Gamma Knife surgery (GKS) for patients with low-grade astrocytomas who underwent surgery at a single institution., Methods: A series of 21 patients (median age 20 years) with 25 intracranial low-grade astrocytomas (World Health Organization Grades I and II) were treated with GKS between 1993 and 2003. Among them, four underwent GKS as a primary treatment. Two underwent GKS as a treatment boost after radiotherapy. In the other 15 patients, GKS was performed as an adjuvant or salvage treatment for residual/recurrent tumors after the patients had undergone craniotomy. Tumor volumes ranged from 0.2 to 13.3 ml (median 2.4 ml). Prescription margin doses ranged from 8 to 18 Gy (median 14.5 Gy). Radiation volumes were 1.3 to 21.6 ml (median 3.6 ml). Patients underwent regular follow up, with neurological evaluation and magnetic resonance imaging studies obtained at 6-month intervals. One patient was lost to follow-up. The clinical follow-up time was 5 to 144 months (median 67 months). Complete tumor remission was seen in three patients. The 10-year progression-free patient survival rate after GKS was 65%. Tumor progression was found in six patients of whom five received further salvage treatment. All the tumor progression occurred within the GKS-treated volumes. Mild-to-moderate adverse radiation effects (AREs) were found in eight patients. Both of the patients who had undergone GKS as a treatment boost after radiotherapy developed AREs, but with good shrinkage of tumors., Conclusions: Gamma Knife surgery provides durable long-term local tumor control with acceptable toxicity for some patients with highly selected low-grade astrocytomas.

Background: The purpose of this report is to present long-term outcomes of gamma knife radiosurgery for intracranial mature teratoma after debulking surgery., Methods: Three patients with intracranial mature teratoma had initial target volumes of 5.4, 18.7, and 5.1 cm(3), respectively, and were treated by gamma knife radiosurgery between 1993 and 2004. Marginal doses of 17, 12.5, and 13.5 Gy, respectively, were delivered to the tumors at isodose levels of 50%, 50%, and 62%, respectively. The first patient received radiosurgery after surgical removal and conventional radiotherapy. The second patient received similar management, including surgery and radiotherapy, with tumor recurrence. Two additional operations and subsequent radiosurgery were performed on this patient. Based on the favorable results of the first 2 patients, we performed radiosurgery instead of conventional radiotherapy after subtotal surgical removal in the last patient. By reviewing literatures concerning the therapeutic modalities and the long-term results of our 3 patients, we discuss the role of radiosurgery in treating intracranial mature teratoma., Results: A follow-up period of 121, 89, and 31 months, respectively, demonstrated tumor volume reduction rates of 70%, 89%, and 48%, respectively. No evidence of further tumor progression and no radiosurgery-related complication or morbidity was noted. The school performances of the affected children are all above average., Conclusions: Gamma knife radiosurgery provides a safe and effective alternative as the adjuvant treatment of intracranial mature teratoma after surgical debulking. Previous conventional radiotherapy does not alter final tumor control. Radiosurgery should be considered when residual tumor growth continues with no related symptoms or evaluations of tumor markers during follow-up.