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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.)

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: 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.)

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.

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.

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.

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.

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.