OBJECTIVE: The aim of this study was to investigate the incidence and risk factors of new-onset hypopituitarism after gamma knife radiosurgery (GKRS) for pituitary adenomas in a single center.
METHODS: In this retrospective study, 241 pituitary adenoma patients who underwent GKRS from 1993 to 2016 were enrolled. These patients had complete endocrine, imaging, and clinical data before and after GKRS. The median follow-up time was 56.0 (range, 12.7-297.6) months.
RESULTS: Fifty patients (20.7%) developed new-onset hypopituitarism after GKRS, including hypogonadism (n = 22), hypothyroidism (n = 29), hypocortisolism (n = 20), and growth hormone deficiency (n = 4). The median time to new-onset hypopituitarism was 44.1 (range, 13.5-141.4) months. The rates of new-onset hypopituitarism were 7%, 16%, 20%, 39%, and 45% at 1, 3, 5, 10, and 15 years, respectively. For those patients treated with a single GKRS, sex (p = 0.012), suprasellar extension (p = 0.048), tumor volume (≥ 5 cm3) (p < 0.001), tumor progression (p = 0.001), pre-existing hypopituitarism (p = 0.011), and previous surgery (p = 0.009) were significantly associated with new-onset hypopituitarism in univariate analysis. In the multivariate analysis, tumor volume (≥ 5 cm3) and tumor progression were associated with new-onset hypopituitarism (hazard ratio [HR] = 3.401, 95% confidence interval [CI] = 1.708-6.773, p < 0.001 and HR = 3.594, 95% CI = 1.032-12.516, p = 0.045, respectively). For patients who received 2 or more times GKRS, no risk factors associated with new-onset hypopituitarism were found.
CONCLUSIONS: New-onset hypopituitarism was not uncommon after GKRS for pituitary adenomas. In this study, large tumor volume (≥ 5 cm3) and tumor progression were associated with new-onset hypopituitarism after a single GKRS.

OBJECTIVE: To evaluate the dosimetric characteristics of ZAP-X stereotactic radiosurgery (SRS) for single brain metastasis by comparing with two mature SRS platforms.
METHODS: Thirteen patients with single brain metastasis treated with CyberKnife (CK) G4 were selected retrospectively. The prescription dose for the planning target volume (PTV) was 18-24 Gy for 1-3 fractions. The PTV volume ranged from 0.44 to 11.52 cc.Treatment plans of thirteen patients were replanned using the ZAP-X plan system and the Gamma Knife (GK) ICON plan system with the same prescription dose and organs at risk (OARs) constraints. The prescription dose of PTV was normalized to 70% for both ZAP-X and CK, while it was 50% for GK. The dosimetric parameters of three groups included the plan characteristics (CI, GI, GSI, beams, MUs, treatment time), PTV (D2, D95, D98, Dmin, Dmean, Coverage), brain tissue (volume of 100%-10% prescription dose irradiation V100%-V10%, Dmean) and other OARs (Dmax, Dmean),all of these were compared and evaluated. All data were read and analyzed with MIM Maestro. One-way ANOVA or a multisample Friedman rank sum test was performed, where p < 0.05 indicated significant differences.
RESULTS: The CI of GK was significantly lower than that of ZAP-X and CK. Regarding the mean value, ZAP-X had a lower GI and higher GSI, but there was no significant difference among the three groups. The MUs of ZAP-X were significantly lower than those of CK, and the mean value of the treatment time of ZAP-X was significantly shorter than that of CK. For PTV, the D95, D98, and target coverage of CK were higher, while the mean of Dmin of GK was significantly lower than that of CK and ZAP-X. For brain tissue, ZAP-X showed a smaller volume from V100% to V20%; the statistical results of V60% and V50% showed a difference between ZAP-X and GK, while the V40% and V30% showed a significant difference between ZAP-X and the other two groups; V10% and Dmean indicated that GK was better. Excluding the Dmax of the brainstem, right optic nerve and optic chiasm, the mean value of all other OARs was less than 1 Gy. For the brainstem, GK and ZAP-X had better protection, especially at the maximum dose.
CONCLUSIONS: For the SRS treating single brain metastasis, all three treatment devices, ZAP-X system, CyberKnife G4 system, and GammaKnife system, could meet clinical treatment requirements. The newly platform ZAP-X could provide a high-quality plan equivalent to or even better than CyberKnife and Gamma Knife, with ZAP-X presenting a certain dose advantage, especially with a more conformal dose distribution and better protection for brain tissue. As the ZAP-X systems get continuous improvements and upgrades, they may become a new SRS platform for the treatment of brain metastasis.

Gamma knife radiosurgery (GKRS) is recommended as the first-line treatment for brain metastases of lung adenocarcinoma (LUAD) in many guidelines, but its specific mechanism is unclear. We aimed to study the changes in the proteome of brain metastases of LUAD in response to the hyperacute phase of GKRS and further explore the mechanism of differentially expressed proteins (DEPs). Cancer tissues were collected from a clinical trial for neoadjuvant stereotactic radiosurgery before surgical resection of large brain metastases (ChiCTR2000038995). Five brain metastasis tissues of LUAD were collected within 24 h after GKRS. Five brain metastasis tissues without radiotherapy were collected as control samples. Proteomics analysis showed that 163 proteins were upregulated and 25 proteins were downregulated. GO and KEGG enrichment analyses showed that the DEPs were closely related to ribosomes. Fifty-three of 70 ribosomal proteins were significantly overexpressed, while none of them were underexpressed. The risk score constructed from 7 upregulated ribosomal proteins (RPL4, RPS19, RPS16, RPLP0, RPS2, RPS26 and RPS25) was an independent risk factor for the survival time of LUAD patients. Overexpression of ribosomal proteins may represent a desperate response to lethal radiotherapy. We propose that targeted inhibition of these ribosomal proteins may enhance the efficacy of GKRS.

OBJECTIVE: To examine the diagnostic value of imaging features in cavernous sinus hemangioma (CSH).
METHODS: The clinical and imaging data of patients with pathologically confirmed CSH, cavernous sinus meningioma, trigeminal schwannoma and pituitary adenoma invading the cavernous sinus between May 2017 and May 2022 were retrospectively analyzed. The cases were divided into the CSH and non-CSH groups to summarize the magnetic resonance imaging (MRI) characteristics of CSH. Univariate χ2 analysis was performed to assess five indexes, including signal intensity on T2WI, homogeneity of T2WI, enhancement of enhanced T1, enhanced T1 with dural tail sign, and cavernous sinus swelling and extrusion sign.
RESULTS: There were significant differences in four features, including hyperintensity on T2WI, homogeneity of T2WI, T1-enhanced without meningeal tail sign, and cavernous sinus swelling and extrusion sign between the CSH and non-CSH groups, with cavernous sinus swelling and extrusion sign showing the most pronounced distinction, with a sensitivity of 100%, a specificity of 93.02%, and an accuracy of 94.23%. The four features could be jointly used as diagnostic criteria, with a sensitivity of 94.44%, a specificity of 100.00%, and an accuracy of 99.04%.
CONCLUSIONS: Cavernous sinus swelling and extrusion sign is a reliable imaging index for CSH diagnosis. Homogenous hyperintensity or marked hyperintensity on T2WI, enhanced T1 without dural tail sign, and cavernous sinus swelling and extrusion sign could be jointly used as diagnostic criteria, which may improve the accuracy of CSH diagnosis.

OBJECTIVE: The purpose of this research was to summarize the clinical and prognostic features of cavernous sinus meningiomas (CSM), evaluate the treatment strategies and long-term prognosis of CSM, and improve the management of CSM and the treatment effect for patients.
METHODS: We retrospectively studied the data of 54 patients who received initial surgical resection and 45 patients who received initial gamma knife radiosurgery (GKRS) for CSM at West China Hospital of Sichuan University from 2009 to 2021. Progression-free survival (PFS), Karnofsky Performance Scale (KPS) scores and neurological function recovery were adopted to assess a comprehensive management strategy for CSM.
RESULTS: Gross total resection (GTR) was performed in 51.9 % of cases with 3.7 % surgical mortality. The average follow-up time was 48.7 months, with a progression rate of 29.3 %. The overall improvement rate for cranial nerve function deficits was 50.0 %. By survival analysis, the extent of resection and the histological grade were significantly related to the prognosis. The role of postoperative GKRS is uncertain. For patients who received initial GKRS, the progression rate was 17.8 %, and the overall improvement rate for cranial nerve function deficits was 61.1 %. Primary treatment with GKRS showed better long-term tumor control in patients with CSM (P = 0.046).
CONCLUSIONS: Maximum safe resection of CSM can improve the neurological function and quality of life of patients, but aggressive resection will cause high perioperative mortality and complication rates. For CSM patients who are suitable for initial gamma knife treatment, choosing GKRS can achieve better long-term tumor control and neurological outcomes.

BACKGROUND: This study aimed to assess the impact of gamma knife radiosurgery on brainstem cavernous malformations (CMs).
METHODS: A total of 85 patients (35 females; median age 41.0 years) who underwent gamma knife radiosurgery for brainstem CMs at our institute between 2006 and 2015 were enrolled in a prospective clinical observation trial. Risk factors for hemorrhagic outcomes were evaluated, and outcomes were compared across different margin doses.
RESULTS: The pre-radiosurgery annual hemorrhage rate (AHR) was 32.3% (44 hemorrhages during 136.2 patient-years). The median planning target volume was 1.292 cc. The median margin and maximum doses were 15.0 and 29.2 Gy, respectively, with a median isodose line of 50.0%. The post-radiosurgery AHR was 2.7% (21 hemorrhages during 769.9 patient-years), with a rate of 5.5% within the first 2 years and 2.0% thereafter. The post-radiosurgery AHR for patients with margin doses of ≤13.0 Gy (n = 15), 14.0-15.0 Gy (n = 50), and ≥16.0 Gy (n = 20) was 5.4, 2.7, and 0.6%, respectively. Correspondingly, transient adverse radiation effects were observed in 6.7 (1/15), 10.0 (5/50), and 30.0% (6/20) of cases, respectively. An increased margin dose per 1 Gy (hazard ratio: 0.530, 95% CI: 0.341-0.826, p = 0.005) was identified as an independent protective factor against post-radiosurgery hemorrhage. Margin doses of ≥16.0 Gy were associated with improved hemorrhagic outcomes (hazard ratio: 0.343, 95% confidence interval [CI]: 0.157-0.749, p = 0.007), but an increased risk of adverse radiation effects (odds ratio: 3.006, 95% CI: 1.041-8.677, p = 0.042).
CONCLUSIONS: The AHR of brainstem CMs decreased following radiosurgery, and our study revealed a significant dose-response relationship. Margin doses of 14-15 Gy were recommended. Further studies are required to validate our findings.

Orbital meningioma is a rare type of orbital tumor with high invasiveness and recurrence rates, making it extremely challenging to treat. Due to the special location of the disease, surgery often cannot completely remove the tumor, requiring postoperative radiation therapy. Here, we report a case of an elderly male patient with right-sided proptosis, visual impairment, and diplopia. Imaging diagnosis revealed a space-occupying lesion in the extraconal space of the right orbit. Pathological and immunohistochemical examination of the resected tumor confirmed it as a grade 3 anaplastic meningioma. Two months after surgery, the patient complained of right eye swelling and a magnetic resonance imaging (MRI) scan showed a recurrence of the tumor. The patient received helical tomotherapy (TOMO) in the postoperative tumor bed and high-risk areas within the orbit with a total dose of 48Gy. However, there was no significant improvement in the patient\'s right eye swelling, and the size of the recurrent lesion showed no significant change on imaging. Gamma knife multifractionated stereotactic radiosurgery (MF-SRS) was then given to the recurrent lesion with 50% prescription dose 13.5Gy/3f, once every other day. An imaging diagnosis performed 45 days later showed that the tumor had disappeared completely. The patient\'s vision remained unchanged, but diplopia was significantly relieved after MF-SRS. We propose a new hybrid treatment model for recurrent orbital meningioma, where conventional radiation therapy ensures local control of high-risk areas around the postoperative cavity, and MF-SRS maximizes the radiation dose to recurrent lesion areas while protecting surrounding tissues and organs.

BACKGROUND: Tentorial dural arteriovenous fistulas (TDAVFs) are abnormal shunts between meningeal arteries and the intradural venous system located in the tentorial dura mater, which typically manifest with haemorrhage or progressive neurological disorders. TDAVFs with pure ocular presentation have been rarely reported.
METHODS: The case of a 56-year-old man presented with unilateral eye redness, proptosis and elevated intraocular pressure was reported herein, which was caused by a TDAVF. The fistula was fed by the left posterior cerebral artery and posterior meningeal artery. The drainage was into the basal vein and internal cerebral veins, which led the arterial blood flow forward to the left superior ophthalmic vein directly. The redundant blood flow caused the rise of episcleral venous pressure, leading to the clinical presentations. Gamma knife radiosurgery was performed then considering the delicate vascular structure and its deep location. The corkscrew hyperaemia was gradually alleviated after the surgery, but the intraocular pressure remained elevated at follow-ups.
CONCLUSIONS: Dural arteriovenous fistulas which are not directly connected to cavernous sinus could cause ocular presentations like proptosis, eye redness and ocular hypertension.

Gamma Knife stereotactic radiosurgery (SRS) is an effective therapeutic option for unresectable brainstem metastases. Currently, staged stereotactic radiosurgery (SSRS) has become available for large brainstem metastases（≥ 1 cm3） despite the limitation of peritumoral edema. The authors developed the so-called \"sandwich therapy\" which integrated 2-stage stereotactic radiosurgery (2-SSRS) with bevacizumab for peritumoral edema reduction and local control of large brainstem metastases.
42 patients with large brainstem metastases ≥1 cm3 who received 2-SSRS simultaneously with bevacizumab were screened from 2019 to 2021 retrospectively. The first SRS margin doses were 13 Gy (range 11-15) and the second SRS margin doses were 12 Gy (range 11-13), one-time vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) of 3.5-5 mg/kg was administrated intravenously the next day after the first SRS. The median interval between the two sessions of SRS was 6 days. Baseline demographics, clinical and radiology imaging follow-ups were recorded to determine symptomatic improvement, peritumoral edema reduction, local control, and disease progression. Median survival was calculated using Kaplan-Meier analysis. Multivariate analysis was performed to identify prognostic factors.
The \"sandwich therapy\" was applied to 42 lesions. Significant reductions of tumor volume (p < 0.05) and peritumoral edema volume (p < 0.01) were achieved at the second SRS in comparison to those at the first SRS. The proportion of favorable Karnofsky performance scale (KPS) (≥80 %) increased significantly at early follow-up time points and reached the highest value of 85.7 %. The median survival time was 9.7 months, the median local control duration was 11.3 months. 8 acute adverse events of CTCAE grade 2 and 3 were observed in 6 patients and resolved with palliative treatment. Tyrosine kinase inhibitor (TKI) treatment was identified as a predictive factor for longer survival.
The \"sandwich therapy\" which integrates 2-SSRS with bevacizumab is a safe and effective option for large brainstem metastases.

UNASSIGNED: To explore the results of the Gamma Knife radiosurgery (GKRS) for World Health Organization (WHO) grade I intracranial meningiomas after surgical resection.
UNASSIGNED: A total of 130 patients who were pathologically diagnosed as having WHO grade I meningiomas and who underwent post-operative GKRS were retrospectively reviewed in a single center.
UNASSIGNED: Of the 130 patients, 51 patients (39.2%) presented with radiological tumor progression with a median follow-up time of 79.7 months (ranging from 24.0 to 291.3 months). The median time to radiological tumor progression was 73.4 months (ranging from 21.4 to 285.3 months), whereas 1-, 3-, 5-, and 10-year radiological progression-free survival (PFS) was 100, 90, 78, and 47%, respectively. Moreover, 36 patients (27.7%) presented with clinical tumor progression. Clinical PFS at 1, 3, 5, and 10 years was 96, 91, 84, and 67%, respectively. After GKRS, 25 patients (19.2%) developed adverse effects, including radiation-induced edema (n = 22). In a multivariate analysis, a tumor volume of ≥10 ml and falx/parasagittal/convexity/intraventricular location were significantly associated with radiological PFS [hazard ratio (HR) = 1.841, 95% confidence interval (CI) = 1.018-3.331, p = 0.044; HR = 1.761, 95% CI = 1.008-3.077, p = 0.047]. In a multivariate analysis, a tumor volume of ≥10 ml was associated with radiation-induced edema (HR = 2.418, 95% CI = 1.014-5.771, p = 0.047). Of patients who presented with radiological tumor progression, nine were diagnosed with malignant transformation. The median time to malignant transformation was 111.7 months (ranging from 35.0 to 177.2 months). Clinical PFS after repeat GKRS was 49 and 20% at 3 and 5 years, respectively. Secondary WHO grade II meningiomas were significantly associated with a shorter PFS (p = 0.026).
UNASSIGNED: Post-operative GKRS is a safe and effective treatment for WHO grade I intracranial meningiomas. Large tumor volume and falx/parasagittal/convexity/intraventricular location were associated with radiological tumor progression. Malignant transformation was one of the main cause of tumor progression in WHO grade I meningiomas after GKRS.