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.

OBJECTIVE: To evaluate the incidence and the independent risk factors of SRS-related epilepsy in patients with supratentorial brain metastases (st-BMs), providing evidences for prevention or reduction secondary epilepsy after SRS.
METHODS: Patients with st-BMs from four gamma knife centers who developed secondary epilepsy after SRS were retrospectively studied between January 1, 2017 and June 31, 2023. The incidence and clinical characteristics of the patients with secondary epilepsy were analyzed. The predictive role of baseline clinical-demographic variables was evaluated according to univariate and multivariate logistic regression model. The impact of secondary epilepsy on patients\' OS was evaluated as well by log-rank test.
RESULTS: 11.3 % (126/1120) of the patients with totally 158 st-BMs experienced secondary epilepsy after SRS in median 21 days. 61.9 % (78/126) of the patients experienced simple partial seizures. 91.3 % (115/126) patients achieved good seizure control after received 1-2 kinds of AEDs for median 90 days, while 7.1 % (9/126) of the patients suffered from refractory epilepsy. Patients had higher risk of secondary epilepsy if the tumor located in cortex and/or hippocampus, peri-tumor edema larger than 20.3 cm3 before SRS, had epilepsy history, and failed to receive bevacizumab prior to SRS. There was no difference in the OS of patients who experience secondary epilepsy or not after SRS.
CONCLUSIONS: The incidence of SRS-related secondary epilepsy is 11.3 % in patients with st-BMs in this retrospective study. The risk of secondary epilepsy is higher in patients with st-BM located in cortex and/or hippocampus area, peri-tumor edema larger than 20.3 cm3 before SRS, and epilepsy history. Bevacizumab is suggested prior to SRS therapy, as it could be used for the control of peri-tumor edema and SRS-related damage, hence reduce the risk of secondary epilepsy. However, whether or not patients suffered from secondary epilepsy after SRS does not affect their OS.

Before the Stereotactic Radiosurgery (SRS) treatment, it is of great clinical significance to avoid secondary genetic damage and guide the personalized treatment plans for patients with brain metastases (BM) by predicting the response to SRS treatment of brain metastatic lesions. Thus, we developed a multi-task learning model termed SRTRP-Net to provide prior knowledge of BM ROI and predict the SRS treatment response of the lesion. In dual-encoder tumor segmentation Network (DTS-Net), two parallel encoders encode the original and mirrored multi-modal MRI images. The differences in the dual-encoder features between foreground and background are enhanced by the symmetrical visual difference block (SVDB). In the bottom layer of the encoder, a transformer is used to extract local contextual features in the spatial and depth dimensions of low-resolution images. Then, the decoder of DTS-Net provides the prior knowledge for predicting the response to SRS treatment by performing BM segmentation. SRS response prediction network (SRP-Net) directly utilizes shared multi-modal MRI features weighted by the signed distance map (SDM) of the masks. The bidirectional multi-dimensional feature fusion module (BMDF) fuses the shared features and the clinical text information features to obtain comprehensive tumor information for characterizing tumors and predicting SRS treatment response. Experiments based on internal and external clinical datasets have shown that SRTRP-Net achieves comparable or better results. We believe that SRTRP-Net can help clinicians accurately develop personalized first-time treatment regimens for BM patients and improve their survival.

In brain metastases, radiation necrosis (RN) is a complication that arises after single or multiple fractionated stereotactic radiosurgery (SRS/FSRS), which is challenging to distinguish from local recurrence (LR). Studies have shown increased RN incidence rates in non-small cell lung cancer (NSCLC) patients with oncogenic driver mutations (ODMs) or receiving tyrosine kinase inhibitors (TKIs). This study investigated enlarging brain lesions following SRS/FSRS, for which additional surgeries were performed to distinguish between RN and LR. We investigated seven NSCLC patients with ODMs undergoing SRS/FSRS for BM and undergoing surgery for suspicion of LR on MRI imaging. Descriptive statistics were performed. Among the seven patients, six were EGFR+, while one was ALK+. The median irradiation dose was 30 Gy (range, 20-35 Gy). The median time to develop RN after SRS/FSRS was 11.1 months (range: 6.3-31.2 months). Moreover, gradually enlarging lesions were found in all patients after 6 months post-SRS/FSR. Brain radiation necrosis was pathologically confirmed in all the patients. RN should be suspected in NSCLC patients when lesions keep enlarging after 6 months post-SRS/FSRS, especially for patients with ODMs and receiving TKIs. Further, this case series indicates that further dose reduction might be necessary to avoid RN for such patients.

UNASSIGNED: While deep learning has shown promise for automated radiotherapy planning, its application to the specific scenario of stereotactic radiosurgery (SRS) for brain metastases using fixed-field intensity modulated radiation therapy (IMRT) on a linear accelerator remains limited. This work aimed to develop and verify a deep learning-guided automated planning protocol tailored for this scenario.
UNASSIGNED: We collected 70 SRS plans for solitary brain metastases, of which 36 cases were for training and 34 for testing. Test cases were derived from two distinct clinical institutions. The envisioned automated planning process comprised (1): clinical dose prediction facilitated by deep-learning algorithms (2); transformation of the forecasted dose into executable plans via voxel-centric dose emulation (3); validation of the envisaged plan employing a precise dosimeter in conjunction with a linear accelerator. Dose prediction paradigms were established by engineering and refining two three-dimensional UNet architectures (UNet and AttUNet). Input parameters encompassed computed tomography scans from clinical plans and demarcations of the focal point alongside organs at potential risk (OARs); the ensuing output manifested as a 3D dose matrix tailored for each case under scrutiny.
UNASSIGNED: Dose estimations rendered by both models mirrored the manual plans and adhered to clinical stipulations. As projected by the dual models, the apex and average doses for OARs did not deviate appreciably from those delineated in the manual plan (P-value≥0.05). AttUNet showed promising results compared to the foundational UNet. Predicted doses showcased a pronounced dose gradient, with peak concentrations localized within the target vicinity. The executable plans conformed to clinical dosimetric benchmarks and aligned with their associated verification assessments (100% gamma approval rate at 3 mm/3%).
UNASSIGNED: This study demonstrates an automated planning technique for fixed-field IMRT-based SRS for brain metastases. The envisaged plans met clinical requirements, were reproducible across centers, and achievable in deliveries. This represents progress toward automated paradigms for this specific scenario.

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.

OBJECTIVE: Jugular foramen schwannomas (JFSs) are rarely seen, benign tumors with slow growth. Today, management options for JFSs include observation, surgery, and radiation. However, the optimal treatment strategy remains controversial. Stereotactic radiosurgery serves as a minimally invasive alternative or adjuvant therapeutic regimen of microsurgery. Gamma Knife radiosurgery is suitable for patients with JFS who have small- and medium-sized tumors and normal cranial nerve (CN) function. Hypofractionated stereotactic radiotherapy (HSRT) offers a potential radiobiological advantage and may result in better preservation of normal structures compared to single-fraction stereotactic radiosurgery. The aim of the article was to review the clinical and radiographic outcomes of patients with JFS who were treated using HSRT.
METHODS: The authors retrospectively analyzed 74 patients with JFS who received HSRT between January 2009 and January 2020 in the authors\' center. Among them, 53 patients were newly diagnosed with JFS, 19 patients had a previous history of microsurgical resection, and the other 2 patients underwent CyberKnife because of tumor recurrence after Gamma Knife radiosurgery. A total of 73 patients had preexisting CN symptoms and signs. The median tumor volume was 14.8 cm3 (range 0.5-41.2 cm3), and most of them (70.3%) were ≥ 10 cm3. The radiation dose regimen was prescribed depending on the tumor size, and more fractions were used in larger tumors. The median margin doses prescribed were 18.2 Gy/2 fractions, 21.0 Gy/3 fractions, and 21.6 Gy/4 fractions.
RESULTS: The median follow-up was 103 months (range 18-158 months). After treatment, 42 (56.8%) patients had tumor regression, 27 (36.5%) patients had stable tumors, and 5 (6.8%) experienced tumor progression. Among them, MRI revealed that 1 patient had a complete response. Three patients received surgery at a median of 25 months because of tumor progression. One patient underwent ventriculoperitoneal shunt insertion for hydrocephalus that developed after HSRT independent of tumor progression. The 5-year progression-free survival rate was 93.2%. Preexisting cranial neuropathies improved in 46 patients, remained stable in 14, and worsened in 14.
CONCLUSIONS: HSRT proved to be a safe and effective primary or adjuvant treatment strategy for JFSs, although 14 patients (18.9%) experienced some degree of delayed symptomatic deterioration posttreatment. This therapeutic option was demonstrated to provide both excellent tumor control and improvement in CN function.

Purpose. To enhance an in-house graphic-processing-unit accelerated virtual particle (VP)-based Monte Carlo (MC) proton dose engine (VPMC) to model aperture blocks in both dose calculation and optimization for pencil beam scanning proton therapy (PBSPT)-based stereotactic radiosurgery (SRS).Methods and materials. A module to simulate VPs passing through patient-specific aperture blocks was developed and integrated in VPMC based on simulation results of realistic particles (primary protons and their secondaries). To validate the aperture block module, VPMC was first validated by an opensource MC code, MCsquare, in eight water phantom simulations with 3 cm thick brass apertures: four were with aperture openings of 1, 2, 3, and 4 cm without a range shifter, while the other four were with same aperture opening configurations with a range shifter of 45 mm water equivalent thickness. Then, VPMC was benchmarked with MCsquare and RayStation MC for 10 patients with small targets (average volume 8.4 c.c. with range of 0.4-43.3 c.c.). Finally, 3 typical patients were selected for robust optimization with aperture blocks using VPMC.Results. In the water phantoms, 3D gamma passing rate (2%/2 mm/10%) between VPMC and MCsquare was 99.71 ± 0.23%. In the patient geometries, 3D gamma passing rates (3%/2 mm/10%) between VPMC/MCsquare and RayStation MC were 97.79 ± 2.21%/97.78 ± 1.97%, respectively. Meanwhile, the calculation time was drastically decreased from 112.45 ± 114.08 s (MCsquare) to 8.20 ± 6.42 s (VPMC) with the same statistical uncertainties of ~0.5%. The robustly optimized plans met all the dose-volume-constraints (DVCs) for the targets and OARs per our institutional protocols. The mean calculation time for 13 influence matrices in robust optimization by VPMC was 41.6 s and the subsequent on-the-fly \'trial-and-error\' optimization procedure took only 71.4 s on average for the selected three patients.Conclusion. VPMC has been successfully enhanced to model aperture blocks in dose calculation and optimization for the PBSPT-based SRS.

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: Brain metastases are the most common intracranial tumours. Variation exists in the use of stereotactic radiosurgery for patients with 10 or more brain metastases. Concerns include an increasing number of brain metastases being associated with poor survival, the lack of prospective, randomised data and an increased risk of toxicity.
METHODS: We performed a systematic review and meta-analysis to assess overall survival of patients with ten or more brain metastases treated with stereotactic radiosurgery as primary therapy. The search strings were applied to MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL). Log hazard ratios and standard errors were estimated from each included study. A random-effects meta-analysis using the DerSimonian and Laird method was applied using the derived log hazard ratios and standard errors on studies which included a control group.
RESULTS: 15 studies were included for systematic review. 12 studies were used for pooled analysis for overall survival at set time points, with a predicted 12 month survival of 20-40%. The random-effects meta-analysis in five studies of overall survival comparing ten or greater metastases against control showed statistically worse overall survival in the 10 + metastases group (1.10, 95% confidence interval 1.03-1.18, p-value = < 0.01, I2 = 6%). A funnel plot showed no evidence of bias. There was insufficient information for a meta-analysis of toxicity.
CONCLUSIONS: Overall survival outcomes of patients with ten or more brain metastases treated with SRS is acceptable and should not be a deterrent for its use. There is a lack of prospective data and insufficient real-world data to draw conclusions on toxicity.
UNASSIGNED: CRD42021246115.
This systematic review and meta-analysis is the first of its kind in the literature and provides information on overall survival outcomes and toxicities encountered in patients with ten or more brain metastases treated with stereotactic radiosurgery. Centres treating patients with ten or more brain metastases are doing so based only on retrospective real-world data analyses, the vast majority of which are from single centres and single radiotherapy platforms. This review provides an additional evidence resource for practitioners of stereotactic radiosurgery to aide in the management of this difficult patient group. The methods used to predict survival outcomes through the calculation of log hazard ratios and standard errors allowed analysis of small, retrospective case series. To our knowledge, this is the first meta-analysis of this patient group gives evidence for acceptable overall survival outcomes post-treatment, and provides further evidence for the use of stereotactic radiosurgery for these patients.Overall survival following stereotactic radiosurgery for ten or more brain metastases: a systematic review and meta-analysis.