OBJECTIVE: To report patient outcomes and local tumor control rates in a cohort of patients with biopsy-proven HER-2 positive breast cancer treated with stereotactic radiosurgery (SRS) for brain metastases (BM).
METHODS: This international, retrospective, multicenter study, included 195 female patients with 1706 SRS-treated BM. Radiologic and clinical outcomes after SRS were determined and prognostic factors identified.
RESULTS: At SRS, median patient age was 55 years [interquartile range (IQR) 47.6-62.0], and 156 (80%) patients had KPS ≥ 80. The median tumor volume was 0.1 cm3 (IQR 0.1-0.5) and the median prescription dose was 16 Gy (IQR 16-18). Local tumor control (LTC) rate was 98%, 94%, 93%, 90%, and 88% at six-, 12-, 24-, 36- and 60-months post-SRS, respectively. On multivariate analysis, tumor volume (p = < 0.001) and concurrent pertuzumab (p = 0.02) improved LTC. Overall survival (OS) rates at six-, 12-, 24-, 36-, 48-, and 60-months were 90%, 69%, 46%, 27%, 22%, and 18%, respectively. Concurrent pertuzumab improved OS (p = 0.032). In this patient subgroup, GPA scores ≥ 2.5 (p = 0.038 and p = 0.003) and rare primary tumor histologies (p = 0.01) were associated with increased and decreased OS, respectively. Asymptomatic adverse radiation events (ARE) occurred in 27 (14.0%) and symptomatic ARE in five (2.6%) patients. Invasive lobular carcinoma primary (p = 0.042) and concurrent pertuzumab (p < 0.001) conferred an increased risk for overall but not for symptomatic ARE.
CONCLUSIONS: SRS affords effective LTC for selected patients with BM from HER-2 positive breast cancer. Concurrent pertuzumab improved LTC and OS but at the same time increased the risk for overall, but not symptomatic, ARE.

UNASSIGNED: Treatment outcome data of stereotactic radiosurgery (SRS) for vestibular schwannomas (VS) in patients ≥75 years (late elderly) are lacking. Approximately 39% of patients ≥75 years with VS were reported to experience severe facial palsy after surgical removal. This study compared the treatment outcomes post-SRS for VS between patients ≥75 and 65-74 years (early elderly).
UNASSIGNED: Of 453 patients who underwent gamma knife SRS for VS, 156 were ≥65 years old. The late and early elderly groups comprised 35 and 121 patients, respectively. The median tumor volume was 4.4 cc, and the median radiation dose was 12.0 Gy.
UNASSIGNED: The median follow-up periods were 37 and 56 months in the late and early elderly groups, respectively. Tumor volume control was observed in 27 (88%) and 95 (83%) patients (P = 0.78), while additional procedures were required in 2 (6%) and 6 (6%) patients (P = 1.00) in the late and early elderly groups, respectively. At the 60th and 120th months post-SRS, the cumulative tumor control rates were 87%, 75%, 85%, and 73% (P = 0.81), while the cumulative clinical control rates were 93% and 87%, 95%, and 89% (P = 0.80), in the late and early elderly groups, respectively. In the early elderly group, two patients experienced facial pain, and one experienced facial palsy post-SRS; there were no adverse effects in the late elderly group (both P = 1.00).
UNASSIGNED: SRS is effective for VS and beneficial in patients ≥75 years old as it preserves the facial nerve.

OBJECTIVE: The present study assesses the safety and efficacy of stereotactic radiosurgery (SRS) versus observation for Koos grade 1 and 2 vestibular schwannoma (VS), benign tumors affecting hearing and neurological function.
METHODS: This multicenter study analyzed data from Koos grade 1 and 2 VS patients managed with SRS (SRS group) or observation (observation group). Propensity score matching balanced patient demographics, tumor volume, and audiometry. Outcomes measured were tumor control, serviceable hearing preservation, and neurological outcomes.
RESULTS: In 125 matched patients in each group with a 36-month median follow-up (P = .49), SRS yielded superior 5- and 10-year tumor control rates (99% CI, 97.1%-100%, and 91.9% CI, 79.4%-100%) versus observation (45.8% CI, 36.8%-57.2%, and 22% CI, 13.2%-36.7%; P < .001). Serviceable hearing preservation rates at 5 and 9 years were comparable (SRS 60.4% CI, 49.9%-73%, vs observation 51.4% CI, 41.3%-63.9%, and SRS 27% CI, 14.5%-50.5%, vs observation 30% CI, 17.2%-52.2%; P = .53). SRS were associated with lower odds of tinnitus (OR = 0.39, P = .01), vestibular dysfunction (OR = 0.11, P = .004), and any cranial nerve palsy (OR = 0.36, P = .003), with no change in cranial nerves 5 or 7 (P > .05). Composite endpoints of tumor progression and/or any of the previous outcomes showed significant lower odds associated with SRS compared with observation alone (P < .001).
CONCLUSIONS: SRS management in matched cohorts of Koos grade 1 and 2 VS patients demonstrated superior tumor control, comparable hearing preservation rates, and significantly lower odds of experiencing neurological deficits. These findings delineate the safety and efficacy of SRS in the management of this patient population.

OBJECTIVE: Gamma Knife radiosurgery (GKRS) has emerged as an effective treatment option for trigeminal neuralgia (TN) in patients with multiple sclerosis (MS). To date, the outcomes of repeat GKRS for patients with TN and MS with recurrent pain have been investigated in a few patients. This study aims to report the outcomes and predictive factors of pain reduction for MS patients undergoing repeat GKRS for recurrent TN.
METHODS: Eighteen patients with MS underwent repeat GKRS for recurrent TN. A retrospective chart review and telephone interviews were conducted to determine background medical history, dosimetric data, and outcomes of the procedure. Facial pain and sensory function were evaluated using the Barrow Neurological Institute (BNI) scales.
RESULTS: Fifteen patients achieved a BNI pain score of IIIa or better, indicating pain reduction, within a median period of 21 days after repeat GKRS. The maximum dose for repeat GKRS ranged from 70 to 85 Gy. Pain recurred in 5 patients after a median period of 12 months after GKRS. Percentages of patients with pain reduction at 1, 2, 3, 5, and 7 years were 60%, 60%, 50%, 50%, and 50%, respectively. Older age at repeat GKRS predicted sustained pain reduction (P = 0.01). Seven patients developed facial sensory disturbances, which were bothersome in two patients.
CONCLUSIONS: Repeat GKRS may be used as an effective treatment modality for prolonging the duration of pain reduction time in patients with MS and TN. After repeat GKRS, facial sensory disturbances are common; however, they are often not bothersome.

BACKGROUND: Colloid cysts often occur in the third ventricle, and they are considered benign, slowly growing lesions. They commonly present with symptoms of intracranial hypertension and rarely sudden death due to acute hydrocephalus. The management options include cerebrospinal fluid diversion procedure by shunt, endoscopic or transcranial surgical excision, and stereotactic aspiration. Complications associated with excisional procedures make them undesirable to some patients. Stereotactic radiosurgery has emerged as a noninvasive less risky treatment option. To date, there is no clinical series in the literature reporting on this treatment modality. The aim of the study was to determine the efficacy and safety of gamma knife (GK) radiosurgery in the treatment of third ventricular colloid cysts.
METHODS: This is a retrospective study involving 13 patients with third ventricular colloid cysts who underwent GK radiosurgery. GK radiosurgery was used as a primary treatment in all the patients. The median prescription dose was 12 Gy (11-12 Gy). The cyst volumes ranged from 0.2 to 10 cc (median 1.6 cc).
RESULTS: The median follow-up was 50 months (18-108 months). Cyst control was achieved in 100% of the patients. Complete or partial response was observed in 12 patients (92%). Eight patients (62%) had hydrocephalus on imaging at the initial diagnosis. Seven of these patients had VP shunt insertion before GK. One patient required shunt insertion after GK.
CONCLUSIONS: GK for third ventricular colloid cysts is a promising treatment, regarding its efficacy and safety, to be added to other treatment options. A longer follow-up is required to confirm long-term control.

OBJECTIVE: The objective of this study was to clarify the detailed clinical course of recurrent clival chordoma and the outcomes of each treatment modality.
METHODS: A single-center retrospective analysis was conducted on patients seen for recurrent clival chordoma. The cohort was identified from those who underwent surgery, stereotactic radiosurgery, or proton therapy at the authors\' institution between 1990 and 2022.
RESULTS: A total of 95 recurrences in 40 patients with a median (interquartile range [IQR]) follow-up of 43 (18-79) months were identified. The median (IQR) age at the time of diagnosis was 48 (36-62) years, and 55% of patients were male. Twenty-three patients were treated with surgery followed by adjuvant radiation before the first recurrence. The median (range) number of recurrences per patient was 2 (1-8), and the median (IQR) time to the first recurrence was 29 (9-51) months. The recurrences were treated with one or more of the following therapies: surgery, radiation, systemic therapy, and laser interstitial thermal therapy (LITT). Surgery was performed for 44 recurrences in 25 patients. Radiation was used to treat 42 recurrences in 28 patients. Patients with recurrences treated with surgery plus radiation had the longest progression-free survival (PFS) (median [95% CI] overall survival [OS] 120 [0-245] months, p < 0.01, log-rank test). Patients with recurrences but without prior radiation had longer PFS than those patients with prior radiation. The median (95% CI) OS after the first recurrence was 68 (54-82) months, 5-year OS after the first recurrence was 48%, and 10-year OS was 27%. Multivariate Cox regression analysis showed that mortality after the first recurrence was significantly associated with no adjuvant radiation (HR 0.149, 95% CI 0.038-0.59, p = 0.0067), older age at the time of the first recurrence (HR 1.04, 95% CI 1.01-1.08, p = 0.021), and total number of recurrences (p = 0.032). Seven patients received systemic therapy, and the median (95% CI) OS of these patients since initiation of systemic therapy was 31 (11-51) months. Imatinib and/or nivolumab were used in 6 patients (15%). One patient (3%) was treated with LITT for his fourth recurrence.
CONCLUSIONS: Despite the aggressive nature of recurrent chordoma, 14 of 29 patients (48%) survived for more than 5 years after the initial recurrence using combined therapies. Multiple treatment options may contribute to the long-term survival of patients with this intractable tumor.

OBJECTIVE: To compare outcomes of proton radiation therapy (PRT), stereotactic radiosurgery (SRS), and x-ray-based radiation with an SRS boost (XRT + SRS) for newly diagnosed clival chordoma.
METHODS: Consecutive patients who underwent PRT or SRS in our facility were retrospectively reviewed.
RESULTS: A total of 59 patients were identified (PRT, 36; SRS, 11; XRT + SRS, 12). The mean age (± standard deviation) was 46 ± 20 years, with 54% being male. The mean tumor diameter (± standard deviation) was 3.7 ± 1.5 cm, and 21 (36%) involved the lower clivus. Gross total or near-total resection was attained in 27 patients (46%), all of whom received PRT. PRT was administered with a median prescribed dose of 70.8 Gy (range, 66.0-76.0). SRS involved a median marginal dose of 16 Gy (range, 14-20) and a median maximal dose of 36 Gy (range, 30-45). The XRT + SRS group was treated with an SRS marginal dose of 12.5 Gy (range, 10-20), a maximal dose of 27 Gy (range, 20-40), and an XRT prescription dose of 50.4 Gy (range, 45.0-59.4). Fifteen recurrences were observed (PRT, 6; SRS, 5; XRT + SRS, 4). For the entire cohort (n = 59), recurrence was associated with the degree of resection (P = 0.042), but not with radiation groups (P = 0.98). For patients after subtotal resection or biopsy (n = 32), the SRS ± XRT group was associated with few recurrences (hazard ratio, 0.260; 95% confidence interval, 0.069-0.98; P = 0.046).
CONCLUSIONS: Patients after subtotal resection or biopsy may benefit from the incorporation of SRS.

Brain metastases (BMs) are the most common expansive intracranial lesions in adults. Approximately 50% of patients diagnosed with new BMs will have >1 BM at the diagnosis. We report our experience with BMs treated with Leksell Gamma Knife stereotactic radiosurgery (GKSR) and evaluate the outcomes.
Patients treated by GKSR in our institution between 2008 and 2021 for BMs were evaluated retrospectively.
A total of 205 patients (56.6% women) were included, with a median age of 59 years (range, 25-83 years). The breast (n = 85; 42.5%) and lung (n = 76; 38%) were the most common original locations for the primary tumors. Of the 205 patients, 103 (50.3%) had a single BM and 102 (49.7%) had ≥2 BMs. The median number of multiple BMs treated was 4 (range, 2-43). The mean overall survival (OS) time was 6.00 months (95% confidence interval [CI], 5.07-6.93 months) for all BMs. The median rate of tumor control after radiosurgery was 65% (range, 20%-99%) during a median follow-up of 6.00 months (95% CI, 3-84 months). In the overall population, the 1-, 2-, and 5-year OS rate was 37.55%, 25.12%, and 18.51%, respectively. The mean OS time was longer for those with multiple BMs than for those with a single BM (mean, 10 months [95% CI, 6.67-13.33 months] vs. mean, 5 months [95% CI, 4.21-5.70 months]; P = 0.03). Retreatment, tumor stability (control), and progression influenced the OS of patients with BMs, whether single or multiple (P < 0.001).
GKSR provides good results in terms of OS and better quality of life for patients with BMs, whether single or multiple. Tumor stability and retreatment influenced the OS of patients with BMs.

The hypothesis that the effectiveness of neurosurgical procedures in Parkinson\'s disease (PD) would be related to connectivity dysfunctions between the site of the stimulation and other brain regions is growing. This study aimed to assess resting-state functional connectivity between thalamic ventral intermediate nucleus (Vim) and the rest of the brain before and after thalamotomy in PD. A 76-year-old right-handed woman with refractory tremor-dominant PD was selected as a candidate for left Vim radiosurgery thalamotomy. Clinical and motion sensor evaluation and brain resting-state functional MRI (rs-fMRI) were carried out before treatment and 3, 6, and 12 months later. Targeted Vim was selected as region of interest and a seed-based rs-fMRI analysis was performed in the patient and ten age- and sex-matched controls at baseline and over time. Furthermore, a correlation analysis between functional connectivity and tremor data was carried out. Both clinical and motion sensor measurements showed a progressive tremor improvement over time on right side after radiosurgery. In the patient, seed-based analysis showed a significantly increased functional connectivity between targeted Vim and ipsilateral visual areas relative to controls before treatment. Over 1 year, a normalization of aberrant pre-therapeutic functional connectivity between Vim and visual areas was obtained. At correlation analysis, the reduction of tremor metrics over time, assessed by clinical evaluation and wearable motion sensors, was related to the reduction of the left Vim-left visual cortex functional connectivity. Our findings support the evidence that fMRI was able to detect targeted Vim connectivity and its changes over time after thalamotomy.

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.