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Brainstem cerebral cavernous malformations (CCM) are clinically more aggressive compared to superficial CCMs. Due to their location, resection can be challenging, making stereotactic radiosurgery (SRS) an attractive alternative for symptomatic patient. Brainstem CCM patients (n = 170) were treated with Gamma Knife SRS at 11 radiosurgical centers. Hemorrhagic risk reduction, risk factors of post-SRS hemorrhage, and clinical outcomes were retrospectively analyzed. Most patients had a single (165/170 patients) brainstem CCMs treated; the majority of CCMs (165/181) presented with bleeding. Single-session SRS decreased the risk of repeat hemorrhage in patients with hemorrhagic brainstem CCM (HR: 0.17, p < 0.001) using recurrent multivariate analysis. The annual hemorrhage rate decreased from 14.8 per 100 CCM-years before SRS to 2.3 after treatment. Using univariate Cox-analysis, the probability of a new hemorrhages after SRS was reduced for patient older than 35 years (HR = 0.21, p = 0.002) and increased with a margin dose > 13 Gy (HR = 2.57, p = 0.044). Adverse radiation effect (ARE) occurred in 9 patients (5.3%) and was symptomatic in four (2.4%). At a median follow-up of 3.4 years (Inter-quartile range: 5.4), 13 patients (8.0%) had a worsened clinical status, with the treated CCM being the cause in 5.6% (10) of the patients. Single-session SRS decreased the risk of repeat hemorrhage in patients with hemorrhagic brainstem CCM and conveyed this benefit with a low risk of advrse radiation effects (ARE) and worsening clinical status., (© 2024. The Author(s).)

Background and Objectives: Better local control but higher rates of adverse radiation events (ARE) have been reported when combining American Society for Radiation Oncology (ASTRO)-guideline-suggested dose (SD) stereotactic radiosurgery (SRS) with immunotherapy or targeted therapy for melanoma brain metastases. The objective of this study is to explore the efficacy and safety of lower prescription doses compared with ASTRO guidelines for single-fraction SRS for patients with melanoma metastases who are concurrently receiving immunotherapy or targeted therapy., Methods: We conducted a retrospective, single-center study on 194 patients who underwent SRS between 2009 and 2022. After propensity score matching, 71 patients with 292 metastases were included in the ASTRO-SD (20-24 Gy for <2 cm, 18 Gy for ≥2 to <3 cm) group and 33 patients with 292 metastases in the reduced dose (RD, <20 Gy for <2 cm, <18 Gy for ≥2 to <3 cm) group., Results: The median diameter (5.4 vs 5.2 mm, P = .6), prescription volume (0.2 vs 0.2 cm3, P = .2), and radiographic follow-up (11 vs 12 months, P = .2) were similar in the 2 groups. The cumulative incidence of progressing metastases was significantly higher in the SD compared with the RD group (P = .018). Higher prescription volumes and ASTRO-suggested radiation doses were associated with local progression in multivariable analysis. Radiographic AREs were significantly more common in the SD compared with the RD group (8.6% vs 3.1%, P = .005). BRAF and other tyrosine kinase inhibitors' concurrent use, higher prescription volumes, and ASTRO-suggested radiation doses were associated with an increased risk of radiographic ARE., Conclusion: This study provides evidence that RD SRS could offer reduced toxicity rates, while maintaining high local control as compared with the current guideline-SDs for the treatment of melanoma brain metastases., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background and Objectives: Studies comparing neurological and radiographic outcomes of repeat to initial stereotactic radiosurgery (SRS) intracranial arteriovenous malformations are scarce. Our aim was to perform a retrospective matched comparison of patients initially treated with SRS with those undergoing a second radiosurgical procedure., Methods: We collected data from arteriovenous malformations managed in 21 centers that underwent initial and repeated radiosurgery from 1987 to 2022. Based on arteriovenous malformations volume, margin dose, deep venous drainage, deep, and critical location, we matched 1:1 patients who underwent an initial SRS for treatment-naive arteriovenous malformations and a group with repeated SRS treatment., Results: After the selection process, our sample consisted of 328 patients in each group. Obliteration in the initial SRs group was 35.8% at 3 and 56.7% at 5 years post-SRS, while the repeat SRS group showed obliteration rates of 33.9% at 3 years and 58.6% at 5 years, without statistically significant differences (P = .75 and P = .88, respectively). There were no statistically significant differences between the 2 groups for obliteration rates (hazard ratio = 0.93; 95% CI, 0.77-1.13; P = .5), overall radiation-induced changes (RIC) (OR = 1.1; 95% CI, 0.75-1.6; P = .6), symptomatic RIC (OR = 0.78; 95% CI, 0.4-1.5; P = .4), and post-SRS hemorrhage (OR = 0.68; 95% CI; P = .3)., Conclusion: In matched cohort analysis, a second SRS provides comparable outcomes in obliteration and RIC compared with the initial SRS. Dose reduction on repeat SRS may not be warranted., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Purpose: 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 cm 3 (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., Conclusion: 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., (© 2024. The Author(s).)

Background and Objectives: Gamma knife radiosurgery (GKRS) is a safe and effective treatment option for hypothalamic hamartomas (HH), but there is no consensus opinion on its timing, dosage, and follow-up. The aim of this study was to define the safety, efficacy, outcome, and complication profile of GKRS in this patient population., Methods: This retrospective multicentric study involved 39 patients with the mean age of 16 ± 14.84 years. Early seizures resulted in an earlier age of diagnosis in 97% of patients. At baseline, no endocrine abnormalities were seen in 75% of patients while 18.9% showed precocious puberty (PP). The median target volume was 0.55 cc (0.1-10.00 cc), and a median margin dose of 16 Gy (8.1-20.0 Gy) was delivered in a single session. All patients were evaluated for clinical, endocrinological, and radiological outcomes., Results: The median follow-up was 5 (0.1-15) years. The median target volume of the cohort was 0.55 (0.35-1.77) cc. The largest HH was of 10 cc. 24/39 (61.5%) were small HH (Regis I-III). At presentation, 94.8% patients suffered from seizures (87.18% with gelastic seizures). 7/39 patients (17.9%) were presented with both PP and epilepsy. Only one (2.6%) patient presented with PP alone. 29 patients had more than 3-year follow-up. All received ≥16 Gy targeting complete HH. 28% of patients showed regression in HH volume. Patients with Regis grade I-III and longer follow-up (>75 months) showed gradual improvement in seizures. 16/29 patients (55.2%) achieved good seizure control (Engel I/II) while 13 (44.8%) were in Engel III/IV status. Nine patients needed adjuvant treatment because of poor seizure control. Eight patients suffered from transient increase in seizures. One patient developed poikilothermia, and 2 patients developed new onset hormonal deficiency., Conclusion: GKRS is a safe and effective modality for treatment of HH with significant improvement in seizure control with minimal disruption of endocrine profile. It provides an excellent safety, efficacy, and complication profile, especially for small HH. Latency of results and its adjuvant nature remain the areas of research and breakthroughs among contemporary treatment options., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: Cerebral cavernous malformations (CCMs) frequently manifest with haemorrhages. Stereotactic radiosurgery (SRS) has been employed for CCM not suitable for resection. Its effect on reducing haemorrhage risk is still controversial. The aim of this study was to expand on the safety and efficacy of SRS for haemorrhagic CCM., Methods: This retrospective multicentric study included CCM with at least one haemorrhage treated with single-session SRS. The annual haemorrhagic rate (AHR) was calculated before and after SRS. Recurrent event analysis and Cox regression were used to evaluate factors associated with haemorrhage. Adverse radiation effects (AREs) and occurrence of new neurological deficits were recorded., Results: The study included 381 patients (median age: 37.5 years (Q1-Q3: 25.8-51.9) with 414 CCMs. The AHR from diagnosis to SRS excluding the first haemorrhage was 11.08 per 100 CCM-years and was reduced to 2.7 per 100 CCM-years after treatment. In recurrent event analysis, SRS, HR 0.27 (95% CI 0.17 to 0.44), p<0.0001 was associated with a decreased risk of haemorrhage, and the presence of developmental venous anomaly (DVA) with an increased risk, HR 1.60 (95% CI 1.07 to 2.40), p=0.022. The cumulative risk of first haemorrhage after SRS was 9.4% (95% CI 6% to 12.6%) at 5 years and 15.6% (95% CI% 9 to 21.8%) at 10 years. Margin doses> 13 Gy, HR 2.27 (95% CI 1.20 to 4.32), p=0.012 and the presence of DVA, HR 2.08 (95% CI 1.00 to 4.31), p=0.049 were factors associated with higher probability of post-SRS haemorrhage. Post-SRS haemorrhage was symptomatic in 22 out of 381 (5.8%) patients, presenting with transient (15/381) or permanent (7/381) neurological deficit. ARE occurred in 11.1% (46/414) CCM and was responsible for transient neurological deficit in 3.9% (15/381) of the patients and permanent deficit in 1.1% (4/381) of the patients. Margin doses >13 Gy and CCM volume >0.7 cc were associated with increased risk of ARE., Conclusion: Single-session SRS for haemorrhagic CCM is associated with a decrease in haemorrhage rate. Margin doses ≤13 Gy seem advisable., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Brain metastases (BM) are associated with poor prognosis and increased mortality rates, making them a significant clinical challenge. Studying BMs can aid in improving early detection and monitoring. Systematic comparisons of anatomical distributions of BM from different primary cancers, however, remain largely unavailable., Methods: To test the hypothesis that anatomical BM distributions differ based on primary cancer type, we analyze the spatial coordinates of BMs for five different primary cancer types along principal component (PC) axes. The dataset includes 3949 intracranial metastases, labeled by primary cancer types and with six features. We employ PC coordinates to highlight the distinctions between various cancer types. We utilized different Machine Learning (ML) algorithms (RF, SVM, TabNet DL) models to establish the relationship between primary cancer diagnosis, spatial coordinates of BMs, age, and target volume., Results: Our findings revealed that PC1 aligns most with the Y axis, followed by the Z axis, and has minimal correlation with the X axis. Based on PC1 versus PC2 plots, we identified notable differences in anatomical spreading patterns between Breast and Lung cancer, as well as Breast and Renal cancer. In contrast, Renal and Lung cancer, as well as Lung and Melanoma, showed similar patterns. Our ML and DL results demonstrated high accuracy in distinguishing BM distribution for different primary cancers, with the SVM algorithm achieving 97% accuracy using a polynomial kernel and TabNet achieving 96%. The RF algorithm ranked PC1 as the most important discriminating feature., Conclusions: In summary, our results support accurate multiclass ML classification regarding brain metastases distribution., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Recent studies have suggested that biologically effective dose (BED) is an important correlate of pain relief and sensory dysfunction after Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The goal of this study was to determine if BED is superior to prescription dose in predicting outcomes in TN patients undergoing GKRS as a first procedure., Methods: This was a retrospective study of 871 patients with type 1 TN from 13 GKRS centers. Patient demographics, pain characteristics, treatment parameters, and outcomes were reviewed. BED was compared with prescription dose and other dosimetric factors for their predictive value., Results: The median age of the patients was 68 years, and 60% were female. Nearly 70% of patients experienced pain in the V2 and/or V3 dermatomes, predominantly on the right side (60%). Most patients had modified BNI Pain Intensity Scale grade IV or V pain (89.2%) and were taking 1 or 2 pain medications (74.1%). The median prescription dose was 80 Gy (range 62.5-95 Gy). The proximal trigeminal nerve was targeted in 77.9% of cases, and the median follow-up was 21 months (range 6-156 months). Initial pain relief (modified BNI Pain Intensity Scale grades I-IIIa) was noted in 81.8% of evaluable patients at a median of 30 days. Of 709 patients who achieved initial pain relief, 42.3% experienced at least one pain recurrence after GKRS at a median of 44 months, with 49.0% of these patients undergoing a second procedure. New-onset facial numbness occurred in 25.3% of patients after a median of 8 months. Age ≥ 63 years was associated with a higher probability of both initial pain relief and maintaining pain relief. A distal target location was associated with a higher probability of initial and long-term pain relief, but also a higher incidence of sensory dysfunction. BED ≥ 2100 Gy2.47 was predictive of pain relief at 30 days and 1 year for the distal target, whereas physical dose ≥ 85 Gy was significant for the proximal target, but the restricted range of BED values in this subgroup could be a confounding factor. A maximum brainstem point dose ≥ 29.5 Gy was associated with a higher probability of bothersome facial numbness., Conclusions: BED and physical dose were both predictive of pain relief and could be used as treatment planning goals for distal and proximal targets, respectively, while considering maximum brainstem point dose < 29.5 Gy as a potential constraint for bothersome numbness.

Objective: The purpose of this study was to describe the long-term outcomes and associated risks related to repeat stereotactic radiosurgery (SRS) for persistent arteriovenous malformations (AVMs) in pediatric patients., Methods: Under the auspices of the International Radiosurgery Research Foundation, this retrospective multicenter study analyzed pediatric patients who underwent repeat, single-session SRS between 1987 and 2022. The primary outcome variable was a favorable outcome, defined as nidus obliteration without hemorrhage or neurological deterioration. Secondary outcomes included rates and probabilities of hemorrhage, radiation-induced changes (RICs), and cyst or tumor formation., Results: The cohort included 83 pediatric patients. The median patient age was 11 years at initial SRS and 15 years at repeat SRS. Fifty-seven children (68.7%) were managed exclusively using SRS, and 42 (50.6%) experienced hemorrhage prior to SRS. Median AVM diameter and volume were substantially different between the first (25 mm and 4.5 cm3, respectively) and second (16.5 mm and 1.6 cm3, respectively) SRS, while prescription dose and isodose line remained similar. At the 5-year follow-up evaluation from the second SRS, nidus obliteration was achieved in 42 patients (50.6%), with favorable outcome in 37 (44.6%). The median time to nidus obliteration and hemorrhage was 35.5 and 38.5 months, respectively. The yearly cumulative probability of favorable outcome increased from 2.5% (95% CI 0.5%-7.8%) at 1 year to 44% (95% CI 32%-55%) at 5 years. The probability of achieving obliteration followed a similar pattern and reached 51% (95% CI 38%-62%) at 5 years. The 5-year risk of hemorrhage during the latency period after the second SRS reached 8% (95% CI 3.2%-16%). Radiographically, 25 children (30.1%) had RICs, but only 5 (6%) were symptomatic. Delayed cyst formation occurred in 7.2% of patients, with a median onset of 47 months. No radiation-induced neoplasia was observed., Conclusions: The study results showed nidus obliteration in most pediatric patients who underwent repeat SRS for persistent AVMs. The risks of symptomatic RICs and latency period hemorrhage were quite low. These findings suggest that repeat radiosurgery should be considered when treating pediatric patients with residual AVM after prior SRS. Further study is needed to define the role of repeat SRS more fully in this population.

Objective: Cerebral cavernous malformations (CCMs) are the second most common vascular anomaly affecting the CNS in children. Although stereotactic radiosurgery (SRS) has been proposed as an alternative to microsurgery in the management of selected cases in adults, there is a paucity of studies focusing on pediatric patients. The aim of this study was to present the outcomes and associated risks of SRS in this subgroup of patients., Methods: This retrospective multicenter study included pediatric patients treated with single-session SRS for CCMs. The annual hemorrhage rate (AHR) was calculated before and after SRS in hemorrhagic lesions. The Engel classification was used to describe post-SRS epileptic control. Adverse radiation effects (AREs) and the occurrence of new neurological deficits were recorded., Results: The study included 50 patients (median age 15.1 [IQR 5.6] years) harboring 62 CCMs. Forty-two (84%) and 22 (44%) patients had a history of hemorrhage or epilepsy prior to SRS, respectively. The AHR from diagnosis to SRS excluding the first hemorrhage was 7.19 per 100 CCM-years, dropping to 3.15 per 100 CCM-years after treatment. The cumulative risk of first hemorrhage after SRS was 7.4% (95% CI 0%-14.3%) at 5 years and 23.6% (95% CI 0%-42.2%) at 10 years. Eight hemorrhagic events involving 6 CCMs in 6 patients were recorded in the post-SRS follow-up period; 4 patients presented with transient symptoms and 4 with permanent symptoms. Of the 22 patients with pre-SRS seizures, 11 were seizure free at the last follow-up (Engel class I), 6 experienced improvement (Engel class II or III), 5 had no improvement (Engel class IVA or IVB), and 1 experienced worsening (Engel class IVC). Radiographic AREs were documented in 14.5% (9/62) of CCMs, with 4 being symptomatic., Conclusions: Single-session SRS reduces the CCM hemorrhage rate in the pediatric population and provides adequate seizure control.

Objective: Patients with deep-seated arteriovenous malformations (AVMs) have a higher rate of unfavorable outcome and lower rate of nidus obliteration after primary stereotactic radiosurgery (SRS). The aim of this study was to evaluate and quantify the effect of AVM location on repeat SRS outcomes., Methods: This retrospective, multicenter study involved 505 AVM patients managed with repeat, single-session SRS. The endpoints were nidus obliteration, hemorrhage in the latency period, radiation-induced changes (RICs), and favorable outcome. Patients were split on the basis of AVM location into the deep (brainstem, basal ganglia, thalamus, deep cerebellum, and corpus callosum) and superficial cohorts. The cohorts were matched 1:1 on the basis of the covariate balancing score for volume, eloquence of location, and prescription dose., Results: After matching, 149 patients remained in each cohort. The 5-year cumulative probability rates for favorable outcome (probability difference -18%, 95% CI -30.9 to -5.8%, p = 0.004) and AVM obliteration (probability difference -18%, 95% CI -30.1% to -6.4%, p = 0.007) were significantly lower in the deep AVM cohort. No significant differences were observed in the 5-year cumulative probability rates for hemorrhage (probability difference 3%, 95% CI -2.4% to 8.5%, p = 0.28) or RICs (probability difference 1%, 95% CI -10.6% to 11.7%, p = 0.92). The median time to delayed cyst formation was longer with deep-seated AVMs (deep 62 months vs superficial 12 months, p = 0.047)., Conclusions: AVMs located in deep regions had significantly lower favorable outcomes and obliteration rates compared with superficial lesions after repeat SRS. Although the rates of hemorrhage in the latency period and RICs in the two cohorts were comparable, delayed cyst formation occurred later in patients with deep-seated AVMs.

Background and Objectives: There are no studies evaluating the efficacy and safety of more than 2 stereotactic radiosurgery (SRS) procedures for cerebral arteriovenous malformations (AVM). The aim of this study was to provide evidence on the role of third single-session SRS for AVM residual., Methods: This multicenter, retrospective study included patients managed with a third single-session SRS procedure for an AVM residual. The primary study outcome was defined as AVM nidus obliteration without AVM bleeding or symptomatic radiation-induced changes (RIC). Secondary outcomes evaluated were AVM obliteration, AVM hemorrhage, asymptomatic, and symptomatic RIC., Results: Thirty-eight patients (20/38 [52.6%] females, median age at third SRS 34.5 [IQR 20] years) were included. The median clinical follow-up was 46 (IQR 14.8) months, and 17/38 (44.7%) patients achieved favorable outcome. The 3-year and 5-year cumulative probability rates of favorable outcome were 23% (95% CI = 10%-38%) and 53% (95% CI = 29%-73%), respectively. The cumulative probability of AVM obliteration at 3 and 5 years after the third SRS was 23% (95% CI = 10%-37%) and 54% (95% CI = 29%-74%), respectively. AVM bleeding occurred in 2 patients, and 1 of them underwent subsequent resection. The cumulative probability rate of post-SRS AVM hemorrhage remained constant at 5.3% (95% CI = 1%-16%) during the first 5 years of follow-up. Transient symptomatic RIC managed conservatively occurred in 5/38 patients (13.2%) at a median time of 12.5 (IQR 22.5) months from third SRS. Radiation-induced cyst formation was noted in 1 patient (4.2%) 19 months post-SRS. No mortality, radiation-associated malignancy, or permanent symptomatic RIC was noted during follow-up., Conclusion: A third single-session SRS to treat a residual intracranial AVM offers obliteration in most patients. The risk of RIC was low, and these effects were transient. While not often required, a third SRS can be performed in patients with persistent residual AVMs., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Objective: There are few reports of outcomes following stereotactic radiosurgery (SRS) for the management of cerebral cavernous malformations (CCMs) of the basal ganglia or thalamus. Therefore, the authors aimed to clarify these outcomes., Methods: Centers participating in the International Radiosurgery Research Foundation were queried for CCM cases managed with SRS from October 2001 to February 2021. The primary outcome of interest was hemorrhage-free survival (HFS) with a secondary outcome of symptomatic adverse radiation events (AREs). Assessment of the association of prognostic factors with HFS was conducted via Kaplan-Meier analysis and log-rank test. Chi-square tests were conducted to assess potential factors associated with the incidence of AREs., Results: Seventy-three patients were identified. The median patient age was 43.5 years (range 4.4-79.5 years). Fifty-nine (80.8%) patients had hemorrhage prior to SRS. The median treatment volume was 0.9 cm3 (range 0.07-10.1 cm3) with a median margin prescription dose (MPD) of 12 Gy (range 10-20 Gy). One-, 3-, 5-, and 10-year HFS were 93.0%, 89.9%, 89.9%, and 83.0%, respectively, with one hemorrhage-related death approximately 1 year after SRS and nearly 60% and 30% of patients having improvement or stability of symptoms, respectively. There was no correlation between lesion size or MPD and HFS. Seven (9.6%) patients experienced AREs (MPDs > 12 Gy in all cases). Lesion size > 1.0 cm3 was correlated with the incidence of an ARE (p = 0.019). Forty-two (93.3%) of 45 patients treated with an MPD ≤ 12 Gy experienced neither hemorrhage nor AREs following SRS versus 17 (60.7%) of 28 patients treated with an MPD > 12 Gy (p = 0.0006)., Conclusions: SRS is a reasonable treatment strategy and confers clinical stability or improvement and hemorrhage avoidance in patients harboring CCMs of the basal ganglia or thalamus. An MPD of approximately 12 Gy is recommended for the management of CCM.

Background and Objectives: There is conflicting evidence on the significance of adrenocorticotrophic hormone (ACTH) staining in the prognosis of nonfunctioning pituitary neuroendocrine tumors (NFpitNETs). The objective of this study was to define the effect of ACTH immunostaining on clinical and radiographic outcomes of stereotactic radiosurgery (SRS) for NFpitNETs., Methods: This retrospective, multicenter study included patients managed with SRS for NFpitNET residuals. The patients were divided into 2 cohorts: (1) silent corticotroph (SC) for NFpitNETs with positive ACTH immunostaining and (2) non-SC NFpitNETs. Rates of local tumor control and the incidence of post-treatment pituitary and neurological dysfunction were documented. Factors associated with radiological and clinical outcomes were also analyzed., Results: The cohort included 535 patients from 14 centers with 84 (15.7%) patients harboring silent corticotroph NFpitNETs (SCs). At last follow-up, local tumor progression occurred in 11.9% of patients in the SC compared with 8.1% of patients in the non-SC cohort (P = .27). No statistically significant difference was noted in new-onset hypopituitarism rates (10.7% vs 15.4%, P = .25) or visual deficits (3.6% vs 1.1%, P = .088) between the 2 cohorts at last follow-up. When controlling for residual tumor volume, maximum dose, and patient age and sex, positive ACTH immunostaining did not have a significant correlation with local tumor progression (hazard ratio = 1.69, 95% CI = 0.8-3.61, P = .17)., Conclusion: In contemporary radiosurgical practice with a single fraction dose of 8-25 Gy (median 15 Gy), ACTH immunostaining in NFpitNETs did not appear to confer a significantly reduced rate of local tumor control after SRS., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Objective: The goal of this study was to characterize local tumor control (LC), overall survival (OS), and safety of stereotactic radiosurgery for colorectal brain metastasis (CRBM)., Methods: Ten international institutions participating in the International Radiosurgery Research Foundation provided data for this retrospective case series. This study included 187 patients with CRBM (281 tumors), with a median age of 62 years and 56.7% being male. Most patients (53.5%) had solitary tumors, although 10.7% had > 5 tumors. The median tumor volume was 2.7 cm3 (IQR 0.22-8.1 cm3), and the median margin dose was 20 Gy (IQR 18-22 Gy)., Results: The 3-year LC and OS rates were 72% and 20%, respectively. Symptomatic adverse radiation effects occurred in 1.6% of patients. In the multivariate analysis, age > 65 years and tumor volume > 4.0 cm3 were significant predictors of tumor progression (hazard ratio [HR] 2.6, 95% CI 1.4-4.9; p = 0.003 and HR 3.4, 95% CI 1.7-6.9; p < 0.001, respectively). Better performance status (Karnofsky Performance Scale score > 80) was associated with a reduced risk of tumor progression (HR 0.38, 95% CI 0.19-0.73; p = 0.004). Patient age > 62 years (HR 1.6, 95% CI 1.1-2.3; p = 0.03) and the presence of active extracranial disease (HR 1.7, 95% CI 1.1-2.4; p = 0.009) were significantly associated with worse OS., Conclusions: Stereotactic radiosurgery offers a high LC rate and a low rate of symptomatic adverse radiation effects for the majority of CRBMs. The OS and LC favored younger patients with high functional performance scores and inactive extracranial disease.

Background and Objectives: Meningiomas in children are uncommon, with distinct characteristics that set them apart from their adult counterparts. The existing evidence for stereotactic radiosurgery (SRS) in this patient population is limited to only case series. The objective of this study was to evaluate the safety and efficacy of SRS in managing pediatric meningiomas., Methods: Children and adolescents who had been treated for meningioma with single-fraction SRS were included in this retrospective, multicenter study. The assessment included local tumor control, any complications related to the tumor or SRS, and the emergence of new neurological deficits after SRS., Results: The cohort included 57 patients (male-to-female ratio 1.6:1) with a mean age of 14.4 years who were managed with single-fraction SRS for 78 meningiomas. The median radiological and clinical follow-up periods were 69 months (range, 6-268) and 71 months (range, 6-268), respectively. At the last follow-up, tumor control (tumor stability and regression) was achieved in 69 (85.9%) tumors. Post-SRS, new neurological deficits occurred in 2 (3.5%) patients. Adverse radiation effects occurred in 5 (8.8%) patients. A de novo aneurysm was observed in a patient 69 months after SRS., Conclusion: SRS seems to be a safe and effective up-front or adjuvant treatment option for surgically inaccessible, recurrent, or residual pediatric meningiomas., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Objective: Stereotactic radiosurgery (SRS) has been proposed as an alternative to resection for epilepsy control in patients with cerebral cavernous malformations (CCM) located in critical areas., Methods: This multicentric, retrospective study evaluated seizure control in patients with a solitary CCM and a history of at least one seizure prior to SRS., Results: 109 patients (median age at diagnosis 28.9 years, interquartile range (IQR) 16.4 years] were included. Prior to SRS, 2 (1.8%) were seizure-free without medication, 35 (32.1%) were seizure-free with antiseizure medications (ASM), 17 (15.6%) experienced an improvement of at least 50% in seizure frequency/intensity with ASM, and 55 (50.5%) experienced an improvement of less than 50% in seizure frequency/intensity with ASM. At a median follow-up of 3.5 years post-SRS (IQR: 4.9), 52 (47.7%) patients were Engel class I, 13 (11.9%) class II, 17 (15.6%) class III, 22 (20.2%) class IVA or IVB and 5 (4.6%) class IVC. For the 72 patients who had seizures despite medication prior to SRS, a delay > 1.5 years between epilepsy presentation and SRS decreased the probability to become seizure-free, HR 0.25 (95% CI 0.09-0.66), p = 0.006. The probability of achieving Engel I at the last follow-up was 23.6 (95% CI 12.7-33.1) and 31.3% (95% CI 19.3-50.8) at 2 and 5 years respectively. 27 patients were considered as having drug-resistant epilepsy. At a median follow-up of 3.1 years (IQR: 4.7), 6 (22.2%) of them were Engel I, 3 (11.1%) Engel II, 7 (25.9%) Engel III, 8 (29.6%) Engel IVA or IVB and 3 (11.1%) Engel IVC., Interpretation: 47.7% of patients managed with SRS for solitary CCM presenting with seizures achieved Engel class I at the last follow-up., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Clival chordomas are challenging because of their proximity to critical neurovascular structures. Stereotactic radiosurgery (SRS) has been proven effective with minimal adverse effects., Objective: To compare the outcomes of histologically confirmed primary clival chordomas in adults who underwent SRS alone (SRS group) vs SRS after fractionated radiotherapy (FRT+SRS group)., Methods: We collected patient data from 10 institutions affiliated with the International Radiosurgery Research Foundation. We evaluated overall survival, tumor control, and freedom from additional treatment (FFAT)., Results: Fifty-seven (77%) patients were included in the SRS group and 17 (23%) in the FRT+SRS group. The median radiological follow-up was 48 months (IQR, 24-85) in the SRS group and 36 months (IQR, 25-41) in the FRT+SRS group. During the follow-up, 8 SRS and 2 FRT+SRS patients died ( P = .80). The groups had comparable 10-year overall survival (SRS: 76% vs FRT+SRS: 80%; logrank test, P = .75) and tumor control rates (SRS: 34% vs FRT+SRS: 45%; logrank test, P = .29). The SRS group had a superior 10-year FFAT rate (40%) compared with FRT+SRS (23%; logrank test, P = .02). This finding persisted in the multivariate analysis of the Cox proportional hazards illustrating a 2.40-fold increase in the relative risk of requiring additional treatment among the FRT+SRS group ( P = .04)., Conclusion: Adjuvant FRT with subsequent boost SRS did not provide superior overall survival or tumor control compared with patients who underwent adjuvant SRS alone. Further studies are required to refine management guidelines among adults with clival chordomas., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Introduction: With the diminishing use of whole-brain radiotherapy (WBRT), there is increasing debate regarding the maximum number of brain metastases that should be treated with stereotactic radiosurgery (SRS). In patients with >10-15 lesions, some groups are proposing a new approach - selected-lesion SRS (SL-SRS) - where only a subset of intracranial lesions are chosen for irradiation. This study is an initial look into this practice., Methods: This is a cross-sectional exploratory survey study. A survey of 19 questions was created by the International Radiosurgery Research Foundation (IRRF) using open-ended and multiple-choice style questions on SL-SRS practices and indications with the goal of qualitatively understanding how SL-SRS is being implemented worldwide. The survey was distributed to physicians in the United States (US) and internationally who are members of the IRRF and who perform SRS frequently. Ten out of 50 IRRF institutions provided responses reflecting the practices of 16 physicians., Results: SL-SRS is being performed at 8/10 institutions. The most common reasons for using SL-SRS included patients with prior WBRT, patients with progressing systemic disease with central nervous system (CNS)-penetrating or immunotherapies available, specific requests from medical oncology, and cooperative studies using this approach. Lesion size was cited as the most important factor when choosing to irradiate any single lesion. The majority of respondents reported 30 mm and 40 mm as size cutoffs (by largest dimension) for treatment of a lesion in eloquent and non-eloquent locations, respectively. Eloquence of lesion location and attributable symptoms were also considered important. Progression of untreated lesions was the most common reason reported for bringing patients back for additional treatment., Conclusion: The responses to this survey show that SL-SRS is being used, allowing for small/asymptomatic brain metastases to be left safely unirradiated. It is currently used in patients who have >10-15 lesions with prior WBRT, those with progression of extracranial disease but with acceptable systemic treatment options, and those with poor functional status. The incorporation of this new approach into clinical trials should be considered for the safe study of the efficacy of new CNS-penetrating systemic therapies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Theriault et al.)

Background: There are limited data regarding outcomes for patients with gastrointestinal (GI) primaries and brain metastases treated with stereotactic radiosurgery (SRS)., Objective: To examine clinical outcomes after SRS for patients with brain metastases from GI primaries and evaluate potential prognostic factors., Methods: The International Radiosurgery Research Foundation centers were queried for patients with brain metastases from GI primaries managed with SRS. Primary outcomes were local control (LC) and overall survival (OS). Kaplan-Meier analysis was used for univariate analysis (UVA) of prognostic factors. Factors significant on UVA were evaluated with a Cox multivariate analysis proportional hazards model. Logistic regressions were used to examine correlations with RN., Results: We identified 263 eligible patients with 543 brain metastases. Common primary sites were rectal (31.2%), colon (31.2%), and esophagus (25.5%) with a median age of 61.6 years (range: 37-91.4 years) and a median Karnofsky performance status (KPS) of 90% (range: 40%-100%). One-year and 2-year LC rates were 83.5% (95% CI: 78.9%-87.1%) and 73.0% (95% CI: 66.4%-78.5%), respectively. On UVA, age >65 years ( P = .001), dose <20 Gy ( P = .006) for single-fraction plans, KPS <90% ( P < .001), and planning target volume ≥2cc ( P = .007) were associated with inferior LC. All factors other than dose were significant on multivariate analysis ( P ≤ .002). One-year and 2-year OS rates were 68.0% (95% CI: 61.5%-73.6%) and 31.2% (95% CI: 24.6%-37.9%), respectively. Age > 65 years ( P = .006), KPS <90% ( P = .005), and extracranial metastases ( P = .05) were associated with inferior OS., Conclusion: SRS resulted in comparable LC with common primaries. Age and KPS were associated with both LC and OS with planning target volume and extracranial metastases correlating with LC and OS, respectively. These factors should be considered in GI cancer patient selection for SRS., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Repeat stereotactic radiosurgery (SRS) for persistent cerebral arteriovenous malformation (AVM) has generally favorable patient outcomes. However, reporting studies are limited by small patient numbers and single-institution biases. The purpose of this study was to provide the combined experience of multiple centers, in an effort to fully define the role of repeat SRS for patients with arteriovenous malformation., Methods: This multicenter, retrospective cohort study included patients treated with repeat, single-fraction SRS between 1987 and 2022. Follow-up began at repeat SRS. The primary outcome was a favorable patient outcome, defined as a composite of nidus obliteration in the absence of hemorrhage or radiation-induced neurological deterioration. Secondary outcomes were obliteration, hemorrhage risk, and symptomatic radiation-induced changes. Competing risk analysis was performed to compute yearly rates and identify predictors for each outcome., Results: The cohort comprised 505 patients (254 [50.3%] males; median [interquartile range] age, 34 [15] years) from 14 centers. The median clinical and magnetic resonance imaging follow-up was 52 (interquartile range, 61) and 47 (interquartile range, 52) months, respectively. At last follow-up, favorable outcome was achieved by 268 (53.1%) patients (5-year probability, 50% [95% CI, 45%-55%]) and obliteration by 300 (59.4%) patients (5-year probability, 56% [95% CI, 51%-61%]). Twenty-eight patients (5.6%) experienced post-SRS hemorrhage with an annual incidence rate of 1.38 per 100 patient-years. Symptomatic radiation-induced changes were evident in 28 (5.6%) patients, with most occurring in the first 3 years. Larger nidus volumes (between 2 and 4 cm 3 , subdistribution hazard, 0.61 [95% CI, 0.44-0.86]; P =0.005; >4 cm 3 , subdistribution hazard, 0.47 [95% CI, 0.32-0.7]; P <0.001) and brainstem/basal ganglia involvement (subdistribution hazard, 0.6 [95% CI, 0.45-0.81]; P <0.001) were associated with reduced probability of favorable outcome., Conclusions: Repeat SRS confers reasonable obliteration rates with a low complication risk. With most complications occurring in the first 3 years, extending the latency period to 5 years generally increases the rate of favorable patient outcomes and reduces the necessity of a third intervention., Competing Interests: Disclosures Dr Palmer has received grants from Genentech Inc. and Varian Medical Systems Inc, speaking fees from Varian Medical Systems Inc, and is a consultant for Novocure Inc. Dr Lunsford has ownership interest (shareholder) in Elekta AB and is a consultant Chair DSMB for Insightec Inc. Dr Cifarelli has received a speaking honorarium from Carl Zeiss Meditech AG. Dr Liscak is a consultant for Elekta AB. Dr McInerney has received funding from Elekta AB for research unrelated to this study. The other authors report no conflicts.

Meningiomas are thought to originate from the meningothelial cells of the arachnoid mater and are the most common primary brain tumor in adults. Histologically confirmed meningiomas occur with an incidence of 9.12/100,000 population and account for 39% of all primary brain tumors and 54.5% of all non-malignant brain tumors. Risk factors for meningioma include age 65 years and older, female gender, African-American race, history of exposure to head and neck ionizing radiation, and certain genetic disorders such as neurofibromatosis II. Intracranial meningiomas are the most commonly benign, WHO Grade I neoplasms. Atypical and anaplastic are considered malignant lesions., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Intraventricular metastases (IVMs) are uncommon, and their optimal management remains debatable., Objective: To define the safety and efficacy of stereotactic radiosurgery (SRS) in the treatment of IVMs., Methods: This retrospective, multicenter study included patients managed with SRS for IVMs. SRS-induced adverse events, local tumor or intracranial progression, and the frequency of new-onset hydrocephalus or leptomeningeal spread were documented. Analyses of variables related to patient neuroimaging or clinical outcomes were also performed., Results: The cohort included 160 patients from 11 centers who underwent SRS for treatment of 1045 intracranial metastases, of which 196 were IVMs. The median survival from SRS was 10 months. Of the 154 patients and 190 IVMs with imaging follow-up, 94 patients (61%) experienced distant intracranial disease progression and 16 IVMs (8.4%) progressed locally. The 12- and 24-month local IVM control rates were 91.4% and 86.1%, respectively. Sixteen (10%) and 27 (17.5%) patients developed hydrocephalus and leptomeningeal dissemination post-SRS, respectively. Adverse radiation effects were documented in 24 patients (15%). Eleven patients (6.9%) died because of intracranial disease progression., Conclusion: SRS is an effective treatment option for IVMs, with a local IVM control rate comparable with SRS for parenchymal brain metastases. Leptomeningeal spread and hydrocephalus in patients with IVM occur in a minority of patients, but these patients warrant careful follow-up to detect these changes., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Background: Surgery is the preferred treatment for large vestibular schwannomas (VS). Good tumor control and cranial nerve outcomes were described in selected Koos IV VS after single-session stereotactic radiosurgery (SRS), but outcomes in elderly patients have never been specifically studied. The aim of this study is to report clinical and radiological outcomes after single-session SRS for Koos IV VS in patients ≥ 65 years old., Method: This multicenter, retrospective study included patients ≥ 65 years old, treated with primary, single-session SRS for a Koos IV VS, and at least 12 months of follow-up. Patients with life-threatening or incapacitating symptoms were excluded. Tumor control rate, hearing, trigeminal, and facial nerve function were studied at last follow-up., Results: One-hundred and fifty patients (median age of 71.0 (IQR 9.0) years old with a median tumor volume of 8.3 cc (IQR 4.4)) were included. The median prescription dose was 12.0 Gy (IQR 1.4). The local tumor control rate was 96.0% and 86.2% at 5 and 10 years, respectively. Early tumor expansion occurred in 6.7% and was symptomatic in 40% of cases. A serviceable hearing was present in 16.1% prior to SRS and in 7.4% at a last follow-up of 46.5 months (IQR 55.8). The actuarial serviceable hearing preservation rate was 69.3% and 50.9% at 5 and 10 years, respectively. Facial nerve function preservation or improvement rates at 5 and 10 years were 98.7% and 91.0%, respectively. At last follow-up, the trigeminal nerve function was improved in 14.0%, stable in 80.7%, and worsened in 5.3% of the patients. ARE were noted in 12.7%. New hydrocephalus was seen in 8.0% of patients., Conclusion: SRS can be a safe alternative to surgery for selected Koos IV VS in patients ≥ 65 years old. Further follow-up is warranted., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: Stereotactic radiosurgery (SRS) is an effective treatment for intracranial metastatic disease, but its role in triple-negative breast cancer requires further study. Herein, the authors report overall survival (OS) and local tumor control in a multiinstitutional cohort with triple-negative breast cancer metastases treated with SRS., Methods: Patients treated from 2010 to 2019 at 9 institutions were included in this retrospective study if they had biopsy-proven triple-negative breast cancer with intracranial metastatic lesions treated with SRS. Patients were excluded if they had undergone prior SRS, whole-brain radiation therapy, or resection of the metastatic lesions. A retrospective chart review was conducted to determine OS, local control, and treatment efficacy., Results: Sixty-eight patients with 315 treated lesions were assessed. Patients had a median Karnofsky Performance Status of 80 (IQR 70-90) and age of 57 years (IQR 48-67 years). Most treated patients had 5 or fewer intracranial lesions, with 34% of patients having a single lesion. Treated lesions were small, having a median volume owf 0.11 cm3 (IQR 0.03-0.60 cm3). Patients were treated with a median margin dose of 18 Gy (IQR 18-20 Gy) to the median 71% isodose line (IQR 50%-84%). Overall, patients had a 1-year OS of 43% and 2-year OS of 20%. Most patients (88%) were followed until death, by which time local tumor progression had occurred in only 7% of cases. Furthermore, 76% of the lesions demonstrated regression. Tumor volume was correlated with local tumor progression (p = 0.012). SRS was very well tolerated, and only 3 patients (5%) developed symptomatic radiation necrosis., Conclusions: SRS is a safe and efficacious treatment for well-selected patients with triple-negative breast cancer, especially for those with a favorable performance status and small- to moderate-volume metastatic lesions.

Objective: Radiological progression occurs in 50%-60% of residual nonfunctioning pituitary adenomas (NFPAs). Stereotactic radiosurgery (SRS) is a safe and effective management option for residual NFPAs, but there is no consensus on its optimal timing. This study aims to define the optimal timing of SRS for residual NFPAs., Methods: This retrospective, multicenter study involved 375 patients with residual NFPAs managed with SRS. The patients were divided into adjuvant (ADJ; treated for stable residual NFPA within 6 months of resection) and progression (PRG) cohorts (treated for residual NFPA progression). Factors associated with tumor progression and clinical deterioration were analyzed., Results: Following propensity-score matching, each cohort consisted of 130 patients. At last follow-up, tumor control was achieved in 93.1% of patients in the ADJ cohort and in 96.2% of patients in the PRG cohort (HR 1.6, 95% CI 0.55-4.9, p = 0.37). Hypopituitarism was associated with a maximum point dose of > 8 Gy to the pituitary stalk (HR 4.5, 95% CI 1.6-12.6, p = 0.004). No statistically significant difference was noted in crude new-onset hypopituitarism rates (risk difference [RD] = -0.8%, p > 0.99) or visual deficits (RD = -2.3%, p = 0.21) between the two cohorts at the last follow-up. The median time from resection to new hypopituitarism was longer in the PRG cohort (58.9 vs 29.7 months, p = 0.01)., Conclusions: SRS at residual NFPA progression does not appear to alter the probability of tumor control or hormonal/visual deficits compared with adjuvant SRS. Deferral of radiosurgical management to the time of radiological progression could significantly prolong the time to radiosurgically induced pituitary dysfunction. A lower maximum point dose (< 8 Gy) to the pituitary stalk portended a more favorable chance of preserving pituitary function after SRS.

Purpose: Surgery is the treatment of choice for large vestibular schwannomas (VS). Stereotactic radiosurgery (SRS) has been suggested as an alternative to resection in selected patients. However, the safety and efficacy of SRS in Koos grade IV patients ≤ 45 years old has not been evaluated. The aim of this study is to describe the clinical and radiological outcomes of Koos grade IV in young patient managed with a single-session SRS., Methods: This retrospective, multicenter analysis included SRS-treated patients, ≤ 45 years old presenting with non-life threatening or incapacitating symptoms due to a Koos Grade IV VS and with follow-up ≥ 12 months. Tumor control and neurological outcomes were evaluated., Results: 176 patients [median age of 36.0 (IQR 9) and median tumor volume of 9.3 cm 3 (IQR 4.7)] were included. The median prescription dose was 12 Gy (IQR 0.5). Median follow-up period was 37.5 (IQR 53.5) months. The 5- and 10-year progression-free survival was 90.9% and 86.7%. Early tumor enlargement occurred in 10.9% of cases and was associated with tumor progression at the last follow-up. The probability of serviceable hearing preservation at 5- and 10-years was 56.8% and 45.2%, respectively. The probability of improvement or preservation of facial nerve function was 95.7% at 5 and 10-years. Adverse radiation effects were noted in 19.9%. New-onset hydrocephalus occurred in 4.0%., Conclusion: Single-session SRS is a safe and effective alternative to surgical resection in selected patients ≤ 45 years old particularly those with medical co-morbidities and those who decline resection. Longer term follow up is warranted., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Surgical removal has been performed as the first line treatment for symptomatic or enlarging hypoglossal schwannomas (HS). Stereotactic radiosurgery (SRS) offers a minimally invasive approach that may afford long-term tumor control for patients with HS particularly those who refuse or are unfit for surgery. This study evaluates outcomes after SRS performed for both newly diagnosed and residual tumors after incomplete resection., Methods: This retrospective, multi-institutional study involved patients treated with adjuvant or primary SRS for HS. The study end-points included local tumor response, clinical outcomes, and procedure-related complications. All the patients had Gamma Knife SRS., Results: The cohort included 12 patients (five females), median age at SRS 49.5 years (range, 37-76)]. The median tumor target volume was 5.9 cm 3 (range, 0.7-27.23). At median imaging follow-up of 37 months (range, 6-153), tumor control was achieved in 11 patients. Tumor enlargement that was managed with surgical resection was noted at the 6-month follow-up in one patient. At median clinical follow-up of 30.5 months (range, 6-157), stability, or improvement of all pre-SRS signs and symptoms was noted in nine patients. Two patients experienced worsening of at least one pre-existing symptoms or sign. New-onset trapezius weakness was noted in one patient and tongue atrophy in two patients., Conclusion: Single-fraction SRS appears to be a safe and effective upfront and adjuvant treatment option for HS. SRS may be recommended as an alternative to surgery for patients presenting with HS or as an adjuvant treatment following subtotal resection and at HS recurrence., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: The role of stereotactic radiosurgery (SRS) in the management of recurrent and residual intracranial primary melanocytomas (PMC) remains unclear. The aim of this study is to evaluate the safety and efficacy of SRS in the management of these rare tumors., Methods: One patient treated with SRS in our institution for an intracranial PMC was retrospectively identified. Additionally, a systematic review of English articles using MEDLINE was performed to identify studies reporting on treatment and tumor characteristics and patient outcomes following SRS-management of intracranial PMC., Results: Including our institution's patient, a total of 13 patients (11 male and 2 female) met the inclusion criteria and were analyzed. The median age at SRS treatment was 49 years (interquartile range [IQR] 27). At a median follow-up of 24 (IQR 48) months, the aggregate local tumor-control rate was 76.9%. Progression occurred in 3 patients and was managed with repeat SRS (1 of 13) or salvage resection (2 of 13). One case of malignant transformation to melanoma leading to leptomeningeal dissemination and death was noted., Conclusions: SRS appears to be a reasonable treatment option for recurrent and residual melanocytomas. A higher prescription dose might be reasonable in the treatment of intermediate grade or recurring PMC. Close longitudinal follow-up for recurrence or malignant transformation of melanocytomas after SRS is recommended., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The purpose of this retrospective, single-institution study was to evaluate radiological and clinical outcomes of patients managed with repeat stereotactic radiosurgery (SRS) for residual cerebral arteriovenous malformation (AVM) after prior SRS., Methods: The authors evaluated the clinical and radiological outcomes of consecutive patients treated with repeat single-session SRS for a residual brain AVM from 1989 to 2021., Results: In total, 170 patients underwent repeat SRS for AVM (90 [52.9%] females; median [interquartile range] age at the first SRS procedure 28 [21.5] years; median [interquartile range] age at the second SRS procedure 32 [22.5] years). After repeat SRS, the actuarial 3-, 5-, and 10-year AVM obliteration rates were 37.6%, 57.3%, and 80.9%, respectively. Higher obliteration rates were associated with margin dose ≥ 19 Gy (p = 0.001). After the second SRS procedure, hemorrhage occurred in 8.2% of patients and was lethal in 1 patient. The risk factors of intracranial hemorrhage were age < 18 years (p = 0.03) and residual AVM diameter > 20 mm (p = 0.004). Lower obliteration rates were noted in patients with residual AVM diameter > 20 mm (p = 0.04) and those < 18 years of age (p = 0.04). Asymptomatic, symptomatic, and permanent radiation-induced changes (RICs) after the second SRS procedure occurred in 25.9%, 8.8%, and 5.3% of patients, respectively, and were associated with RIC after the first SRS procedure (p = 0.006). There was 1 case of a radiation-induced meningioma 12 years after SRS., Conclusions: Repeat SRS is a reasonable therapeutic option, in particular for patients with residual AVM. Repeat SRS was associated with more favorable outcomes in adult patients and those with residual AVM smaller than 20 mm in maximum diameter. To increase the rate of residual AVM obliteration, a prescription dose ≥ 19 Gy should ideally be used for repeat SRS.

Objective: Though stereotactic radiosurgery (SRS) is an established safe treatment for small- and medium-sized vestibular schwannomas (VSs), its role in the management of Koos grade IV VS is still unclear. In this retrospective multicenter study, the authors evaluated tumor control and the patient outcomes of primary, single-session SRS treatment for Koos grade IV VS., Methods: This study included patients treated with primary, single-session SRS for Koos grade IV VS at 10 participating centers. Only those patients presenting with non-life-threatening or incapacitating symptoms and at least 12 months of clinical and neuroimaging follow-up were eligible for inclusion. Relevant data were collected, and the Kaplan-Meier method was used to perform time-dependent analysis for post-SRS tumor control, hearing preservation, and facial nerve function preservation. Univariate and multivariate analyses were performed for outcome measures using Cox regression analysis., Results: Six hundred twenty-seven patients (344 females, median patient age 54 [IQR 22] years) treated with primary SRS were included in this study. The median tumor volume was 8.7 (IQR 5) cm3. Before SRS, serviceable hearing, facial nerve weakness (House-Brackmann grade > I), and trigeminal neuropathy were present in 205 (33%), 48 (7.7%), and 203 (32.4%) patients, respectively. The median prescription dose was 12 (IQR 1) Gy. At a median radiological follow-up of 38 (IQR 54) months, tumor control was achieved in 94.1% of patients. Early tumor expansion occurred in 67 (10.7%) patients and was associated with a loss of tumor control at the last follow-up (p = 0.001). Serviceable hearing preservation rates at the 5- and 10-year follow-ups were 65% and 44.6%, respectively. Gardner-Robertson class > 1 (p = 0.003) and cochlear dose ≥ 4 Gy (p = 0.02) were risk factors for hearing loss. Facial nerve function deterioration occurred in 19 (3.0%) patients at the last follow-up and was associated with margin doses ≥ 13 Gy (p = 0.03) and early tumor expansion (p = 0.04). Post-SRS, 33 patients developed hydrocephalus requiring shunting. Adverse radiation effects occurred in 92 patients and were managed medically or surgically in 34 and 18 cases, respectively., Conclusions: SRS is a safe and effective method of obtaining tumor control in patients with Koos grade IV VS presenting with non-life-threatening or debilitating symptoms, especially those with surgical comorbidities that contraindicate resection. To decrease the incidence of post-SRS facial palsy, a prescription dose < 13 Gy is recommended.

Background: The optimal management of asymptomatic, presumed WHO grade I meningiomas remains controversial., Objective: To define the safety and efficacy of stereotactic radiosurgery (SRS) compared with active surveillance for the management of patients with asymptomatic parafalcine/parasagittal (PFPS) meningiomas., Methods: Data from SRS-treated patients from 14 centers and patients managed conservatively for an asymptomatic, PFPS meningioma were compared. Local tumor control rate and new neurological deficits development were evaluated in the active surveillance and the SRS-treated cohorts., Results: There were 173 SRS-treated patients and 98 patients managed conservatively in the unmatched cohorts. After matching for patient age and tumor volume, there were 98 patients in each cohort. The median radiological follow-up period was 43 months for the SRS cohort and 36 months for the active surveillance cohort (P = .04). The median clinical follow-up for the SRS and active surveillance cohorts were 44 and 36 months, respectively. Meningioma control was noted in all SRS-treated patients and in 61.2% of patients managed with active surveillance (P < .001). SRS-related neurological deficits occurred in 3.1% of the patients (n = 3), which were all transient. In the active surveillance cohort, 2% of patients (n = 2) developed neurological symptoms because of tumor progression (P = 1.0), resulting in death of 1 patient (1%)., Conclusion: Up-front SRS affords superior radiological PFPS meningioma control as compared with active surveillance and may lower the risk of meningioma-related permanent neurological deficit and/or death., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Hypoglossal schwannomas (HS) are extremely rare neoplasms. Surgical resection has historically been the treatment of choice but carries a significant risk of postoperative neurological deficits and mortality. Stereotactic radiosurgery (SRS) is a minimally invasive approach that may afford long-term tumour growth. However, literature to determine the safety and effectiveness of SRS in the treatment of HS is scarce. We report on a patient who presented with progressive headache and dysphagia as well as tongue deviation to the left, due to a space-occupying lesion, consistent on brain MRI with a left HS. Primary SRS using a prescription dose of 12 Gy in a single fraction was used to treat the tumour without complications. By last follow-up, the tumour regressed, and the patient's symptoms improved. Our case shows that radiosurgery can be safe and effective for the management of HS., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The optimal treatment for recurrent and residual gangliogliomas remains unclear. The aim of this study was to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in the management of patients with recurrent or residual intracranial ganglioglioma., Methods: This retrospective multicenter study involved patients managed with SRS for ganglioglioma. The study endpoints included local tumor control and tumor- or SRS-related neurological morbidity following treatment. Factors associated with tumor progression and neurological morbidity were also analyzed., Results: The cohort included 20 patients (11 males [55%]) with a median age of 24.5 (IQR 14) years who had been managed with SRS for ganglioglioma. Five-year radiological progression-free survival was 85.6%. After SRS, 2 patients (10%) experienced transient neurological deterioration. At a median clinical follow-up of 88.5 (IQR 112.5) months, 1 patient (5%) experienced seizure worsening and 1 (5%) required further resection of the tumor because of radiological progression. No mortality was noted in this series., Conclusions: SRS appears to be a safe and effective treatment option for surgically inaccessible, recurrent, and residual gangliogliomas. In this series, the 5-year progression-free survival rate after SRS was 85.6%. Gross-total resection remains the primary treatment of choice for patients with newly diagnosed or recurrent ganglioglioma. SRS may be considered for patients unfit for surgery and those with surgically inaccessible newly diagnosed, residual, and recurrent lesions.

Meningioma is a common incidental finding, and clinical course varies based on anatomical location. The aim of this sub-analysis of the IMPASSE study was to compare the outcomes of patients with an incidental frontobasal meningioma who underwent active surveillance to those who underwent upfront stereotactic radiosurgery (SRS). Data were retrospectively collected from 14 centres. The active surveillance (n = 28) and SRS (n = 84) cohorts were compared unmatched and matched for age, sex, and duration of follow-up (n = 25 each). The study endpoints included tumor progression, new symptom development, and need for further intervention. Tumor progression occurred in 52.0% and 0% of the matched active surveillance and SRS cohorts, respectively (p < 0.001). Five patients (6.0%) treated with SRS developed treatment related symptoms compared to none in the active monitoring cohort (p = 0.329). No patients in the matched cohorts developed symptoms attributable to treatment. Three patients managed with active surveillance (10.7%, unmatched; 12.0%, matched) underwent an intervention for tumor growth with no persistent side effects after treatment. No patients subject to SRS underwent further treatment. Active monitoring and SRS confer a similarly low risk of symptom development. Upfront treatment with SRS improves imaging-defined tumor control. Active surveillance and SRS are acceptable treatment options for incidental frontobasal meningioma.

Background: The optimal treatment strategy of asymptomatic, convexity meningiomas, remains unclear., Objective: The purpose of this study was to define the safety and efficacy of stereotactic radiosurgery (SRS) in the management of patients with asymptomatic convexity meningiomas., Methods: Data of SRS-treated patients from 14 participating centers and patients managed conservatively for an asymptomatic, convexity-located meningioma were compared. Local tumor control rate and development of new neurologic deficits were evaluated in the active surveillance and in the SRS-treated cohorts., Results: In the unmatched cohorts, there were 99 SRS-treated patients and 140 patients managed conservatively for an asymptomatic, convexity meningioma. Following propensity score matching for age, there were 98 patients in each cohort. In the matched cohorts, tumor control was achieved in 99% of SRS-treated, and in 69.4% of conservatively managed patients (p < 0.001). New neurological deficits occurred in 2.0% of patients in each of the matched cohorts (p = 1.00). Increasing age was predictive of tumor growth [(OR 1.1; 95% CI (1.04 - 1.2), (p < 0.001)]., Conclusion: This is one of the first reports to suggest that SRS is a low risk and effective treatment strategy for asymptomatic incidentally discovered convexity meningiomas. In this study, tumor control was achieved in significantly more patients after radiosurgery compared to those managed with active surveillance. SRS may be offered at diagnosis of an asymptomatic convexity meningioma and should be recommended when meningioma growth is noted on follow-up., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Brain metastases represent a major indication for stereotactic radiosurgery (SRS), but further study is needed regarding repeat SRS (SRS2) after local or marginal recurrence after prior SRS (SRS1). We report local tumor control (LC) after SRS2 and identify predictors of radiation necrosis (RN) and symptomatic RN (SRN)., Methods and Materials: Patients had biopsy-proven non-small cell lung cancer and at least 1 brain metastasis previously treated with SRS. SRS2 was performed from 2015 to 2020 and required overlap of the prescription isodose lines with those from SRS1. Patients treated with preoperative SRS were excluded. Primary endpoints were LC by Response Assessment in Neuro-oncology criteria, RN, and SRN., Results: From 8 institutions, 102 patients with 123 treated lesions were included. SRS2 was performed at a median 12 months after SRS1. SRS2 delivered a median 18 Gy (interquartile range [IQR], 16-18) margin dose to the 50% (IQR, 50%-70%) isodose line, maximum dose of 30.5 Gy (IQR, 25.0-36.0), and V12Gy of 3.38 cm 3 (IQR, 0.83-7.64). One-year and 2-year LC were 79% and 72%, respectively. Local tumor control was improved with tumor volume ≤1 cm 3 (P < .005). There were 25 (20%) cases of RN and 9 (7%) cases of SRN. For SRS1 and SRS2, SRN rates were higher with maximum doses ≥40 Gy or SRS2 V12Gy >9 cm 3 (P < .025 for each). SRS1 and SRS2 maximum dose ≥40 Gy was also predictive of increased RN (P < .05 for each). Prior immunotherapy was not predictive of RN or SRN., Conclusions: Repeat SRS afforded a high rate of local tumor control and a low rate of SRN. At SRS2, V12Gy ≤9 cm 3 and maximum dose <40 Gy may reduce the risks of RN and SRN. These results are most applicable to lesions with approximately 1 cm 3 volume and 1-year interval between SRS courses., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The object of this study was to evaluate the safety, efficacy, and long-term outcomes of stereotactic radiosurgery (SRS) in the management of intracranial chordomas., Methods: This retrospective multicenter study involved consecutive patients managed with single-session SRS for an intracranial chordoma at 10 participating centers. Radiological and neurological outcomes were assessed after SRS, and predictive factors were evaluated via statistical methodology., Results: A total of 93 patients (56 males [60.2%], mean age 44.8 years [SD 16.6]) underwent single-session SRS for intracranial chordoma. SRS was utilized as adjuvant treatment in 77 (82.8%) cases, at recurrence in 13 (14.0%) cases, and as primary treatment in 3 (3.2%) cases. The mean tumor volume was 8 cm3 (SD 7.3), and the mean prescription volume was 9.1 cm3 (SD 8.7). The mean margin and maximum radiosurgical doses utilized were 17 Gy (SD 3.6) and 34.2 Gy (SD 6.4), respectively. On multivariate analysis, treatment failure due to tumor progression (p = 0.001) was associated with an increased risk for post-SRS neurological deterioration, and a maximum dose > 29 Gy (p = 0.006) was associated with a decreased risk. A maximum dose > 29 Gy was also associated with improved local tumor control (p = 0.02), whereas the presence of neurological deficits prior to SRS (p = 0.04) and an age > 65 years at SRS (p = 0.03) were associated with worse local tumor control. The 5- and 10-year tumor progression-free survival rates were 54.7% and 34.7%, respectively. An age > 65 years at SRS (p = 0.01) was associated with decreased overall survival. The 5- and 10-year overall survival rates were 83% and 70%, respectively., Conclusions: SRS appears to be a safe and relatively effective adjuvant management option for intracranial chordomas. The best outcomes were obtained in younger patients without significant neurological deficits. Further well-designed studies are necessary to define the best timing for the use of SRS in the multidisciplinary management of intracranial chordomas.

Objective: The optimal management of asymptomatic, skull-based meningiomas is not well defined. The aim of this study is to compare the imaging and clinical outcomes of patients with asymptomatic, skull-based meningiomas managed either with upfront stereotactic radiosurgery (SRS) or active surveillance., Methods: This retrospective, multicenter study involved patients with asymptomatic, skull-based meningiomas. The study end-points included local tumor control and the development of new neurological deficits attributable to the tumor. Factors associated with tumor progression and neurological morbidity were also analyzed., Results: The combined unmatched cohort included 417 patients. Following propensity score matching for age, tumor volume, and follow-up 110 patients remained in each cohort. Tumor control was achieved in 98.2% and 61.8% of the SRS and active surveillance cohorts, respectively. SRS was associated with superior local tumor control (p < 0.001, HR = 0.01, 95% CI = 0.002-0.13) compared to active surveillance. Three patients (2.7%) in the SRS cohort and six (5.5%) in the active surveillance cohort exhibited neurological deterioration. One (0.9%) patient in the SRS-treated and 11 (10%) patients in the active surveillance cohort required surgical management of their meningioma during follow-up., Conclusions: SRS is associated with superior local control of asymptomatic, skull-based meningiomas as compared to active surveillance and does so with low morbidity rates. SRS should be offered as an alternative to active surveillance as the initial management of asymptomatic skull base meningiomas. Active surveillance policies do not currently specify the optimal time to intervention when meningioma growth is noted. Our results indicate that if active surveillance is the initial management of choice, SRS should be recommended when radiologic tumor progression is noted and prior to clinical progression., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The initial management of asymptomatic, incidentally discovered, cavernous sinus (CS) meningiomas remains incompletely defined. This study evaluated the safety and efficacy of stereotactic radiosurgery (SRS) for patients presenting with an asymptomatic CS meningioma., Methods: This is an international, retrospective study included patients treated with upfront SRS for an asymptomatic CS meningioma. Local tumor control, tumor and SRS-related complications, and the development of new neurologic deficits after SRS were evaluated., Results: A total of 37 patients (29 men; mean ± SD age: 55.05 ± 11.56 years) treated with upfront SRS for an asymptomatic, CS meningioma were included in the study. The mean ± SD margin dose was 12.27 ± 2.3 Gy. The median clinical and radiological follow-up periods were 66 (IQR 84) and 72 (IQR 84) months, respectively. At the last follow-up, tumor regression and stability were noted in 19 (51.35%) and 18 (48.65%) of CS meningiomas, respectively. SRS-related complications occurred in 2 patients (5.4%) and were managed conservatively., Conclusions: Upfront SRS is a safe and effective treatment option for asymptomatic CS meningiomas. SRS may be considered at the time of initial diagnosis of a CS meningioma. If observation is the initial management chosen, SRS should be recommended when CS meningioma growth is documented on follow-up imaging., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The optimal management of patients with incidental meningiomas remains unclear. The aim of this study was to characterize the radiologic and neurological outcomes of expectant and stereotactic radiosurgery (SRS) management of asymptomatic meningioma patients., Methods: Using data from 14 centers across 10 countries, the study compares SRS outcomes to active surveillance of asymptomatic meningiomas. Local tumor control of asymptomatic meningiomas and development of new neurological deficits attributable to the tumor were evaluated in the SRS and conservatively managed groups., Results: In the unmatched cohorts, 727 meningioma patients underwent SRS and were followed for a mean of 57.2 months. In the conservatively managed cohort, 388 patients were followed for a mean of 43.5 months. Tumor control was 99.0% of SRS and 64.2% of conservatively managed patients (P < .001; OR 56.860 [95% CI 26.253-123.150]). New neurological deficits were 2.5% in the SRS and 2.8% of conservatively managed patients (P = .764; OR 0.890 [95% CI 0.416-1.904]). After 1:1 propensity matching for patient age, tumor volume, location, and imaging follow-up, tumor control in the SRS and conservatively managed cohorts was 99.4% and 62.1%, respectively (P < .001; OR 94.461 [95% CI 23.082-386.568]). In matched cohorts, new neurological deficits were noted in 2.3% of SRS-treated and 3.2% of conservatively managed patients (P = .475; OR 0.700 [95% CI 0.263-1.863])., Conclusions: SRS affords superior radiologic tumor control compared to active surveillance without increasing the risk of neurological deficits in asymptomatic meningioma patients. While SRS and active surveillance are reasonable options, SRS appears to alter the natural history of asymptomatic meningiomas including tumor progression in the majority of patients treated., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The optimal management of intraventricular metastases remains debatable. The aim of this study is to define the safety and efficacy of Gamma-Knife radiosurgery in the treatment of intraventricular metastases., Methods: This retrospective, single-center study involved patients that were treated with stereotactic radiosurgery (SRS) for intraventricular metastases. The study end points included SRS-related toxicity, local and distal intracranial tumor control, as well as the incidence of post-treatment hydrocephalus and leptomeningeal dissemination. Factors associated with radiologic and clinical outcomes were also analyzed., Results: The cohort included 17 consecutive patients who underwent stereotactic radiosurgery for treatment of 41 intracranial metastases, of which 23 were primary intraventricular (intraventricular metastasis). Median overall survival from primary tumor diagnosis and from SRS treatment were 28 and 5 months, respectively. With a median radiological follow-up of 3 (interquartile range 3) months, 7 patients (41.18%) experienced overall intracranial disease progression, whereas 7 (27.27%) intraventricular metastases progressed radiologically. Four (23.53%) and 3 (17.65%) patients developed hydrocephalus and leptomeningeal dissemination post-SRS, respectively. Four patients (23.53%) died due to intracranial disease progression., Conclusions: SRS offers a reasonable chance of local tumor control for patients with intraventricular brain metastasis. However, the risk of hydrocephalus and leptomeningeal spread of disease is not inconsequential and merits close follow-up for patients with brain metastasis involving the ventricular system., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The optimal management of asymptomatic, petroclival meningiomas remains incompletely defined. The purpose of this study was to evaluate the safety and efficacy of upfront stereotactic radiosurgery (SRS) for patients with asymptomatic, petroclival region meningiomas., Methods: This retrospective, international, multicenter study involved patients treated with SRS for an asymptomatic, petroclival region meningioma. Study endpoints included local tumor control rate, procedural complications, and the emergence of new neurological deficits., Results: There were 72 patients (22 males, mean age 59.53 years (SD ± 11.9)) with an asymptomatic meningioma located in the petroclival region who were treated with upfront SRS. Mean margin dose and maximum dose were 13.26 (SD ± 2.72) Gy and 26.14 (SD ± 6.75) Gy respectively. Median radiological and clinical follow-up periods post-SRS were 52.5 (IQR 61.75) and 47.5 months (IQR 69.75) respectively. At last follow-up, tumor control was achieved in all patients. SRS-related complications occurred in 6 (8.33%) patients, with 3 of them (4.17%) exhibiting new neurological deficits., Conclusions: Upfront SRS for asymptomatic, petroclival region meningiomas affords excellent local tumor control and does so with a relatively low risk of SRS-related complications. SRS can be considered at diagnosis of an asymptomatic petroclival region meningioma. If active surveillance is initially chosen, SRS should be recommended when growth is noted during radiological follow-up., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)