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Melanoma brain metastases are commonly treated with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs). However, the toxicity of these 2 treatments is largely unknown when administered concurrently.To evaluate the risk of radiation necrosis (RN) with concurrent and nonconcurrent SRS and ICIs.The guidelines from the Strengthening the Reporting of Observational Studies in Epidemiology checklist were used. Inverse probability of treatment weighting, univariable and multivariable logistic regression, and the Kaplan-Meier method was utilized.There were 203 patients with 1388 brain metastases across 11 international institutions in 4 countries with a median follow-up of 15.6 months. The rates of symptomatic RN were 9.4% and 8.2% in the concurrent and nonconcurrent groups, respectively ( P =.766). On multivariable logistic regression, V12 ≥ 10 cm 3 (odds ratio [OR]: 2.76; P =.006) and presence of BRAF mutation (OR: 2.20; P =.040) were associated with an increased risk of developing symptomatic RN; the use of concurrent over nonconcurrent therapy was not associated with an increased risk (OR: 1.06; P =.877). There were 20 grade 3 toxic events reported, and no grade 4 events reported. One patient experienced a grade 5 intracranial hemorrhage. The median overall survival was 36.1 and 19.8 months for the concurrent and nonconcurrent groups (log-rank P =.051), respectively.Concurrent administration of ICIs and SRS are not associated with an increased risk of RN. Tumors harboring BRAF mutation, or perhaps prior exposure to targeted agents, may increase this risk. Radiosurgical optimization to maintain V1210 cm 3 is a potential strategy to reduce the risk of RN.

The optimal management of asymptomatic, presumed WHO grade I meningiomas remains controversial.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.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.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%).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.

BACKGROUND Stereotactic radiosurgery (SRS) is increasingly considered for selected olfactory groove meningiomas (OGMs). OBJECTIVE To investigate the safety and efficacy of SRS for OGMs. METHODS From 20 institutions participating in the International Radiosurgery Research Foundation, we pooled patients who underwent SRS for histologically confirmed or radiologically suspected WHO grade I OGMs and were followed for 6 mo or more after the SRS. RESULTS In total, 278 (median age 57 yr) patients underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) WHO grade I OGMs Median treatment volume was 4.60 cm3 (range: 0.12-27.3 cm3), median prescription dose was 12 Gy, and median dose to the olfactory nerve was 11.20 Gy. During median post-SRS imaging follow-up of 39 mo (range: 6-240 mo), 43% of patients had partial or marginal response, 54% of patients had stable disease, and 3% of patients experienced progression. During median post-SRS clinical follow-up of 51 mo (range: 6-240 mo), 36 (13%) patients experienced clinical and/or radiological adverse radiation events (AREs). Elevated risk of AREs was associated with larger OGM volume (P = .009) and pre-SRS peritumoral T2/fluid-attenuated inversion-recovery signal abnormalities (P

BACKGROUND Pediatric brain arteriovenous malformations (AVMs) are a significant cause of morbidity but the role of multimodal therapy in the treatment of these lesions is not well understood. OBJECTIVE To compare the outcomes of stereotactic radiosurgery (SRS) with and without prior embolization for pediatric AVMs. METHODS We retrospectively evaluated the International Radiosurgery Research Foundation pediatric AVM database. AVMs were categorized, based on use of pre-embolization (E + SRS) or lack thereof (SRS-only). Outcomes were compared in unadjusted and inverse probability weight (IPW)-adjusted models. Favorable outcome was defined as obliteration without post-SRS hemorrhage or permanent radiation-induced changes (RIC). RESULTS The E + SRS and SRS-only cohorts comprised 91 and 448 patients, respectively. In unadjusted models, the SRS-only cohort had higher rates of obliteration (68.5% vs 43.3%

Intraventricular metastases (IVMs) are uncommon, and their optimal management remains debatable.The aim is to define the safety and efficacy of stereotactic radiosurgery (SRS) in the treatment of IVMs.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.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.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.

BACKGROUND: Stereotactic radiosurgery (SRS) is increasingly used for management of perioptic meningiomas. OBJECTIVE: To study the safety and effectiveness of SRS for perioptic meningiomas. METHODS: From 12 institutions participating in the International Radiosurgery Research Foundation (IRRF), we retrospectively assessed treatment parameters and outcomes following SRS for meningiomas located within 3 mm of the optic apparatus. RESULTS: A total of 438 patients (median age 51 yr) underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) perioptic meningiomas. Median treatment volume was 8.01 cm(3). Median prescription dose was 12 Gy, and median dose to the optic apparatus was 8.50 Gy. A total of 405 patients (93%) underwent single-fraction SRS and 33 patients (7%) underwent hypofractionated SRS. During median imaging follow-up of 55.6 mo (range: 3.15-239 mo), 33 (8%) patients experienced tumor progression. Actuarial 5-yr and 10-yr progression-free survival was 96% and 89%, respectively. Prescription dose of ≥12 Gy (HR: 0.310; 95% CI [0.141-0.679], P = .003) and single-fraction SRS (HR: 0.078; 95% CI [0.016-0.395], P = .002) were associated with improved tumor control. A total of 31 (10%) patients experienced visual decline, with actuarial 5-yr and 10-yr post-SRS visual decline rates of 9% and 21%, respectively. Maximum dose to the optic apparatus ≥10 Gy (HR = 2.370; 95% CI [1.086-5.172], P = .03) and tumor progression (HR = 4.340; 95% CI [2.070-9.097], P

BACKGROUND Atypical and anaplastic meningiomas have reduced progression-free/overall survival (PFS/OS) compared to benign meningiomas. Stereotactic radiosurgery (SRS) for atypical meningiomas (AMs) and anaplastic meningiomas (malignant meningiomas, MMs) has not been adequately described. OBJECTIVE To define clinical/radiographic outcomes for patients undergoing SRS for AM/MMs. METHODS An international, multicenter, retrospective cohort study was performed to define clinical/imaging outcomes for patients receiving SRS for AM/MMs. Tumor progression was assessed with response assessment in neuro-oncology (RANO) criteria. Factors associated with PFS/OS were assessed using Kaplan-Meier analysis and a Cox proportional hazards model. RESULTS A total of 271 patients received SRS for AMs (n = 233, 85.9%) or MMs (n = 38, 14.0%). Single-fraction SRS was most commonly employed (n = 264, 97.4%) with a mean target dose of 14.8 Gy. SRS was used as adjuvant treatment (n = 85, 31.4%), salvage therapy (n = 182, 67.2%), or primary therapy (1.5%). The 5-yr PFS/OS rate was 33.6% and 77.0%, respectively. Increasing age (hazard ratio (HR) = 1.01, P 15% (HR = 1.66, P

Background Choroid plexus tumors (CPT) are rare epithelial tumors of the choroid plexus. Gross total resection (GTR) may be curative, but it is not always possible. Objective To evaluate the role of Gamma Knife stereotactic radiosurgery (GKSRS) as either a primary or adjuvant management option for WHO grade I-III CPT through a multicenter project. Methods A total of 32 patients (20 females) with a total of 43 treated tumors were included in the analysis. A total of 25 patients (78%) had undergone initial surgical resection. The median total tumor volume was 2.2 cc, and the median margin and maximum doses were 13 and 25.5 Gy, respectively. Results Local tumor control was achieved in 69% of cases. Local tumor progression-free survival (PFS) rate for low-grade tumors at 1, 3, and 5 yr was 90%, 77%, 58%, respectively. The actuarial local tumor PFS rate for high-grade tumors at 1, 3, and 5 yr was 77%, 62%, and 62%, respectively. There was no significant difference in local tumor control rates between low- and high-grade CPT (P = .3). Gender, age, and degree of resection were not associated with treated tumor PFS. Distant intracranial spread developed in 6 patients at a median of 22 mo after initial SRS. Actuarial distant brain tumor PFS rate at 1, 2, 5, and 10 yr was 93%, 88%, 78%, and 65%, respectively. Three patients (9%) developed persistent symptomatic adverse radiation effects at a median of 11 mo after the procedure. Conclusion GKSRS represents a minimally invasive alternative management strategy for imaging defined or surgically recurrent low- and high-grade CPT.

Background Embolization of brain arteriovenous malformations (AVMs) using ethylene-vinyl alcohol copolymer (Onyx) embolization may influence the treatment effects of stereotactic radiosurgery (SRS) differently than other embolysates. Objective To compare the outcomes of pre-SRS AVM embolization with vs without Onyx through a multicenter, retrospective matched cohort study. Methods We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Embolized AVMs treated with SRS were selected and categorized based on embolysate usage into Onyx embolization (OE + SRS) or non-Onyx embolization (NOE + SRS) cohorts. The 2 cohorts were matched in a 1:1 ratio using de novo AVM features for comparative analysis of outcomes. Results The matched cohorts each comprised 45 patients. Crude AVM obliteration rates were similar between the matched OE + SRS vs NOE + SRS cohorts (47% vs 51%; odds ratio [OR] = 0.837, P = .673). Cumulative probabilities of obliteration were also similar between the OE + SRS vs NOE + SRS cohorts (subhazard ratio = 0.992, P = .980). Rates of post-SRS hemorrhage, all-cause mortality, radiation-induced changes, cyst formation, and embolization-associated complications were similar between the matched cohorts. Sensitivity analysis for AVMs in the OE + SRS cohort embolized with Onyx alone revealed a higher rate of asymptomatic embolization-associated complications in this subgroup compared to the NOE + SRS cohort (36% vs 15%; OR = 3.297, P = .034), but the symptomatic complication rates were similar. Conclusion Nidal embolization using Onyx does not appear to differentially impact the outcomes of AVM SRS compared with non-Onyx embolysates. The embolic agent selected for pre-SRS AVM embolization should reflect both the experience of the neurointerventionalist and target of endovascular intervention.

Background Long-term data regarding stereotactic radiosurgery (SRS) as a standalone therapy for unruptured pediatric brain arteriovenous malformations (AVMs) are incompletely defined. Objective To evaluate, in a multicenter, retrospective cohort study, the outcomes after SRS for unruptured, intervention-naive pediatric AVMs. Methods To retrospectively analyze the International Radiosurgery Research Foundation pediatric AVM database from 1987 to 2018. Pediatric patients with unruptured, previously untreated AVMs who underwent SRS were included. The primary endpoint was a composite of hemorrhagic stroke, death, or permanently symptomatic radiation-induced changes. Results The study cohort comprised 101 patients (mean follow-up 80.8 mo). The primary endpoint occurred in 14%, comprising hemorrhagic stroke, death, and permanent radiation-induced changes in 6%, 3%, and 8%, respectively. Estimated probabilities of the primary endpoint were 5.2%, 10.8%, and 23.0% at 2, 5, and 10 yr, respectively. Estimated probabilities of AVM obliteration at 5 and 10 yr were 64% and 82%, respectively. Single SRS treatment (P = .007) and higher margin dose (P = .005) were predictors of obliteration. Subgroup analysis of Spetzler-Martin grade I-III AVMs estimated primary endpoint probabilities of 3.7%, 8.4%, and 18.7% at 2, 5, and 10 yr, respectively. Conclusion Treatment of unruptured, intervention-naive AVMs in the pediatric population with SRS carries an approximately 2% annual risk of morbidity and mortality, which appears to plateau after 10 yr. The poorly described natural history of pediatric AVMs renders any comparison of SRS vs conservative management imperfect.

Background Dural arteriovenous fistulas (DAVFs) can be categorized based on location. Objective To compare stereotactic radiosurgery (SRS) outcomes between cavernous sinus (CS) and non-CS DAVFs and to identify respective outcome predictors. Methods This is a retrospective study of DAVFs treated with SRS between 1988 and 2016 at 10 institutions. Patients' variables, DAVF characters, and SRS parameters were included for analyses. Favorable clinical outcome was defined as angiography-confirmed obliteration without radiological radiation-induced changes (RIC) or post-SRS hemorrhage. Other outcomes were DAVFs obliteration and adverse events (including RIC, symptomatic RIC, and post-SRS hemorrhage). Results The overall study cohort comprised 131 patients, including 20 patients with CS DAVFs (15%) and 111 patients with non-CS DAVFs (85%). Rates of favorable clinical outcome were comparable between the 2 groups (45% vs 37%, P = .824). Obliteration rate after SRS was higher in the CS DAVFs group, even adjusted for baseline difference (OR = 4.189, P = .044). Predictors of favorable clinical outcome included higher maximum dose (P = .014) for CS DAVFs. Symptomatic improvement was associated with obliteration in non-CS DAVFs (P = .005), but symptoms improved regardless of whether obliteration was confirmed in CS DAVFs. Non-CS DAVFs patients with adverse events after SRS were more likely to be male (P = .020), multiple arterial feeding fistulas (P = .018), and lower maximum dose (P = .041). Conclusion After SRS, CS DAVFs are more likely to obliterate than non-CS ones. Because these 2 groups have different total predictors for clinical and radiologic outcomes after SRS, they should be considered as different entities.

Background Prior comparisons of brain arteriovenous malformations (AVMs) treated using stereotactic radiosurgery (SRS) with or without embolization were inherently flawed, due to differences in the pretreatment nidus volumes. Objective To compare the outcomes of embolization and SRS, vs SRS alone for AVMs using pre-embolization malformation features. Methods We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Patients were categorized into the embolization and SRS (E + SRS) or SRS alone (SRS-only) cohorts. The 2 cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was defined as AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiologic and symptomatic radiation-induced changes (RIC), and cyst formation. Results The matched cohorts each comprised 101 patients. Crude AVM obliteration rates were similar between the matched E + SRS vs SRS-only cohorts (48.5% vs 54.5%; odds ratio = 0.788, P = .399). Cumulative probabilities of obliteration at 3, 4, 5, and 6 yr were also similar between the E + SRS (33.0%, 46.4%, 56.2%, and 60.8%, respectively) and SRS-only (32.9%, 46.2%, 56.0%, and 60.6%, respectively) cohorts (subhazard ratio (SHR) = 1.005, P = .981). Cumulative probabilities of radiologic RIC at 3, 4, 5, and 6 yr were lower in the E + SRS (25.0%, 25.7%, 26.7%, and 26.7%, respectively) vs SRS-only (45.3%, 46.2%, 47.8%, and 47.8%, respectively) cohort (SHR = 0.478, P = .004). Symptomatic and asymptomatic embolization-related complication rates were 8.3% and 18.6%, respectively. Rates of post-SRS hemorrhage, all-cause mortality, symptomatic RIC, and cyst formation were similar between the matched cohorts. Conclusion This study refutes the prevalent notion that AVM embolization negatively affects the likelihood of obliteration after SRS.

BACKGROUND Obsessive compulsive disorder (OCD) across its full spectrum of severity is a psychiatric illness affecting ∼2% to 3% of the general population and results in significant functional impairment. There are few large patient series regarding Gamma ventral capsulotomy (GVC). OBJECTIVE To evaluate clinical outcomes of severe medically refractory OCD treated with GVC. METHODS This is an international, multicenter, retrospective cohort study. Forty patients with pre-GVC Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores ≥ 24 (indicating severe OCD) were included. GVC was performed with 1 or 2 isocenters with a median maximum dose of 135 Gy (range, 120-180 Gy). Patients were deemed "responders" to GVC if there was ≥35% reduction of follow-up Y-BOCS scores, and considered in remission if their Y-BOCS scores were ≤16. The median follow-up was 36 mo (range, 6-96 mo). RESULTS The median pre-SRS Y-BOCS score was 35 (range, 24-40). Eighteen patients (45%) were considered "responders," and 16 (40%) of them were in remission at their last follow-up. Nineteen patients (47.5%) remained stable with Y-BOCS of 33 (range, 26-36) following GVC, whereas 3 patients (7.5%) experienced worsening in Y-BOCS scores. Patients treated with 2 isocenters were more likely to have improvement in Y-BOCS score at 3 and 5 yr (P

Background Stereotactic radiosurgery (SRS) is a highly effective management approach for patients with vestibular schwannomas (VS), with 10-yr control rates up 98%. When it fails, however, few data are available to guide management. Objective To perform a retrospective analysis of patients who underwent 2 SRS procedures on the same VS to assess the safety and efficacy of this practice. Methods This study was opened to centers of the International Gamma Knife Research Foundation (IGKRF). Data collected included patient characteristics, clinical symptoms at the time of SRS, radiosurgery dosimetric data, imaging response, clinical evolution, and survival. Actuarial analyses of tumor responses were performed. Results Seventy-six patients from 8 IGKRF centers were identified. Median follow-up from the second SRS was 51.7 mo. Progression after the first SRS occurred at a median of 43 mo. Repeat SRS was performed using a median dose of 12 Gy. Actuarial tumor control rates at 2, 5, and 10 yr following the second SRS were 98.6%, 92.2%, and 92.2%, respectively. Useful hearing was present in 30%, 8%, and 5% of patients at first SRS, second SRS, and last follow-up, respectively. Seventy-five percent of patients reported stable or improved symptoms following the second SRS. Worsening of facial nerve function attributable to SRS occurred in 7% of cases. There were no reports of radionecrosis, radiation-associated edema requiring corticosteroids, radiation-related neoplasia, or death attributable to the repeat SRS procedure. Conclusion Patients with progressing VS after radiosurgery can be safely and effectively managed using a second SRS procedure.

Background Stereotactic radiosurgery (SRS) is a potentially important option for intracranial ependymoma patients. Objective To analyze the outcomes of intracranial ependymoma patients who underwent SRS as a part of multimodality management. Methods Seven centers participating in the International Gamma Knife Research Foundation identified 89 intracranial ependymoma patients who underwent SRS (113 tumors). The median patient age was 16.3 yr (2.9-80). All patients underwent previous surgical resection and radiation therapy (RT) of their ependymomas and 40 underwent previous chemotherapy. Grade 2 ependymomas were present in 42 patients (52 tumors) and grade 3 ependymomas in 48 patients (61 tumors). The median tumor volume was 2.2 cc (0.03-36.8) and the median margin dose was 15 Gy (9-24). Results Forty-seven (53%) patients were alive and 42 (47%) patients died at the last follow-up. The overall survival after SRS was 86% at 1 yr, 50% at 3 yr, and 44% at 5 yr. Smaller total tumor volume was associated with longer overall survival (P = .006). Twenty-two patients (grade 2: n = 9, grade 3: n = 13) developed additional recurrent ependymomas in the craniospinal axis. The progression-free survival after SRS was 71% at 1 yr, 56% at 3 yr, and 48% at 5 yr. Adult age, female sex, and smaller tumor volume indicated significantly better progression-free survival. Symptomatic adverse radiation effects were seen in 7 patients (8%). Conclusion SRS provides another management option for residual or recurrent progressive intracranial ependymoma patients who have failed initial surgery and RT.

Background Facial nerve schwannomas are rare, challenging tumors to manage due to their nerve of origin. Functional outcomes after stereotactic radiosurgery (SRS) are incompletely defined. Objective To analyze the effect of facial nerve segment involvement on functional outcome for these tumors. Methods Patients who underwent single-session SRS for facial nerve schwannomas with at least 3 mo follow-up at 11 participating centers were included. Preoperative and treatment variables were recorded. Outcome measures included radiological tumor response and neurological function. Results A total of 63 patients (34 females) were included in the present study. In total, 75% had preoperative facial weakness. Mean tumor volume and margin dose were 2.0 ± 2.4 cm3 and 12.2 ± 0.54 Gy, respectively. Mean radiological follow-up was 45.5 ± 38.9 mo. Progression-free survival at 2, 5, and 10 yr was 98.1%, 87.2%, and 87.2%, respectively. The cumulative proportion of patients with regressing tumors at 2, 5, and 10 yr was 43.1%, 63.6%, and 63.6%, respectively. The number of involved facial nerve segments significantly predicted tumor progression (P = .04). Facial nerve function was stable or improved in 57 patients (90%). Patients with involvement of the labyrinthine segment of the facial nerve were significantly more likely to have an improvement in facial nerve function after SRS (P = .03). Hearing worsened in at least 6% of patients. Otherwise, adverse radiation effects included facial twitching (3 patients), facial numbness (2 patients), and dizziness (2 patients). Conclusion SRS for facial nerve schwannomas is effective and spares facial nerve function in most patients. Some patients may have functional improvement after treatment, particularly if the labyrinthine segment is involved.

BACKGROUND: Despite a high incidence of brain metastases in patients with small-cell lung cancer (SCLC), limited data exist on the use of stereotactic radiosurgery (SRS), specifically Gamma Knife™ radiosurgery (Elekta AB), for SCLC brain metastases. OBJECTIVE: To provide a detailed analysis of SCLC patients treated with SRS, focusing on local failure, distant brain failure, and overall survival (OS). METHODS: A multi-institutional retrospective review was performed on 293 patients undergoing SRS for SCLC brain metastases at 10 medical centers from 1991 to 2017. Data collection was performed according to individual institutional review boards, and analyses were performed using binary logistic regression, Cox-proportional hazard models, Kaplan-Meier survival analysis, and competing risks analysis. RESULTS: Two hundred thirty-two (79%) patients received SRS as salvage following prior whole-brain irradiation (WBRT) or prophylactic cranial irradiation, with a median marginal dose of 18 Gy. At median follow-up after SRS of 6.4 and 18.0 mo for surviving patients, the 1-yr local failure, distant brain failure, and OS were 31%, 49%, and 28%. The interval between WBRT and SRS was predictive of improved OS for patients receiving SRS more than 1 yr after initial treatment (21%, 1 yr, P = .01). On multivariate analysis, older age was the only significant predictor for OS (hazard ratio 1.63, 95% CI 1.16-2.29, P = .005). CONCLUSION: SRS plays an important role in the management of brain metastases from SCLC, especially in salvage therapy following WBRT. Ongoing prospective trials will better assess the value of radiosurgery in the primary management of SCLC brain metastases and potentially challenge the standard application of WBRT in SCLC patients.

Background The role of intervention in the management of unruptured brain arteriovenous malformations (AVM) is controversial. Objective To analyze in a multicenter, retrospective cohort study, the outcomes following radiosurgery for unruptured AVMs and determine predictive factors. Methods We evaluated and pooled AVM radiosurgery data from 8 institutions participating in the International Gamma Knife Research Foundation. Patients with unruptured AVMs and ≥12 mo of follow-up were included in the study cohort. Favorable outcome was defined as AVM obliteration, no postradiosurgical hemorrhage, and no permanently symptomatic radiation-induced changes. Results The unruptured AVM cohort comprised 938 patients with a median age of 35 yr. The median nidus volume was 2.4 cm 3 , 71% of AVMs were located in eloquent brain areas, and the Spetzler-Martin grade was III or higher in 57%. The median radiosurgical margin dose was 21 Gy and follow-up was 71 mo. AVM obliteration was achieved in 65%. The annual postradiosurgery hemorrhage rate was 1.4%. Symptomatic and permanent radiation-induced changes occurred in 9% and 3%, respectively. Favorable outcome was achieved in 61%. In the multivariate logistic regression analysis, smaller AVM maximum diameter ( P = .001), the absence of AVM-associated arterial aneurysms ( P = .001), and higher margin dose ( P = .002) were found to be independent predictors of a favorable outcome. A margin dose ≥ 20 Gy yielded a significantly higher rate of favorable outcome (70% vs 36%; P Conclusion Radiosurgery affords an acceptable risk to benefit profile for patients harboring unruptured AVMs. These findings justify further prospective studies comparing radiosurgical intervention to conservative management for unruptured AVMs.

Background There are presently no grading scales that specifically address the outcomes of cranial dural arteriovenous fistula (dAVF) after stereotactic radiosurgery (SRS). Objective To design a practical grading system that would predict outcomes after SRS for cranial dAVFs. Methods From the International Radiosurgery Research Foundation (University of Pittsburgh [41 patients], University of Pennsylvania [6 patients], University of Sherbrooke [2 patients], University of Manitoba [1 patient], West Virginia University [2 patients], University of Puerto Rico [1 patient], Beaumont Health System 1 [patient], Na Homolce Hospital [13 patients], the University of Virginia [48 patients], and Yale University [6 patients]) centers, 120 patients with dAVF treated with SRS were included in the study. The factors predicting favorable outcome (obliteration without post-SRS hemorrhage) after SRS were assessed using logistic regression analysis. These factors were pooled with the factors that were found to be predictive of obliteration from 7 studies with 736 patients after a systematic review of literature. These were entered into stepwise multiple regression and the best-fit model was identified. Results Based on the predictive model, 3 factors emerged to develop an SRS scoring system: cortical venous reflux (CVR), prior intracerebral hemorrhage (ICH), and noncavernous sinus location. Class I (score of 0-1 points) predicted the best favorable outcome of 80%. Class II patients (2 points score) had an intermediate favorable outcome of 57%, and class III (score 3 points) had the least favorable outcome at 37%. The ROC analysis showed better predictability to prevailing grading systems (AUC = 0.69; P = .04). Kaplan-Meier analysis showed statistically significant difference between the 3 subclasses of the proposed grading system for post-SRS dAVF obliteration (P = .001). Conclusion The proposed dAVF grading system incorporates angiographic, anatomic, and clinical parameters and improves the prediction of the outcomes following SRS for dAVF as compared to the existing scoring systems.

Background Gamma Knife radiosurgery (GKRS) is commonly used in treating small vestibular schwannomas; however, its use for larger vestibular schwannomas is still controversial. Objective To assess the long-term safety and efficacy of treating eligible Koos grade 4 vestibular schwannomas with GKRS. Methods We conducted a single-center, retrospective evaluation of patient undergoing GKRS for Koos grade 4 vestibular schwannomas. We evaluated clinical, imaging, and treatment characteristics and assessed treatment outcome. Inclusion criteria were tumor size of ≥4 cm and follow-up of at least 6 months. Patients with neurofibromatosis type 2 were excluded. Primary outcomes measured were tumor control rate, hearing and facial function preservation rate, and complications. All possible factors were analyzed to assess clinical significance. Results Sixty-eight patients met inclusion criteria. Median follow-up was 47 months (range, 6-125 months). Baseline hearing was serviceable in 60%. Median tumor volume at radiosurgery was 7.4 cm (range, 4-19 cm). The median marginal dose used was 12 Gy at the 50% isodose line. Actuarial tumor control rates were 95% and 92% at 2 and 10 years, respectively. Actuarial serviceable hearing preservation rates were 89% and 49% at 2 and 5 years, respectively. Facial nerve preservation was 100%. Clinical complications included balance disturbance (11%), facial pain (10%), facial numbness (5%), and tinnitus (10%). Most complications were mild and transient. Hydrocephalus occurred in 3 patients, requiring ventriculoperitoneal shunt insertion. Larger tumor size was significantly associated with persisting symptoms post-treatment. Conclusion Patients with Koos grade 4 vestibular schwannomas and minimal symptoms can be treated safely and effectively with GKRS.

Background Targeted stereotactic radiosurgery (SRS) with sparing of the residual pituitary is the traditional radiosurgical method for pituitary adenomas. Whole-sella SRS is an alternative choice for radiologically indeterminate or large adenomas, the safety and efficacy of which has yet to be determined. Objective To determine if whole-sella SRS in acromegaly would have comparable radiographic and biochemical control to targeted SRS. We performed a multicenter, retrospective matched cohort study to compare outcomes between groups. Methods We conducted a retrospective review of acromegalic patients who underwent SRS from 1990 to 2016 at 10 centers participating in the International Radiosurgery Research Foundation. Whole-sella and targeted SRS patients were then matched in a 1:1 ratio. Results A total of 128 patients were eligible for inclusion. Whole-sella patients had a higher pre-SRS random serum growth hormone, larger treatment volume, and higher maximum point dose to the optic apparatus. The rates of initial/durable endocrine remission, new loss of pituitary function, and new cranial neuropathy were similar between groups. Mortality and new visual deficit were higher in the whole-sella cohort, though not statistically significant. Conclusion There was no difference in biochemical remission or recurrence between treatment groups. Although not statistically significant, the higher rates of tumor regression and lower rates of mortality and new visual deficit may suggest consideration of targeted SRS over whole-sella SRS in acromegaly treatment. Further research is needed to determine the association between visual deficits and mortality with whole-sella SRS.

Background Facial pain response (PR) to various surgical interventions in patients with multiple sclerosis (MS)-related trigeminal neuralgia (TN) is much less optimal. No large patient series regarding stereotactic radiosurgery (SRS) has been published. Objective To evaluate the clinical outcomes of MS-related TN treated with SRS. Methods This is a retrospective cohort study. A total of 263 patients contributed by 9 member tertiary referral Gamma Knife centers (2 in Canada and 7 in USA) of the International Gamma Knife Research Consortium (IGKRF) constituted this study. Results The median latency period of PR after SRS was 1 mo. Reasonable pain control (Barrow Neurological Institute [BNI] Pain Scores I-IIIb) was achieved in 232 patients (88.2%). The median maintenance period from SRS was 14.1 months (range, 10 days to 10 years). The actuarial reasonable pain control maintenance rates at 1 yr, 2 yr, and 4 yr were 54%, 35%, and 24%, respectively. There was a correlation between the status of achieving BNI-I and the maintenance of facial pain recurrence-free rate. The median recurrence-free rate was 36 mo and 12.2 mo in patients achieving BNI-I and BNI > I, respectively (P = .046). Among 210 patients with known status of post-SRS complications, the new-onset of facial numbness (BNI-I or II) after SRS occurred in 21 patients (10%). Conclusion In this largest series SRS offers a reasonable benefit to risk profile for patients who have exhausted medical management. More favorable initial response to SRS may predict a long-lasting pain control.

Background External ventricular drainage (EVD) catheters provide reliable and accurate means of monitoring intracranial pressure and alleviating elevated pressures via drainage of cerebrospinal fluid (CSF). CSF infections occur in approximately 9% of patients. Antibiotic-impregnated (AI) EVD catheters were developed with the goal of reducing the occurrence of EVD catheter-related CSF infections and their associated complications. Objective To present an international, prospective, randomized, open-label trial to evaluate infection incidence of AI vs standard EVD catheters. Methods Infection was defined as (1) proven infection, positive CSF culture and positive Gram stain or (2) suspected infection: (A) positive CSF culture with no organisms identified on initial Gram stain; (B) negative CSF culture with a gram-positive or -negative stain; (C) CSF leukocytosis with a white blood cell/red blood cell count >0.02. Results Four hundred thirty-four patients underwent implantation of an EVD catheter. One hundred seventy-six patients in the AI-EVD cohort and 181 in the standard EVD catheter cohort were eligible for evaluation of infection. The 2 groups were similar in all clinical characteristics. Proven infection was documented in 9 (2.5%) patients (AI: 4 [2.3%] vs standard: 5 [2.8%], P = 1.0). Suspected infection was documented in 31 (17.6%) patients receiving AI and 37 (20.4%) patients receiving standard EVD catheters, P = .504. Duration of time to suspected infection was prolonged in the AI cohort (8.8 ± 6.1 days) compared with the standard EVD cohort (4.6 ± 4.2 days), P = .002. Conclusion AI-EVD catheters were associated with an extremely low rate of catheter-related infections. AI catheters were not associated with risk reduction in EVD infection compared to standard catheters. Use of AI-EVD catheters is a safe option for a wide variety of patients requiring CSF drainage and monitoring, but the efficacy of AI-EVD catheters was not supported in this trial.

Objective Radiation-induced meningiomas of the brain are typically managed with surgical resection. Stereotactic radiosurgery (SRS) has become an important primary or adjuvant management for patients with intracranial meningiomas, but the value of this approach for radiation-induced tumors is unclear. Methods This series consisted of 19 patients (mean age, 40 years) with 24 tumors. The patients met criteria for a radiation-induced meningioma and underwent gamma knife radiosurgery. Seven patients had undergone a previous resection. The World Health Organization tumor grades for those with prior histology were Grade I (n = 5) and Grade II (n = 2). The median tumor volume was 4.4 cm3. Radiosurgery was performed using a median margin dose of 13 Gy. Results Serial imaging was evaluated in all patients at a median follow-up of 44 months. The control rate was 75% after primary radiosurgery. Delayed resection after radiosurgery was performed in 5 patients (26%) at an average of 39 months. The median latency between radiation therapy for original disease and SRS for radiation-induced meningiomas was 29.7 years (range, 7.3-59.0 years). The overall survival after SRS was 94.1% and 80.7% at 3 and 5 years, respectively. No patient developed a subsequent radiation-induced tumor. The overall morbidity rate was 5.3% (1 optic neuropathy). Asymptomatic peritumoral imaging changes compatible with an adverse radiation effect developed in 1 patient. Conclusion SRS provides satisfactory control rates either after resection or as an alternative to resection. Its role is most valuable for patients whose tumors affect critical neurological regions and who are poor candidates for resection.

OBJECTVE: Adjuvant irradiation after resection of brain metastases reduces the risk of local recurrence. Whole-brain radiation therapy can be associated with significant neurotoxicity in long-term survivors of brain metastases. This retrospective study evaluates the role of tumor bed stereotactic radiosurgery as an alternative method of irradiation after initial resection of brain metastases to prevent local recurrence. METHODS: Forty patients underwent tumor bed radiosurgery after resection of brain metastases at two separate academic medical centers. The median age was 59.5 years. Twenty patients (67.5%) had single metastases. Resection was complete in 80% and partial in 20% of the patients. At the time of radiosurgery, systemic disease was active in 57.5%, inactive in 32.5%, and in remission in 10% of the patients. The median Karnofsky Performance Scale score was 80% (range, 60-100%). Radiosurgery was performed a median of 4 weeks after tumor resection. The median cavity radiosurgery volume was 9.1 ml (range, 0.6-39.9 ml). The median margin and maximum radiation dose were 16 and 32 Gy, respectively. RESULTS: Local control at the resection site was achieved in 73% of patients at a median follow-up period of 13 months. No variable significantly affected local control. New remote brain metastases occurred in 54% of the patients. Symptomatic radiation effect was seen in 5.4% of the patients. The median survival was 13 months after radiosurgery (range, 2-56 mo). CONCLUSION: Tumor bed radiosurgery provides effective local control of the tumor after resection in most patients. These preliminary data support radiosurgery after resection rather than traditional radiation therapy.

Objective Stereotactic radiosurgery has become an important primary or adjuvant minimally invasive management strategy for patients with intracranial meningiomas with the goals of long-term tumor growth prevention and maintenance of patient neurological function. We evaluated clinical and imaging outcomes of meningiomas stratified by histological tumor grade. Methods The patient cohort consisted of 972 patients with 1045 intracranial meningiomas managed during an 18-year period. The series included 70% women, 49% of whom had undergone a previous resection and 5% of whom had received previous fractionated radiation therapy. Tumor locations included middle fossa (n = 351), posterior fossa (n = 307), convexity (n = 126), anterior fossa (n = 88), parasagittal region (n = 113), or other (n = 115). Results The overall control rate for patients with benign meningiomas (World Health Organization Grade I) was 93%. In those without previous histological confirmation (n = 482), tumor control was 97%. However, for patients with World Health Organization Grade II and III tumors, tumor control was 50 and 17%, respectively. Delayed resection after radiosurgery was necessary in 51 patients (5%) at a mean of 35 months. After 10 years, Grade 1 tumors were controlled in 91% (n = 53); in those without histology, 95% (n = 22) were controlled. None of the patients developed a radiation-induced tumor. The overall morbidity rate was 7.7%. Symptomatic peritumoral imaging changes developed in 4% of the patients at a mean of 8 months. Conclusion Stereotactic radiosurgery provided high rates of tumor growth control or regression in patients with benign meningiomas with low risk. This study confirms the role of radiosurgery as an effective management choice for patients with small to medium-sized symptomatic, newly diagnosed or recurrent meningiomas of the brain.

OBJECTIVE: Vestibular schwannomas present significant management challenges in patients with neurofibromatosis Type 2 (NF2). We evaluated the results of gamma knife radiosurgery for the management of these tumors, focusing on tumor response, hearing preservation, and other factors affecting outcomes. METHODS: Stereotactic radiosurgery was performed to manage 74 schwannomas in 62 patients. Ipsilateral serviceable hearing was present in 35% of tumors before the procedure. The mean tumor volume was 5.7 cm3. The mean margin and maximum dose used were 14 and 27.5 Gy, respectively. Cox regression analyses were performed to to identify factors affecting outcomes. RESULTS: The median follow-up period was 53 months, and two patients were lost to follow-up. Actuarial local control rates at were 85, 81, and 81 % at 5, 10, and 15 years, respectively. Tumor volume was significant as a predictor of local control. Since 1992, using current radiosurgery techniques (magnetic resonance imaging scan targeting and reduced margin dose to 14 Gy or less), the actuarial serviceable hearing preservation rate is 73% at 1 year, 59% at 2 years, and 48% at 5 years after radiosurgery. Facial neuropathy occurred in 8% of tumors, trigeminal neuropathy occurred in 4%, and vestibular dysfunction occurred in 4%. Radiation dose and tumor volume were predictive of development of new deficits. No radiosurgery-associated secondary tumors or atypical or malignant changes were noted. CONCLUSION: Stereotactic radiosurgery is a safe and effective management modality for neurofibromatosis Type 2 vestibular schwannomas. Although results do not seem to be as good as for patients with sporadic unilateral tumors, gamma knife radiosurgery results seem favorable and indicate that radiosurgery should be strongly considered for primary tumor management in selected patients.

BACKGROUND: Although considered slow-growing, low-grade malignancies, chordomas are locally aggressive and destructive tumors with high recurrence rates. OBJECTIVE: To assess patient survival, tumor control, complications, and selected variables that predict outcome in patients who underwent Gamma Knife stereotactic radiosurgery (SRS) as primary, adjuvant, or salvage management for chordomas of the skull base. METHODS: Six participating centers of the North American Gamma Knife Consortium identified 71 patients who underwent SRS for chordoma. The median patient age was 45 years (range, 7-80 years). The median SRS target volume was 7.1 cm 3 (range, 0.9-109 cm 3 ), and median margin dose was 15.0 Gy (range, 9-25 Gy). RESULTS: At a median follow-up of 5 years (range, 0.6-14 years) after SRS, 23 patients died of tumor progression. The 5-year actuarial overall survival after SRS was 80% for the entire group, 93% for the no prior fractionated radiation therapy (RT) group (n = 50), and 43% for the prior RT group (n = 21). Younger age, longer interval between initial diagnosis and SRS, no prior RT, < 2 cranial nerve deficits, and smaller total tumor volume were significantly associated with longer patient survival. The 5-year treated tumor control rate after SRS was 66% for the entire group, 69% for the no prior RT group, and 62% for the prior RT group. Older age, recurrent group, prior RT, and larger tumor volume were significantly associated with worse tumor control. CONCLUSION: Stereotactic radiosurgery is a potent treatment option for small sized chordomas, especially in younger patients and as part of a multipronged attack that includes surgical resection when possible.

OBJECTIVE: Jugular foramen region schwannomas are rare intracranial tumors that usually present with multiple lower cranial nerve deficits. For some patients, complete surgical resection is possible but may be associated with significant morbidity. Stereotactic radiosurgery is a minimally invasive alternative or adjunct to microsurgery for such tumors. We reviewed our clinical and imaging outcomes after patients underwent gamma knife radiosurgery for management of jugular foramen schwannomas. METHODS: Thirty-four patients with 35 tumors (one patient had bilateral tumors) underwent radiosurgery between May 1990 and December 2005. Twenty-two patients had previous microsurgical resection and all patients experienced various cranial neuropathies. A median of six isocenters were used. Median marginal and maximum doses were 14 and 28 Gy, respectively. RESULTS: None of the patients were lost to evaluation and the mean duration of follow-up was 83 months. Tumors regressed in 17 patients, remained stable in 16, and progressed in two. Five- and 10-year actuarial control rates were 97 and 94%, respectively. Preexisting cranial neuropathies improved in 20% and remained stable in 77% after radiosurgery. One patient worsened. The function of all previous intact nerves was preserved after radiosurgery. CONCLUSION: Stereotactic radiosurgery proved to be a safe and effective management for newly diagnosed or residual jugular foramen schwannomas. Long-term tumor control rates and stability or improvement in cranial nerve function was confirmed.

OBJECTIVE: Radiosurgery is increasingly used to manage malignant melanoma brain metastases. We reviewed our series of patients who underwent radiosurgery for melanoma brain metastases to assess clinical outcomes and identify prognostic factors for survival and cerebral disease control. METHODS: Two hundred forty-four patients had radiosurgery for the management of 754 metastatic tumors. A mean of 2.6 tumors were irradiated per procedure. The median tumor volume was 4.4 cm3. The median margin and maximum doses used were 18 and 32 Gy, respectively. RESULTS: The median survival was 5.3 months after radiosurgery (mean, 10 mo; range, 0.2-114.3 mo). Patients survived a median of 7.8 months (mean, 13.4 mo) from the diagnosis of brain metastases and 44.9 months (mean, 69 mo) after the diagnosis of the primary tumor. Survival was better in patients with controlled systemic disease (12.7 mo), single brain metastasis (6.8 mo), and a Karnofsky performance score of 90 or 100% (6.3 mo). Sustained local control was achieved in 86.2% of tumors. Increased tumor volume and previous evidence of hemorrhage increased the risk of local failure. Multiple lesions and failure to provide systemic immunotherapy were predictors for the occurrence of new brain metastases, which developed in 41.7% of the patients. Symptomatic radiation changes occurred in 6.6% of the patients. Overall, 71.4% of the patients improved or remained clinically stable. Brain disease was the cause of death in 40.5% of the patients, usually from the development of new metastases. CONCLUSION: Gamma knife radiosurgery for malignant melanoma brain metastases is safe and effective and provides a high rate of durable local control. Improved survival can be achieved in patients with single metastasis, controlled systemic disease, and a high Karnofsky performance score.