Clinical and Imaging Outcomes After Trigeminal Schwannoma Radiosurgery: Results From a Multicenter, International Cohort Study.

BACKGROUND AND OBJECTIVES: An international, multicenter, retrospective study was conducted to evaluate the long-term clinical outcomes and tumor control rates after stereotactic radiosurgery (SRS) for trigeminal schwannoma. METHODS: Patient data (N = 309) were collected from 14 international radiosurgery centers. The median patient age was 50 years (range 11-87 years). Sixty patients (19%) had prior resections. Abnormal facial sensation was the commonest complaint (49%). The anatomic locations were root (N = 40), ganglion (N = 141), or dumbbell type (N = 128). The median tumor volume was 4 cc (range, 0.2-30.1 cc), and median margin dose was 13 Gy (range, 10-20 Gy). Factors associated with tumor control, symptom improvement, and adverse radiation events were assessed. RESULTS: The median and mean time to last follow-up was 49 and 65 months (range 6-242 months). Greater than 5-year follow-up was available for 139 patients (45%), and 50 patients (16%) had longer than 10-year follow-up. The overall tumor control rate was 94.5%. Tumors regressed in 146 patients (47.2%), remained unchanged in 128 patients (41.4%), and stabilized after initial expansion in 20 patients (6.5%). Progression-free survival rates at 3 years, 5 years, and 10 years were 91%, 86%, and 80 %. Smaller tumor volume (less than 8 cc) was associated with significantly better progression-free survival ( P = .02). Seventeen patients with sustained growth underwent further intervention at a median of 27 months (3-144 months). Symptom improvement was noted in 140 patients (45%) at a median of 7 months. In multivariate analysis primary, SRS ( P = .003) and smaller tumor volume ( P = .01) were associated with better symptom improvement. Adverse radiation events were documented in 29 patients (9%). CONCLUSION: SRS was associated with long-term freedom (10 year) from additional management in 80% of patients. SRS proved to be a valuable salvage option after resection. When used as a primary management for smaller volume tumors, both clinical improvement and prevention of new deficits were optimized.

Vestibular Schwannoma Stereotactic Radiosurgery in Octogenarians: Case Series.

BACKGROUND AND OBJECTIVES: The management of octogenarians with vestibular schwannomas (VS) has received little attention. However, with the increase in octogenarian population, more effort is needed to clarify the value of stereotactic radiosurgery (SRS) in this population. The aim of this study was to evaluate the safety and efficacy of SRS in this patient age group. METHODS: A retrospective study of 62 patients aged 80 years or older who underwent single-session SRS for symptomatic VS during a 35-year interval was performed. The median patient age was 82 years, and 61.3% were male. SRS was performed as planned adjuvant management or for delayed progression after prior partial resection in 5 patients. RESULTS: SRS resulted in a 5-year tumor control rate of 95.6% with a 4.8% risk of adverse radiation effects (ARE). Tumor control was unrelated to patient age, tumor volume, Koos grade, sex, SRS margin dose, or prior surgical management. Four patients underwent additional management including 1 patient with symptomatic progression requiring surgical resection, 2 patients with symptomatic hydrocephalus requiring cerebrospinal fluid diversion, and 1 patient whose tumor-related cyst required delayed cyst aspiration. Three patients developed ARE, including 1 patient with permanent facial weakness (House-Brackmann grade II), 1 who developed trigeminal neuropathy, and 1 who had worsening gait disorder. Six patients had serviceable hearing preservation before SRS, and 2 maintained serviceable hearing preservation after 4 years. A total of 44 (71%) patients died at an interval ranging from 6 to 244 months after SRS. CONCLUSION: SRS resulted in tumor and symptom control in most octogenarian patients with VS.

Comparison of first-line radiosurgery for small-cell and non-small cell lung cancer brain metastases (CROSS-FIRE).

INTRODUCTION: Historical reservations regarding stereotactic radiosurgery (SRS) for small-cell lung cancer (SCLC) brain metastases include concerns for short-interval and diffuse central nervous system (CNS) progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small cell lung cancer (NSCLC) where SRS is well established. METHODS: Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000 to 2022 were retrospectively collected (n = 892 SCLC, n = 4785 NSCLC). Data from the prospective Japanese Leksell Gamma Knife Society (JLGK0901) clinical trial of first-line SRS were analyzed as a comparison cohort (n = 98 SCLC, n = 814 NSCLC). Overall survival (OS) and CNS progression were analyzed using Cox proportional hazard and Fine-Gray models, respectively, with multivariable adjustment for cofactors including age, sex, performance status, year, extracranial disease status, and brain metastasis number and volume. Mutation-stratified analyses were performed in propensity score-matched retrospective cohorts of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) positive NSCLC, mutation-negative NSCLC, and SCLC. RESULTS: OS was superior for patients with NSCLC compared to SCLC in the retrospective dataset (median OS = 10.5 vs 8.6 months; P < .001) and in the JLGK0901 dataset. Hazard estimates for first CNS progression favoring NSCLC were similar in both datasets but reached statistical significance in the retrospective dataset only (multivariable hazard ratio = 0.82, 95% confidence interval = 0.73 to 0.92, P = .001). In the propensity score-matched cohorts, there were continued OS advantages for NSCLC patients (median OS = 23.7 [EGFR and ALK positive NSCLC] vs 13.6 [mutation-negative NSCLC] vs 10.4 months [SCLC], pairwise P values < 0.001), but no statistically significant differences in CNS progression were observed in the matched cohorts. Neurological mortality and number of lesions at CNS progression were similar for NSCLC and SCLC patients. Leptomeningeal progression was increased in patients with NSCLC compared to SCLC in the retrospective dataset only (multivariable hazard ratio = 1.61, 95% confidence interval = 1.14 to 2.26, P = .007). CONCLUSIONS: After SRS, SCLC histology was associated with shorter OS compared to NSCLC. CNS progression occurred earlier in SCLC patients overall but was similar in patients matched on baseline factors. SCLC was not associated with increased neurological mortality, number of lesions at CNS progression, or leptomeningeal progression compared to NSCLC. These findings may better inform clinical expectations and individualized decision making regarding SRS for SCLC patients.

Radiosurgery outcomes in infratentorial juvenile pilocytic astrocytomas.

PURPOSE: To assess survival and neurological outcomes for patients who underwent primary or salvage stereotactic radiosurgery (SRS) for infratentorial juvenile pilocytic astrocytomas (JPA). METHODS: Between 1987 and 2022, 44 patients underwent SRS for infratentorial JPA. Twelve patients underwent primary SRS and 32 patients underwent salvage SRS. The median patient age at SRS was 11.6 years (range, 2-84 years). Prior to SRS, 32 patients had symptomatic neurological deficits, with ataxia as the most common symptom in 16 patients. The median tumor volume was 3.22 cc (range, 0.16-26.6 cc) and the median margin dose was 14 Gy (range, 9.6-20 Gy). RESULTS: The median follow-up was 10.9 years (range, 0.42-26.58 years). Overall survival (OS) after SRS was 97.7% at 1-year, and 92.5% at 5- and 10-years. Progression free survival (PFS) after SRS was 95.4% at 1-year, 79.0% at 5-years, and 61.4% at 10-years. There is not a significant difference in PFS between primary and salvage SRS patients (p = 0.79). Younger age correlated with improved PFS (HR 0.28, 95% CI 0.063-1.29, p = 0.021). Sixteen patients (50%) had symptomatic improvements while 4 patients (15.6%) had delayed onset of new symptoms related to tumor progression (n = 2) or treatment related complications (n = 2). Tumor volumetric regression or disappearance after radiosurgery was found in 24 patients (54.4%). Twelve patients (27.3%) had delayed tumor progression after SRS. Additional management of tumor progression included repeat surgery, repeat SRS, and chemotherapy. CONCLUSIONS: SRS was a valuable alternative to initial or repeat resection for deep seated infratentorial JPA patients. We found no survival differences between patients who had primary and salvage SRS.

Stereotactic Radiosurgery for Vestibular Schwannoma in Neurofibromatosis Type 2: An International Multicenter Case Series of Response and Malignant Transformation Risk.

BACKGROUND: Vestibular schwannomas (VSs) related to neurofibromatosis type 2 (NF2) are challenging tumors. The increasing use of stereotactic radiosurgery (SRS) necessitates further investigations of its role and safety. OBJECTIVE: To evaluate tumor control, freedom from additional treatment (FFAT), serviceable hearing preservation, and radiation-related risks of patients with NF2 after SRS for VS. METHODS: We performed a retrospective study of 267 patients with NF2 (328 VSs) who underwent single-session SRS at 12 centers participating in the International Radiosurgery Research Foundation. The median patient age was 31 years (IQR, 21-45 years), and 52% were male. RESULTS: A total of 328 tumors underwent SRS during a median follow-up time of 59 months (IQR, 23-112 months). At 10 and 15 years, the tumor control rates were 77% (95% CI: 69%-84%) and 52% (95% CI: 40%-64%), respectively, and the FFAT rate were 85% (95% CI: 79%-90%) and 75% (95% CI: 65%-86%), respectively. At 5 and 10 years, the serviceable hearing preservation rates were 64% (95% CI: 55%-75%) and 35% (95% CI: 25%-54%), respectively. In the multivariate analysis, age (hazards ratio: 1.03 [95% CI: 1.01-1.05]; P = .02) and bilateral VSs (hazards ratio: 4.56 [95% CI: 1.05-19.78]; P = .04) were predictors for serviceable hearing loss. Neither radiation-induced tumors nor malignant transformation were encountered in this cohort. CONCLUSION: Although the absolute volumetric tumor progression rate was 48% at 15 years, the rate of FFAT related to VS was 75% at 15 years after SRS. None of the patients with NF2-related VS developed a new radiation-related neoplasm or malignant transformation after SRS.

Efficacy and safety of corticosteroid in the treatment of hand osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the efficacy and safety of corticosteroid therapy including oral corticosteroid and intra-articular corticosteroid in patients with hand osteoarthritis (OA), to provide treatment recommendations, and provide data-driven suggestions for future studies. METHODS: A systematic review of the literature was performed from inception to February 19, 2020, and the study was conducted on February 20, 2020. All controlled trials in Ovid MEDLINE, EMBASE, and Cochrane library reporting the efficacy on pain, functional recovery, and adverse events of corticosteroids in hand osteoarthritis were selected. The primary outcome was pain assessed on a visual analogue scale (VAS) lasting for up to 24 weeks. Pooled mean difference (MD) for continuous variable and risk ratio (RR) for dichotomous variable, with 95% confidence intervals (CIs), was assessed by a random effects model. RESULTS: Overall, seven trials totaling 511 participants were included in this study. The pooled analysis showed a significant difference in VAS pain (MD, - 5.75; 95% CI, - 10.08 to - 1.42, I2 = 40%). No significant differences were observed in any of the adverse events. CONCLUSION: Our data suggest corticosteroids in hand OA might improve local pain and promote functional recovery. However, since these findings were based on only 7 studies and due to significant heterogeneity across the included studies, these findings need to be confirmed by future clinical trials with a higher number of patients. KEY POINTS: • Current evidences of glucocorticoids for the management of hand osteoarthritis (OA) were insufficient and more evidences were needed. • The results of the present meta-analysis revealed corticosteroids in hand OA might improve local pain and promote functional recovery. • These findings need to be confirmed by future clinical trials with a higher number of patients.

Chronic encapsulated expanding hematomas after stereotactic radiosurgery for intracranial arteriovenous malformations.

OBJECTIVE: Cerebral arteriovenous malformations (AVMs) are rare cerebral vascular lesions that are associated with high morbidity and mortality from hemorrhage; however, stereotactic radiosurgery (SRS) is a well-validated treatment modality. Few reports have delineated a subgroup of patients who develop delayed chronic encapsulated expanding hematomas (CEEHs) despite angiographic evidence of AVM obliteration following radiosurgery. In this report, the authors performed a retrospective review of more than 1000 radiosurgically treated intracranial AVM cases to delineate the incidence and management of this rare entity. METHODS: Between 1988 and 2019, 1010 patients with intracranial AVM underwent Gamma Knife SRS at the University of Pittsburgh Medical Center. In addition to a review of a prospective institutional database, the authors performed a retrospective chart review of the departmental AVM database to specifically identify patients with CEEH. Pertinent clinical and radiological characteristics as well as patient outcomes were recorded and analyzed. RESULTS: Nine hundred fifty patients with intracranial AVM (94%) had sufficient clinical follow-up for analysis. Of these, 6 patients with CEEH underwent delayed resection (incidence rate of 0.0045 event per person-year). These patients included 4 males and 2 females with a mean age of 45.3 ± 13.8 years at the time of initial SRS. Four patients had smaller AVM volumes (4.9-10 cm3), and 3 of them were treated with a single SRS procedure. Two patients had larger-volume AVMs (55 and 56 cm3), and both underwent multimodal management that included staged SRS and embolization. Time to initial recognition of the CEEH after initial SRS ranged between 66 and 243 months. The time between CEEH recognition and resection ranged from 2 to 9 months. Resection was required because of progressive neurological symptoms that correlated with imaging evidence of gradual hematoma expansion. All 6 patients had angiographically confirmed obliteration of their AVM. Pathology revealed a mixed chronicity hematoma with areas of fibrosed blood vessels and rare areas of neovascularization with immature blood vessels but no evidence of a persistent AVM. All 6 patients reported persistent clinical improvement after hematoma resection. CONCLUSIONS: CEEH after SRS for AVM is a rare complication with an incidence rate of 0.0045 event per person-year over the authors' 30-year experience. When clinical symptoms progress and imaging reveals progressive enlargement over time, complete resection of a CEEH results in significant clinical recovery. Knowledge of this rare entity facilitates timely detection and eventual surgical intervention to achieve optimal outcomes.

Stereotactic radiosurgery as the first-line treatment for intracanalicular vestibular schwannomas.

OBJECTIVE: This report evaluates the outcomes of stereotactic radiosurgery (SRS) as the first-line treatment of intracanalicular vestibular schwannomas (VSs). METHODS: Between 1987 and 2017, the authors identified 209 patients who underwent SRS as the primary intervention for a unilateral intracanalicular VS. The median patient age was 54 years (range 22-85 years); 94 patients were male and 115 were female. Three patients had facial neuropathy at the time of SRS. One hundred fifty-five patients (74%) had serviceable hearing (Gardner-Robertson [GR] grades I and II) at the time of SRS. The median tumor volume was 0.17 cm3 (range 0.015-0.63 cm3). The median margin dose was 12.5 Gy (range 11.0-25.0 Gy). The median maximum dose was 24.0 Gy (range 15.7-50.0 Gy). RESULTS: The progression-free survival rates of all patients with intracanalicular VS were 97.5% at 3 years, 95.6% at 5 years, and 92.1% at 10 years. The rates of freedom from the need for any additional intervention were 99.4% at 3 years, 98.3% at 5 years, and 98.3% at 10 years. The serviceable hearing preservation rates in GR grade I and II patients at the time of SRS were 76.6% at 3 years, 63.5% at 5 years, and 27.3% at 10 years. In univariate analysis, younger age (< 55 years, p = 0.011), better initial hearing (GR grade I, p < 0.001), and smaller tumor volumes (< 0.14 cm3, p = 0.016) were significantly associated with improved hearing preservation. In multivariate analysis, better hearing (GR grade I, p = 0.001, HR 2.869, 95% CI 1.569-5.248) and smaller tumor volumes (< 0.14 cm3, p = 0.033, HR 2.071, 95% CI 1.059-4.047) at the time of SRS were significantly associated with improved hearing preservation. The hearing preservation rates of patients with GR grade I VS were 88.1% at 3 years, 77.9% at 5 years, and 38.1% at 10 years. The hearing preservation rates of patients with VSs smaller than 0.14 cm3 were 85.5% at 3 years, 77.7% at 5 years, and 42.6% at 10 years. Facial neuropathy developed in 1.4% from 6 to 156 months after SRS. CONCLUSIONS: SRS provided sustained tumor control in more than 90% of patients with intracanalicular VS at 10 years and freedom from the need for additional intervention in more than 98% at 10 years. Patients with initially better hearing and smaller VSs had enhanced serviceable hearing preservation during an observation interval up to 10 years after SRS.

Does the Timing of Radiosurgery after Grade 1 Meningioma Resection Affect Long-Term Outcomes?

BACKGROUND: Meningiomas are the most common benign intracranial tumors. Gamma Knife® stereotactic radiosurgery (GKSRS) has become a preferred management for recurrent or residual meningiomas. This study focuses on the relationship between tumor control and the time interval between resection of a World Health Organization (WHO) grade 1 meningioma and GKSRS. METHODS: This single institution retrospective analysis reviewed our experience in 238 patients who underwent GKSRS after a pathologically confirmed WHO grade 1 meningioma resection. The median follow-up was 7.4 years. The median aggregate tumor volume at GKSRS was 6 cm3 and a median margin dose of 13 Gy was utilized. Neurological symptoms were evident in 60% of patients at the time of procedure. RESULTS: Overall actuarial tumor control rates achieved were 91.3% at 5 years, 83.4% at 10 years, and 76% at 15 years. There were 35 patients (15%) who developed tumor progression within or directly adjacent to the GKSRS treatment field. The median time until progression was 6.3 years. The duration between surgical intervention and GKSRS did not show statistical significance at 3 months (p = 0.9), 6 months (p = 0.8), 12 months (p = 0.5), or 24 months (p = 0.9). Fifteen patients (6%) had tumor progression at an anatomically distinct location outside the GKSRS target volume. Neurological symptomatic improvement was more likely with early radiosurgery intervention (p = 0.007). CONCLUSION: Postoperative GKSRS was associated with excellent long-term tumor control for WHO grade 1 meningiomas, regardless of the interval after initial surgery. In addition, earlier radiosurgery was associated with superior symptom improvement.

Does Variceal Drainage Affect Arteriovenous Malformation Obliteration and Hemorrhage Rates After Stereotactic Radiosurgery? A Case-Matched Analysis.

BACKGROUND: Stereotactic radiosurgery (SRS) is widely accepted as a minimally invasive alternative to surgery in the management of arteriovenous malformations (AVMs). Dilated AVM outflow veins or varices may be caused by high-flow or partial outflow obstruction, which may increase the risk of a hemorrhage before or after SRS. OBJECTIVE: To compare the obliteration and hemorrhage risks in patients with and without AVM varices (AVMv). METHODS: From our prospective database of 1012 AVM patients who underwent Gamma Knife® (Elekta) SRS, we identified 103 patients with AVMv, and 847 patients without varices. The median follow-up was 52 mo. Balancing variable score matching was performed to compare obliteration and hemorrhage rates between the 2 groups. RESULTS: Obliteration rates in the AVMv group were 38% at 3 yr, 65% at 4 yr, and 70% at 5 yr. Patients with an AVMv had no difference in the final obliteration rate compared to patients who did not have variceal drainage (P = .35). Actuarial hemorrhage after SRS in the matched patients with AVMv was 4.9%, 13%, and 13.7%, at 1, 3, and 5 yr, respectively. The rate of hemorrhage in the group with no varix was 2.9%, 5.4%, and 9.1% at 1, 3, and 5 yr, respectively (P = .14). CONCLUSION: The presence of AVM variceal venous drainage did not affect the obliteration rate and did not confer a higher risk of a subsequent hemorrhage both before and after SRS.

Useful hearing preservation is improved in vestibular schwannoma patients who undergo stereotactic radiosurgery before further hearing deterioration ensues.

INTRODUCTION: The present study evaluates whether hearing deterioration during observation reduces serviceable hearing preservation rates after stereotactic radiosurgery (SRS) in vestibular schwannoma (VS) patients with useful hearing. METHODS: We retrospectively analyzed 1447 VS patients who underwent SRS between 1992 and 2017. We identified 100 VS patients who had Grade I Gardner- Robertson (GR) hearing at initial diagnosis but were observed without surgery or SRS. We compared hearing after SRS in 67 patients who retained GR Grade I hearing from initial diagnosis to SRS (the hearing maintenance or HM group) to 33 patients whose hearing worsened from GR grade I to grade II (the hearing deterioration or HD group). We also investigated whether a decline in pure tone average (PTA) or speech discrimination score (SDS) before SRS affected hearing preservation after SRS. RESULTS: The serviceable hearing (GR I and II) preservation in HM patients was 80%s, 63%, and 51% at 3, 5, and 10 years, respectively. The serviceable hearing preservation in HD patients was 40%, 33%, and 20% at 3, 5, and 10 years, respectively. In multivariate analysis, younger age (< 55 years, p = 0.045) and HM during observation (p = 0.001) improved serviceable hearing preservation rates. Patients whose PTA increased ≥ 15 dB (p = 0.024) or whose SDS declined ≥ 10% (p = 0.019) had reduced serviceable hearing preservation rates. CONCLUSIONS: Hearing deterioration during observation before SRS reduced long term hearing preservation rate in VS patients with GR grade I hearing at initial diagnosis. SRS before hearing deterioration was recommended for hearing preservation.

Stereotactic radiosurgery as the primary management for patients with Koos grade IV vestibular schwannomas.

OBJECTIVE: While extensive long-term outcome studies support the role of stereotactic radiosurgery (SRS) for smaller-volume vestibular schwannomas (VSs), its role in the management for larger-volume tumors remains controversial. METHODS: Between 1987 and 2017, the authors performed single-session SRS on 170 patients with previously untreated Koos grade IV VSs (volumes ranged from 5 to 20 cm3). The median tumor volume was 7.4 cm3. The median maximum extracanalicular tumor diameter was 27.5 mm. All tumors compressed the middle cerebellar peduncle and distorted the fourth ventricle. Ninety-three patients were male, 77 were female, and the median age was 61 years. Sixty-two patients had serviceable hearing (Gardner-Robertson [GR] grades I and II). The median margin dose was 12.5 Gy. RESULTS: At a median follow-up of 5.1 years, the progression-free survival rates of VSs treated with a margin dose ≥ 12.0 Gy were 98.4% at 3 years, 95.3% at 5 years, and 90.7% at 10 years. In contrast, the tumor control rate after delivery of a margin dose < 12.0 Gy was 76.9% at 3, 5, and 10 years. The hearing preservation rates in patients with serviceable hearing at the time of SRS were 58.1% at 3 years, 50.3% at 5 years, and 35.9% at 7 years. Younger age (< 60 years, p = 0.036) and initial GR grade I (p = 0.006) were associated with improved serviceable hearing preservation rate. Seven patients (4%) developed facial neuropathy during the follow-up interval. A smaller tumor volume (< 10 cm3, p = 0.002) and a lower margin dose (≤ 13.0 Gy, p < 0.001) were associated with preservation of facial nerve function. The probability of delayed facial neuropathy when the margin dose was ≤ 13.0 Gy was 1.1% at 10 years. Nine patients (5%) required a ventriculoperitoneal shunt because of delayed symptomatic hydrocephalus. Fifteen patients (9%) developed detectable trigeminal neuropathy. Delayed resection was performed in 4% of patients. CONCLUSIONS: Even for larger-volume VSs, single-session SRS prevented the need for delayed resection in almost 90% at 10 years. For patients with minimal symptoms of tumor mass effect, SRS should be considered an effective alternative to surgery in most patients, especially those with advanced age or medical comorbidities.

Treatment of WHO Grade 2 Meningiomas With Stereotactic Radiosurgery: Identification of an Optimal Group for SRS Using RPA.

PURPOSE: This study assesses a large multi-institutional database to present the outcomes of World Health Organization grade 2 meningiomas treated with stereotactic radiosurgery (SRS). We also compare the 3-year progression-free survival (PFS) to that reported in the Radiation Therapy Oncology Group 0539 phase 2 cooperative group meningioma trial. METHODS AND MATERIALS: From an international, multicenter group, data were collected for grade 2 meningioma patients treated with SRS for demonstrable tumor from 1994 to 2019. Statistical methods used included the Kaplan-Meier method, Cox proportional hazards analysis, and recursive partitioning analysis. RESULTS: Two hundred thirty-three patients treated at 12 institutions were included. Patients presented at a median age of 60 years (range, 13-90), and many had at least 2 prior resections (30%) or radiation therapy (22%). Forty-eight percent of patients had prior gross total resection. At SRS, the median treatment volume was 6.1 cm3 (0.1-97.6). A median 15 Gy (10-30) was delivered to a median percent isodose of 50 (30-80), most commonly in 1 fraction (95%). A model was developed using recursive partitioning analysis, with one point attributed to age >50 years, treatment volume >11.5 cm3, and prior radiation therapy or multiple surgeries. The good-prognostic group (score, 0-1) had improved PFS (P < .005) and time to local failure (P < .005) relative to the poor-prognostic group (score, 2-3). Age >50 years (hazard ratio = 1.85 [95% confidence interval, 1.09-3.14]) and multiple prior surgeries (hazard ratio = 1.80 [1.09-2.99]) also portended reduced PFS in patients without prior radiation therapy. Two hundred eighteen of 233 patients in this study qualified for the high-risk group of Radiation Therapy Oncology Group 0539, and they demonstrated similar outcomes (3-year PFS: 53.9% vs 58.8%). The good-prognostic group of SRS patients demonstrated slightly improved outcomes (3-year PFS: 63.1% vs 58.8%). CONCLUSIONS: SRS should be considered in carefully selected patients with atypical meningiomas. We suggest the use of our good-prognostic group to optimize patient selection, and we strongly encourage the initiation of a clinical trial to prospectively validate these outcomes.

Stereotactic Radiosurgery for Atypical (World Health Organization II) and Anaplastic (World Health Organization III) Meningiomas: Results From a Multicenter, International Cohort Study.

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 < .05) and a Ki-67 index > 15% (HR = 1.66, P < .03) negatively correlated with PFS. MMs (HR = 3.21, P < .05), increased age (HR = 1.04, P = .04), and reduced KPS (HR = 0.95, P = .04) were associated with shortened OS. Adjuvant versus salvage SRS did not impact PFS/OS. A shortened interval between surgery and SRS improved PFS for AMs (HR = 0.99, P = .02) on subgroup analysis. Radiation necrosis occurred in 34 (12.5%) patients. Five-year rates of repeat surgery/radiation were 33.8% and 60.4%, respectively. CONCLUSION: AM/MMs remain challenging tumors to treat. Elevated proliferative indices are associated with tumor recurrence, while MMs have worse survival. SRS can control AM/MMs in the short term, but the 5-yr PFS rates are low, underscoring the need for improved treatment options for these patients.

Outcomes after stereotactic radiosurgery for schwannomas of the oculomotor, trochlear, and abducens nerves.

OBJECTIVE: Cranial nerve (CN) schwannomas are intracranial tumors that are commonly managed by stereotactic radiosurgery (SRS). There is a large body of literature supporting the use of SRS for vestibular schwannomas. Schwannomas of the oculomotor nerves (CNs III, IV, and VI) are rare skull base tumors, occurring close to the brainstem and often involving the cavernous sinus. Resection can cause significant morbidity, including loss of nerve function. As for other schwannomas, SRS can be used to manage these tumors, but only a handful of cases have been published so far, often among reports of other uncommon schwannoma locations. METHODS: The goal of this study was to collect retrospective multicenter data on tumor control, clinical evolution, and morbidity after SRS. This study was performed through the International Radiosurgery Research Foundation. Patients managed with single-session SRS for an oculomotor cranial nerve schwannoma (CN III, IV, or VI) were included. The diagnosis was based on diplopia or ptosis as the main presenting symptom and anatomical location on the trajectory of the presumed cranial nerve of origin, or prior resection confirming diagnosis. Demographic, SRS dose planning, clinical, and imaging data were collected from chart review of the treated patients. Chi-square and Kaplan-Meier analyses were performed. RESULTS: Seven institutions submitted data for a total of 25 patients. The median follow-up time was 41 months. The median age at the time of treatment was 52 years. There were 11 CN III schwannomas, 11 CN IV schwannomas, and 3 CN VI schwannomas. The median target volume was 0.74 cm3, and the median marginal dose delivered was 12.5 Gy. After SRS, only 2 patients (including the only patient with neurofibromatosis type 2) had continued tumor growth. Crude local control was 92% (23/25), and the 10-year actuarial control was 86%. Diplopia improved in the majority of patients (11/21), and only 3 had worsening following SRS, 2 of whom also had worsened ptosis, both in the context of tumor progression. CONCLUSIONS: SRS for schwannomas of the oculomotor, trochlear, and abducens nerves is effective and provides tumor control rates similar to those for other cranial nerve schwannomas. SRS allows improvement of diplopia in the majority of patients. SRS should therefore be considered as a first-line treatment option for oculomotor nerve schwannomas.

Management of thoracic spinal cord injury in a professional American football athlete: illustrative case.

BACKGROUND: A case of catastrophic thoracic spinal cord injury (SCI) sustained by a professional American football player with severe scoliosis is presented. OBSERVATIONS: A 25-year-old professional football player sustained an axial loading injury while tackling. Examination revealed a T8 American Spinal Injury Association Impairment Scale grade A complete SCI. Methylprednisolone and hypothermia protocols were initiated. Computed tomography scan of the thoracic spine demonstrated T8 and T9 facet fractures on the left at the apex of a 42° idiopathic scoliotic deformity. Magnetic resonance imaging (MRI) demonstrated T2 spinal cord hyperintensity at T9. He regained trace movement of his right lower extremity over 12 hours, which was absent on posttrauma day 2. Repeat MRI revealed interval cord compression and worsening of T2 signal change at T7-T8 secondary to hematoma. Urgent decompression and fusion from T8 to T10 were performed. Additional treatment included high-dose omega-3 fatty acids and hyperbaric oxygen therapy. A 2-month inpatient spinal cord rehabilitation program was followed by prolonged outpatient physical therapy. He currently can run and jump with minimal residual distal left lower limb spasticity. LESSONS: This is the first known football-related thoracic SCI with idiopathic scoliosis. Aggressive medical and surgical intervention with intensive rehabilitation formed the treatment protocol, with a favorable outcome achieved.

Comparative efficacy and safety of pharmacological prophylaxis and intermittent pneumatic compression for prevention of venous thromboembolism in adult undergoing neurosurgery: a systematic review and network meta-analysis.

Whether intermittent pneumatic compression (IPC) is a more effective form of thromboprophylaxis than anticoagulants in individuals undergoing neurosurgery remains controversial. Relevant studies are sparse and inconsistent. Therefore, direct comparisons are difficult to perform and impractical. Hence, we summarized and compared the efficacy and safety of IPC and anticoagulants for the prevention of venous thromboembolism (VTE) in adults undergoing cranial or spinal procedures. Several electronic databases were searched for randomized controlled trials on the use of IPC and anticoagulants for thromboembolism prevention in neurosurgical patients, from inception to August 6, 2019. Studies reporting the selected endpoints were included in direct and Bayesian network meta-analyses to estimate the relative effects of the interventions. Overall, our analysis included 18 trials comprising 2474 patients. Both IPC (RR, 0.41; 95% CrI, 0.26-0.60) and chemical prophylaxis (RR, 0.48; 95% CrI, 0.28-0.68) were found to be more efficacious than the placebo in reducing the risk of deep vein thrombosis (DVT). In addition, our analysis also demonstrated that both IPC (RR, 0.10; 95% CrI, 0.01-0.60) and chemical prophylaxis (RR, 0.31; 95% CrI, 0.05-1.00) reduced the risk of pulmonary embolism (PE) significantly more than the placebo. Based on the available evidence of moderate-to-good quality, IPC is equivalent to anticoagulants for thromboprophylaxis in terms of efficacy. Evidence to support or negate the use of pharmacological prophylaxis in terms of safety is lacking. The results of ongoing and future large randomized clinical trials are needed.

Long-term survival in patients with long-segment complex meningiomas occluding the dural venous sinuses: illustrative cases.

BACKGROUND: Invasive sagittal sinus meningiomas are difficult tumors to cure by resection alone. Stereotactic radiosurgery (SRS) can be used as an adjuvant management strategy to improve tumor control after incomplete resection. OBSERVATIONS: The authors reported the long-term retrospective follow-up of two patients whose recurrent parasagittal meningiomas eventually occluded their superior sagittal sinus. Both patients underwent staged radiosurgery and fractionated radiation therapy to achieve tumor control that extended to 20 years after their initial surgery. After initial subtotal resection of meningiomas that had invaded major cerebral venous sinuses, adjuvant radiosurgery was performed to enhance local tumor control. Over time, adjacent tumor progression required repeat SRS and fractionated radiation therapy to boost long-term tumor response. Staged multimodality intervention led to extended survival in these patients with otherwise unresectable meningiomas. LESSONS: Multimodality management with radiosurgery and fractionated radiation therapy was associated with long-term survival of two patients with otherwise surgically incurable and invasive meningiomas of the dural venous sinuses.

Stereotactic Radiosurgery for Choroid Plexus Tumors: A Report of the International Radiosurgery Research Foundation.

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.

Effect of levothyroxine on pregnancy outcomes in women with thyroid autoimmunity: a systematic review with meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate whether levothyroxine is associated with improved live birth and other benefits in women with thyroid autoimmunity. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women positive for thyroid peroxidase antibody. INTERVENTION(S): MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched without any language restrictions. Pooled effect sizes were calculated using random-effects models. MAIN OUTCOME MEASURE(S): The primary outcome was the incidence of live birth, miscarriage, preterm birth, clinical pregnancy, ectopic pregnancy, neonatal admission, and birth weight. The summary measures were reported as relative risk (RR) with 95% confidence interval. RESULT(S): Levothyroxine supplementation was not associated with an increased rate of live birth or a decreased risk of miscarriage. Results were similar in subgroup analyses of live birth by age, baseline thyrotropin, baseline thyroid peroxidase antibody, body mass index, and use of assisted conception. For live birth, the effect estimate lay within the futility boundary for RR of 20% and 15%, but at a 10% RR, the effect estimate lay between the futility boundary and the inferior boundary. CONCLUSION(S): High- to moderate-quality evidence demonstrated that the use of levothyroxine was not associated with improvements in clinical pregnancy outcomes among women positive for thyroid peroxidase antibody. REGISTRATION NUMBER: PROSPERO CRD42019132976.