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.

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.

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.

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.

Adjunctive Intermittent Pneumatic Compression in Hospitalized Patients Receiving Pharmacologic Prophylaxis for Venous Thromboprophylaxis: A Systematic Review and Meta-Analysis.

OBJECTIVES: This study assessed the effect of adjunctive intermittent pneumatic compression (IPC) on venous thromboembolism incidence in hospitalized patients receiving pharmacologic thromboprophylaxis. METHODS: We searched Medline, Embase, and the Cochrane Central Register with no language restrictions from inception until May 15, 2019, for randomized clinical trials comparing adjunctive IPC in pharmacologic thromboprophylaxis and pharmacologic thromboprophylaxis for venous thromboembolism. Two researchers extracted data from published reports independently. A meta-analysis was conducted to calculate the risk ratio (RR) using random-effects models. Primary outcomes were deep venous thrombosis (DVT) and pulmonary embolism (PE). RESULTS: Eight trials with a total of 7,354 participants were eligible for analysis. Addition of IPC to pharmacologic prophylaxis compared to pharmacologic prophylaxis alone reduced the risk of DVT by 43% (RR 0.57, 95% confidence interval [CI] 0.35-0.93; I2 = 0%), with benefit only seen in surgical patients (RR 0.30, 95% CI 0.15-0.59; I2 = 0%) and not in medical patients (RR 0.80, 95% CI 0.60-1.07; I2 = 0%; p for interaction = .008). Addition of IPC reduced the risk for PE by 54% (RR 0.46, 95% CI 0.30-0.72; I2 = 0%), with benefit only seen in surgical patients (RR 0.40, 95% CI 0.24-0.65; I2 = 0%) and not in medical patients (RR 0.82, 95% CI 0.32-2.26; I2 = 0%; p for interaction = .18) CONCLUSIONS: Addition of IPC to pharmacologic prophylaxis confers moderate benefit on venous thromboembolism, with benefit confined to surgical patients. For medical patients, there was a trend toward reduced DVT with adjunctive IPC, which warrants further investigation. CLINICAL RELEVANCE: Venous thromboembolism is not unusual among hospitalized patients despite pharmacologic thromboprophylaxis. Nursing personnel should use adjunctive IPC in surgical patients receiving pharmacologic thromboprophylaxis to prevent venous thromboembolism.

Stereotactic Radiosurgery for Unruptured Versus Ruptured Pediatric Brain Arteriovenous Malformations.

Background and Purpose- The effects of prior hemorrhage on stereotactic radiosurgery (SRS) outcomes for pediatric arteriovenous malformations (AVMs) are not well defined. The aim of this multicenter, retrospective cohort study is to compare the SRS outcomes for unruptured versus ruptured pediatric AVMs. Methods- The International Radiosurgery Research Foundation pediatric AVM database from 1987 to 2018 was reviewed retrospectively. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes. Associations between prior hemorrhage and outcomes were adjusted for baseline differences, inverse probability weights, and competing risks. Results- The study cohort comprised 153 unruptured and 386 ruptured AVMs. Favorable outcome was achieved in 48.4% and 60.4% of unruptured and ruptured AVMs, respectively (adjusted odds ratio, 1.353; P=0.190). Cumulative AVM obliteration probabilities were 51.2%, 59.4%, 64.2%, and 70.0% for unruptured and 61.0%, 69.3%, 74.0%, and 79.3% for ruptured AVMs at 4, 6, 8, and 10 years, respectively (subhazard ratio, 1.311; P=0.020). Cumulative post-SRS hemorrhage probabilities were 4.5%, 5.6%, 5.6%, and 9.8% for unruptured and 4.7%, 6.1%, 6.1%, and 10.6% for ruptured AVMs at 4, 6, 8, and 10 years, respectively (subhazard ratio, 1.086; P=0.825). Probabilities of AVM obliteration (adjusted subhazard ratio, 0.968; P=0.850) and post-SRS hemorrhage (adjusted subhazard ratio, 1.663; P=0.251) were comparable between the 2 cohorts after inverse probability weight adjustments. Symptomatic (15.8% versus 8.1%; adjusted odds ratio, 0.400; P=0.008) and permanent (9.2% versus 5.0%; adjusted odds ratio, 0.441; P=0.045) radiation-induced change were more common in unruptured AVMs. Conclusions- The overall outcomes after SRS for unruptured versus ruptured pediatric AVMs are comparable. However, symptomatic and permanent radiation-induced change occur more frequently in pediatric patients with unruptured AVMs.

Increased versus stable dose of inhaled corticosteroids for asthma exacerbations: A systematic review and meta-analysis.

BACKGROUND: Increasing the dose of inhaled corticosteroids (ICS) is commonly used at early signs of loss of asthma control. However, the potential benefits and harms of this strategy remain unclear. We performed a systematic review and meta-analysis to compare increased dose with stable dose of ICS among adults and children with asthma. METHODS: We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception to August 02, 2018. Randomized clinical trials comparing increased doses vs stable doses of ICS for home management of asthma exacerbations in adults or children were included. RESULTS: The analyses included 8 trials totalling 3866 patients. Four trials were judged as low risk of bias, three were unclear risk, and one was ranked as high risk. Increased dose of ICS was associated with a significantly reduced risk of treatment failure compared with stable dose (OR 0.82, 95% CI 0.70-0.97, I2  = 6%; 314 (281 to 351) vs 358 events per 1000 patients; moderate-quality evidence). There was no significant difference in unscheduled physician visits or hospital admission between increased or stable dose of ICS. However, increased dose of ICS increased the risk of non-serious adverse events (OR 3.50, 95% CI 1.93-6.35, I2  = 0%) but not serious adverse events. CONCLUSIONS: Current evidence of moderate quality supports increasing the dose of ICS as part of a self-initiated action plan to reduce risk of requiring a course of systemic corticosteroids in people with an asthma exacerbation. However, we did not find evidence for an impact on hospital admissions or unscheduled physician visits, and increased ICS dose increased risk of non-serious adverse events.

Primary or salvage stereotactic radiosurgery for brain metastatic small cell lung cancer.

PURPOSE: We evaluated the outcomes after stereotactic radiosurgery (SRS) for patients who developed new or progressive brain disease regardless of whether they had no prior radiation, PCI, or WBRT. METHODS: We retrospectively identified 90 SCLC patients who had SRS between 1991 and 2018. Thirty-one patients had no evidence of brain disease at the time of initial diagnosis but received prophylactic cranial irradiation. Twenty-six without initial brain disease underwent delayed SRS after brain disease was identified. Seventeen patients with synchronous systemic and brain disease underwent WBRT at the time of diagnosis. Fifteen patients had brain disease detected at the time of initial diagnosis and had initial SRS. RESULTS: We found no difference in overall survival between patients who received initial PCI or WBRT compared to patients treated with SRS alone at the time when brain metastases were identified. PCI was not associated with a longer duration between initial diagnosis and the development of brain metastasis. Local tumor control was achieved in 49 out of 58 patients who had follow up MRI available for review (84.5%). Actuarial local tumor control at 3, 6, and 12 months was calculated as 92%, 85%, and 80%, respectively. Radiation therapy (PCI or WBRT) before SRS was not associated with better or worse local tumor control. CONCLUSION: In this experience neither prior PCI nor WBRT improved survival or local tumor control in SCLC patients who underwent SRS for new or recurrent brain disease.

Long term results of primary radiosurgery for vestibular schwannomas.

BACKGROUND: Stereotactic radiosurgery (SRS) has become a primary option for management for both newly diagnosed vestibular schwannomas (VS), as well as VS that enlarge after initial observation. METHODS: A retrospective review of our prospectively maintained data base found 871 patients who underwent Gamma knife® SRS as their initial (primary) management between 1987 and 2008. Follow-up ranged from 1-25 years (median = 5.2 years) Median tumor volume was 0.9 cc (0.02-36) and median margin dose was 13 Gy (12-25). RESULTS: Progression free survival (PFS) after SRS was 97% at 3 years, 95% at 5 years, and 94% at 10 years. Freedom from delayed surgical resection was found in 98.7% of patients. Smaller tumor volume was significantly associated with improved PFS. There were 326 patients with serviceable hearing (Gardner-Robertson 1 or 2) at the time of SRS with audiological follow-up of ≥ 1 year. Serviceable hearing preservation rates after SRS were 89.8% at 1 year, 76.9% at 3 years, 68.4% at 5 years, 62.5% at 7 years, and 51.4% at 10 years. Factors associated with improved serviceable hearing preservation included younger age, Gardner-Robertson grade 1 at SRS, and absence of subjective complaints of dysequilibrium or vertigo (vestibulopathy). Fifty-one patients (5.8%) developed trigeminal neuropathy. Fourteen (1.6%) developed a transient House-Brackmann grade 2 or 3 facial neuropathy. CONCLUSIONS: In this report with extended follow-up, primary SRS achieved tumor growth control in 94% of patients. Optimization of long- term cranial nerve outcomes remains an important achievement of this management strategy for VS.

Seizure and cognitive outcomes after resection of glioneuronal tumors in children.

OBJECTIVE: Glioneuronal tumors (GNTs) are well-recognized causes of chronic drug-resistant focal epilepsy in children. Our practice involves an initial period of radiological surveillance and antiepileptic medications, with surgery being reserved for those with radiological progression or refractory seizures. We planned to analyze the group of patients with low-grade GNTs, aiming to identify factors affecting seizure and cognitive outcomes. METHODS: We retrospectively reviewed the medical records of 150 children presenting to Great Ormond Street Hospital with seizures secondary to GNTs. Analysis of clinical, neuroimaging, neuropsychological, and surgical factors was performed to determine predictors of outcome. Seizure outcome at final follow-up was classified as either seizure-free (group A) or not seizure-free (group B) for patients with at least 12-months follow-up postsurgery. Full-scale intelligence quotient (FSIQ) was used as a measure of cognitive outcome. RESULTS: Eighty-six males and 64 females were identified. Median presurgical FSIQ was 81. One hundred twenty-one patients (80.5%) underwent surgery. Median follow-up after surgery was 2 years, with 92 patients (76%) having at least 12 months of follow-up after surgery. Seventy-four patients (80%) were seizure-free, and 18 (20%) continued to have seizures. Radiologically demonstrated complete tumor resection was associated with higher rates of seizure freedom (P = .026). Higher presurgical FSIQ was related to shorter epilepsy duration until surgery (P = .012) and to older age at seizure onset (P = .043). SIGNIFICANCE: A high proportion of children who present with epilepsy and GNTs go on to have surgical tumor resection with excellent postoperative seizure control. Complete resection is associated with a higher chance of seizure freedom. Higher presurgical cognitive functioning is associated with shorter duration of epilepsy prior to surgery and with older age at seizure onset. Given the high rate of eventual surgery, early surgical intervention should be considered in children with continuing seizures associated with GNTs.

Cranial nerve outcomes after primary stereotactic radiosurgery for symptomatic skull base meningiomas.

OBJECTIVE: To evaluate cranial nerve (CN) outcomes after primary stereotactic radiosurgery (SRS) for petroclival, cavernous sinus, and cerebellopontine angle meningiomas. METHODS: From our prospectively maintained database of 2022 meningioma patients who underwent Leksell stereotactic radiosurgery (SRS) during a 30-year interval, we found 98 patients with petroclival, 242 with cavernous sinus, and 55 patients with cerebellopontine angle meningiomas. Primary radiosurgery was performed in 245 patients. Patients included in this report had at least one CN deficit at the time of initial presentation and a minimum of 12 month follow up. Median age at the time of SRS was 58 years. Median follow up was 58 months (range 12-300 months), Median tumor volume treated with SRS was 5.9 cm3 (range 0.5-37.5 cm3), and median margin dose was 13 Gy (range 9-20Gy). RESULTS: Tumor control was achieved in 229 patients (93.5%) at a median follow up of 58 months. Progression free survival rate (PFS) after SRS was 98.7% at 1 year, 96.4% at 3 years, 93.7% at 5 years, and 86.4% at 10 years Overall, 114 of the 245 patients (46.5%) reported improvement of CN function. Patients with CP angle meningiomas demonstrated lower rates of CN improvement compared to petroclival and cavernous sinus meningioma patients. Deterioration of CN function after SRS developed in 24 patients (10%). The rate of deterioration was 2.8% at 1 year, 5.2% at 3 years, and 8% at 10 years. CONCLUSION: Primary SRS provides effective tumor control and favorable rate of improvement of preexisting CN deficit.

Tight glycemic control in critically ill pediatric patients: a systematic review and meta-analysis.

BACKGROUND: Hyperglycemia is prevalent in patients in the pediatric intensive care unit. The purpose of this study was to describe the benefits and risks of tight glucose control (TGC) in critically ill children. METHODS: A systemic review and meta-analysis of the literature was carried out on randomized controlled trials of TGC in critically ill children admitted to the pediatric intensive care unit. The databases searched were Medline, Embase, and CENTRAL databases until May 1, 2017. Paired reviewers independently screened citations, assessed risk of bias of included studies, and extracted data. A random-effects model was used to report all outcomes. The Grading of Recommendations Assessment, Development and Evaluation system was used to quantify absolute effects and quality of evidence. The primary outcome was hospital mortality. The secondary outcomes were hypoglycemia (any, severe), sepsis, new need for dialysis, and seizures. RESULTS: A total of 4030 patients were included from six studies. All six studies were rated as at low risk of bias. Our meta-analysis showed that TGC did not result in a decrease in risk of hospital mortality (odds ratio (OR), 0.95; 95% confidence interval (CI), 0.62-1.45; I2 = 40%; moderate quality), sepsis (OR, 0.82; 95% CI, 0.63-1.08), or seizures (OR, 0.98; 95% CI, 0.59-1.63). TGC was associated with a decrease in new need for dialysis (OR, 0.63; 95% CI, 0.45-0.86). However, TGC was associated with a significant increase in any hypoglycemia (OR, 4.39; 95% CI, 2.39-8.06) and severe hypoglycemia (OR, 4.11; 95% CI, 2.67-6.32). CONCLUSIONS: Among critically ill children with hyperglycemia, TGC does not result in a decrease in hospital mortality, but appears to reduce a new need for dialysis. However, TGC is associated with higher incidence of hypoglycemia. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42017074039 .

Macrophages as Nanocarriers for Drug Delivery: Novel Therapeutics for Central Nervous System Diseases.

Many central nervous system (CNS) diseases were thought to be untreatable due to the presence of the blood-brain barrier (BBB). The chemokine gradients secreted from CNS parenchyma can induce macrophage migration to the brain, induce firm adherence to the endothelium of BBB, and eventually to enter the brain parenchyma. Macrophages migrating into CNS can promote neuron regeneration, induce inflammation and angiogenesis. These properties can potentially allow macrophages to act as carriers for drug/nano formulations across the BBB, and reach the potential target sites. Many nanomaterials cannot be used for the management of CNS diseases because of their low carrying efficiency. Macrophage which transports nanomaterials to pathological sites is rendered as an attractive tool for the transportation of drugs to previously inaccessible regions within the brain parenchyma. Nanomaterials engulfed by macrophages can be released at target sites, and be used for therapeutic or diagnostic purposes. In this review, we focus on macrophages as the cell-carrier to deliver nano-drugs into CNS, describe the biological behavior of macrophages during pathological conditions and discuss the application of cell drug delivery system in recent years.

A Case of Symptomatic Granular Cell Tumor of the Pituitary Treated with Stereotactic Radiosurgery.

BACKGROUND: Granular cell tumors (GCT) of the pituitary are rare. Surgery is considered the primary management option. However, complete resection is often difficult, and surgery is associated with high rates of postoperative complications. AIMS: To report a unique case of pituitary GCT treated with stereotactic radiosurgery (SRS). CASE DESCRIPTION: We report a case of a 40-year-old female with endocrine dysfunction who underwent stereotactic biopsy and then SRS for the management of a suprasellar granular cell tumor. Over the ensuing 10 years, tumor regression was observed. Thirteen years after SRS, the patient remained asymptomatic; however, follow-up MRI demonstrated tumor progression. Fifteen years after SRS, the patient required endoscopic endonasal surgery after developing a new optic neuropathy. Her images demonstrated further tumor growth beyond the targeted area. CONCLUSION: SRS resulted in long-term tumor control without additional endocrine dysfunction, but the onset of new optic neuropathy associated with delayed tumor growth prompted surgical decompression.

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.

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.

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.

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.