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Jacob H. Bagley, Ranjith Babu, Allan H. Friedman and Cory Adamson

Object

Low-grade gliomas (LGGs) are indolent tumors that have the potential to dedifferentiate into malignant high-grade tumors. Recent studies have demonstrated that cerebellar low-grade tumors have a better prognosis than supratentorial tumors, although no study has focused on the risk factors for poor prognosis in cerebellar LGGs in adults. The authors of the current study aimed to address both of these concerns by using a large cohort derived from a national cancer registry and a smaller cohort derived from their institution's experience.

Methods

Adults with diagnosed Grade I and Grade II gliomas of the cerebellum were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox proportional hazard models were used to predict rates of survival, and the log-rank test was applied to evaluate differences in Kaplan-Meier survival curves. An institutional cohort was created by isolating all patients whose surgical pathology revealed an LGG of the cerebellum. Excluded from analysis were patients in whom a glioma was first diagnosed under the age of 18 years and those whose tumors could not be definitively determined to arise from the cerebellum.

Results

Data from the local cohort (11 patients) demonstrated that the most common presenting symptom was headache, which occurred in more than 70% of the cohort. Approximately half of the patients in this cohort had symptomatic improvement after treatment. Results from the SEER cohort (166 patients) revealed that adults with Grade I gliomas were slightly younger than those with Grade II tumors (p < 0.01), but no other demographic differences were observed. Patients with Grade I tumors were twice as likely to undergo gross-total resection (54% vs 21%), and those with Grade II gliomas were much more likely to receive postoperative radiation (3% vs 48%). Five-year survival was greater in the patients with Grade I gliomas than in those with Grade II lesions (91% vs 70%). Multivariate analysis revealed that an age ≥ 40 years (HR 7.30, 95% CI 3.55–15.0, p < 0.0001) and Grade II tumors (HR 2.76, 95% CI 1.12–6.84, p = 0.028) were risk factors for death, whereas female sex was protective (HR 0.28, 95% CI 0.14–0.59, p < 0.001). Log-rank tests revealed that a cerebellar location was protective (p < 0.0001), but this relationship was only true for Grade II tumors (p < 0.0001). Survival in patients with Grade I gliomas was not different based on the various lesion locations (p = 0.21).

Conclusions

Taken together, adults with cerebellar WHO Grade I and II astrocytomas have a much more favorable survival curve than those with similar supratentorial tumors. Research demonstrates that the primary driver of this phenomenon is the improved survival in patients with cerebellar Grade II gliomas.

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Ranjith Babu, Richa Sharma, Jacob H. Bagley, Jeffrey Hatef, Allan H. Friedman and Cory Adamson

Object

There are a variety of treatment options for the management of vestibular schwannomas (VSs), including microsurgical resection, radiotherapy, and observation. Although the choice of treatment is dependent on various patient factors, physician bias has been shown to significantly affect treatment choice for VS. In this study the authors describe the current epidemiology of VS and treatment trends in the US in the modern era. They also illustrate patient and tumor characteristics and elucidate their effect on tumor management.

Methods

Patients diagnosed with VS were identified through the Surveillance, Epidemiology, and End Results database, spanning the years 2004–2009. Age-adjusted incidence rates were calculated and adjusted using the 2000 US standard population. The chi-square and Student t-tests were used to evaluate differences between patient and tumor characteristics. Multivariate logistic regression was performed to determine the effects of various patient and tumor characteristics on the choice of tumor treatment.

Results

A total of 6225 patients with VSs treated between 2004 and 2009 were identified. The overall incidence rate was 1.2 per 100,000 population per year. The median age of patients with VS was 55 years, with the majority of patients being Caucasian (83.16%). Of all patients, 3053 (49.04%) received surgery only, with 1466 (23.55%) receiving radiotherapy alone. Both surgery and radiation were only used in 123 patients (1.98%), with 1504 patients not undergoing any treatment (24.16%). Increasing age correlated with decreased use of surgery (OR 0.95, 95% CI 0.95–0.96; p < 0.0001), whereas increasing tumor size was associated with the increased use of surgery (OR 1.04, 95% CI 1.04–1.05; p < 0.0001). Older age was associated with an increased likelihood of conservative management (OR 1.04, 95% CI 1.04–1.05; p < 0.0001). Racial disparities were also seen, with African American patients being significantly less likely to receive surgical treatment compared with Caucasians (OR 0.50, 95% CI 0.35–0.70; p < 0.0001), despite having larger tumors at diagnosis.

Conclusions

The incidence of vestibular schwannomas in the US is 1.2 per 100,000 population per year. Although many studies have demonstrated improved outcomes with the use of radiotherapy for small- to medium-sized VSs, surgery is still the most commonly used treatment modality for these tumors. Racial disparities also exist in the treatment of VSs, with African American patients being half as likely to receive surgery and nearly twice as likely to have their VSs managed conservatively despite presenting with larger tumors. Further studies are needed to elucidate the reasons for treatment disparities and investigate the nationwide trend of resection for the treatment of small VSs.

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Ranjith Babu, Jacob H. Bagley, Jong G. Park, Allan H. Friedman and Cory Adamson

Object

Low-grade astrocytomas are slow-growing, infiltrative gliomas that over time may progress into more malignant tumors. Various factors have been shown to affect the time to progression and overall survival including age, performance status, tumor size, and the extent of resection. However, more recently it has been suggested that histological subtypes (fibrillary, protoplasmic, and gemistocytic) may impact patient outcome. In this study the authors have performed a large comparative population-based analysis to examine the characteristics and survival of patients with the various subtypes of WHO Grade II astrocytomas.

Methods

Patients diagnosed with fibrillary, protoplasmic, and gemistocytic astrocytomas were identified through the Surveillance, Epidemiology, and End Results (SEER) database. The chi-square test and Student t-test were used to evaluate differences in patient and treatment characteristics between astrocytoma subtypes. Kaplan-Meier analysis was used to assess overall survival, and the log-rank test was used to evaluate the differences between survival curves. Univariate and multivariate analyses were also performed to determine the effect of various patient, tumor, and treatment variables on overall survival.

Results

A total of 500 cases were included in the analysis, consisting of 326 fibrillary (65.2%), 29 protoplasmic (5.8%), and 145 gemistocytic (29%) variants. Gemistocytic astrocytomas presented at a significantly older age than the fibrillary variant (46.8 vs 37.7 years, p < 0.0001), with protoplasmic and fibrillary subtypes having a similar age. Although protoplasmic and fibrillary variants underwent radiotherapy at similar rates, gemistocytic tumors more frequently received radiotherapy (p = 0.0001). Univariate analysis revealed older age, larger tumor size, and the use of radiotherapy to be poor prognostic factors, with resection being associated with improved survival. The gemistocytic subtype (hazard ratio [HR] 1.62 [95% CI 1.27–2.07], p = 0.0001) also resulted in significantly worse survival than fibrillary tumors. Bivariate analyses demonstrated that older age, the use of radiotherapy, and resection significantly influenced median survival. Tumor subtype also affected median survival; patients who harbored gemistocytic tumors experienced less than half the median survival of fibrillary and protoplasmic tumors (38 vs 82 months, p = 0.0003). Multivariate analysis revealed increasing age (HR 1.05 [95% CI 1.04–1.05], p < 0.0001), larger tumor size (HR 1.02 [95% CI 1.01–1.03], p = 0.0002), and the use of resection (HR 0.70 [95% CI 0.52–0.94], p = 0.018) to be independent predictors of survival. Examination of tumor subtype revealed that the gemistocytic variant (HR 1.30 [95% CI 0.98–1.74], p = 0.074) was associated with worse patient survival than fibrillary tumors, although this only approached significance. The protoplasmic subtype did not affect overall survival (p = 0.33).

Conclusions

Gemistocytic tumor histology was associated with worse survival than fibrillary and protoplasmic astrocytomas. As protoplasmic astrocytomas have a survival similar to fibrillary tumors, there may be limited utility to the identification of this rare variant. However, increased attention should be paid to the presence of gemistocytes in low-grade gliomas as this is associated with shorter time to progression, increased malignant transformation, and reduced overall survival.

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Ranjith Babu, Jacob H. Bagley, Chunhui Di, Allan H. Friedman and Cory Adamson

Intracerebral hemorrhage (ICH) is a subtype of stoke that may cause significant morbidity and mortality. Brain injury due to ICH initially occurs within the first few hours as a result of mass effect due to hematoma formation. However, there is increasing interest in the mechanisms of secondary brain injury as many patients continue to deteriorate clinically despite no signs of rehemorrhage or hematoma expansion. This continued insult after primary hemorrhage is believed to be mediated by the cytotoxic, excitotoxic, oxidative, and inflammatory effects of intraparenchymal blood. The main factors responsible for this injury are thrombin and erythrocyte contents such as hemoglobin. Therapies including thrombin inhibitors, N-methyl-D-aspartate antagonists, chelators to bind free iron, and antiinflammatory drugs are currently under investigation for reducing this secondary brain injury. This review will discuss the molecular mechanisms of brain injury as a result of intraparenchymal blood, potential targets for therapeutic intervention, and treatment strategies currently in development.