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Giant cell glioblastoma (GCG) is a rare subtype of glioblastoma (GBM) that is believed to carry an improved prognosis. However, given the rarity of this tumor, best management practices for GCG have yet to be ascertained. Here, we present our experience in managing GCG tumors at the University of California, San Francisco. Patients were retrospectively identified through chart review, and data pertaining to patient demographics, treatment plans, and follow-up were extracted from existing medical records. Overall survival (OS) and progression-free survival (PFS) were the primary and secondary endpoints, respectively. In sum, we identified 22 patients who were managed or followed for GCG. Most patients (78%) initially underwent subtotal resection as primary treatment for their tumor, and most also received post-operative adjuvant therapy (90%), with radiation being the most frequently administered modality (85%). Within this institutional cohort, median OS and PFS were 15.4 months and 5.7 months, respectively. On multivariate survival analysis, age (p=0.84), sex (p=0.05), and adjuvant radiation plus temozolomide (p=0.12) were not associated with prolonged OS. However, adjuvant radiation plus temozolomide was associated with longer PFS (p=0.01), and patients receiving this therapy demonstrated a median PFS of 32.9 months versus 13.1 months. These findings confirm the comparatively improved prognosis of GCG over GBM. Moreover, they suggest that extent of resection may not significantly delay recurrence or extend survival, and that combination radiation with temozolomide may represent the optimum adjuvant paradigm to delay tumor progression., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Intracranial chondrosarcomas are primary cartilaginous neoplasms that represent 6% of all skull base tumors. Intracranial extraskeletal chondrosarcomas are more rare, often arising from the meninges at the falx, tentorium, or cerebral convexity. They are generally characterized as classical or mesenchymal, with the latter associated with worse outcomes. We present our institutional series of falcine and parasagittal chondrosarcomas along with a review of the literature. Although skull base chondrosarcomas pose significant challenges due to their invasive biology and proximity to vital brainstem structures and cranial nerves, intracranial extraskeletal chondrosarcomas are generally associated with a good prognosis. Our review of the literature identified 29 patients with falcine and parasagittal chondrosarcomas. There were six recurrences, five among patients with the mesenchymal subtype and one in a patient with the classical subtype. All deaths occurred in patients with the mesenchymal subtype. Management of skull base chondrosarcomas is controversial but extraskeletal intracranial tumors can generally be managed by surgical resection alone. Treatment should be tailored to the biology of the tumor, with radiation therapy reserved for patients with the mesenchymal subtype., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Despite the relatively low-grade of most central neurocytomas (CN), evidence suggests the existence of an aggressive subset with a propensity for recurrence. Recent studies have found the MIB-1 labeling index to be a prognostic indicator in CN. Here we review our experience with CN to analyze the relationships between extent of resection, adjuvant therapy, tumor histology, and clinical outcomes based on aggressive histology, as defined by MIB-1 labeling. A retrospective review was performed on histologically proven CN surgically resected from 1993 to 2009 at the University of California at San Francisco. Recurrence rates were analyzed using the Kaplan-Meier method with respect to MIB-1 labeling and extent of resection. All MIB-1 labeling indices were analyzed. A total of 18 patients were identified with a mean age of 30 years (range 17-58 years) and median follow-up of 40 months (5-173 months). The treatments were: gross total resection (GTR) alone (17% of patients), subtotal resection (STR) alone (50% of patients), STR plus radiotherapy (XRT: external beam or stereotactic radiosurgery: 28% of patients), or STR plus chemotherapy (5% of patients). The extent of resection and a MIB-1 labeling index >4% was predictive of recurrence (p<0.01). In the 33% of the patients in whom the tumor recurred, all had STR with MIB-1 labeling >4% with median time to recurrence of 23.5 months. The 2-year and 4-year recurrence rates in patients with MIB-1 labeling >4% were 50% and 75% respectively. No patient with a MIB-1 labeling index <4% who received STR alone had a recurrence. Thus, in patients with CN who were treated with STR, histology demonstrating a MIB-1 labeling index >4% can be a clinically useful prognostic indicator and can help guide adjuvant treatment., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Intracranial hemangiopericytoma (HPC) is an aggressive meningothelial neoplasm. A particularly challenging aspect of management of patients with HPC is optimizing treatment for recurrence, progression, and extracranial metastasis. Here we describe a modern cohort of patients with recurrent HPC to better understand treatment strategies that may improve outcome. Patients managed at UCSF for recurrent intracranial HPC were compiled into a single database based on a retrospective review of patient records, including operative, radiologic, and clinic reports. Cox regression was performed to determine factors that independently predicted treatment outcomes. At UCSF, 14 patients with available treatment and follow-up data were seen for management of HPC recurrence. Eight patients underwent repeat surgical resection, of whom four received adjuvant external beam radiotherapy (EBRT), one received additional Gamma Knife radiosurgery (GKS), and one received brachytherapy. Radiosurgical intervention alone was utilized for recurrence in six patients, with four receiving GKS and two receiving CyberKnife. Nine patients suffered a second recurrence at a median time of 3.5 years following reintervention. Nine patients died following reintervention, with a median survival of 7.9 years following intervention for recurrence. In univariate analysis, factors associated with increased time to second recurrence included non-posterior fossa location (log rank, p < 0.05) and surgical resection with adjuvant EBRT (log rank, p < 0.05). The addition of adjuvant EBRT to surgical resection similarly extended overall survival compared to surgical resection alone (log rank, p < 0.05). GKS was associated with earlier second recurrence compared to surgically based strategies (log rank, p < 0.05). We conclude that when combined with surgical resection, EBRT appears promising in the extension of second recurrence-free survival and overall survival. This multimodality approach also appears to outperform GKS in extending time to second recurrence. Accordingly, when safe and feasible, surgical resection of recurrent HPC with adjuvant EBRT should be the first steps in management., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Gangliogliomas are rare central nervous system tumors, most commonly affecting children and young adults. Chronic seizure and epilepsy are the most frequent presentation of patients with gangliogliomas. In this report, we review the modern literature regarding the effects of early surgical intervention on the clinical outcome of patients with ganglioglioma. A boolean search of PubMed using key words "ganglioglioma", "adult", "seizure control", "treatment", "surgical intervention", and "observation", alone and in combination was performed. The inclusion criteria for articles were that: (i) clinical outcomes were reported specifically for gangliogliomas; (ii) data were reported for adult patients older than the age of 18 years; (iii) treatment data were included for the treatment of gangliogliomas; and (iv) ganglioglioma was the only pathological diagnosis for the evaluation of the tumor. Data were analyzed as a whole then stratified into two groups: early and late treatment intervention. The query identified a total of 99 articles including 1,089 cases of ganglioglioma meeting our inclusion and exclusion criteria. There was a 55% prevalence of males, representing a statistically significant predilection (51-59%, 95% confidence interval). Seizure control was significantly improved when surgical intervention occurred less than 3 years after symptom onset (78% versus 48%; p = 0.0001). Ganglioglioma in adults represents a rare group of tumors, and our systematic analysis suggests a higher prevalence in males. Our findings also support that an early surgical intervention is significantly associated with improved clinical seizure control., (2010. Published by Elsevier Ltd.)

Central neurocytomas (CN) are rare tumors. Since their first description in 1982, the number of case reports and series has been rapidly increasing. Although they are considered low-grade neoplasms, they can be associated with an aggressive primary course or recurrence after resection. The cellular origin of central neurocytoma (CN) and the molecular events leading to tumorigenesis have been largely unknown. Here, we present a review of the scientific literature contributing to our knowledge of CN focusing on cellular origin and oncogenic alterations, and how these findings inform areas amenable to future research and therapeutic intervention. Our discussion is expanded to include important and related insights into the cellular origin and classification of central nervous system tumors., (2010. Published by Elsevier Ltd.)

The ability of glioma cells to escape the immune system remains a significant barrier to successful immunotherapy. Here we demonstrate that loss of the PTEN tumor suppressor gene, with associated activation of the PI3K/Akt/mTOR pathway, leads to a human glioma phenotype that induces autologous T-cell apoptosis upon contact. The PTEN status of pathologically confirmed glioblastoma specimens was defined, and primary cultures established after surgical resection of tumor from 26 patients. Autologous T-cells were isolated from these patients, and after T-cell activation was induced, these cells were co-cultured with matched autologous glioma cells, either alone, or after treatment with one of three inhibitors of the PI3K/Akt/mTOR pathway. When co-cultured with autologous T-cells, PTEN wild-type tumor cells induced apoptosis in a minimal number of activated T-cells (6-12% of T-cells), whereas tumors with PTEN loss induced much more profound levels of T-cell apoptosis (42-56% of T-cells). Prior treatment of PTEN-deficient tumor cells with specific inhibitors of the PI3K/Akt/mTOR pathway diminished T-cell apoptosis to levels seen after co-culture with wild-type PTEN tumor cells, suggesting that PTEN loss confers this immunoresistant phenotype through the PI3K/Akt/mTOR pathway. These results suggest that PTEN-deficient glioblastoma patients are suboptimal candidates for immunotherapy. In addition, our results raise the possibility of combining T-cell based immunotherapy protocols with clinical inhibitors of the PI3K/Akt/mTOR pathway., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

A growing body of evidence supports the significant interplay between the immune system and glioma pathogenesis. Here we investigate whether the extent of local glioma-associated CD8+ T-cell infiltrate at initial presentation correlates with long-term survival in patients with glioblastoma multiforme (GBM). The study was conducted by the University of California San Francisco Brain Tumor Research Center as part of the San Francisco Bay Area Adult Glioma Study, which included over 519 patients with GBM. A central neuropathology review was performed and populations of infiltrating CD8+ T-cells were quantified histologically. Of 108 patients studied, 43 patients had poor survival (<95days) and 65 patients had extended long-term survival of >403days. Tumors from long-term survivors were more likely than short-term survivors to have intermediate or extensive T-cell infiltrates compared to focal or rare infiltrates, and this association appears to be most significant in Caucasian women (p < 0.006). Thus, CD8+ T-cell infiltrate is associated with prolonged survival. Our data provide the impetus for more sophisticated studies to further elucidate prospectively the specific T-cell subtypes associated with long-term survival., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Gangliogliomas are rare benign tumors of the central nervous system that typically involve the temporal lobe in younger patients. We present a 63-year-old man with an unusual occipital ganglioma with new seizures resolving after resection. A search of the literature revealed only three reports of occipital ganglioma in adults over 30 years old. Therefore, ganglioglioma of the occipital lobe in older patients is rare, but is a diagnostic consideration., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Hemangiopericytoma of the pineal region is exceedingly rare. We describe a patient with a large pineal region hemangiopericytoma who underwent a third ventriculostomy followed by a gross total resection by a unilateral interhemispheric approach with adjuvant radiotherapy. The patient remains recurrence free 4 years after treatment., (Copyright 2010 Elsevier Ltd. All rights reserved.)