Hemispheric Low-grade Gliomas Research Articles

MiR-1248: a new prognostic biomarker able to identify supratentorial hemispheric pediatric low-grade gliomas patients associated with progression

BackgroundPediatric low-grade gliomas (pLGGs), particularly incompletely resected supratentorial tumours, can undergo progression after surgery. However to date, there are no predictive biomarkers for progression. Here, we aimed to identify pLGG-specific microRNA signatures and evaluate their value as a prognostic tool.MethodsWe identified and validated supratentorial incompletey resected pLGG-specific microRNAs in independent cohorts from four European Pediatric Neuro-Oncology Centres.ResultsThese microRNAs demonstrated high accuracy in differentiating patients with or without progression. Specifically, incompletely resected supratentorial pLGGs with disease progression showed significantly higher miR-1248 combined with lower miR-376a-3p and miR-888-5p levels than tumours without progression. A significant (p < 0.001) prognostic performance for miR-1248 was reported with an area under the curve (AUC) of 1.00. We also highlighted a critical oncogenic role for miR-1248 in gliomas tumours. Indeed, high miR-1248 levels maintain low its validated target genes (CDKN1A (p21)/FRK/SPOP/VHL/MTAP) and consequently sustain the activation of oncogenic pathways.ConclusionsAltogether, we provide a novel molecular biomarker able to successfully identify pLGG patients associated with disease progression that could support the clinicians in the decision-making strategy, advancing personalized medicine.

MiR-1248 a New Biomarker for Progression Risk Stratification of Incompletely Resected Supratentorial Hemispheric Pediatric Low-Grade Gliomas

MiR-1248 a New Biomarker for Progression Risk Stratification of Incompletely Resected Supratentorial Hemispheric Pediatric Low-Grade Gliomas

LGG-36. DESMOPLASTIC INFANTILE GANGLIOGLIOMA (DIG) WITH A PPP1CB-ALK FUSION IN A 6-YEAR-OLD GIRL

Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are benign glioneuronal tumors that typically occur in infants, involve the superficial cerebral cortex, and have an excellent prognosis. DIA/DIG are a distinct molecular entity based on DNA methylation profiling. BRAF600 mutations are frequently reported in DIG/DIA. A recent comprehensive genetic analysis of infantile hemispheric gliomas identified 2 unique groups: group 1 harbored alterations in the receptor tyrosine kinase (RTK) genes ALK, ROS1, NTRK, and MET and group 2 harbored alterations in the RAS/MAPK pathway. We report a case of a 6.5-year-old girl who presented with seizures and right homonymous hemianopia. MRI of her brain demonstrated a large cystic/solid left hemispheric mass with remodelling of the overlying skull, consistent with a long-standing process. She underwent a gross total resection (GTR) and pathology demonstrated a DIG with a PPP1CB-ALK gene fusion (exon 5 to exon 20) identified by RNA sequencing. She remains disease free 12 months following GTR. A literature review identified 4 reported cases of pediatric brain tumors with PPP1CB-ALK gene fusions including: a 3-month-old with a hemispheric high-grade glioma which recurred 4 years later and pathology showed mature ganglioglioma, with both tumors showing the identical PPP1CB-ALK gene fusion; a 10-month-old infant with a hemispheric low-grade glioma; an infant with a “congenital” hemispheric high-grade glioma; and a child with an astrocytoma with no further clinical data. PPP1CB-ALK gene fusion appears to be a rare oncogenic driver in gliomas of infancy, including DIG.

LGG-46. MOLECULAR CHARACTERIZATION OF HEMISPHERIC LOW-GRADE GLIOMAS IN CHILDREN

BACKGROUNDHeterogeneous pathology in hemispheric low-grade gliomas (hemLGG) stress the importance of molecular testing in terms of prognosis prediction and targeted therapy options.METHODSDemographic data was collected and targeted genomic approach was employed in the single institutional study. RT-PCR was used to screen for KIAA1549-BRAF fusion and FGFR1 tyrosine-kinase domain duplication (FGFR1-ITD). Direct sequencing evaluated point mutations (BRAF ex15 and ex11, FGFR1 ex12 and ex14). Samples with no detected alteration were subjected to panel RNA-sequencing (FusionPlex Archer Diagnostics).RESULTSWithin 2000–2019 were diagnosed 76 patients with hemLGG (median age 11.1y, range 0.0y–18.5y) comprising predominantly of ganglioglioma, dysembryoplastic neuroepithelial tumors, and diffuse astrocytoma. 40 % of hemLGG were characterized by BRAF alterations with over 2/3 of those cases harboring BRAF point mutations (two BRAFex11, 12 BRAFV600E). Notably, BRAF fusions were uncommon and detected only in six patients (two KIAA-BRAF fusion, two minor oncogenic BRAF variants, two non-KIAA BRAF fusion). 25 % of alterations were found in genes for receptor tyrosine kinases, consisting of seven patients with FGFR1-ITD, three FGFR2/3 fusions, two FGFR1 mutations, two ALK fusions, and one ROS fusion. Out of MAP kinase pathway, the most frequent alteration was IDH1 mutations (n=9). Two angiocentric gliomas were characterized by MYB-QKI fusion.CONCLUSIONTargeted sequencing combined with RNA-sequencing is feasible to establish molecular diagnosis in majority of cases and reveal new and rare alterations. Significant prevalence of non-BRAF alterations explains heterogeneity among hemLGG.

Advanced MR imaging in hemispheric low-grade gliomas before surgery; the indications and limits in the pediatric age.

Advanced magnetic resonance imaging (MRI) techniques is an umbrella term that includes diffusion (DWI) and diffusion tensor (DTI), perfusion (PWI), spectroscopy (MRS), and functional (fMRI) imaging. These advanced modalities have improved the imaging of brain tumors and provided valuable additional information for treatment planning. Despite abundant literature on advanced MRI techniques in adult brain tumors, few reports exist for pediatric brain ones, potentially because of technical challenges. The authors review techniques and clinical applications of DWI, PWI, MRS, and fMRI, in the setting of pediatric hemispheric low-grade gliomas. The authors propose their personal experience to highlight benefits and limits of advanced MR imaging in diagnosis, grading, and presurgical planning of pediatric hemispheric low-grade gliomas. Advanced techniques should be used as complementary tools to conventional MRI, and in theory, the combined use of the three techniques should ensure achieving the best results in the diagnosis of hemispheric low-grade glioma and in presurgical planning to maximize tumor resection and preserve brain function. In the setting of pediatric neurooncology, these techniques can be used to distinguish low-grade from high-grade tumor. However, these methods have to be applied on a large scale to understand their real potential and clinical relapse, and further technical development is required to reduce the excessive scan times and other technical limitations.

Neurosurgical tools to extend tumor resection in hemispheric low-grade gliomas: conventional and contrast enhanced ultrasonography.

Pediatric low-grade gliomas (LGGs) are the most frequent solid tumor in childhood. Based on an increasing number of literature reports, maximal safe resection is recommended as the first line of treatment whenever possible. However, distinguishing tumor tissue from the surrounding normal brain is often challenging with infiltrating neoplasms, even with the assistance of intraoperative, microscopic and conventional neuronavigation systems. Therefore, any technique that enhances the detection and visualization of LGGs intraoperatively is certainly desirable. In this paper, we reviewed the role of intraoperative conventional ultrasound and contrast-enhanced ultrasound (CEUS) as a tool for extending tumor resection in LGGs. Moreover, our experience with this technology is reported and discussed. Both B-mode and CEUS are helpful in highlighting LGGs, detecting tumor margins and providing additional information such as vascularization, thus improving the safety of a more radical resection. Although the full potentialities of the method are yet to be explored, intraoperative ultrasound is a promising tool in oncologic surgery and LGG surgery.

An integrative molecular and genomic analysis of pediatric hemispheric low-grade gliomas: an update.

Hemispheric low-grade gliomas account for the second most common location in pediatric low-grade gliomas (PLGGs) after the cerebellum. The pathological spectrum includes gangliogliomas, dysembryoplastic neuroepithelial tumors (DNETs), diffuse astrocytomas, pilocytic astrocytomas, and pleomorphic xanthoastrocytomas (PXAs), among others. Clinically, hemispheric PLGGs represent a well-recognized cause of intractable epilepsy in children and adolescents. With an excellent long-term outcome, surgery remains the cornerstone and patients with gross total resection typically do not need any further therapies. The recent literature about hemispheric PLGGs was reviewed to provide an up-to-date overview of the molecular and cell biology of these tumors. Hemispheric PLGGs can harbor multiple alterations involving BRAFV600E, FGFR, NTRK, MYB/MYBL1, IDH, and BRAF-KIAA1549 fusions. However, the clinical significance of most of these alterations is still to be defined. The role of RAS/MAPK mutations and other alterations in hemispheric PLGGs is of interest from diagnostic, prognostic, and therapeutic perspectives. Molecular testing for these tumors should be encouraged, since the findings can have an important impact not only in prognosis but also in therapeutic strategies.

PET and SPECT studies in children with hemispheric low-grade gliomas

Molecular imaging is playing an increasing role in the pretreatment evaluation of low-grade gliomas. While glucose positron emission tomography (PET) can be helpful to differentiate low-grade from high-grade tumors, PET imaging with amino acid radiotracers has several advantages, such as better differentiation between tumors and non-tumorous lesions, optimized biopsy targeting, and improved detection of tumor recurrence. This review provides a brief overview of single-photon emission computed tomography (SPECT) studies followed by a more detailed review of the clinical applications of glucose and amino acid PET imaging in low-grade hemispheric gliomas. We discuss key differences in the performance of the most commonly utilized PET radiotracers and highlight the advantage of PET/MRI fusion to obtain optimal information about tumor extent, heterogeneity, and metabolism. Recent data also suggest that simultaneous acquisition of PET/MR images and the combination of advanced MRI techniques with quantitative PET can further improve the pretreatment and post-treatment evaluation of pediatric brain tumors.

Conventional chemotherapy and perspectives for molecular-based oncological treatment in pediatric hemispheric low-grade gliomas

Pediatric low-grade gliomas (PLGG) are the most common primary central nervous system tumor in children. Patients in whom gross total resection can be achieved have an excellent overall (OS) and event-free survival (EFS) and do not require adjuvant therapy. However, children with unresectable tumors often experience multiple progressions and require additional treatment. Radiotherapy results in long-term tumor control, but it is associated with significant toxicity, making chemotherapy the preferred therapeutic option. Several chemotherapy combinations have been found to be successful in PLGG, but 5-year EFS has been below 60% with most of them. Recent molecular advances have led to a better understanding of the molecular pathways involved in the biology of LGG, allowing the development of promising tumor-specific, molecularly targeted therapies.

Awake surgery for hemispheric low-grade gliomas: oncological, functional and methodological differences between pediatric and adult populations.

Brain mapping through a direct cortical and subcortical electrical stimulation during an awake craniotomy has gained an increasing popularity as a powerful tool to prevent neurological deficit while increasing extent of resection of hemispheric diffuse low-grade gliomas in adults. However, few case reports or very limited series of awake surgery in children are currently available in the literature. In this paper, we review the oncological and functional differences between pediatric and adult populations, and the methodological specificities that may limit the use of awake mapping in pediatric low-grade glioma surgery. This could be explained by the fact that pediatric low-grade gliomas have a different epidemiology and biologic behavior in comparison to adults, with pilocytic astrocytomas (WHO grade I glioma) as the most frequent histotype, and with WHO grade II gliomas less prone to anaplastic transformation than their adult counterparts. In addition, aside from the issue of poor collaboration of younger children under 10years of age, some anatomical and functional peculiarities of children developing brain (cortical and subcortical myelination, maturation of neural networks and of specialized cortical areas) can influence direct electrical stimulation methodology and sensitivity, limiting its use in children. Therefore, even though awake procedure with cortical and axonal stimulation mapping can be adapted in a specific subgroup of children with a diffuse glioma from the age of 10years, only few pediatric patients are nonetheless candidates for awake brain surgery.

The Value of Pre- and Intraoperative Adjuncts on the Extent of Resection of Hemispheric Low-Grade Gliomas: A Retrospective Analysis.

To achieve maximal resection with minimal risk of postoperative neurologic morbidity, different neurosurgical adjuncts are being used during low-grade glioma (LGG) surgery. To investigate the effect of pre- and intraoperative adjuncts on the extent of resection (EOR) of hemispheric LGGs. Medical records were reviewed to identify patients of any sex, ≥ 18 years of age, who underwent LGG surgery at X Hospital between January 2005 and July 2013. Patients were divided into eight subgroups based on the use of various combinations of a neuronavigation system alone (NN), functional MRI-diffusion tensor imaging (fMRI-DTI) guided neuronavigation (FD), intraoperative MRI (MR), and direct electrical stimulation (DES). Initial and residual tumors were measured, and mean EOR was compared between groups. Of all 128 patients, gross total resection was achieved in 23.4%. Overall mean EOR was 81.3% ± 20.5%. Using DES in combination with fMRI-DTI (mean EOR: 86.7% ± 12.4%) on eloquent tumors improved mean EOR significantly after adjustment for potential confounders when compared with NN alone (mean EOR: 76.4% ± 25.5%; p = 0.001). Using DES in combination with fMRI and DTI significantly improves EOR when LGGs are located in eloquent areas compared with craniotomies in which only NN was used.

The assessment of prognostic factors in surgical treatment of low-grade gliomas: A prospective study

ObjectiveA prospective volumetric analysis of extent of resection (EOR) was carried out to assess surgical outcomes in adults diagnosed with hemispheric low grade gliomas (LGGs). Materials and methods68 consecutive patients diagnosed with LGGs were enrolled in the study. Pre- and post-operative tumor volumes and EOR were measured based on FLAIR MRI. Dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC MRI) was used for the assessment of relative cerebral blood volume (rCBV). Three outcome measures were assessed: overall survival (OS), progression-free survival (PFS), and malignant degeneration-free survival (MFS). ResultsIn 6 (9%) patients permanent neurologic deficits were observed. No statistically significant dependence between the EOR and the occurrence of permanent deficits was found. The eloquent or close to the eloquent location was statistically connected with lower EOR (p=0.023). The preoperative volume of tumors treated with gross total resection was significantly smaller than the volume of tumors in subtotal or partial resection groups (p=0.020, p<0.001, respectively). OS was predicted by age at diagnosis (p=0.032), and rCBV (p=0.002). Progression and malignant transformation occurred in 22 (32%) and 11 (16%) out of 68 patients. PFS was predicted by preoperative tumor volume (p=0.005), postoperative tumor volume (p=0.008), the EOR (p=0.001), and by the rCBV (p=0.033). MFS was predicted by preoperative tumor volume (p=0.034), the EOR (pp=0.020), and by rCBV (p=0.022). Postoperative tumor volume was associated with a trend of improved MFS (p=0.072). The univariate analysis shows the statistical trend for the relationship between histological subtype and PFS and MFS (p=0.079, p=0.078, respectively). Multivariate analysis selected preoperative tumor volume and rCBV as independently associated with PFS (p=0.009, p=0.019, respectively) and MFS (p=0.023, p=0.035, respectively). EOR was associated with a trend of improved PFS, and MFS (p=0.069, p=0.094, respectively). ConclusionsTumor resection of LGG with the use of intraoperative monitoring and neuronavigation is associated with a low risk of new permanent deficits, but EOR significantly decreases with the size of the tumor and/or its location in/close to the eloquent areas. Smaller preoperative tumor volume and greater EOR are significantly associated with longer OS, PFS and MFS. Preoperative rCBV is one of the important prognostic factors significantly connected with survival. Prognosis in LGGs is still under discussion. Other factors such as age, histopathological subtype and KPS should not be underestimated.

Sparing of the hippocampus, limbic circuit and neural stem cell compartment during partial brain radiotherapy for glioma: A dosimetric feasibility study

The aim of this study was to assess the feasibility of sparing contralateral or bilateral neural stem cell (NSC) compartment, hippocampus and limbic circuit during partial brain radiotherapy (PBRT). Treatment plans were generated for five hemispheric high-grade gliomas, five hemispheric low-grade gliomas and two brainstem gliomas (12 patients). For each, standard intensity-modulated radiotherapy (IMRT) plans were generated, as well as IMRT plans which spared contralateral (hemispheric cases) or bilateral (brainstem cases) limbic circuit, hippocampus, and NSC. Biologically equivalent dose for late effects (BED(late effects)) was generated for limbic circuit, hippocampus and NSC. Per cent relative reduction in mean physical dose and BED was calculated for each plan (standard vs. sparing). We were able to reduce physical dose and BED(late effects) to these critical structures by 23.5-56.8% and 23.6-66%, respectively. It is possible to spare contralateral limbic circuit, NSC and hippocampus during PBRT for both high- and low-grade gliomas using IMRT, and to spare the hippocampus bilaterally during PBRT for brainstem low-grade gliomas. This approach may reduce late cognitive sequelae of cranial radiotherapy.

Recurrence and malignant degeneration after resection of adult hemispheric low-grade gliomas

Unlike their malignant counterparts, low-grade gliomas are associated with prolonged survival. However, these tumors have a propensity to progress after resection and ultimately undergo malignant degeneration. The factors associated with recurrence and malignant degeneration remain relatively unknown. The authors set out to determine factors that were independently associated with recurrence and malignant degeneration in patients who underwent resection of a hemispheric low-grade glioma. Adult patients who underwent craniotomy and resection of a hemispheric low-grade glioma (WHO Grade II) at the Johns Hopkins Medical Institution's academic tertiary-care institution between 1996 and 2006 were retrospectively reviewed. Multivariate proportional hazards regression analyses were used to identify associations with tumor recurrence and malignant degeneration. Of the 191 consecutive patients with low-grade gliomas in this series (89 fibrillary astrocytomas, 89 oligodendrogliomas, and 13 mixed gliomas), 83 (43%) and 44 (23%) experienced tumor recurrence and malignant degeneration at last follow-up, respectively. The 5-year progression-free and malignancy-free survival rates were 44 and 74%, respectively. Independent predictors of recurrence were duration of longest lasting symptom (relative risk [RR] 0.978, 95% CI 0.954-0.996, p = 0.01), tumor size (RR 1.328, 95% CI 1.109-1.602, p = 0.002), and preoperative contrast enhancement (RR 2.558, 95% CI 1.241-5.021, p = 0.01). Independent factors associated with malignant degeneration were fibrillary astrocytoma pathology (RR 1.800, 95% CI 1.008-4.928, p = 0.04), tumor size (RR 1.086, 95% CI 1.044-1.358, p = 0.04), and gross-total resection (RR 0.526, 95% CI 0.221-1.007, p = 0.05). The identification and consideration of factors associated with recurrence and malignant progression may help guide treatment strategies aimed at delaying recurrence and preventing malignant degeneration for patients with hemispheric low-grade gliomas.

Prognostic significance of contrast-enhancing low-grade gliomas in adults and a review of the literature

Objectives: Survival and tumor recurrence for patients with low-grade gliomas is heterogeneous, with reported survival and recurrence times varying by several months to years. The prognostic implications of a contrast-enhancing low-grade glioma remain less well understood.Methods: We retrospectively reviewed all adult patients who underwent a craniotomy for a hemispheric low-grade glioma (WHO grade II) from 1996 to 2006 at a single institution. Multivariate proportional hazards regression analysis was used to identify independent associations with survival, recurrence and malignant degeneration. Furthermore, a review of the literature for all works on low-grade gliomas and contrast enhancement was conducted.Results: One hundred eighty-nine patients (87 fibrillary astrocytomas, 89 oligodendrogliomas and 13 mixed gliomas) were available for analysis, with 64 (34%) and 125 (66%) contrast-enhancing and non-enhancing tumors, respectively. There were no significant differences in clinical and treatment-related variables between patients with and without contrast enhancement. After multivariate analysis, contrast enhancement was independently associated with decreased survival (p=0.006) and increased recurrence (p=0.04) and trended toward significance with malignant degeneration (p=0.15). Five-year overall survival, progression-free survival and malignancy-free survival rates for patients with enhancement versus patients without enhancement were 70 versus 85% (p=0.002), 32 versus 49% (p=0.008) and 74 versus 90% (p=0.002), respectively. The review of the literature identified 14 works that fit our criteria. The majority of these published works had design-related limitations including small population size as well as the inclusion of non-WHO grade II gliomas, pediatric patients and patient undergoing biopsy.Discussion: This study may provide insights into risk stratifying patients with low-grade gliomas and most specifically those that contrast enhance.

Preoperative prognostic classification system for hemispheric low-grade gliomas in adults

Hemispheric low-grade gliomas (LGGs) have an unpredictable progression and overall survival (OS) profile. As a result, the objective in the present study was to design a preoperative scoring system to prognosticate long-term outcomes in patients with LGGs. The authors conducted a retrospective review with long-term follow-up of 281 adults harboring hemispheric LGGs (World Health Organization Grade II lesions). Clinical and radiographic data were collected and analyzed to identify preoperative predictors of OS, progression-free survival (PFS), and extent of resection (EOR). These variables were used to devise a prognostic scoring system. The 5-year estimated survival probability was 0.86. Multivariate Cox proportional hazards modeling demonstrated that 4 factors were associated with lower OS: presumed eloquent location (hazard ratio [HR] 4.12, 95% confidence interval [CI] 1.71-10.42), Karnofsky Performance Scale score < or = 80 (HR 3.53, 95% CI 1.56-8.00), patient age > 50 years (HR 1.96, 95% CI 1.47-3.77), and tumor diameter > 4 cm (HR 3.43, 95% CI 1.43-8.06). A scoring system calculated from the sum of these factors (range 0-4) demonstrated risk stratification across study groups, with the following 5-year cumulative survival estimates: Scores 0-1, OS = 0.97, PFS = 0.76; Score 2, OS = 0.81, PFS = 0.49; and Scores 3-4, OS = 0.56, PFS = 0.18 (p < 0.001 for both OS and PFS, log-rank test). This proposed scoring system demonstrated a high degree of interscorer reliability (kappa = 0.86). Four illustrative cases are described. The authors propose a simple and reliable scoring system that can be used to preoperatively prognosticate the degree of lesion resectability, PFS, and OS in patients with LGGs. The application of a standardized scoring system for LGGs should improve clinical decision-making and allow physicians to reliably predict patient outcome at the time of the original imaging-based diagnosis.

Factors Associated with Recurrence and Malignant Degeneration after Surgical Resection of a Hemispheric Low-grade Glioma

Factors Associated with Recurrence and Malignant Degeneration after Surgical Resection of a Hemispheric Low-grade Glioma

Preoperative System Characterizes Hemispheric Low-Grade Gliomas

Preoperative System Characterizes Hemispheric Low-Grade Gliomas

745 Contribution of Intraoperative Corticosubcortical Stimulations in Surgery of Low-grade Gliomas: A Comparative Study between Two Series without and with Functional Mapping

INTRODUCTION: Despite a growing use of intraoperative functional mapping in surgery of supratentorial hemispheric low-grade gliomas (LGGs), very few comparative studies of patients operated on without and with direct cortical and subcortical electrical stimulations (DES) in the same institution were reported in the literature. Here, we compare the rate of LGG surgeries performed in eloquent areas, the rate of postoperative sequelae, and the quality of resection during two consecutive periods in the same department: the first one without the use of intraoperative electrophysiology, the second one with DES. METHODS: From 1985 to 1996, 100 patients harboring a supratentorial LGG underwent surgery with no functional mapping (S1). From 1996 to 2003, 122 patients were operated on in the same department for a supratentorial hemispheric LGG using intraoperative corticosubcortical DES (S2). RESULTS: Comparison between the two series showed that 35% of LGG were operated on in eloquent areas (S1) versus 62% (S2) (P < 0.0001), with 17% of severe permanent deficits (S1) versus 6.5% (S2) (P < 0.019). On control magnetic resonance imaging, 37% of resections were subtotal and 6% total (S1), versus respectively 50.8% and 25.4% (S2) (P < 0.001). CONCLUSION: Our results allow for the first time a quantification of the contribution of intraoperative cortico-subcortical DES during LGG resection. Indeed, the use of this method leads to 1) the extension of indications of LGG surgeries within eloquent areas, 2) a decrease of the risk of sequelae, and 3) an increase of the quality of tumor resection.

The impact of technical adjuncts in the surgical management of cerebral hemispheric low-grade gliomas of childhood.

Pediatric brain tumors occur with a frequency of 24 to 27 cases/year within a cohort of 1 million children. Nearly 25% of these lesions will involve the cerebral hemisphere, with the low-grade glioma representing the most common group of tumors in this location. Pilocytic and fibrillary astrocytomas are the most frequently encountered glioma, although other variants, such as the ganglioglioma, pleomorphic xanthoastrocytoma, astroblastoma, ependymoma, and oligodendroglioma, must also be considered in the differential diagnosis. The etiology of these tumors remains obscure, although may be linked to therapeutic radiotherapy, previous history of hematopoietic malignancy and maternal exposure to nitrosamine-laden foods. An associated link to a phakomatosis, e.g., neurofibromatosis, tuberous sclerosis, has also been documented to exist with astrocytomas, in particular. The goals of surgery include a complete removal, in most circumstances, with an attempt to alleviate an associated seizure disorder when intractable. This is possible in nearly every type of hemispheric glioma with the aid of intraoperative navigational systems, i.e., frameless stereotaxy, neurophysiological based stimulation mapping, and electrocorticography. In the setting where a complete removal is possible, no further therapy is warranted. For those lesions that are incompletely resected, conservative management with routine diagnostic imaging follow-up is appropriate. Reoperation is necessary if recurrence is documented and radiotherapy is utilized for those lesions that are incompletely resected following recurrence.