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The insular gliomas were classified based on their locations and extensions to the adjacent areas. The insular and orbitofrontal cortices with underlying fiber tracts were studied on ten (20 sides) human cadaveric brains and two heads. Twenty patients with insular gliomas with the orbitofrontal or septal region extensions were studied on preoperative magnetic resonance imaging (MRI). Insular gliomas can extend to the orbitofrontal area dorsolaterally and/or ventromedially through the subdivision of the uncinate fasciculus. The dorsolateral part of the uncinate fasciculus interconnects the temporopolar area to the lateral orbitofrontal cortex through insula, and the ventromedial part of the uncinate fasciculus interconnects the temporopolar area to the medial orbital cortex, gyrus rectus, and septal region. The gyrus rectus infiltration on MRI indicates a ventromedial involvement by passing through the ventromedial part of the uncinate fasciculus. Diffusion tensor imaging (DTI) MRI demonstration of the UF is difficult due to the interruption of the fiber tracts by tumor. Tumor infiltration extending to the gyrus rectus requires a 15° lateral tilting with vertex toward contralateral side, as well as 70° head rotation to the contralateral side of lesion, for exposure of frontal base, septal region, and lateral border of the anterior perforating substance at the same time with the exposure of whole sylvian fissure via transsylvian approach of the insular tumors. An understanding of the orbitofrontal extension of the insular tumor based on the subdivisions of UF is useful in preoperative surgical planning and can assist for gross total resection., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Cell culture plays a pivotal role in cancer research. However, culture-induced changes in biological properties of tumor cells profoundly affect research reproducibility and translational potential. Establishing culture conditions tailored to the cancer cell of origin could resolve this problem. For glioma research, it has been previously shown that replacing serum with defined growth factors for neural stem cells (NSCs) greatly improved the retention of gene expression profile and tumorigenicity. However, among all molecular subtypes of glioma, our laboratory and others have previously shown that the oligodendrocyte precursor cell (OPC) rather than the NSC serves as the cell of origin for the proneural subtype, raising questions regarding the suitability of NSC-tailored media for culturing proneural glioma cells., Methods: OPC-originated mouse glioma cells were cultured in conditions for normal OPCs or NSCs, respectively, for multiple passages. Gene expression profiles, morphologies, tumorigenicity, and drug responsiveness of cultured cells were examined in comparison with freshly isolated tumor cells., Results: OPC media-cultured glioma cells maintained tumorigenicity, gene expression profiles, and morphologies similar to freshly isolated tumor cells. In contrast, NSC-media cultured glioma cells gradually lost their OPC features and most tumor-initiating ability and acquired heightened sensitivity to temozolomide., Conclusions: To improve experimental reproducibility and translational potential of glioma research, it is important to identify the cell of origin, and subsequently apply this knowledge to establish culture conditions that allow the retention of native properties of tumor cells., (© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Maximal safe resection is associated with prolonged survival in patients with low-grade glioma (LGG). It has been suggested that neoadjuvant temozolomide may provide sufficient tumor shrinkage to facilitate aggressive surgical debulking. We examined the impact of temozolomide upon volume reduction and resectability of LGG. We retrospectively identified 20 adult patients with biopsy-proven, deemed not totally resectable LGGs, treated initially with temozolomide. Volumetric 3D (calculated from serial FLAIR images) and 2D tumor measurements were obtained prior to treatment and at 3 months post-treatment. The anticipated extent of resection (EOR) at the 2 time points was measured based on anatomical limitations, calculated as: [(total tumor volume - unresectable tumor volume)/total tumor volume] ×100. Eloquent cortex, deep structures and corpus callosum were considered unresectable. Mean tumor volume was 68.4 cm(3) pre-treatment and 49.5 cm(3) at 3 months post-treatment. The mean change from baseline to 3 months after treatment was -32.5 % (p < 0.001). Mean 2D pre-treatment area was 28.6 and 23.3 cm(2) at 3 months post-treatment. The 2D change was also significant, with mean change of -17% (p < 0.001). 5% had partial response; 40% minor response; 45% stable disease; and 10% progressive disease by RANO criteria. Mean pre-treatment anticipated EOR was 67.2 and 71.5% at 3 months post-treatment. The mean change from baseline was 4.3% (p = 0.10). Our findings demonstrate significant volumetric and 2D reduction of LGG with temozolomide. Although this tumor shrinkage might facilitate radical surgical resection in some cases, our data failed to show statistically significant improvement in anticipated EOR.

Introduction: Gliomas remain difficult to treat, in part, due to our inability to accurately delineate the margins of the tumor. The goal of our study was to evaluate if a combination of advanced MR imaging techniques and a multimodal imaging model could be used to predict tumor infiltration in patients with diffuse gliomas., Methods: Institutional review board approval and written consent were obtained. This prospective pilot study enrolled patients undergoing stereotactic biopsy for a suspected de novo glioma. Stereotactic biopsy coordinates were coregistered with multiple standard and advanced neuroimaging sequences in 10 patients. Objective imaging values were assigned to the biopsy sites for each of the imaging sequences. A principal component analysis was performed to reduce the dimensionality of the imaging dataset without losing important information. A univariate analysis was performed to identify the statistically relevant principal components. Finally, a multivariate analysis was used to build the final model describing nuclear density., Results: A univariate analysis identified three principal components as being linearly associated with the observed nuclear density (p values 0.021, 0.016, and 0.046, respectively). These three principal component composite scores are predominantly comprised of DTI (mean diffusivity or average diffusion coefficient and fractional anisotropy) and PWI data (rMTT, Ktrans). The p value of the model was <0.001. The correlation between the predicted and observed nuclear density was 0.75., Conclusion: A multi-input, single output imaging model may predict the extent of glioma invasion with significant correlation with histopathology.

Object: Seizures occur in approximately 80% of patients with low-grade gliomas (LGGs). The majority of patients are treated with anticonvulsant monotherapy; however, many patients require multidrug therapy, or their seizures are refractory to antiepileptic drugs altogether. The oral alkylating agent temozolomide has emerged as a potential initial treatment option for LGG. A few reports suggest an association between temozolomide and reduced seizure frequency in patients with intractable epilepsy., Methods: Using their clinical database, the authors identified adult patients whose LGGs were treated using temozolomide as the initial antineoplastic therapy at the University of Virginia Health System. As a control group, the authors assessed patients whose LGGs were under observation. All patients had seizure disorders that were treated with anticonvulsants. Seizure frequency in patients with intractable epilepsy was analyzed before and after treatment with temozolomide. Age at diagnosis, sex, antiepileptic drugs, pathological subtype, surgical treatment, and follow-up until progression were also assessed. Interval seizure frequency was meticulously analyzed at each neurooncology clinic visit. A meaningful difference in seizures was defined as a reduction in seizure frequency of greater than 50% per month., Results: Thirty-nine patients were identified in the temozolomide cohort and 30 patients in the control cohort. The median age at diagnosis was 46 years for the former cohort and 41.5 years for the latter. The median length of follow-up was 39 months for the temozolomide group and 37 months for the control group. There was a significant difference in reduced seizure frequency between patients receiving temozolomide (59%) and those who did not receive temozolomide (13%, p < 0.001). Seven patients (18%) in the temozolomide group displayed this improvement independent of antiepileptic drug adjustment compared with no patient in the control group (p < 0.001)., Conclusions: The authors' data suggest that a subset of patients with LGGs experience improvement in seizure frequency during treatment with temozolomide independent of antiepileptic drug adjustment. This decrease in seizure frequency appears independent of the natural history of seizures in patients whose tumors are under observation. Consequently, seizures in patients with LGGs may be better controlled with the combination of AEDs and temozolomide.

Low-grade gliomas (LGG) are increasingly being diagnosed in older patients (>or=60 years). The rising incidence is incompletely understood but demands an analysis of the natural history and prognostic factors to determine if there are differences compared to younger populations. We retrospectively review a consecutive series of 20 older patients who presented between 1991 and 2004 with LGG to characterize the presentation, management, outcomes, and prognostic factors in older patients with LGG. Median follow-up was 27.3 months. Thirty-five percent of patients harboured oligodendrogliomas. Patients presented in equal numbers with seizure, focal neurological deficit, and mental status change. Median overall survival (OS) was 27.3 months. Patients who survive beyond 2 years experience prolonged periods of progression-free survival. Younger age, seizure presentation, and radiation treatment were prognostic of OS on multivariate analysis. Similarities with previous reports of LGG suggest that age should not affect the management of LGG patients. Prospective studies of older patients with LGG are needed to further characterize the optimum management of these patients.

The benefits of surgery for the management of low-grade gliomas have been difficult to determine from the literature. This difficulty might be explained by the inconsistency of the published data, and also by advances in both neuroimaging and neurosurgical techniques, which have made surgical intervention a safer and more viable option than it has been in the past, making the earlier studies less applicable to modern care. In this article, we critically analyze the utility of surgery in the management of low-grade gliomas, including the value of observation without surgical intervention, the relative risks and benefits of biopsy versus craniotomy and resection, and recent advances that have made surgery safer and gross total resection a more realistic proposition. As we will discuss, the literature provides modest evidence that surgery leads to improved outcomes through a reduction in tumor burden. As a result of advances in surgical techniques, the time might now be right to effectively and accurately assess the influence of aggressive surgical resection on the prognosis of low-grade gliomas.

Advances in the fields of molecular and translational research, oncology, and surgery have emboldened the medical community to believe that intrinsic brain tumors may be treatable. Intraoperative imaging and brain mapping allow operations adjacent to eloquent cortex and more radical resection of tumors with increased confidence and safety. Despite these advances, the infiltrating edge of a neoplasm and distant microscopic satellite lesions will never be amendable to a surgical cure. Indeed, it is continued research into the delivery of an efficacious chemobiologic agent that will eventually allows us to manage this primary cause of treatment failure.

Protracted low dose temozolomide (75 mg/m(2)/day on days 1-21 of 28 days) offers potential advantages over standard temozolomide schedules (200 mg/m(2)/day on days 1-5 of 28 days) including greater cumulative drug exposure and depletion of O(6)-alkylguanine DNA alkyltransferase levels, theoretically overcoming intrinsic chemoresistance. We retrospectively review our experience in 25 patients with pathologically proven low grade gliomas (LGG) treated with protracted low dose temozolomide to primarily quantify its toxicity and secondarily to assess efficacy. None had previously received radiation. Tumor response was graded based on changes in tumor size, steroid requirements, and clinical exam. About 243 cycles of protracted low dose temozolomide were administered. Three patients (12%) were changed to standard temozolomide dosing due to side effects, including intractable nausea (n = 2) and multiple cytopenias (n = 1). The most frequent toxicities were fatigue (76%), lymphopenia (72% [48% high grade]), constipation (56%), and nausea (52%). High grade toxicities (other than lymphopenia) included secondary malignancy, pruritus, hyponatremia, neutropenia, leukopenia, and cognitive decline (n = 1 for each). Tumor response rate was 52% and and disease control rate was 84%. Six month PFS was 92% and 12 month PFS was 72%. Response rates and PFS were independent of pathological subtype, deletion status, and indication for chemotherapy. Protracted low dose temozolomide has a distinct spectrum of toxicities compared to standard dosing but is well tolerated in most patients and may provide improved response rates compared to standard dosing. The results of larger randomized trials are needed to assess its potential advantages over other management schemes.

Gliomas are the most common primary brain tumor in adults, and those within or relating to the ventricular surface represent a less common but important subcategory. The most common intraventricular gliomas include ependymomas, SEs, and SEGAs. Other less common varieties have been reported, including chordoid gliomas, glioblastoma multiforme, and mixed glial-neuronal tumors. Each type of intraventricular glioma is associated with its own unique constellation of epidemiologic, clinical, radiologic, and pathologic defining characteristics. Each tumor type has its own management considerations and nuances with unique prognostic indicators and outcomes. The outcome for certain intraventricular gliomas (especially ependymomas) remains relatively poor. Future advancements in surgical technique are likely to have only a modest impact on improvement of outcome. Translational research aiming to advance the knowledge of tumor biology into new targeted cellular and molecular therapies holds tremendous promise to improve the overall outcome. Additionally, more thorough delineation of prognostic factors as well as modifications and refinements to radiation and chemotherapy may help to improve the still significantly poor outcomes for patients harboring these lesions. Future cooperative intra- and interinstitutional efforts between scientists and clinicians will hopefully culminate in an improved outlook and eventual cure for patients with gliomas.

The surgical neuro-oncology literature testifies to the longstanding argument about the benefits (or lack thereof) of aggressive debulking of high-grade gliomas. Publications from the last decade addressing this question will be reviewed. The absence of randomized clinical trials and paucity of prospectively collected information continue to leave this issue unresolved, although most evidence continues to support a modest benefit of debulking over biopsy.

Primary spinal cord astrocytomas are rare, fatal, and poorly studied. This study included a 2-center, retrospective analysis of primary spinal cord astrocytoma patients from 1997 to 2020. Patients with drop metastases or without at least one follow-up were excluded. Seven World Health Organization grade I, 6 grade II, 7 grade III, and 4 grade IV astrocytoma patients were included. Older patients had higher grades (median 20 years in grade I vs. 36.5 in grade IV). The median follow-up was 15 months. Thirteen patients were discharged to rehabilitation. Eight patients demonstrated radiographic progression. Adjuvant therapy was utilized more in higher grades (5 of 13 grades III vs. all 11 grades IIIIV). Six patients died (1 death in grades III vs. 5 in grades IIIIV). Ten patients had worsened symptoms at the last follow-up. The median progression-free survival in grade I, II, III, and IV tumors was 116, 36, 8, and 8.5 months, respectively. The median overall survival in grade I, II, III, and IV tumors was 142, 69, 19, and 12 months, respectively. Thrombotic complications occurred in 2 patients, one with isocitrate dehydrogenasewild type glioblastoma. Outcomes worsen with higher grades and lead to difficult postoperative periods. Clinicians should be vigilant for thromboembolic complications. Further research is needed to understand these rare tumors. [ABSTRACT FROM AUTHOR]