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Background: Irinotecan demonstrates anti-tumor efficacy in preclinical glioma models but clinical results are modest due to drug delivery limitations. Convection enhanced delivery (CED) improves drug delivery by increasing intratumoral drug concentration. Real-time magnetic resonance imaging of infusate delivery during CED may optimize tumor coverage. This phase 1 trial examines the safety and tolerability of liposomal irinotecan and gadolinium delivered via CED using real-time MRI guidance in recurrent high-grade glioma patients., Methods: Initially, a 3 + 3 dose-escalating, single dose trial was planned with 4 cohorts based on a fixed drug dose and volume. After 9 patients, a protocol amendment allowed for variable volume and dose of the study agent based on tumor size. The amended design specified 'personalized' drug volume but fixed concentration of 20 mg/mL of liposomal irinotecan in the first cohort escalating to 40 mg/mL in the second cohort., Results: Eighteen patients with recurrent WHO grade 3 or 4 gliomas (diameter 1-4 cm) were treated. Based on the tumor volume, the total dose of liposomal irinotecan was 20-680 mg in a total volume of 2-17 ml. Technical challenges were overcome by real-time MRI guidance and protocol amendment. The only dose-limiting toxicity (DLT) was a grade 3 stroke. Safety and survival information is presented., Conclusions: CED of liposomal irinotecan using real-time MRI in patients with recurrent high-grade glioma is feasible. Image-guidance allowed for improved placement of CED cannulas and optimal tumor coverage. Our results warrant further study with repeat CED dosing., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Gliomas are the most malignant tumors of the central nervous system. One of the factors in their high drug resistance is avoiding programmed death (PCD) induction. This is related to the overexpression of intracellular survival pathways: PI3K-Akt/PKB-mTOR and Ras-Raf-MEK-ERK. Apoptosis and autophagy are co-existing processes due to the interactions between Bcl-2 and beclin-1 proteins. Their complex may be a molecular "toggle-switch" between PCD types. The aim of this research was to investigate the role of Bcl-2:beclin-1 complex in glioma cell elimination through the combined action of LY294002 and sorafenib., Methods: Drug cytotoxicity was estimated with an MTT test. The type of cell death was evaluated using variant microscopy techniques (fluorochrome staining, immunocytochemistry, and transmission electron microscopy), as well as the Bcl-2:beclin-1 complex formation and protein localization. Molecular analysis of PCD indicators was conducted through immunoblotting, immunoprecipitation, and ELISA testing. SiRNA was used to block Bcl-2 and beclin-1 expression., Results: The results showed the inhibitors used in simultaneous application resulted in Bcl-2:beclin-1 complex formation and apoptosis becoming dominant. This was accompanied by changes in the location of the tested proteins., Conclusions: "Switching" between apoptosis and autophagy using PI3K and Raf inhibitors with Bcl-2:beclin-1 complex formation opens new therapeutic perspectives against gliomas.

Aim: High-grade glial tumors remain as one of the most lethal malignancies. Cyclin D1 is expressed in some human malignancies and is the potential target of intervention. The present study aims to determine the relationship of cyclin D1 expression with other clinicopathological parameters., Materials and Methods: A cross-sectional study was carried out in a tertiary care center. Biopsy proven 66 cases of glial tumor patients were included in the study. The patients with incomplete clinical details were excluded from the study. Immunohistochemistry using antibodies for IDH 1 and cyclin d1 was done in all the cases. Glial tumors were reclassified according to WHO 2016 classification. Data analysis was performed using SPSS 26.0 for the windows., Result: Among 66 patients, 49 (74.3%) were males and 17 (25.7%) were females. The age of the patients ranged from 20 years to 70 years. Overall, 6.02% were of grade I Glial tumors, 22.7% were of grade II Glial tumors, 19.6% patients were of grade III Glial tumors, and 51.6% patients were of grade IV Glial tumors. Of 66 samples tested cyclin D1 was positive in 25 (37.87%) as high expressers and 7 (10.60%) were low expressers. Our study showed a significant correlation between the expression of cyclin D1 with grade and IDH mutation status, No significant correlation of cyclin D1 was noted with age or sex of the patient., Conclusion: Cyclin D1 was associated with a higher grade of the glial tumor. It can be a potential marker both for prognosis and treatment of glial tumors., Competing Interests: None

This chapter provides a comprehensive overview of malignant gliomas, the most common primary brain tumor in adults. These tumors are varied in their cellular origin, genetic profile, and morphology under the microscope, but together they share some of the most dismal prognoses of all neoplasms in the body. Although there is currently no cure for malignant glioma, persistent efforts to improve outcomes in patients with these tumors have led to modest increases in survival, and researchers worldwide continue to strive toward a deeper understanding of the factors that influence glioma development and response to treatment. In addition to well-established epidemiology, clinical manifestations, and common histopathologic and radiologic features of malignant gliomas, this section considers recent advances in molecular biology that have led to a more nuanced understanding of the genetic changes that characterize the different types of malignant glioma, as well as their implications for treatment. Beyond the traditional classification of malignant gliomas based on histopathological features, this chapter incorporates the World Health Organization's 2016 criteria for the classification of brain tumors, with special focus on disease-defining genetic alterations and newly established subcategories of malignant glioma that were previously unidentifiable based on microscopic examination alone. Traditional therapeutic modalities that form the cornerstone of treatment for malignant glioma, such as aggressive surgical resection followed by adjuvant chemotherapy and radiation therapy, and the studies that support their efficacy are reviewed in detail. This provides a foundation for additional discussion of novel therapeutic methods such as immunotherapy and convection-enhanced delivery, as well as new techniques for enhancing extent of resection such as fluorescence-guided surgery., (© 2023. Springer Nature Switzerland AG.)

Objective: To study the effect of TERT mutation on overall and relapse-free survival in patients with IDH -negative diffuse astrocytomas grade III (anaplastic gliomas)., Material and Methods: The study included 45 patients aged 45.5 years. Forty-two patients underwent resection of tumor, other 3 ones - stereotactic biopsy. TERT mutation was identified in 21 patients. External beam radiation therapy was performed in 35 patients (60 Gy), chemotherapy - in 34 patients (mainly temozolomide). Follow-up data were available in 44 patients., Results: Median of overall survival in patients with TERT mutation was 15.3 months, in patients with TERT -negative tumors - 65.1 months. Median of relapse-free survival in patients with TERT-positive anaplastic astrocytoma (AA) was 13.3 months, in patients with TERT -negative glioma - 57.7 months. These differences were not significant. Relapse-free survival was higher in patients with AA and no TERT mutation at all intervals, but especially at early stages (12 and 24 months)., Conclusion: Inclusion of TERT mutation in mandatory examination panel for gliomas in general and, in particular, gliomas grade II/III without IDH mutation can lead to sub-classification of these tumors in the near future. Routine analysis of TERT mutation in these patients will be valuable for correct medical consultation regarding prognosis and adequate adjuvant treatment.

GKNS has a limited role in the management of malignant gliomas. It has little or nothing to offer in primary treatment. However, there is evidence that with recurrent tumors which are 4cm in diameter or less, in younger patients, GKNS used together with bevacizumab can prolong overall survival. Nonetheless, more research is required to determine the precise role of the technique., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Prior reports demonstrate the expression of estrogen and progesterone receptors in high-grade gliomas (HGGs), but the relationship between hormone receptor-positive disease and risk of HHGs in patients with breast cancer (BC) remains uncharacterized., Methods: Using the SEER 18 registries (2000-2017), we examined the temporal trend of the incidence of HGGs and BC. The standardized incidence ratio was calculated to assess the risk of subsequent HGG in BC patients., Results: During the study period, the incidence of BC and HGGs remained comparable for men and women. Among 976,134 patients with BC, we found a decreased incidence of HGGs in females, but not in males. Female BC patients with hormone receptor-positive disease were at a lower risk of developing glioblastoma and anaplastic astrocytoma., Conclusion: Our study findings allude to the protective role of hormone exposure in the development of HGGs, which may lead to the development of therapies targeting hormonal pathways., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Objectives: Most diffuse gliomas are reported to harbor isocitrate dehydrogenase ( IDH ) mutations. However, when these mutations are tested in clinical practice, the results are often negative., Methods: This study examined the frequency of IDH1 and IDH2 mutations in gliomas classified according to the revised 2016 World Health Organization classification, and investigated their prognostic relevance. We tested 87 gliomas for IDH1 and IDH2 mutations using the peptide nucleic acid clamp method., Results: IDH1 mutations were observed in 42% of diffuse astrocytomas, 23% of anaplastic astrocytomas, all oligodendrogliomas and anaplastic oligodendrogliomas, and 17% of glioblastomas. An IDH2 mutation was identified in one case of diffuse astrocytoma. In the survival analysis of diffuse astrocytic tumors, patients with IDH1/2 -wildtype anaplastic astrocytomas tended to have a poor prognosis, similar to that of glioblastomas., Conclusions: IDH2 mutations were infrequent in gliomas. In anaplastic astrocytomas, the frequency of IDH1/2 -wildtype was relatively high, and the prognosis of patients with this type of tumor was very similar to that of those with glioblastomas. It may therefore be necessary to reconsider the classification and treatment strategies for IDH1/2 -wildtype anaplastic astrocytomas.

Despite their low incidence rate globally, high-grade gliomas (HGG) remain a fatal primary brain tumor. The recommended therapy often is incapable of resecting the tumor entirely and exclusively targeting the tumor leads to tumor recurrence and dismal prognosis. Additionally, many HGG patients are not well suited for standard therapy and instead, subjected to a palliative approach. HGG tumors are highly infiltrative and the complex tumor microenvironment as well as high tumor heterogeneity often poses the main challenges towards the standard treatment. Therefore, a one-fit-approach may not be suitable for HGG management. Thus, a multimodal approach of standard therapy with immunotherapy, nanomedicine, repurposing of older drugs, use of phytochemicals, and precision medicine may be more advantageous than a single treatment model. This multimodal approach considers the environmental and genetic factors which could affect the patient's response to therapy, thus improving their outcome. This review discusses the current views and advances in potential HGG therapeutic approaches and, aims to bridge the existing knowledge gap that will assist in overcoming challenges in HGG.

Objective: To evaluate the possibilities of dynamic preoperative 11 C-methionine (MET) PET/CT in differential diagnosis of various types of brain gliomas in adults., Material and Methods: The study included 74 patients aged 48±14 years with supratentorial gliomas: Grade IV - glioblastoma (GB, n =33), Grade III - anaplastic oligodendroglioma (AOD, n =10) and anaplastic astrocytoma (AA, n =12), Grade II - diffuse astrocytoma (DA, n =13) and oligodendroglioma (OD, n =6). All patients underwent standard MRI and dynamic MET PET/CT within 20 minutes after intravenous injection of radiopharmaceutical. Then, we compared MRI and PET/CT data and comprehensively analyzed the early stages of time-activity curve using 2 parameters: the first pass peak (FPP) and the first peak of maximum uptake (Pmax)., Results: We have significantly distinguished high-grade tumors (GB and AA+AOD) and certain benign gliomas (DA and OD) ( p <0.05). AUC was over 0.7 and 0.8 for FPP and Pmax in differential diagnosis of various gliomas, respectively. We found that difficulties in differential diagnosis of gliomas arise mainly if oligodendrogliomas are included in the control group., Conclusion: Dynamic PET/CT with analysis of FPP and Pmax increases specificity of differential diagnosis of various gliomas compared to standard static imaging. These data are valuable for choice of optimal treatment strategy, as well as fundamental research of metabolic processes and vascularization of various tumors.

Objective: Tumors of the CNS are the main causes of childhood cancer and have an incidence that exceeds that of leukemia. In addition, they are the leading causes of cancer-related death in childhood. High-grade gliomas account for 11% of such neoplasms and are characterized by aggressive clinical behavior and high morbidity and mortality. There is a lack of studies focusing on the factors that can prolong survival in these patients or guide therapeutic interventions. The authors aimed to investigate the factors related to longer survival durations, with a focus on reoperation for gross-total resection (GTR)., Methods: In this retrospective cohort study, the authors analyzed 78 patients diagnosed with high-grade gliomas occurring across all CNS locations except diffuse intrinsic pontine gliomas. Patients 0 to < 19 years of age were followed up at the Pediatric Oncology Institute. Overall survival (OS) and progression-free survival (PFS) were analyzed in the context of various prognostic factors, such as age, sex, histology, extent of tumor resection, reoperation for GTR, adjuvant treatment, and treatment initiation from 2010 onward., Results: With a mean age at diagnosis of 8.7 years, 50% of the patients were female and approximately 39% underwent GTR at some point, which was already achieved in approximately 46% of them in the first surgery. The median OS was 17 months, and PFS was 10 months. In terms of median OS, the authors found no significant difference between those with reoperation for GTR and patients without GTR during treatment. Significant differences were observed in the OS in terms of the extent of resection in the first surgery, age, sex, Ki-67 expression, adjuvant treatment, and treatment initiation from 2010 onward. Furthermore, the PFS values significantly differed between those with GTR in the first surgery and Ki-67 expression ≥ 50%., Conclusions: This study demonstrates the importance of GTR for these neoplasms, highlights the role of surgeons in its achievement in the first attempt, and questions the role of reoperation for this purpose. Finally, this study further supports the use of combined adjuvant treatment for the improvement of OS and PFS.

Background: One of the greatest neuro-oncological concern remains the lack of knowledge about the etiopathogenesis and physiopathology of gliomas. Several studies reported a strict correlation between radiological features and biological behaviour of gliomas; in this way the velocity of diametric expansion (VDE) correlate with lower grade glioma aggressiveness. However, there are no the same strong evidences for high grade gliomas (HGG) because of the lack of several preoperative MRI., Patients and Methods: We describe a series of 4 patients affected by HGG followed from 2014 to January 2019. Two patients are male and two female; two had a pathological diagnosis of glioblastoma (GBM), one of anaplastic astrocytoma (AA) and one had a neuroradiological diagnosis of GBM. The VDE and the acceleration time (AT) was calculated for fluid attenuated inversion recovery (FLAIR) volume and for the enhancing nodule (EN). Every patients underwent sequential MRI study along a mean period of 413 days., Results: Mean VDE evaluated on FLAIR volume was 39.91 mm/year. Mean percentage ratio between peak values and mean value of acceleration was 282.7%. Median appearance time of EN after first MRI scan was 432 days. Mean VDE was 45.02 mm/year. Mean percentage ratio between peak values and mean value of acceleration was 257.52%., Conclusions: To our knowledge, this is the first report on VDE and acceleration growth in HGG confirming their strong aggressiveness. In a case in which we need to repeat an MRI, time between consecutive scans should be reduced to a maximum of 15-20 days and surgery should be executed as soon as possible., (© 2021 Roberto Altieri, Francesco Certo, Giuseppe La Rocca, Antonio Melcarne, Diego Garbossa, Alberto Bianchi, Salvatore Crimi, Alessandro Pluchino, Simone Peschillo, Giuseppe M.V. Barbagallo, published by Sciendo.)

Introduction: It is common practice to prescribe prophylactic antiepileptic drugs (AED) to high-grade glioma (HGG) patients without a history of seizures, yet with limited evidence supporting its use. Ideally, the effectiveness of prophylactic anticonvulsants must outweigh the occurrence of adverse effects and interactions related to AED. The authors conducted a systematic review and metanalysis of longitudinal studies regarding the effectiveness of prophylactic AED in seizure-naïve HGG patients., Materials and Methods: PubMed/MEDLINE, Cochrane Central Register of Controlled trials, Embase and clinicaltrials.gov databases were systematically searched. Of the initial 1773 studies identified, 15 were finally selected for data extraction and analysis. Heterogeneity among studies, pooled hazard ratios, publication bias and sensitivity analyses were performed separately for a 15-study group (HGG patients within larger series of brain tumors) and a 6-study group (exclusively HGG patients)., Results: AED prophylaxis did not significantly reduce the incidence of postoperative seizures compared with controls, both in the 15-study group (Mantel-Haenszel random-effects pooled OR 1.08, 95% CI 0.82-1.43, 2123 patients) and in the 6-study group (pooled OR 1.22, 95% CI 0.77-1.92, 540 patients). However, some issues (paucity of prospective trials, overall moderate-risk of bias, and few studies addressing HGG patients exclusively) preclude firm conclusions against routine prophylactic AED prescription. Reported adverse effects attributable to AED were acceptable in the majority of studies., Conclusions: Within the limitations of this review, the results of this metanalysis do not support the routine administration of prophylactic AED to HGG patients without a history of seizures., (Copyright © 2020 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.)

Anaplastic Astrocytoma(AA) is a malignant, diffusely infiltrating, primary brain tumor. According to the WHO 2016 classification of central-nervous-system tumors, AA has been described as a glial tumor with no co-deletion of 1p/19q, and is divided into IDH mutated tumor, characterized by better prognosis, and IDH wild-type form, with worse prognosis. The standard of care is maximal safe resection followed by radiotherapy and chemotherapy with temozolomide. Several efforts have been made to evaluate, according to molecular selection, which is the best post-surgical treatment. At recurrence, the treatment remains challenging and some trials are ongoing to evaluate new potential drugs, alone or in combination with chemotherapy. We performed a description of the status of the art on diagnosis, molecular characteristics and treatment of AA. In particular, we focused our details on new drugs; indeed, a deeper knowledge of the molecular characteristics of gliomas could lead to to development of active personalized treatments according with precision medicine., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: To estimate the incidence of epileptic seizures in patients with glial and metastatic brain tumors and to identify clinical and morphological risk factors for epileptic seizures in patients with glial and metastatic brain tumors., Material and Methods: The study included 225 (88.6%) patients with glial brain tumors and 29 patients (11.4%) with metastatic tumors., Results: Statistically significant differences in the incidence of epileptic seizures depending on age, histological characteristics of the tumor, degree of malignancy, tumor localization, involvement of the cerebral cortex, the presence of the midline shift were obtained., Conclusions: Epilepsy and epileptic seizures was found to develop in 51.11% and 24.14% of cases in glial and metastatic brain tumors, respectively. Risk factors for developing epileptic seizures include younger age (up to 57 years), histological characteristics corresponding to diffuse astrocytomas, anaplastic astrocytomas, oligodendrogliomas, oligoastrocytomas, grade I-III malignancy, lesion of the temporal lobe, involvement of the cerebral cortex. Factors that reduce the risk for attacks include age over 57, histological characteristics corresponding to glioblastomas and metastatic tumors, grade IV malignancy, subcortical localization of the tumor, damage to the occipital lobe, involvement of the commissural pathways, subtentorial localization of the tumor, the absence of lesions of the temporal and frontal lobes of the brain, the involvement of both brain hemispheres, damage to two or more brain lobes, the presence of a midline shift.

Background: The 2016 World Health Organization (WHO) classification of central nervous system tumors stratifies isocitrate dehydrogenase (IDH)-mutant gliomas into 2 major groups depending on the presence or absence of 1p/19q codeletion. However, the grading system remains unchanged and it is now controversial whether it can be still applied to this updated molecular classification., Methods: In a large cohort of 911 high-grade IDH-mutant gliomas from the French national POLA network (including 428 IDH-mutant gliomas without 1p/19q codeletion and 483 anaplastic oligodendrogliomas, IDH-mutant and 1p/19q codeleted), we investigated the prognostic value of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene homozygous deletion as well as WHO grading criteria (mitoses, microvascular proliferation, and necrosis). In addition, we searched for other retinoblastoma pathway gene alterations (CDK4 amplification and RB1 homozygous deletion) in a subset of patients. CDKN2A homozygous deletion was also searched in an independent series of 40 grade II IDH-mutant gliomas., Results: CDKN2A homozygous deletion was associated with dismal outcome among IDH-mutant gliomas lacking 1p/19q codeletion (P < 0.0001 for progression-free survival and P = 0.004 for overall survival) as well as among anaplastic oligodendrogliomas, IDH-mutant + 1p/19q codeleted (P = 0.002 for progression-free survival and P < 0.0001 for overall survival) in univariate and multivariate analysis including age, extent of surgery, adjuvant treatment, microvascular proliferation, and necrosis. In both groups, the presence of microvascular proliferation and/or necrosis remained of prognostic value only in cases lacking CDKN2A homozygous deletion. CDKN2A homozygous deletion was not recorded in grade II gliomas., Conclusions: Our study pointed out the utmost relevance of CDKN2A homozygous deletion as an adverse prognostic factor in the 2 broad categories of IDH-mutant gliomas stratified on 1p/19q codeletion and suggests that the grading of these tumors should be refined., (© The Author(s) 2019. 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.)

The degree of primary resection of malignant brain gliomas (MBGs) has correlated positively with progression-free and overall survival. The indications for surgery and reoperation in MBG relapse remain controversial. Surgery will not be curative and should be followed by adjuvant treatment. We reviewed the reported studies with respect to repeat resection and the various methods of intraoperative radiotherapy for MBGs from the initial experience with high-energy linear accelerators in Japan to modern, integrated brachytherapy solutions using solid and balloon applicators. Because of the findings from our review, we have begun to research into the use of intraoperative balloon brachytherapy for recurrent MBGs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Purpose: We conducted a phase I trial of alisertib, an oral aurora kinase inhibitor, with fractionated stereotactic re-irradiation therapy (FSRT) for patients with recurrent high grade glioma (HGG)., Materials and Methods: Adult patients with recurrent HGG were enrolled from Feb 2015 to Feb 2017. Patients were treated with concurrent FSRT and alisertib followed by maintenance alisertib. Concurrent alisertib dose was escalated from 20 mg to 50 mg twice daily (BID)., Results: 17 patients were enrolled. Median follow-up was 11 months. Median FSRT dose was 35 Gy. There were 6, 6, 3, and 2 patients enrolled in 20 mg, 30 mg, 40 mg, and 50 mg cohort, respectively. Only one DLT was observed. One patient in the 20 mg cohort had severe headache (Grade 3) resolved with steroids. There was no non-hematological grade 3 or higher toxicity. There were two Grade 4 late toxicities (one with grade 4 neutropenia and leukopenia, one with pulmonary embolism). One patient developed radiation necrosis (Grade 3). Sixteen patients finished concurrent treatment and received maintenance therapy (median cycles was 3, range 1-9). OS for all cohorts at 6 months was 88.2% with median survival time of 11.1 months. PFS at 6 months was 35.3% with median time to progression of 4.9 months. The trial stopped early due to closure of alisertib program with only 2 of 3 planned patients enrolled in the 50 mg cohort., Conclusion: Re-irradiation with FSRT combined with alisertib is safe and well tolerated for HGG with doses up to 40 mg BID. Although no DLT observed in the 50 mg cohort, this cohort was not fully enrolled and MTD was not reached. Clinical outcomes appear comparable to historical results. (NCT02186509)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Numerous studies have shown that the degree of primary resection of malignant gliomas of the brain (MG) directly correlates with rates of relapse-free and overall patient survival. Currently, there is no unequivocal opinion regarding the indications and effectiveness of repeated resection in relapse of MG after combined treatment. Surgical intervention, taking into account the pathomorphological features of these tumors, is not healing and should be supplemented with certain methods of adjuvant treatment. The article reviews and analyzes publications devoted to repeated resection and various methods of intraoperative radiation therapy in the treatment of MG. Based on the analysis, the authors of the article came to the conclusion that it is advisable to start their own research on the use of intraoperative balloon brachytherapy in the treatment of recurrent MG based on modern technological solutions.

OBJECTIVEThe goal of this article is to review the history of surgery for low- and high-grade gliomas located within the insula with particular focus on microsurgical technique, anatomical considerations, survival, and postoperative morbidity.METHODSThe authors reviewed the literature for published reports focused on insular region anatomy, neurophysiology, surgical approaches, and outcomes for adults with World Health Organization grade II-IV gliomas.RESULTSWhile originally considered to pose too great a risk, insular glioma surgery can be performed safely due to the collective efforts of many individuals. Similar to resection of gliomas located within other cortical regions, maximal resection of gliomas within the insula offers patients greater survival time and superior seizure control for both newly diagnosed and recurrent tumors in this region. The identification and the preservation of M2 perforating and lateral lenticulostriate arteries are critical steps to preventing internal capsule stroke and hemiparesis. The transcortical approach and intraoperative mapping are useful tools to maximize safety.CONCLUSIONSThe insula's proximity to middle cerebral and lenticulostriate arteries, primary motor areas, and perisylvian language areas makes accessing and resecting gliomas in this region challenging. Maximal safe resection of insular gliomas not only is possible but also is associated with excellent outcomes and should be considered for all patients with low- and high-grade gliomas in this area.

Background: Cannabinoid receptors have been detected in human gliomas and cannabinoids have been proposed as novel drug candidates in the treatment of brain tumors., Aims: To test the in vitro antitumor activity of COR167, a novel cannabinoid CB2-selective agonist displaying a high binding affinity for human CB2 receptors, on tumor cells isolated from human glioblastoma multiforme and anaplastic astrocytoma., Methods: Glioma cell cultures were established from two glioblastoma multiforme and two anaplastic astrocytomas. Proliferation was measured in the presence or absence of COR167 with a bromodeoxyuridine (BrdU) cell proliferation ELISA assay. CB2 receptor expression was detected by western blotting. Apoptosis was assessed with phycoerythrin (PE) annexin V flow cytometry kit. TGF-beta 1 and 2 levels were analyzed in culture supernatants with commercial ELISAs., Results: COR167 was found to significantly reduce the proliferation of both glioblastoma and anaplastic astrocytoma in a dose-dependent manner at lower doses than other known, less specific CB2 agonists. This activity is independent of apoptosis and is associated with a significant reduction of TGF-beta 1 and 2 levels in supernatants of glioma cell cultures., Conclusion: These findings add to the role of cannabinoid CB2 receptor as a possible pharmacological target to counteract glial tumor growth and encourage further work to explore any other pharmacological effect of this novel CB2 agonist useful in the treatment of human gliomas., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Pediatric high-grade brainstem gliomas are aggressive tumors with dismal prognoses. Large-scale studies are needed to further characterize these tumors and determine factors influencing cancer-specific mortality and survival at varying time points., Methods: We used the SEER (Surveillance Epidemiology and End Results) database to conduct a population-based study of pediatric patients with histologically confirmed anaplastic astrocytoma or glioblastoma tumors located within the brainstem. Multivariate analyses incorporating patient demographics, tumor characteristics, and treatments were used to determine predictors of cancer-specific mortality and survival at 6 months, 9 months, 1 year, and 2 years., Results: We included 154 patients from the SEER database: 72 patients with anaplastic astrocytoma (47%) and 82 (53%) with glioblastoma. Median survival for the entire cohort was 10.0 months. Glioblastoma histology, developmental stage, and large tumor size were significantly associated with cancer-specific mortality. Six-month, 9-month, 1-year, and 2-year survival was 75%, 57%, 42%, and 20%, respectively. Glioblastoma histology was associated with worsened survival at 6 months (odds ratio [OR], 0.19; P = 0.0081), 9 months (OR, 0.18; P < 0.001), 1 year (OR, 0.19; P < 0.001), and 2 years (OR, 0.14; P = 0.0055). Radiation therapy was associated with improved survival at 6 (OR, 8.53; P = 0.0012) and 9 months (OR, 3.58; P = 0.035) but not at 1 or 2 years. Radiation therapy was associated with improved survival in glioblastoma (9.0 vs. 3.0 months; P < 0.001)., Conclusions: This population-based study showed that glioblastoma histology is associated with a poor prognosis in pediatric patients with high-grade brainstem gliomas. Regardless of histology, radiation therapy improved survival at 6 and 9 months but not long-term., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: We report on five patients with gadolinium-negative (non-enhancing magnetic resonance imaging-MRI) but 18 F-fluoroethyl tyrosine positron-emission tomography (FET-PET) positive glioma (NEG) undergoing surgery under fluorescence-guidance with fluorescein sodium 10% (FL, Alkon, Germany) in combination with a dedicated light filter (YELLOW 560 nm, Carl Zeiss Meditec, Germany)., Patients and Method: Since 2017, five patients (3 female, 2 male; mean age 45.4 years) underwent fluorescence-guided surgery for supratentorial, intracerebral lesions which showed no contrast-enhancement in the preoperative MRI but were, however, strongly suspicious for gliomas. Accordingly, all patients received a preoperative FET-PET scan and detailed histopathological workup was performed. After giving written informed consent, all patients received 5 mg/kg of FL at the induction of anesthesia. Surgery was conducted under white light and under the YELLOW 560 nm filter. We reviewed the surgical protocols, navigational storage and the image databases of our surgical microscopes for evidence of intraoperative fluorescence that corresponded to the FET-PET positive area., Results: In all patients we found distinct accordances between the FET-PET positive areas and the fluorescing regions within the targeted lesions. Histopathological workup of the fluorescent tissue revealed anaplastic oligodendroglioma, IDH-mutant and 1p/19-codeleted (WHO grade III) (n = 2), anaplastic astrocytoma, IDH-mutant (WHO grade III) (n = 1), oligodendroglioma, IDH-mutant and 1p/19q-codeleted (WHO grade II) (n = 1) and pilocytic astrocytoma (WHO grade I) (n = 1). No adverse events were noted., Discussion and Conclusion: Despite the lack of gadolinium-enhancement in the preoperative MRI, all patients intravenously received FL to guide resection. Irrespective of the final grading, FL was extremely helpful in detecting the lesions and in identifying their border zones. In selected patients with NEG, but strong metabolic activity according to the FET-PET, FL may significantly increase the accuracy of surgery., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: A standard post-concomitant radiochemotherapy involving adjuvant temozolomide (TMZ) was stopped after 6 cycles for high-grade gliomas (HGG). Several studies demonstrated that prolonged TMZ treatment increased survival for these patients., Methods: This retrospective study aimed to compare changes in tumor volume during and after adjuvant TMZ treatment and overall survival (OS)., Results: There were 90 patients were administered adjuvant TMZ treatment. Comparing average tumor volume changes during TMZ treatment and after TMZ was stopped, a significant decrease in tumor volume was observed during TMZ treatment in the total patient population, the anaplastic astrocytoma (AA) group, and the glioblastoma multiforme (GBM) group (P ≤ 0.001, P = 0.042, and P = 0.005, respectively). Median overall survival was 78.4 weeks, which was significant regarding the surgical tumor resection rate (r = 0.241; P = 0.04) and total TMZ treatment cycles (r = 0.631; P ≤ 0.001)., Conclusions: During adjuvant TMZ treatment, tumor volume decreased significantly (P = 0.042, and P = 0.005, respectively) in patients with GBM and AA. Prolonged TMZ administration improved OS, without increased toxicity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Positron emission tomography combined with computed tomography (PET/CT) enables assessment of not only anatomical and structural but also metabolic changes in tumor mass. 18 F-fluoroethyl tyrosine ( 18 F-FET) PET/CT is based on evaluation of transport of 18 F-labeled tyrosine in tissues. We present a clinical case of a patient with a newly diagnosed brain tumor, demonstrating the capabilities of 18 F-FET PET/CT in assessing the reliable volume and degree of tumor anaplasia, which is important when choosing the treatment approach for a patient.

The SEOM/GEINO clinical guidelines provide recommendations for radiological, and molecular diagnosis, treatment and follow-up of adult patients with anaplastic gliomas (AG). We followed the 2016 WHO classification which specifies the major diagnostic/prognostic and predictive value of IDH1/IDH2 missense mutations and 1p/19q codeletions in AG. The diagnosis of anaplastic oligoastrocytoma is discouraged. Surgery, radiotherapy and chemotherapy with PCV or TMZ are the first-line standard of care for AG with slight modifications according to molecular variables. A multidisciplinary team is highly recommended in the management of these tumors.

Temozolomide (TMZ) for malignant gliomas is traditionally dosed in 5 out of a 28-day cycle, however alternative regimens exist, including dose-dense. Continuous daily dosing is available, but the acceptable dose and duration of therapy is unknown. We document a 40-year-old male with recurrent anaplastic astrocytoma, IDH mutant and MGMT promotor methylation negative, who has well-tolerated continuous daily TMZ for 20 months at 100 mg per day for nearly the length of this period. A trial at 80 mg per day demonstrated disease progression with response upon return to 100 mg per day. Prior to the daily TMZ, the patient underwent three surgical resections, radiation therapy with concurrent TMZ according to the EORTC-NCIC protocol, and subsequently bevacizumab in combination with use of the Optune device. Long-term survival of patients with recurrent malignant gliomas is uncommon, and currently no standard treatment strategies exist for these patients. We present this case to demonstrate the tolerability and dose dependency of prolonged daily TMZ dosing as a therapeutic option for recurrent anaplastic astrocytomas.

Mutations in the telomerase reverse transcriptase gene promoter (TERTp) are common in glioblastomas (GBMs) and oligodendrogliomas (ODGs), and therefore, have a key role in tumorigenesis and may be of prognostic value. However, the extent of their prognostic importance in various gliomas is controversial. We studied 168 patients separated into five groups: Group 1: 65 patients with ODG carrying an IDH1 or IDH2 mutation (IDH-mutant) and 1p/19q-codeletion, Group 2: 23 patients with anaplastic astrocytoma (AA), IDH-mutant, Group 3: 13 patients with GBM, IDH-mutant, Group 4: 15 patients with AA, IDH-wildtype (WT), and Group 5: 52 patients with GBM, IDH-WT. TERTp mutations were found in 96.9%, 4.4%, 76.9%, 20.0%, and 84.6% of patients in Groups 1, 2, 3, 4, and 5, respectively. The R132H mutation in IDH1 was found in 60.5% (23/38) of patients in the AA cohort (Groups 2 and 4) and 20.0% (13/65) of patients from our GBM cohort (Groups 3 and 5), whereas all patients with ODG (Group 1) had a mutation either in IDH1 (n = 62) or IDH2 (n = 3). Using Kaplan Meier survival analysis, we found that the TERTp mutation was correlated with poor overall survival (OS) in Groups 2 and 4 combined (P = 0.001) and in Group 4 (P = 0.113), and in multivariate analysis, the TERTp mutant group was associated with significantly poor survival in Group 5 (P = 0.045). However, IDH mutation, MGMT methylation, and younger patient age (<55 years old) were significantly correlated with favorable OS (all P < 0.05) in our cohort of astrocytic and ODGs. In patients with ODG (Group 1), mutant IDH and TERTp did not have prognostic value because these mutations were universally present. Based on the revised 2016 WHO classification of gliomas, we found that TERTp mutation was frequently present in patients with GBM or ODG and because it was strongly correlated with poor survival outcome in patients with IDH-WT GBM in multivariate analysis, it may be of prognostic value in this subgroup of patients with gliomas.

Standard treatment for GBM is radiation (RT) and temozolomide (TMZ). Arsenic trioxide (ATO) is synergistic with RT based on several mechanisms of action previously identified, however not tested herein. The MTD of ATO, RT and TMZ was determined in a Phase I trial. We now present the combined Phase I/II data. Patients with newly diagnosed malignant gliomas were eligible for treatment. Patients were treated with RT (60 GY), TMZ (75 mg/m 2 daily × 42 days) and ATO 0.20 mg/kg daily in week 1 then twice a week ×5 weeks, after completing RT they were treated with TMZ 5/28 for up to 12 months. MRIs were performed every 8 weeks. A total of 42 patients were enrolled in both the Phase I and II trials for this study treatment. Of the 42 enrolled patients (24 M and 18 W) the median age was 54 (24-80) and median KPS 90 (60-100). 28 patients had a GBM and 14 had anaplastic glioma (AG). All patients completed RT/TMZ/ATO and went on to maintenance TMZ. Median number of post RT cycles of TMZ was 4 (0-12). Median PFS was 7 m for GBM and 75 m for AG and median OS was 17 m for GBM and NR for AG. Best response was CR in 2, SD in 28, PR in 5 and PD in 7. There were no unexpected adverse events. Grade 3 toxicities likely attributable to ATO included prolonged Qtc (n = 1), elevated liver enzymes (n = 2 for ALT/n = 1 for AST) and elevated bilirubin (n = 1). Adding ATO to RT and TMZ is feasible with no increased side effects. The addition of arsenic did not improve overall survival in the GBM patients as compared to historic data. MGMT status was analyzed in 20 of the 42 patients where tissue was available for retrieval and MGMT testing.

Background: The paradigm of evidence-based medicine dictates that clinical practice should reflect the shifting landscape of the peer-reviewed literature. Here, we examined the extent to which this premise is fulfilled as it pertains to the surgical resection of high-grade gliomas (HGGs)., Objective: We assessed trends in published literature regarding HGG survival after resection in conjunction with trends in clinical practice patterns of HGG resection., Methods: We performed a comprehensive PubMed search to identify articles that examined whether gross total resection (GTR) improves HGG survival. Temporal trends in the literature were compared with rates of GTR in the Surveillance Epidemiology and End Results (SEER) database, the Veterans Health Administration database, and published data series from academic neuro-oncology centers., Results: Before 2000, the ratio of articles supporting survival benefit of GTR relative to those not supporting it ranged from approximately 1:5 to 1:1. Since 2000, this ratio has steadily increased such that by the post-2013 period, 32 of the 33 published articles (>30:1) supported the survival benefit of GTR. Although the frequency of GTR increased during the 2000-2004 period in the SEER and Veterans Health Administration database, no further increase in the frequency of GTR was observed thereafter. In contrast, resection rates in academic neuro-oncology centers continued to increase subsequent to 2004., Conclusions: Our results indicate that clinical practice patterns mirror publication patterns for HGG resection, suggesting that neurosurgical oncology is a field in which clinical practice is informed by the peer-reviewed literature., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Angiocentric glioma (AG) is a low grade glioma, that was first described in 2002. Since this description, 83 patients with AG have been described, including ours. AG typically presents in childhood with medically refractory seizures that are cured with gross surgical resection. Whilst the natural history is that of a benign tumour, there have been reports of recurrence, transformation, and malignant features that suggest that AG is potentially malignant. We add to the literature a case of a 16-year-old girl who presented in May 2011 with a 3-month history of complex partial seizures, with MRI showing a T2-weighted hyperintense lesion in the left insula and inferior frontal lobe. This was confirmed on biopsy as AG and was followed with surveillance imaging. In April 2012, she presented with disease progression and underwent a left temporal lobectomy, with histology showing both AG and grade II astrocytoma. Adjuvant radiotherapy of 50 Gray in 28 fractions was administered. A small area of contrast enhancement appeared in the left parietal lobe in December 2012, which progressed over subsequent months. In June 2013, she underwent a near total excision, with histology showing anaplastic ependymoma. She received six cycles of adjuvant temozolamide. Despite this, the tumour continued to progress, with her seizure control deteriorating, and the development of a right hemiparesis. The patient died in January 2014, aged 19years., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: Though challenging, maximal safe resection of insular gliomas enhances overall and progression-free survival and deters malignant transformation. Previously published reports have shown that surgery can be performed with low morbidity. The authors previously described a Berger-Sanai zone classification system for insular gliomas. Using a subsequent dataset, they undertook this study to validate this zone classification system for predictability of extent of resection (EOR) in patients with insular gliomas., Methods: The study population included adults who had undergone resection of WHO Grade II, III, or IV insular gliomas. In accordance with our prior published report, tumor location was classified according to the Berger-Sanai quadrant-style classification system into Zones I through IV. Interobserver variability was analyzed using a cohort of newly diagnosed insular gliomas and independent classification scores given by 3 neurosurgeons at various career stages. Glioma volumes were analyzed using FLAIR and T1-weighted contrast-enhanced MR images., Results: One hundred twenty-nine procedures involving 114 consecutive patients were identified. The study population from the authors' previously published experience included 115 procedures involving 104 patients. Thus, the total experience included 244 procedures involving 218 patients with insular gliomas treated at the authors' institution. The most common presenting symptoms were seizure (68.2%) and asymptomatic recurrence (17.8%). WHO Grade II glioma histology was the most common (54.3%), followed by Grades III (34.1%) and IV (11.6%). The median tumor volume was 48.5 cm(3). The majority of insular gliomas were located in the anterior portion of the insula with 31.0% in Zone I, 10.9% in Zone IV, and 16.3% in Zones I+IV. The Berger-Sanai zone classification system was highly reliable, with a kappa coefficient of 0.857. The median EOR for all zones was 85%. Comparison of EOR between the current and prior series showed no change and Zone I gliomas continue to have the highest median EOR. Short- and long-term neurological complications remain low, and zone classification correlated with short-term complications, which were highest in Zone I and in Giant insular gliomas., Conclusions: The previously proposed Berger-Sanai classification system is highly reliable and predictive of insular glioma EOR and morbidity.

Recent advances in genomic technology and genome-wide analysis have identified key molecular alterations that are relevant to the diagnosis and prognosis of brain tumors. Molecular information such as mutations in isocitrate dehydrogenase (IDH) genes or 1p/19q co-deletion status will be more actively incorporated into the histological classification of diffuse gliomas. BRAF V600E mutations are found frequently in circumscribed low-grade gliomas such as pleomorphic xanthoastrocytoma (PXA) and extra-cerebellar pilocytic astrocytoma, or epithelioid glioblastomas (E-GBM), a rare variant of GBM. This mutation is relatively rare in other types of diffuse gliomas, especially in adult onset cases. Here, we present an adult onset case of IDH wild-type/BRAF V600E-mutated diffuse glioma, evolving from grade III to grade IV. The tumor displayed atypical exophytic growth and had unusual histological features not fully compatible with, but indicative of PXA and E-GBM. We discuss differential diagnosis of the tumor, and review previously described diffuse gliomas with the BRAF V600E mutation.

Objective: Radiation-induced malignant gliomas (RIMGs) are known uncommon risks of brain irradiation. We describe 4 cases of RIMG that occurred at our institution and conduct the largest comprehensive review of the literature to characterize RIMGs better., Methods: Patients were identified through the PubMed database. Pearson R linear correlation test was used to evaluate the correlation between radiotherapy (RT) dose and age and latency period. Student t test was used to evaluate differences between latency periods for original tumor lesions. A normalized biologic equivalent dose analysis was performed to indicate the minimum and maximum radiation threshold for neoplasia. A Kaplan-Meier analysis was used to illustrate the overall survival curves., Results: The analysis included 172 cases from the PubMed database and 4 cases occurring at our institution. The median RT dose administered was 35.6 Gy, with the most common dosage ranges being 21-30 Gy (31%) and 41-50 Gy (21.5%). Median latency period was 9 years until diagnosis of RIMG, and RIMG occurred within 15 years in 82% of the patients. There was no correlation between the age of the patient at the time RT was administered (R(2) = 0.00081) or amount of RT (R(2) = 0.00005) and latency period for RIMG. The mean biologic equivalent dose for neoplasia of a RIMG was 63.3 Gy. The median survival of patients with RIMG improved over time (P = 0.004), with median survival of 9 months before 2007 and 11.5 months after 2007., Conclusions: The risk of RIMG appears to be the same for all age groups, histologies, and RT dosages. Although the risk is low, patients should be aware of RIMG as a possible complication of brain irradiation., (Published by Elsevier Inc.)

We have recently reported that glioblastoma (GB)-initiating cells (GIC) with low expression and/or mutation of TP53 and high expression of PI3K ("responder" genetic profile) can be effectively and safely radiosensitized by the ATM inhibitor KU60019. We report here on drug's diffusion and elimination from the animal body and brain, its effects on orthotopic GB and efficacy toward pediatric GIC. Healthy mice were infused by convection enhanced delivery (CED) with KU60019 and the drug kinetics followed by high performance liquid chromatography-mass spectrometry. Already at the end of CED, KU60019 had diffused from the injection site to the ipsilateral and, to a lower extent, controlateral hemisphere. After 24 hr, no drug could be detected all over the brain or in other organs, indicating rapid draining and excretion. After intraperitoneal injection, traces only of KU60019 could be detected in the brain, indicating inability to cross the brain-blood barrier. Consistent with the induction of cell cycle progression previously observed in vitro, KU60019 stimulated proliferation of orthotopic GB cells with the highest effect observed 96 hr after drug delivery. Adult GIC with high expression of TP53 and low expression of PI3K could be radiosensitized by KU60019, although less promptly than GIC bearing the "responder" profile. Consistent with the kinetics of proliferation induction, the highest radiosensitizing effect was observed 96 hr after delivery of KU60019 to GIC. Pediatric GIC could be similarly radiosensitized after exposure to KU60019. The results indicate that ATM inhibition may allow to radiosensitize a wide range of adult and pediatric high-grade gliomas., (© 2014 UICC.)

Several previous reports indicated that microRNA-504 (miR-504) has an oncogenic function through negatively regulating p53. On the other hand, a recent study revealed that miR-504 inhibits cancer cell proliferation through targeting CDK6 in hypopharyngeal squamous cell carcinoma (HSCC), suggesting the tumor suppressive role of this miRNA. However, the role of miR-504 in human malignant glioma remains unclear. Therefore, the aim of this study was to investigate the clinical significance of miR-504 expression in high pathological grade glioma. Quantitative real-time reverse transcriptive-PCR (qRT-PCR) was performed to examine miR-504 expression levels in 63 glioma tissues including 13 anaplastic astrocytomas (AA, WHO grade III) and 50 glioblastomas (GBM, WHO grade IV), as well as 10 non-neoplastic brain tissues. Associations between miR-504 expression and clinicopathological factors and prognosis of glioma patients were statistically analyzed. MiR-504 showed significant decreased expression levels both in AAs and GBMs relative to non-neoplastic brains (P ≤ 0.001, respectively). Additionally, low expression level of miR-504 was significantly associated with advanced WHO grade (P = 0.01). Moreover, Kaplan-Meier survival analysis showed that patients with low expression of miR-504 had significantly poor survival rate (P = 0.002). Cox regression analysis showed that miR-504 expression was independent prognosis-predicting factor for malignant glioma patients (P = 0.038; risk ration = 2.5). Our results suggest that miR-504 may be a prognostic predictor and be involved in tumorigencity as a tumor suppressor of malignant glioma.

Aims: Relapsed high-grade gliomas (HGGs) have poor prognoses and there is no standard treatment. HGGs have ischemia/hypoxia associated and, as such, drugs and oxygen have low access, with increased resistance to chemotherapy and radiotherapy. Tumor hypoxia modification can improve outcomes and overall survival in some patients with these tumors. In previous works, we have described that cervical spinal cord stimulation can modify tumor microenvironment in HGG by increasing tumor blood flow, oxygenation, and metabolism. The aim of this current, preliminary, nonrandomized, study was to assess the clinical effect of spinal cord stimulation during brain reirradiation and chemotherapy deployed for the treatment of recurrent HGG; the hypothesis being that an improvement in oxygenated blood supply would facilitate enhanced delivery of the scheduled therapy., Materials and Methods: Seven patients had spinal cord stimulation applied during the scheduled reirradiation and chemotherapy for the treatment of recurrent HGG (6 anaplastic gliomas and 1 glioblastoma). Median dose of previous irradiation was 60 Gy (range = 56-72 Gy) and median dose of reirradiation was 46 Gy (range = 40-46 Gy). Primary end point of the study was overall survival (OS) following confirmation of HGG relapse., Results: From the time of diagnosis of last tumor relapse before reirradiation, median OS was 39 months (95% CI = 0-93) for the overall study group: 39 months (95% CI = 9-69) for those with anaplastic gliomas and 16 months for the patient with glioblastoma. Posttreatment, doses of corticosteroids was significantly decreased (P = .026) and performance status significantly improved (P = .046)., Conclusions: Spinal cord stimulation during reirradiation and chemotherapy is feasible and well tolerated. In our study, spinal cord stimulation was associated with clinical improvement and longer survival than previously reported in recurrent anaplastic gliomas. Spinal cord stimulation as adjuvant during chemotherapy and reirradiation in relapsed HGGs merits further research., (© The Author(s) 2014.)

Background: Previously published randomized evidence did not report a survival advantage for patients diagnosed with grade IV glioma who were treated with stereotactic radiosurgery followed by external beam radiation therapy and chemotherapy when compared to patients treated with external beam radiation therapy and chemotherapy alone. In recent years, gamma knife radiosurgery has become increasingly popular as a salvage treatment modality for patients diagnosed with recurrent high-grade glioma. The purpose of this article is to review the efficacy of gamma knife radiosurgery for patients who suffer from this malignancy., Methods: Retrospective, prospective, and randomized clinical studies published between the years 2000 and 2012 analyzing gamma knife radiosurgery for patients with high-grade glioma were reviewed., Results: After assessing patient age, Karnofsky performance status, tumor histology, and extent of resection, gamma knife radiosurgery is a viable, minimally invasive treatment option for patients diagnosed with recurrent high-grade glioma. The available prospective and retrospective evidence suggests that gamma knife radiosurgery provides patients with a high local tumor control rate and a median survival after tumor recurrence ranging from 13 to 26 months. Gamma knife radiosurgery followed by chemotherapy for recurrent high-grade glioma may provide select patients with increased levels of survival. However, further investigation into this matter is needed due to the limited number of published reports. Additional clinical research is also needed to analyze the efficacy and radiation-related toxicities of fractionated gamma knife radiosurgery due to its potential to limit treatment-associated morbidity., Conclusions: Gamma knife radiosurgery is a safe and effective treatment option for select patients diagnosed with recurrent high-grade glioma. Although treatment outcomes have improved, further evidence in the form of phase III randomized trials is needed to assess the durability of treating patients in specific clinical situations., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Brain tumors are a major cause of cancer-related mortality in children. Overexpression of epidermal growth factor receptor (EGFR) is detected in pediatric brain tumors and receptor density appears to increase with tumor grading. Nimotuzumab is an IgG1 antibody that targets EGFR. Twenty-three children with high-grade glioma (HGG) were enrolled in an expanded access program in which nimotuzumab was administered alone or with radio-chemotherapy. The mean number of doses was 39. Nimotuzumab was well-tolerated and treatment with the antibody yielded a survival benefit: median survival time was 32.66 mo and the 2-y survival rate was 54.2%. This study demonstrated the feasibility of prolonged administration of nimotuzumab and showed preliminary evidence of clinical benefit in HGG patients with poor prognosis.

Abstract Background Current guidelines for the treatment of anaplastic astrocytoma (AA) recommend maximal safe resection followed by radiotherapy and chemotherapy. Despite this multimodal treatment approach, patients have a limited life expectancy. In the present study, we identified variables associated with overall survival (OS) and constructed a model score to predict the OS of patients with AA at the time of their primary diagnosis. Methods We retrospectively evaluated 108 patients with newly diagnosed AA. The patient and tumor characteristics were analyzed for their impact on OS. Variables significantly associated with OS on multivariable analysis were included in our score. The final algorithm was based on the 36-month survival rates corresponding to each characteristic. Results On univariate analysis, age, Karnofsky performance status, isocitrate dehydrogenase status, and extent of resection were significantly associated with OS. On multivariable analysis all four variables remained significant and were consequently incorporated in the score. The total score ranges from 20 to 33 points. We designated three prognostic groups: A (20–25), B (26–29), and C (30–33 points) with 36-month OS rates of 23%, 71%, and 100%, respectively. The OS rate at 5 years was 8% in group A, 61% in group B and 88% in group C. Conclusions Our model score predicts the OS of patients newly diagnosed with AA and distinguishes patients with a poor survival prognosis from those with a greater life expectancy. Independent and prospective validation is needed. The upcoming changes of the WHO classification of brain tumors as well as the practice changing results from the CATNON trial will most likely require adaption of the score.

Children with high-grade glioma (HGG) have a poor prognosis compared to those with low-grade glioma (LGG). Adjuvant chemotherapy may be beneficial, but its optimal use remains undetermined. Histology and extent of resection are important prognostic factors. We tested the hypothesis that patients with midline HGG treated on Children's Cancer Group Study (CCG) CCG-945 have a worse prognosis compared to the entire group. Of 172 children eligible for analysis, 60 had midline tumors primarily localized to the thalamus, hypothalamus and basal ganglia. Time-to-progression and death were determined from the date of initial diagnosis, and survival curves were calculated. Univariate analyses were undertaken for extent of resection, chemotherapy regimen, anatomic location, histology, proliferation index, MGMT status and p53 over-expression. For the entire midline tumor group, 5-year PFS and OS were 18.3 ± 4.8 and 25 ± 5.4 %, respectively. Many patients only had a biopsy (43.3 %). The sub-groups with near/total resection and hypothalamic location appeared to have better PFS and OS. However, the effect of tumor histology on OS was significant for children with discordant diagnoses on central pathology review of LGG compared to HGG. Proliferative index (MIB-1 > 36 %), MGMT and p53 over-expression correlated with poor outcomes. Children treated on CCG-945 with midline HGG have a worse prognosis when compared to the entire group. The midline location may directly influence the extent of resection. Central pathology review and entry of patients on clinical trials continue to be priorities to improve outcomes for children with HGG.

Objective. To determine the incidence and identify the clinical-morphological risk factors for the development of epileptic seizures in patients with glial and metastatic brain tumors. Materials and methods. The study included 225 patients (88.6%) with glial and 29 (11.4%) with metastatic brain tumors. Results. Statistically significant differences in the incidence of epileptic seizures depending on age and histological characteristics of tumors, level of malignancy, location, involvement of the cerebral cortex, and displacement of midline structures were found. Conclusions. Epilepsy and epileptic seizures developed in 51.11% and 24.14% cases of glial and metastatic brain tumors, respectively. Risk factors for epileptic seizures were younger age (up to 57 years), histological characteristics corresponding to diffuse astrocytoma, anaplastic astrocytoma, oligodendroglioma, and oligoastrocytoma, malignancy grades I–III, lesions to the temporal lobe, and involvement of the cerebral cortex. Factors decreasing the risk of seizures were age over 57 years, histological characteristics corresponding to glioblastoma, metastatic tumors, malignancy grade IV, subcortical location of neoplasm, lesions to the occipital cortex, involvement of the conducting tracts (commissures) in the pathological process, subtentorial tumor location, absence of lesion in the temporal and frontal lobes of the brain, involvement of both hemispheres of the brain in the pathological process, lesions of two or more lobes of the brain, and displacement of midline structures. [ABSTRACT FROM AUTHOR]

The immune microenvironment is important for the development, progression, and prognosis of anaplastic glioma (AG). This complex milieu has not been fully elucidated, and a high-dimensional analysis is urgently required. Utilizing mass cytometry (CyTOF), we performed an analysis of immune cells from 5 patients with anaplastic astrocytoma, IDH-mutant (AAmut) and 10 patients with anaplastic oligodendroglioma, IDH-mutant and 1p/19q codeletion (AOD) and their paired peripheral blood mononuclear cells (PBMCs). Based on a panel of 33 biomarkers, we demonstrated the tumor-driven immune changes in the AG immune microenvironment. Our study confirmed that mononuclear phagocytes and T cells are the most abundant immunocytes in the AG immune microenvironment. Glioma-associated microglia/macrophages in both AAmut and AOD samples showed highly immunosuppressive characteristics. Compared to those in the PBMCs, the ratios of immune checkpoint-positive exhausted CD4+ T cells and CD8+ T cells were higher at the AG tumor sites. The AAmut immune milieu exhibits more immunosuppressive characteristics than that in AOD.

Abstract Background Astrocytomas are the most common malignant glial tumors. With improved prognosis, it is possible for patients to pursue pregnancy post-treatment. However, with potential gonadotoxicity of oncology treatments, fertility preservation prior to chemotherapy and/or radiation therapy should be considered. This requires close collaboration between the oncologist and reproductive endocrinologist. To our knowledge this is the first report of successful pregnancies following fertility preservation for AA. Case presentation 33-year-old nulligravid woman with newly diagnosed anaplastic astrocytoma (AA; WHO grade III, IDH1-negative) sought fertility preservation. Prior to chemotherapy and radiation for AA, the patient underwent in vitro fertilization (IVF) for fertility preservation, resulting in 8 vitrified embryos. Following chemo-radiation, the patient underwent two rounds of frozen embryo transfers (FET), each resulting in a successful singleton pregnancy. Conclusion This case illustrates the realistic possibility, in carefully selected patients with brain tumors, of oocyte or embryo cryo-preservation prior to chemo-radiation and subsequent pregnancies.

The immune microenvironment is important for the development, progression, and prognosis of anaplastic glioma (AG). This complex milieu has not been fully elucidated, and a high-dimensional analysis is urgently required. Utilizing mass cytometry (CyTOF), we performed an analysis of immune cells from 5 patients with anaplastic astrocytoma, IDH-mutant (AAmut) and 10 patients with anaplastic oligodendroglioma, IDH-mutant and 1p/19q codeletion (AOD) and their paired peripheral blood mononuclear cells (PBMCs). Based on a panel of 33 biomarkers, we demonstrated the tumor-driven immune changes in the AG immune microenvironment. Our study confirmed that mononuclear phagocytes and T cells are the most abundant immunocytes in the AG immune microenvironment. Glioma-associated microglia/macrophages in both AAmut and AOD samples showed highly immunosuppressive characteristics. Compared to those in the PBMCs, the ratios of immune checkpoint-positive exhausted CD4+ T cells and CD8+ T cells were higher at the AG tumor sites. The AAmut immune milieu exhibits more immunosuppressive characteristics than that in AOD. [ABSTRACT FROM AUTHOR]

Background: Current guidelines for the treatment of anaplastic astrocytoma (AA) recommend maximal safe resection followed by radiotherapy and chemotherapy. Despite this multimodal treatment approach, patients have a limited life expectancy. In the present study, we identified variables associated with overall survival (OS) and constructed a model score to predict the OS of patients with AA at the time of their primary diagnosis.Methods: We retrospectively evaluated 108 patients with newly diagnosed AA. The patient and tumor characteristics were analyzed for their impact on OS. Variables significantly associated with OS on multivariable analysis were included in our score. The final algorithm was based on the 36-month survival rates corresponding to each characteristic.Results: On univariate analysis, age, Karnofsky performance status, isocitrate dehydrogenase status, and extent of resection were significantly associated with OS. On multivariable analysis all four variables remained significant and were consequently incorporated in the score. The total score ranges from 20 to 33 points. We designated three prognostic groups: A (20-25), B (26-29), and C (30-33 points) with 36-month OS rates of 23%, 71%, and 100%, respectively. The OS rate at 5 years was 8% in group A, 61% in group B and 88% in group C.Conclusions: Our model score predicts the OS of patients newly diagnosed with AA and distinguishes patients with a poor survival prognosis from those with a greater life expectancy. Independent and prospective validation is needed. The upcoming changes of the WHO classification of brain tumors as well as the practice changing results from the CATNON trial will most likely require adaption of the score. [ABSTRACT FROM AUTHOR]