Management Of Low-grade Gliomas Research Articles

State of the Art in Low-Grade Glioma Management: Insights From Isocitrate Dehydrogenase and Beyond.

Low-grade gliomas present a formidable challenge in neuro-oncology because of the challenges imposed by the blood-brain barrier, predilection for the young adult population, and propensity for recurrence. In the past two decades, the systematic examination of genomic alterations in adults and children with primary brain tumors has uncovered profound new insights into the pathogenesis of these tumors, resulting in more accurate tumor classification and prognostication. It also identified several common recurrent genomic alterations that now define specific brain tumor subtypes and have provided a new opportunity for molecularly targeted therapeutic intervention. Adult-type diffuse low-grade gliomas are frequently associated with mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2), resulting in production of 2-hydroxyglutarate, an oncometabolite important for tumorigenesis. Recent studies of IDH inhibitors have yielded promising results in patients at early stages of disease with prolonged progression-free survival (PFS) and delayed time to radiation and chemotherapy. Pediatric-type gliomas have high rates of alterations in BRAF, including BRAF V600E point mutations or BRAF-KIAA1549 rearrangements. BRAF inhibitors, often combined with MEK inhibitors, have resulted in radiographic response and improved PFS in these patients. This article reviews emerging approaches to the treatment of low-grade gliomas, including a discussion of targeted therapies and how they integrate with the current treatment modalities of surgical resection, chemotherapy, and radiation.

Focus on current and emerging treatment options for glioma: A comprehensive review.

This comprehensive review delves into the current updates and challenges associated with the management of low-grade gliomas (LGG), the predominant primary tumors in the central nervous system. With a general incidence rate of 5.81 per 100000, gliomas pose a significant global concern, necessitating advancements in treatment techniques to reduce mortality and morbidity. This review places a particular focus on immunotherapies, discussing promising agents such as Zotiraciclib and Lerapolturev. Zotiraciclib, a CDK9 inhibitor, has demonstrated efficacy in glioblastoma treatment in preclinical and clinical studies, showing its potential as a therapeutic breakthrough. Lerapolturev, a viral immunotherapy, induces inflammation in glioblastoma and displays positive outcomes in both adult and pediatric patients. Exploration of immunotherapy extends to Pembrolizumab, Nivolumab, and Entrectinib, revealing the challenges and variabilities in patient responses. Despite promising preclinical data, the monoclonal antibody Depatuxizumab has proven ineffective in glioblastoma treatment, emphasizing the critical need to understand resistance mechanisms. The review also covers the success of radiation therapy in pediatric LGG, with evolving techniques, such as proton therapy, showing potential improvements in patient quality of life. Surgical treatment is discussed in the context of achieving a balance between preserving the patient's quality of life and attaining gross total resection, with the extent of surgical resection significantly influencing the survival outcomes. In addition to advancements in cancer vaccine development, this review highlights the evolving landscape of LGG treatment, emphasizing a shift toward personalized and targeted therapies. Ongoing research is essential for refining strategies and enhancing outcomes in the management of LGG.

Introduction: Contemporary management of low-grade gliomas: from tumor biology to the patient's quality of life.

Introduction: Contemporary management of low-grade gliomas: from tumor biology to the patient's quality of life.

The T2FLAIR mismatch novel radiogenomic marker in the newly suspected low-grade gliomas

Background. The T2-FLAIR (fluid-attenuated inversion recovery) mismatch sign has been defined over the last few years as an important novel radiogenomic marker highly suggestive of isocitrate dehydrogenase mutated (IDH-mut) 1p19q non-codeleted gliomas (astrocytomas). Existing studies have demonstrated that this has good specificity but limited sensitivity for IDH-mut astrocytomas. Thenew 2021 WHO Classification of Tumors of the Central Nervous System (WHO CNS5) has introduced a layered grading system in which all IDH mutant diffuse astrocytic tumours are considered a single type (Astrocytoma, IDH-mutant) and are graded as CNS WHO grade 2, 3, or 4. Because of the growing importance of molecular information in CNS tumour classification, diagnoses and diagnostic reports need to combine different data types into a single diagnosis. Whether the T2FLAIR mismatch sign is of clinical relevance for the management of low-grade gliomas still needs to be further determined.Methods. We included histologically verified supratentorial low-grade gliomas (LGG) WHO grade 2-3 retrospectively during the period 2013–2018 (n=18). For the period 2019–2023 (n=27), patients with a radiological presumptive diagnosis of low-grade glioma were prospectively included, and we took into consideration the fact that in this group we could encounter other diagnoses than glioma.Clinical, radiological and histology data were collected. We aimed to examine the association of the T2-FLAIR mismatch sign (where identified) with clinical factors and outcomes. We evaluated the diagnostic reliability of the mismatch sign and its relation to the definitive histological diagnosis, the co-existence of an MR spectroscopy signature; we have also tried to determine whether the identification of the radiogenomic marker had any impact on the clinical outcome through the decision-making in neurosurgical management.Results. Out of 45 patients with radiological suspected glioma, 30 had a definitive diagnosis of diffuse astrocytoma grade 2 and 3 (Astrocytoma, IDH-mutant according to WHOCNS5). 6 patients had a diagnosis of glioblastoma (Glioblastoma, IDH-wildtype according to WHOCNS5). 8 patients have been diagnosed with oligodendroglioma (Oligodendroglioma, IDH-mutant, and 1p/19q-codeleted according to WHOCNS5) and 1 case had a definitive histology of cerebral abscess. Out of the 30 patients with IDH-mut astrocytoma, 6 (20.0%) showed a mismatch sign. The sensitivity and specificity of the mismatch sign for IDH-mut astrocytoma detection were 20% and98.6%, respectively. There were no differences between patients with an IDH-mut astrocytoma with or without T2FLAIR mismatch sign when grouped according to this with related to baseline characteristics, clinical outcome and presenting symptoms. MR spectroscopy sequences were analyzed where available for the retrospective and prospective cohort. There were 7 cases where MR spectroscopy was performed and, for the IDH-mut astrocytoma cases (n=4) it showed a persistent high Cho/NAA ratio without any difference between the patients with or without the T2FLAIR mismatch sign.Conclusion. In our relatively small retrospective and prospective cohorts, the T2-FLAIR mismatch sign, where identified, was not correlated with clinical features at presentation, prognosis or outcome. Until recently, the grading of CNS tumours has been focusing mainly on histology characteristics, but specific molecular markers can now be used for valuable prognostic information. For this reason, molecular-specific information has been added as an essential feature in grading and it is considered very useful for further estimation of prognosis within variable tumor types. We could not determine if the IDH-mut astrocytomas with mismatch sign represent a specific subgroup. Our study has confirmed that the T2-FLAIR mismatch sign is a reliable and specific marker of IDH-mut astrocytomas.

Magnetic Resonance-Guided Laser Interstitial Thermal Therapy for Management of Low-Grade Gliomas and Radiation Necrosis: A Single-Institution Case Series.

Laser interstitial thermal therapy (LITT) has emerged as a minimally invasive treatment modality for ablation of low-grade glioma (LGG) and radiation necrosis (RN). To evaluate the efficacy, safety, and survival outcomes of patients with radiographically presumed recurrent or newly diagnosed LGG and RN treated with LITT. The neuro-oncological database of a quaternary center was reviewed for all patients who underwent LITT for management of LGG between 1 January 2013 and 31 December 2020. Clinical data including demographics, lesion characteristics, and clinical and radiographic outcomes were collected. Kaplan-Meier analyses comprised overall survival (OS) and progression-free survival (PFS). Nine patients (7 men, 2 women; mean [SD] age 50 [16] years) were included. Patients underwent LITT at a mean (SD) of 11.6 (8.5) years after diagnosis. Two (22%) patients had new lesions on radiographic imaging without prior treatment. In the other 7 patients, all (78%) had surgical resection, 6 (67%) had intensity-modulated radiation therapy and chemotherapy, respectively, and 4 (44%) had stereotactic radiosurgery. Two (22%) patients had lesions that were wild-type IDH1 status. Volumetric assessment of preoperative T1-weighted contrast-enhancing and T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences yielded mean (SD) lesion volumes of 4.1 (6.5) cm3 and 26.7 (27.9) cm3, respectively. Three (33%) patients had evidence of radiographic progression after LITT. The pooled median (IQR) PFS for the cohort was 52 (56) months, median (IQR) OS after diagnosis was 183 (72) months, and median (IQR) OS after LITT was 52 (60) months. At the time of the study, 2 (22%) patients were deceased. LITT is a safe and effective treatment option for management of LGG and RN, however, there may be increased risk of permanent complications with treatment of deep-seated subcortical lesions.

Management of Low-Grade Gliomas – Extent of Resection Matters But Not All Tumours Are Amenable to Surgery

Abstract AIMS To present and review our experience in the management of low-grade gliomas. METHOD Retrospective case note review of all patients with WHO grade 2 glioma from 2011 to 2018 (based on WHO criteria at time of diagnosis). Data collected on demographics, presentation, location, initial management, histology, treatment, progression free (PFS) and overall survival (OS). RESULTS 130 eligible patients. Median follow 4.6 years (up to 10.5). Median age 40 years (range: 18-83). There were 70 (53.8%) astrocytomas, 44 (33.8%) oligodenrogliomas, 16 (12.3%) oligoastrocytomas. 66%(n=86) presented with seizures, 10.7%(n=14) with sensory symptoms, 8.5%(n=11) with speech disturbance, 5.3%(n=4) with motor symptoms and 12.3%(n=16) were identified incidentally. 50.1%(n=65) were frontal, 27.7%(n=36) temporal and 9.2%(n=12) parietal. 1st line treatment was resection in 70.7%(n=92), biopsy in 23.8%(n=31) and observation in 4.6%(n=6). 15.4%(n=20) received adjuvant radiotherapy alone and 6.1%(n=8) received adjuvant radiotherapy followed by chemotherapy . At first recurrence, 31.6%(n=12) received further surgery and 95%(n=38) received radiotherapy and/or chemotherapy . Median PFS from 1st line treatment 66, 44 and 33 months for gross total resection (GRT), subtotal resection (STR), and biopsy respectively. Overall survival was 95.1%, 79.3% and 69.% for GTR, STR and biopsy respectively. CONCLUSION Management of low-grade gliomas remains challenging. Extent of resection impacts prognosis but not all patients have gliomas amenable to surgery. The effects of chemoradiotherapy will be presented in future meetings as this is an ongoing project.

Challenges in the Diagnosis and Management of Low-Grade Gliomas

Low-grade gliomas are clinically challenging entities. Patients with these tumors tend to be relatively young at presentation, and lesions are often incidental findings or are identified because the patient presents with a seizure. Rapidly emerging and evolving molecular classifications of gliomas have influenced treatment paradigms. Importantly, low-grade gliomas can be classified on the basis of IDH mutation status, whereby low-grade astrocytomas harbor the IDH mutation, while oligodendrogliomas are defined by both IDH mutant status and 1p/19q co-deletion. Given the importance of molecular classification for diagnosis, treatment planning, and prognostication, tissue samples are necessary for proper management. Literature supports improved overall survival and outcomes with increased extent of resection for low-grade glioma. Awake craniotomies and resection of insular low-grade gliomas both have been demonstrated as safe and improve outcomes for patients with lesions located in eloquent areas. Given the younger age at diagnosis of these lesions compared with higher-grade gliomas, fertility, fertility preservation, and potential malignant transformation should be discussed with patients of childbearing age.

Foundations of the Diagnosis and Management of Low-Grade Gliomas

In the past, low-grade gliomas-World Health Organization (WHO) grade I and II tumors-were generally expected to have a much better prognosis than higher-grade (WHO grade III and IV) gliomas. However, diffuse gliomas (WHO grade II), unlike WHO grade I gliomas, are by definition infiltrative, limiting resection and potentially contributing to poor outcomes like those seen with malignant gliomas. Rapid progress in the understanding of the pathogenesis of these tumors indicates that specific molecular factors, especially isocitrate dehydrogenase mutation status and the presence or absence of the 1p/19q codeletion (deletion of the short arm of chromosome 1 and long arm of chromosome 19), are much more important than grade in determining prognosis and response to treatment. These molecular characteristics outweigh the histologic distinctions and have been quickly incorporated into the WHO classification of gliomas. Management of these tumors with surgery, radiation, and chemotherapy has similarly been transformed by these developments, highlighting the need for a customized approach for patients with low-grade gliomas.

Innovations in the Diagnosis and Surgical Management of Low-Grade Gliomas

Low-grade gliomas are a broad category of tumors that can manifest at different stages of life. As a group, their prognosis has historically been considered to be favorable, and surgery is a mainstay of treatment. Advances in the molecular characterization of individual lesions has led to newer classification systems, a better understanding of the biological behavior of different neoplasms, and the identification of previously unrecognized entities. New prospective genetic and molecular data will help delineate better treatment paradigms and will continue to change the taxonomy of central nervous system tumors in the coming years. Advances in the field of radiomics will help predict the molecular profile of a particular tumor through noninvasive testing. Similarly, more precise methods of intraoperative tumor tissue analysis will aid surgical planning. Improved surgical outcomes propelled by novel surgical techniques and intraoperative adjuncts and emerging forms of medical treatment in the field of immunotherapy have enriched the management of these lesions. We review the contemporary management and innovations in the treatment of low-grade gliomas.

Establishment of three heterogeneous subtypes and a risk model of low-grade gliomas based on cell senescence-related genes.

BackgroundCellular senescence is a key element in the occurrence and progression of a variety of tumors. As a result, cellular senescence-related markers can be categorized based on the prognosis status of patients. Due to the heterogeneity and the complexity of the tumor microenvironment (TME), the long-term effectiveness of low-grade glioma (LGG) treatment remains a clinical challenge. Consequently, developing and refining effective treatment approaches to aid with LGG management is critical.MethodsBased on the expressions of cell senescence-related genes (CSRGs) acquired from the cellAge database, consensus clustering was utilized to identify stable molecular subtypes. Clinical features, immune infiltration, route modifications, and genetic changes of various subtypes were also assessed. Following that, the least absolute shrinkage and selection operator (LASSO) regression and univariate Cox regression analysis were used for developing the cell senescence-related risk score (CSRS) model. Finally, a correlation study of the CSRS model with molecular, immunological, and immunotherapy parameters was performed.ResultsC1, C2, and C3, are the three senescence-related subtypes that were identified. Patients belonging to the C1 subtype had poor prognoses and a substantial proportion of them was in the grade G3. The differentially expressed genes (DEGs) among the three subtypes were used to develop the CSRS model. In both the training and independent validation cohort, the model had a high area under the receiver operating characteristic (ROC) curve in predicting the overall survival (OS) of patients. As a result, this model can predict clinical features and responses to immunotherapy in a variety of patients and it is a potential independent prognostic factor for LGG.ConclusionThis research discovered three LGG subtypes related to cell senescence and created a CSRS model for six genes. Cell senescence was highly associated with unfavorable prognosis in LGG. The CSRS model can be used to predict the prognosis of patients and identify patients who would benefit from immunotherapy.

Dilemma in low-grade glioma surgery: Review of litreture and when to operate

Diffuse low-grade gliomas (LGG) are tumours of the glial tissue, which are generally slow-growing, but have the potential to undergo anaplastic progression into more aggressive tumours. Diffuse low-grade gliomas (LGG) represent a heterogeneous group of primary brain tumour arising from supporting glial cells. The role of surgery in the management of human low- gliomas has been controversial. The current adjuvant therapies have facilitated treatment of patients, and have rendered neurosurgical removal without morbidity or mortality more commonplace than ever before. Here, we investigated the role of neurosurgery in the management of adults with low-grade gliomas. The management of low- grade glioma is one of the most controversial areas in clinical neuro-oncology. The concept of management of low-grade gliomas is not unitary but much more a composite of different challenges depending on the clinical presentation, signs, neuroradiology, perspectives of neurologists, the opinion of the neurosurgeon, and perhaps most importantly, the aspirations of the patient. It is true therefore that in many patients there will be a dilemma about what is considered optimal management since there is no good evidence base to underpin any single management. Even though there is substantial evidence which claims that surgery have a role to play in extending patient survival.

Duchenne muscular dystrophy gene expression is an independent prognostic marker for IDH mutant low-grade glioma

Alterations in the expression of the Duchenne muscular dystrophy (DMD) gene have been associated with the development, progression and survival outcomes of numerous cancers including tumours of the central nervous system. We undertook a detailed bioinformatic analysis of low-grade glioma (LGG) bulk RNAseq data to characterise the association between DMD expression and LGG survival outcomes. High DMD expression was significantly associated with poor survival in LGG with a difference in median overall survival between high and low DMD groups of over 7 years (P = < 0.0001). In a multivariate model, DMD expression remained significant (P = 0.02) and was an independent prognostic marker for LGG. The effect of DMD expression on overall survival was only apparent in isocitrate dehydrogenase (IDH) mutant cases where non-1p/19q co-deleted LGG patients could be further stratified into high/low DMD groups. Patients in the high DMD group had a median overall survival time almost halve that of the low DMD group. The expression of the individual DMD gene products Dp71, Dp71ab and Dp427m were also significantly associated with overall survival in LGG which have differential biological effects relevant to the pathogenesis of LGG. Differential gene expression and pathway analysis identifies dysregulated biological processes relating to ribosome biogenesis, synaptic signalling, neurodevelopment, morphogenesis and immune pathways. Genes spanning almost the entirety of chromosome 1p are upregulated in patients with high overall DMD, Dp71 and Dp427m expression which worsens survival outcomes for these patients. We confirmed dystrophin protein is variably expressed in LGG tumour tissue by immunohistochemistry and, overall, demonstrate that DMD expression has potential utility as an independent prognostic marker which can further stratify IDH mutant LGG to identify those at risk of poor survival. This knowledge may improve risk stratification and management of LGG.

Management and Outcomes of Low-Grade Gliomas in Africa: A Scoping Review Protocol.

Background:Over the last decade, many advancements have been made in the management of low-grade gliomas (LGGs). Overall survival outcomes are correlated with factors such as postoperative residual volumes and specific tumor biomolecular profiles such as IDH mutation status. It is unclear whether these advancements have benefited LGG patients in Africa. This scoping review protocol outlines how the authors will evaluate the epidemiology, presentations, management and outcomes of LGGs in Africa.Methods:MEDLINE, Embase and African Journals Online will be searched from database inception to date in order to identify the relevant studies. Patients of all ages with histologically and/or radiologically confirmed LGGs that were managed in an African country will be included. Surgical and chemoradiation management of LGG tumours will be considered. Original research, reviews, commentaries, editorials and case reports will be included.Results:Primary outcomes of the review will include LGG management, morbidity and mortality. Secondary outcomes include epidemiology and recurrence of LGGs.Discussion:This scoping review will be the first to evaluate the current landscape of LGG management and outcomes in Africa, highlighting pertinent themes that may be used to guide further research as well as health system strengthening efforts by policymakers and stakeholders.Scoping Review Registration:The protocol has been registered on the Open Science Framework (OSF; registration link: https://doi.org/10.17605/OSF.IO/E732G).Highlights:LGGs account for 17% to 22% of total brain tumours and have a median survival time between 5.6 and 13.3 years.Despite many recent advancements in the management of LGGs, there is a paucity in the data within the African landscape.This scoping review will be the first to evaluate the current landscape of LGG management and outcomes in Africa, highlighting pertinent themes that may be used to guide further research and policymaking efforts.

A Cohort Analysis of Truly Incidental Low-Grade Gliomas

Management of low-grade gliomas (LGGs) is controversial. Incidental LGGs are thought to represent an earlier stage in the disease process compared with symptomatic LGGs. With advanced imaging techniques, the discovery of these lesions is expected to increase, resulting in clinical need for further understanding of these tumors. This study aimed to identify the incidence of incidental LGGs across 2 large European neurosurgical centers and review management and survival of tumors compared with symptomatic cranial LGGs over a 5-year period. LGGs managed during 2015-2019 at the Royal Victoria Infirmary and Münster University Hospital were retrospectively reviewed. An incidental finding was strictly defined as one discovered secondary to routine clinical or research imaging, not associated with investigation for a space-occupying lesion, with no associated symptoms. All histomolecular pathology reports were reviewed. Of 150 cases of World Health Organization grade II tumors identified at both centers, 82 were symptomatic, diffuse LGGs, with 20 discovered incidentally. There were 48 nondiffuse and/or pediatric tumors, which were excluded. Incidental LGGs were mostly IDH mutated and oligodendroglial with a trend toward improved overall survival and significantly increased progression-free survival compared with symptomatic LGGs (P= 0.024). In all cases, regardless of presentation, progression-free survival and overall survival were significantly improved following gross total resection versus biopsy (hazard ratio 0.45 [95% confidence interval 0.21-0.95], P= 0.037 vs. hazard ratio 0.10 [95% confidence interval 0.02-0.44], P= 0.003). In this study, differences in characteristics and survival between incidental and symptomatic LGGs were present, yet not significant owing to the rarity, and therefore small sample size, of incidental LGGs. Further global collaboration and development of an international glioma registry with a focus on symptoms, imaging indications (if incidental), histomolecular data, and management are needed.

Mutational profiling of low-grade gliomas identifies prognosis and immunotherapy-related biomarkers and tumour immune microenvironment characteristics.

Low‐grade glioma (LGG) is a heterogeneous tumour with the median survival rate less than 10 years. Therefore, it is urgent to develop efficient immunotherapy strategies of LGG. In this study, we analysed mutation profiles based on the data of 510 LGG patients from the Cancer Genome Atlas (TCGA) database and investigated the prognostic value of mutated genes and evaluate their immune infiltration. Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to indicate the characteristics of gliomas that respond to immune checkpoint blockade (ICB) therapy. Univariate and multivariate cox regression analysis was performed to identify indicators to construct the nomogram model. 485 (95.47%) of 508 LGG samples showed gene mutation, and 9 mutated genes were significantly related to overall survival (OS), among which 6 mutated genes were significantly correlated with OS between mutation and wildtypes. Immune infiltration and immune score analyses revealed that these six mutated genes were significantly associated with tumour immune microenvironment in LGG. The response of LGG with different characteristics to ICB was evaluated by TIDE algorithm. Finally, CIC gene was screened through both univariate and multivariate Cox regression analyses, and the nomogram model was established to determine the potential prognostic value of CIC in LGG. Our study provides comprehensive analysis of mutated genes in LGG, supporting modulation of mutated genes in the management of LGG.

MRI-Based Radiomics and Radiogenomics in the Management of Low-Grade Gliomas: Evaluating the Evidence for a Paradigm Shift.

Low-grade gliomas (LGGs) are tumors that affect mostly adults. These neoplasms are comprised mainly of oligodendrogliomas and diffuse astrocytomas. LGGs remain vexing to current management and therapeutic modalities although they exhibit more favorable survival rates compared with high-grade gliomas (HGGs). The specific genetic subtypes that these tumors exhibit result in variable clinical courses and the need to involve multidisciplinary teams of neurologists, epileptologists, neurooncologists and neurosurgeons. Currently, the diagnosis of an LGG pivots mainly around the preliminary radiological findings and the subsequent definitive surgical diagnosis (via surgical sampling). The introduction of radiomics as a high throughput quantitative imaging technique that allows for improved diagnostic, prognostic and predictive indices has created more interest for such techniques in cancer research and especially in neurooncology (MRI-based classification of LGGs, predicting Isocitrate dehydrogenase (IDH) and Telomerase reverse transcriptase (TERT) promoter mutations and predicting LGG associated seizures). Radiogenomics refers to the linkage of imaging findings with the tumor/tissue genomics. Numerous applications of radiomics and radiogenomics have been described in the clinical context and management of LGGs. In this review, we describe the recently published studies discussing the potential application of radiomics and radiogenomics in LGGs. We also highlight the potential pitfalls of the above-mentioned high throughput computerized techniques and, most excitingly, explore the use of machine learning artificial intelligence technologies as standalone and adjunct imaging tools en route to enhance a personalized MRI-based tumor diagnosis and management plan design.

Low-Grade Glioma Case Series: Lessons Learned from an Evolving 10-Year Single-Institution Multidisciplinary Team Practice

Low-grade gliomas are a heterogeneous group with significant changes in their management during the last decade. To assess how our multidisciplinary team approach to the management of low-grade glioma has evolved over the past 10 years and its implications for outcomes. Retrospective single-center cohort study of adult patients with a pathologically confirmed diagnosis of World Health Organization grade II glioma between 2009 and 2018. Demographic, clinical, and pathologic data were collected. Ninety-five patients were included. There was a statistically significant difference in the surgical approach, with more patients having gross total resection (45.7% vs. 18.4%) and fewer patients having a biopsy (21.8% vs. 49.0%) (P= 0.002) after 2014. There was a significantly better overall survival after 2014 (<2014, 16.3%; ≥2014, 0 deaths; P= 0.010) measured at the mean time of follow-up. The use of adjuvant chemotherapy (P= 0.045) and radiotherapy (P= 0.001) significantly decreased after 2014. A subgroup analysis showed that the impact of extent of surgical resection was the greatest for survival in the 1p19q noncodeleted tumors (P= 0.029) and for seizure outcomes in the 1p19q codeleted group (P= 0.018). There was no statistically significant increase in neurologic disability with more radical surgery, incorporating intraoperative neuromonitoring, as measured by modified Rankin Scale score (P > 0.05). More radical surgery was associated with increased survival, less need for postoperative adjuvant therapy and better seizure control, without significant morbidity. Molecular markers are useful tools for stratification of benefits after such surgery.

Identification and validation of an individualized prognostic signature of lower-grade glioma based on nine immune related long non-coding RNA

BackgroundLow-grade glioma (LGG)is one of the most common and aggressive neurological malignant tumors of the central nervous system. Mounting evidence indicates that aberrantly expressed long non-coding RNA (lncRNAs) and immune cell infiltration influence low-grade glioma development. Despite the increasing amount of research on lncRNA, there are very few immune-related lncRNA for LGG studies. MethodsWe evaluated immune cell infiltration in 529 low-grade glioma patient specimens from TCGA and 1152 normal brain tissue samples from GTEx. ssGSEA was used to generate high, medium, and low immune cell infiltration groups and to examine the heterogeneity of the low-grade glioma immune microenvironment. A risk model of immune-related lncRNAs based on immune gene sets was developed. Sequential single-factor Cox regression, Lasso regression, and stepwise multiple Cox regression analyses uncovered immune-related lncRNAs with low-grade glioma prognostic value. Kaplan-Meier analysis, ROC analysis, and nomograms were used to predict low-grade glioma OS. At length, We performed GO term and KEGG enrichment analyses and used standardized enrichment scores (NES) to identify signaling pathways that were significantly enriched. ResultsWe identified nine immune-associated lncRNAs with low-grade glioma prognostic value (AC009283.1, AC009227.1, AL121899.1, LINC00174, LINC02166, AC018647.1, AC061961.1, NRAV, and LINC00320).These prognostic lncRNAs were used to establish prognostic markers. Kaplan-Meier Survival analysis revealed a 10-year survival rate of 22.68 % (95 % CI: 13.54–38 %] in high-risk LGG vs. 54 % (95 % CI: 39.04–74.8 %] in low-risk LGG patients. Univariate Cox regression analysis showed that the HR of risk score and 95 % CI were 1.081 and (1.060–1.102) (p < 0.001), respectively. In contrast, those from multivariate Cox regression analysis were 1.066 and (1.046–1.087) (p < 0.001). This indicated that nine LncRNAs are independent prognostic factors for patients with low-grade glioma. GSEA suggests that the identified lncRNAs influence low-grade glioma tumorigenesis and prognosis by modulating immune responses and cancer pathways. ConclusionsOur data highlight the potential prognostic value of the nine immune-related lncRNA in low-grade glioma and may open new research lines and guide low-grade glioma management.

New treatment modalities in NF-related neuroglial tumors.

The management of low-grade gliomas (LGGs) and other neuroglial tumors in children with neurofibromatosis type 1 (NF1) has not changed over the past 2-3 decades. With the widespread utilization of chemotherapy for younger children with progressive LGGs, outcomes have been good for most patients who have required treatment. However, some may progress after the initiation of chemotherapy and others, although radiographically responding or with stable disease, may develop progressive neurologic and visual deterioration. Molecular-targeted therapy has become an option for patients who have progressed after receiving chemotherapy and the mTOR inhibitors and bevacizumab have already shown some degree of efficacy. However, the greatest impact has been the introduction of the MEK inhibitors. A variety of different MEK inhibitors are in clinical trials and have already demonstrated the ability to result in radiographic tumor shrinkage in the majority of children with NF1 and progressive LGGs. Because of this efficacy, the MEK inhibitors have moved rapidly from phase I studies to ongoing phase III studies comparing their benefit directly to that of chemotherapy. The long-term ability of these agents to not only control disease, but improve visual and/or neurological function, as well as their short- and long-term safety, are open questions that can only be answered by well-constructed prospective, often randomized, clinical trials.

The Ethical Dilemma in the Surgical Management of Low Grade Gliomas According to the Variable Availability of Resources and Surgeon Experience.

Low grade gliomas (LGGs) affect young individuals in the prime of life. Management may alternatively include biopsy and observation or surgical resection. Recent evidence strongly favors maximal and supramaximal resection of LGGs in optimizing survival metrics. Awake craniotomy with cortical mapping and electrical stimulation along with other preoperative and intraoperative surgical adjuncts, including intraoperative magnetic resonance and diffusion tensor imaging, facilitates maximization of resection and eschews precipitating neurological deficits. Intraoperative imaging permits additional resection of identified residual to be completed within the same surgical session, improving extent of resection and consequently progression free and overall survival. These resources are available in only a few centers throughout the United States, raising an ethical dilemma as to where patients harboring LGGs should most appropriately be treated.