Diffuse Infiltrative Gliomas Research Articles

Pediatric brain tumor cell lines exhibit miRNA-depleted, Y RNA-enriched extracellular vesicles.

Medulloblastoma (MB) and diffuse infiltrative pontine glioma (DIPG) are malignant pediatric tumors. Extracellular vesicles (EVs) and their bioactive cargoes have been implicated in tumorigenesis. Most studies have focused on adult tumors, therefore the role of EVs and the noncoding RNA (ncRNA) landscape in pediatric brain tumors is not fully characterized. The overall aim of this pilot study was to isolate EVs from MB and DIPG patient-derived cell lines and to explore the small ncRNA transcriptome. EVs from 3 DIPG and 4MB patient-derived cell lines were analyzed. High-throughput next generation sequencing interrogated the short non-coding RNA (ncRNA) transcriptome. Known and novel miRNAs were quantified. Differential expression analysis, in silico target prediction, and functional gene enrichment were performed. EV secretomes from MB and DIPG patient-derived cell lines demonstrated discrete ncRNA biotypes. Notably, miRNAs were depleted and Y RNAs were enriched in EV samples. Hierarchical cluster analysis revealed high discrimination in miRNA expression between DIPG and MB cell lines and RNA-Seq identified novel miRNAs not previously implicated in MB or DIPG pathogenesis. Known and putative target genes of dysregulated miRNAs were identified. Functional annotation analysis of the target genes for differentially expressed EV-and parental-derived miRNAs revealed significant cancer-related pathway involvement. This hypothesis-generating study demonstrated that pediatric brain tumor-derived cell lines secrete EVs comprised of various ncRNA cargoes. Validation of these findings in patient samples may provide new insights into the pediatric brain tumor microenvironment and identification of novel therapeutic candidates.

Dissociation of structural and functional connectomic coherence in glioma patients

With diffuse infiltrative glioma being increasingly recognized as a systemic brain disorder, the macroscopically apparent tumor lesion is suggested to impact on cerebral functional and structural integrity beyond the apparent lesion site. We investigated resting-state functional connectivity (FC) and diffusion-MRI-based structural connectivity (SC) (comprising edge-weight (EW) and fractional anisotropy (FA)) in isodehydrogenase mutated (IDHmut) and wildtype (IDHwt) patients and healthy controls. SC and FC were determined for whole-brain and the Default-Mode Network (DMN), mean intra- and interhemispheric SC and FC were compared across groups, and partial correlations were analyzed intra- and intermodally. With interhemispheric EW being reduced in both patient groups, IDHwt patients showed FA decreases in the ipsi- and contralesional hemisphere, whereas IDHmut patients revealed FA increases in the contralesional hemisphere. Healthy controls showed strong intramodal connectivity, each within the structural and functional connectome. Patients however showed a loss in structural and reductions in functional connectomic coherence, which appeared to be more pronounced in IDHwt glioma patients. Findings suggest a relative dissociation of structural and functional connectomic coherence in glioma patients at the time of diagnosis, with more structural connectomic aberrations being encountered in IDHwt glioma patients. Connectomic profiling may aid in phenotyping and monitoring prognostically differing tumor types.

DIPG-23. SINGLE CASE REPORT OF LOW DOSE RADIOTHERAPY AND CHEMOTHERAPY IN THE TREATMENT OF DIPG

A 3 year-old girl, was noted to have progressive gait problem since Nov. 2017 and brought to hospital for checkup. Brain MRI on Jan. 2018 showed T2 hyperintensity infiltrative pontine lesion, favoring diffuse infiltrative pontine glioma and mild obstructive hydrocephalus, received VP-shunting on Jan. 15, 2018. Due to the refusal of surgical biopsy for tissue proof, we started the radiotherapy from Jan. 24, 2018, using Rapidarc technique with 6MV photon energy to treat the brain stem lesion, ended on Feb. 24, 2018 with total dose of 25.5Gy in 17 fractions as our usual practice. Following the completion of radiotherapy, we started the adjuvant chemotherapy using 1-week on, 1-week off regimen of temozolomide using dosage of 75 mg/sq-m/day, and this patient’s general condition returned back to nearly normal. Serial follow-up images of brain MRI on 04/30/2018, 08/01/2018, 11/30/2018, 02/26/2019, 05/30/2019, 08/28/2019 showed slow progression of the pontine lesion, without the development of contrast enhanced new lesion. She maintained the functional independent until Sep. 2019, she was noted to have symptoms of ataxic gait, esotropia and choking on drinking liquid. We started the retreatment of radiotherapy from Oct.7, 2019, using same technique, ended on Nov. 5, 2019 with total dose of 30Gy in 20 fractions. The symptoms improved partially after the treatment, with residual weakness over left extremity. We are still treating the patient with adjuvant temozolomide, and she has survived most of time functionally independent in these 2 years.

TAMI-20. POLY(ADP-RIBOSE) GLYCOHYDROLASE INHIBITION SEQUESTERS NAD+ TO POTENTIATE THE METABOLIC LETHALITY OF ALKYLATING CHEMOTHERAPY IN IDH MUTANT TUMOR CELLS

Abstract Mutations in IDH1 or IDH2 characterize the majority of diffuse infiltrative gliomas of younger adulthood. DNA alkylator chemotherapy has proven to be an effective treatment for IDH mutant glioma, yet recurrences remain frequent and improved treatments are needed. Upon exposure of cancer cells to DNA alkylating agents, poly(ADP-ribose) polymerases (PARPs) catalyze the transient oligomerization of nicotinamide adenine dinucleotide (NAD+) into poly-ADP-ribose (PAR) chain-assemblies, which stimulate the DNA damage response. Here, we find that, in IDH mutant glioma cells, alkylator-induced cytotoxicity is dramatically augmented by pharmacologic inhibition or genetic knockout of the PAR breakdown enzyme poly(ADP-ribose) glycohydrolase (PARG). Mechanistically, we show this augmentation is driven by a metabolic state pairing amplified alkylator-induced DNA damage with catastrophic depletion of NAD+. IDH mutant cancer cells have low basal levels of NAD+, rendering them vulnerable to prolonged NAD+ depletion. Either of two clinically-utilized monofunctional alkylators, procarbazine (PCZ) or temozolomide (TMZ), when exposed to multiple IDH mutant lines, activated PARP conversion of cellular NAD+ monomers into polymerized PAR. Subsequent PAR breakdown and recycling of NAD+ monomers was then halted by concomitant PARG inactivation, amplifying PARylation-mediated DNA damage signaling and critically depleting free NAD+, resulting in profound cytotoxicity. This effect was partially reversed by NAD+ rescue supplementation, confirming the key contribution of metabolic stress. Combined alkylator treatment and PARG inhibition in vivo maximized both NAD+ depletion and cytotoxicity in an endogenous IDH mutant cancer model. Thus, alkyating DNA damaging agents expose a metabolic liability in IDH mutant cancers, and subsequent targeted blockade of PAR breakdown and NAD+ metabolite recovery can exploit this vulnerability to provide genotype-specific therapeutic benefit.

Diffuse infiltrative pontine glioma biopsy in children with neuronavigation, frameless procedure: A single center experience of 10 cases

IntroductionThis study presented pediatric DIPG ‘s biopsy with frameless Neuronavigation. Patients and methodsWe report our experience about 10 patients who had Diffuse Intrinsic Pontine Glioma between 2014 and 2018. All patients were biopsied with BrainLab Varioguide Neuronavigation®. We always used fusion between specific CT Scan and MRI to selected target, made planning and biopsies. All patients were included in BIOMEDE after scientific and ethic discussions. We always selected a trans-cerebellar trajectory and made same procedure (lot of biopsies at one level). All patients have MRI at J1 to verify site of biopsy and to eliminate complication. ResultsThe average age was 8.1 years. Symptoms were common with principally headaches and nystagmus. All biopsies were contributive for histopathological diagnosis and establish molecular profile for molecular study. We have no definitive morbidity and procedure duration was 93minutes in average. All MRI didn’t showed intracranial complication after procedure and showed great precision of biopsy compared with the selected target. DiscussionWe reviewed the literature and compare our results with series of DIPG biopsies using stereotactic frame or robotic assisted frameless. It was a safe, accuracy and easiness procedure. We always have histopathological and molecular result to proceed next step of treatment. This modality is an alternative possibility to biopsy very young patients with low morbidity.

EPID-21. THE NATIONAL SPECTRUM OF NEWLY-DIAGNOSED BRAIN TUMORS IN ADULT PATIENTS VARIES SIGNIFICANTLY BY PATIENT DEMOGRAPHICS

Abstract INTRODUCTION Herein we examine the epidemiology and outcomes of the entire spectrum of intracranial tumors in the contemporary era. METHODS Adult patients (≥20yo) presenting between 2010–2015 where the first evidence of cancer involves an intracranial tumor were queried from the National Cancer Database, which comprises >70% of cancers newly-diagnosed in the U.S. Tumor types were classified by WHO2016 ICD-O3, and stratified by patient characteristics. RESULTS 361,841 adults without a history of cancer presented with intracranial tumors between 2010–2015. Across all ages, these were comprised of 1) brain metastases (BMs; 25%: 29% in males vs. 23% in females); 2) meningiomas (25%: 15% in males, but 34% in females) including atypical (n=4,565) and anaplastic (n=833); 3) diffuse infiltrative gliomas (21%: 26% in males vs. 17% in females), mostly GBMs (14%); followed by 4) sellar (14%), 5) cranial nerve (6%), and PCNSL (3%) tumors. The remaining types each comprised ≤2 % of brain tumors, including mesenchymal non-meningothelial tumors (2%), intracranial ependymal (0.8%), mixed neuronal-glial (0.7%), circumscribed “other astrocytomas” (0.6%, mostly pilocytic astrocytomas n=1,307 and PXAs n=272), CNS embryonal (0.3%), pineal (0.2%), GCTs (0.1%), and choroid plexus (0.1%) tumors. In the 91,686 patients presenting with a BM, the most common primaries were lung adenocarcinoma (39%), lung SmallCC (14%), lung SqCC (8%), breast (8% of females), melanoma (3%), kidney (3%), colorectal (2%), and esophageal (1%). The distributions of brain tumor types differed significantly by age, sex, race/ethnicity, and insurance status. CONCLUSIONS In adult patients where the first manifestation of cancer includes an intracranial tumor, the most common diagnosis is either metastatic disease (predominantly from NSCLC) in males or benign meningiomas in females; but varies substantially by age group. Notably, our results adjust the traditional teaching that half of all new brain masses are BMs, which in fact represent only ~25% of new intracranial masses.

Tumor Immunized Autologous Natural Killer Cell (NK) Therapy/Compassionate Use

As well known, diffuse infiltrative pontine glioma (DIPG)-despite all available treatment modalities- carries a dismal prognosis with a mean survival of around one year [1]. A four year old boy was referred to me with a radiological diagnosis of DIPG. He was irradiated and a ventriculoperitoneal shunt (VPs) was inserted in a health facility in Europe. On admission (seven months after the diagnosis), patient was tracheostomized, conscious, quariparetic and with bilateral abducens and lower cranial nerve paresis. I decided to operate on the patient in order to debulk the necrotic pontine mass and to verify the radiological diagnosis histopathologically. Additionally, I planned to co-culture the tumoral cells with the natural killer (NK) cells isolated from the peripheral venous blood to investigate the immunization and potentiation of autologous NK cells against glioma cells in vitro after the ethical committee approval was obtained from the Istanbul Aydin University. In January 2019, pontine mass was partially removed via telo-velar approach under neurophysiological monitorization with no additional post op deficits and the unilateral abducens nerve recovery. Tumor specimens were sent to the tissue culture labs and the cell culture procedures were carried out meticulously. Meanwhile, routine histopathological evaluation reported the pontine lesion as DIPG (Grade 4 astrocytoma) officially.

Long term survival in diffuse infiltrative brainstem gliomas in children and adolescents treated with radiotherapy and Nimotuzumab

Objectives This study is devoted to the evaluation of the possibility and effectiveness of re irradiation treatment of children and adolescents with the relapses of diffusely growing brainstem tumor BST Methods Repeated radiotherapy was performed in patients aged from to years who had a relapse of a BST in terms from months to years after the first curses radiation treatment in doses of Gy In the case of re irradiation single fractions of Gy were used five times a week to total doses from to Gy Results The tolerability of repeated irradiation was satisfactory Improvement of the condition of the patients was achieved in the condition of the three patients did not change and the two worsened which caused the interruption of treatment at a dose of and Gy On further observation children died of progression of the tumor in a period of to months their median life expectancy was months Three patients dropped out of observation and two were alive for years and years after re irradiation with residual neurologic disorders with the tumor residue detected on the MRI without signs of radiation necrosis Both had a pilocitic astrocytoma Conclusion Repeated radiotherapy for the relapse of BST can improve the quality of life for most children and provide a long term stabilization of tumor growth in low grade gliomas

Long term survival in diffuse infiltrative brainstem gliomas in children and adolescents treated with radiatherapy and Nimotuzumab

Background Brainstem gliomas have a short survival time chemotherapy has not improved outcome We report the result obtained with the combination of Radiotherapy and the monoclonal antibody Nimotuzumab in a series of these tumors Material and methods children and adolescents treated with irradiation and Nimotuzumab were included between Jan and December all with the diagnosis of diffuse infiltrative pontine gliomas DIPG irradiated at the Instituto Nacional de Oncologia y Radiobiologia in Havana Cuba Nimotuzumab was applied during the period receiving Radiotherapy and them monthly for one year or more Results Median age at diagnosis was years range years old median survival was months and Kaplan Meier survival was at years and at years established till years Addition of Nimotuzumab was safe and well tolerated Conclusion Combination of Nimotuzumab and Radiotherapy is safe and could increase survival

A novel high-sensitivity assay to detect a small fraction of mutant IDH1 using droplet digital PCR.

Detection of mutations in the isocitrate dehydrogenase 1 (IDH1) gene is useful for accurate diagnosis of lower grade gliomas, as described in the 2016 World Health Organization classification of tumors of the central nervous system. Conventional analysis tools, including Sanger DNA sequencing and immunohistochemistry, might fail to detect a small fraction of mutant IDH1 owing to their limited sensitivity. Considering that lower grade gliomas are infiltrative in nature, a highly sensitive detection assay for IDH1 mutation is required for their accurate diagnosis. In this study, we successfully established a droplet digital PCR (ddPCR) system to detect a small fraction of IDH1 mutation. We could detect 0.05% of mutant IDH1 allele in 30ng DNA. Using this assay, we could detect a small fraction of mutant IDH1 in a glioma case, identified as a wildtype tumor according to the conventional assays. Additionally, in a small amount of DNA derived from the cerebrospinal fluid, we could detect an IDH1 mutation. In conclusion, the ddPCR system is useful to identify a small fraction of IDH1 mutation in diffuse infiltrative gliomas. This might be useful for precision medicine of these gliomas in the near future and also for the non-invasive diagnosis of these gliomas.

Accurate Delineation of Glioma Infiltration by Advanced PET/MR Neuro-Imaging (FRONTIER Study)

Glioma imaging, used for diagnostics, treatment planning, and follow-up, is currently based on standard magnetic resonance imaging (MRI) modalities (T1 contrast-enhancement for gadolinium-enhancing gliomas and T2 fluid-attenuated inversion recovery hyperintensity for nonenhancing gliomas). The diagnostic accuracy of these techniques for the delineation of gliomas is suboptimal. To assess the diagnostic accuracy of advanced neuroimaging compared with standard MRI modalities for the detection of diffuse glioma infiltration within the brain. A monocenter, prospective, diagnostic observational study in adult patients with a newly diagnosed, diffuse infiltrative glioma undergoing resective glioma surgery. Forty patients will be recruited in 3 years. Advanced neuroimaging will be added to the standard preoperative MRI. Serial neuronavigated biopsies in and around the glioma boundaries, obtained immediately preceding resective surgery, will provide histopathologic and molecular characteristics of the regions of interest, enabling comparison with quantitative measurements in the imaging modalities at the same biopsy sites. In this clinical study, we determine the diagnostic accuracy of advanced imaging in addition to standard MRI to delineate glioma. The results of our study can be valuable for the development of an improved standard imaging protocol for glioma treatment. We hypothesize that a combination of positron emission tomography, MR spectroscopy, and standard MRI will have a superior accuracy for glioma delineation compared with standard MRI alone. In addition, we anticipate that advanced imaging will correlate with the histopathologic and molecular characteristics of glioma. CHO, [11C-]CholineCRF, case report formsFET, [18F-]Fluoroethyl-tyrosineFLAIR, fluid-attenuated inversion recoveryMETC, Medical Ethical CommitteeMRS, magnetic resonance spectroscopyPET, positron emission tomographyVUmc, VU University Medical Center.

Early detection of human glioma sphere xenografts in mouse brain using diffusion MRI at 14.1 T.

Glioma models have provided important insights into human brain cancers. Among the investigative tools, MRI has allowed their characterization and diagnosis. In this study, we investigated whether diffusion MRI might be a useful technique for early detection and characterization of slow-growing and diffuse infiltrative gliomas, such as the proposed new models, LN-2669GS and LN-2540GS glioma sphere xenografts. Tumours grown in these models are not visible in conventional T2 -weighted or contrast-enhanced T1 -weighted MRI at 14.1 T. Diffusion-weighted imaging and diffusion tensor imaging protocols were optimized for contrast by exploring long diffusion times sensitive for probing the microstructural alterations induced in the normal brain by the slow infiltration of glioma sphere cells. Compared with T2 -weighted images, tumours were properly identified in their early stage of growth using diffusion MRI, and confirmed by localized proton MR spectroscopy as well as immunohistochemistry. The first evidence of tumour presence was revealed for both glioma sphere xenograft models three months after tumour implantation, while no necrosis, oedema or haemorrhage were detected either by MRI or by histology. Moreover, different values of diffusion indices, such as mean diffusivity and fractional anisotropy, were obtained in tumours grown from LN-2669GS and LN-2540GS glioma sphere lines. These observations highlighted diverse tumour microstructures for both xenograft models, which were reflected in histology. This study demonstrates the ability of diffusion MRI techniques to identify and investigate early stages of slow-growing, invasive tumours in the mouse brain, thus providing a potential imaging biomarker for early detection of tumours in humans.

Rapid Intraoperative Molecular Characterization of Glioma

Conclusive intraoperative pathologic confirmation of diffuse infiltrative glioma guides the decision to pursue definitive neurosurgical resection. Establishing the intraoperative diagnosis by histologic analysis can be difficult in low-cellularity infiltrative gliomas. Therefore, we developed a rapid and sensitive genotyping assay to detect somatic single-nucleotide variants in the telomerase reverse transcriptase (TERT) promoter and isocitrate dehydrogenase 1 (IDH1). This assay was applied to tissue samples from 190 patients with diffuse gliomas, including archived fixed and frozen specimens and tissue obtained intraoperatively. Results demonstrated 96% sensitivity (95% CI, 90%-99%) and 100% specificity (95% CI, 95%-100%) for World Health Organization grades II and III gliomas. In a series of live cases, glioma-defining mutations could be identified within 60 minutes, which could facilitate the diagnosis in an intraoperative timeframe. The genotyping method described herein can establish the diagnosis of low-cellularity tumors like glioma and could be adapted to the point-of-care diagnosis of other lesions that are similarly defined by highly recurrent somatic mutations.

Trends in Fluorescence Image-Guided Surgery for Gliomas

Mounting evidence suggests that a more extensive surgical resection is associated with an improved life expectancy for both low-grade and high-grade glioma patients. However, radiographically complete resections are not often achieved in many cases because of the lack of sensitivity and specificity of current neurosurgical guidance techniques at the margins of diffuse infiltrative gliomas. Intraoperative fluorescence imaging offers the potential to improve the extent of resection and to investigate the possible benefits of resecting beyond the radiographic margins. Here, we provide a review of wide-field and high-resolution fluorescence-imaging strategies that are being developed for neurosurgical guidance, with a focus on emerging imaging technologies and clinically viable contrast agents. The strengths and weaknesses of these approaches will be discussed, as well as issues that are being addressed to translate these technologies into the standard of care.

Mathematical modeling of glioma therapy using oncolytic viruses

Diffuse infiltrative gliomas are adjudged to be the most common primary brain tumors in adults and they tend to blend in extensively in the brain micro-environment. This makes it difficult for medical practitioners to successfully plan effective treatments. In attempts to prolong the lengths of survival times for patients with malignant brain tumors, novel therapeutic alternatives such as gene therapy with oncolytic viruses are currently being explored. Based on such approaches and existing work, a spatio-temporal model that describes interaction between tumor cells and oncolytic viruses is developed. Conditions that lead to optimal therapy in minimizing cancer cell proliferation and otherwise are analytically demonstrated. Numerical simulations are conducted with the aim of showing the impact of virotherapy on proliferation or invasion of cancer cells and of estimating survival times.

Aspectos clinicopatológicos y moleculares de valor diagnóstico y pronóstico en gliomas

Diffuse infiltrative gliomas, the most common primary brain tumours, account for almost 80% of malignant brain tumours. 60-70% of gliomas are astrocytic and over 80% of these tumours is considered high grade malignancy (grade III and IV) according to current World Health Organization classification. Infiltrating gliomas include diffuse astrocytomas, oligodendrogliomas and oligoastrocytomas. To review the clinical and histological features of cerebral gliomas, and molecular alterations that add relevant information for novel approaches in diagnosis, prognosis and treatment. The current gold standard diagnosis of these tumours relies on histopathological classification, which provides a grading of malignancy as a predictor of biological behaviour. However emerging molecular abnormalities have been discovered in the last years and these molecular changes are playing an increasingly prominent role as predictive biomarkers or in the development of diagnostic and prognostic. Now the neuropathologist is in crossroads between pathology and molecular biology and he plays a significant role in implementation of treatments and/or clinical trials. The study of proteomics and molecular biomarkers should complement the histopathological analysis and sometimes allows to determine direct or indirect predictive factors as well as the study of affected pathways which may become selective therapeutic targets.

Cognition and resective surgery for diffuse infiltrative glioma: an overview

Compared to classical oncological outcome measures such as time to progression and survival, the importance of cognitive functioning in patients with diffuse infiltrative brain tumors has only recently been recognized. Apart from the relatively low incidence and the invariably fatal outcome of gliomas, the general assumption that cognitive assessment is time-consuming and burdensome contributes to this notion. Our understanding of the effects of brain surgery on cognition, for instance, is largely based on studies in surgical patients with refractory epilepsy, with only a limited number of studies in surgical patients with gliomas. The impact of other factors affecting cognition in glioma patients such as direct tumor effects, radiotherapy and chemotherapy, and medical treatment, including anti-epileptic drugs and steroids, have been studied more extensively. The purpose of this paper is to provide an overview of cognition in patients with diffuse infiltrative gliomas and the impact of resective surgery as well as other tumor and treatment-related factors.

Abstract 4307: Establishment of a patient-derived diffuse infiltrative pontine glioma primary cell line and animal model: Implications for future investigations and treatment

Abstract Diffuse infiltrating brainstem glioma arises almost exclusively in children and despite advances in imaging, neurosurgery and radiotherapy, the majority of patients die within 2 years after initial diagnosis. Because of the infiltrative nature and anatomic location in an eloquent area of the brain, most brainstem gliomas are treated without a surgical biopsy. The corresponding lack of tissue samples has resulted in a limited understanding of the underlying genetic and biochemical abnormalities associated with these tumors, and is a substantial obstacle for the development of animal model designed specifically for the preclinical testing of specific molecular target of brainstem gliomas. We established a brainstem glioma cells originated from human biopsy sample of a low grade brainstem glioma. The brainstem glioma cells were subsequently modified with hTERT (human telomerase ribonucleoprotein reverse transcriptase) to immortalize the cells and analyzed genetic and biochemical abnomalities of the cells. The established human brainstem glioma cells were tumorgenic in athymic rodents and the developed brainstem tumor was recapitulated the infiltrative growth of diffuse infiltrating brainstem glioma in patients, and can be monitored for tumor growth noninvasively by bioluminescence imaging (BLI). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4307. doi:10.1158/1538-7445.AM2011-4307

Guidelines on management of low‐grade gliomas: report of an EFNS–EANO* Task Force

Diffuse infiltrative low-grade gliomas of the cerebral hemispheres in the adult are a group of tumors with distinct clinical, histological and molecular characteristics, and there are still controversies in management. The scientific evidence of papers collected from the literature was evaluated and graded according to EFNS guidelines, and recommendations were given accordingly. WHO classification recognizes grade II astrocytomas, oligodendrogliomas and oligoastrocytomas. Conventional MRI is used for differential diagnosis, guiding surgery, planning radiotherapy and monitoring treatment response. Advanced imaging techniques can increase the diagnostic accuracy. Younger age, normal neurological examination, oligodendroglial histology and 1p loss are favorable prognostic factors. Prophylactic antiepileptic drugs are not useful, whilst there is no evidence that one drug is better than the others. Total/near total resection can improve seizure control, progression-free and overall survival, whilst reducing the risk of malignant transformation. Early post-operative radiotherapy improves progression-free but not overall survival. Low doses of radiation are as effective as high doses and better tolerated. Modern radiotherapy techniques reduce the risk of late cognitive deficits. Chemotherapy can be useful both at recurrence after radiotherapy and as initial treatment after surgery to delay the risk of late neurotoxicity from large-field radiotherapy. Neurocognitive deficits are frequent and can be caused by the tumor itself, tumor-related epilepsy, treatments and psychological distress.

Imagerie des gliomes

The imaging of gliomas, as well as diffuse infiltrative gliomas or as more recently individualized entities, has been profoundly modified these last years. Correlated with the classic morphological MRI , numerous new sequences have appeared that allowed a more metabolic approach of the tumors, such as diffusion, perfusion – related to angiogenesis – and spectroscopy – reflecting metabolic data. Their development in daily practice allows to precise the diagnostic, to definite the more active areas (correlated with the hyperperfused or more metabolic active areas in relation with the Ki67 index) and so optimize the biopsy and/or evaluate the evolution of the lesion. When associated, they allow also and perhaps especially to precise the diagnostic, particularly with other tumoral masses such as lymphomas or metastases that can present misleading patterns, but also with other more benign lesions such as abcesses. Always critically analysed, and reevaluated along the time if necesary, they can sometimes help the histological diagnosis, but never can be used in place of it.