Cerebral Gliomas Research Articles

Prospects for the use of perampanel in the treatment of epilepsy in patients with malignant gliomas of the brain

Epilepsy occurs in 35–95% of patients with low-grade malignant cerebral gliomas and in 29–71% of patients with high-grade gliomas. Seizures can be the first manifestation of a malignant cerebral glioma or may develop in the postoperative period and during chemoradiation therapy. This necessitates the use of antiepileptic drugs that can control seizures, ensure seizure prevention, and provide secondary seizure prophylaxis without reducing the effectiveness of anticancer therapy or the patient’s quality of life. The processes of epileptogenesis and oncogenesis are closely interrelated through common developmental mechanisms, with glutamate playing a key role. Increased glutamate secretion is accompanied by elevated expression and activation of its receptors, which raises seizure susceptibility. This is associated with increased levels of brain-derived neurotrophic factor, the number of synapses between peritumoral neurons and glioma cells, and the expression of various growth factors, all of which contribute to tumor progression. In this context, special attention is given to perampanel, a glutamate receptor antagonist and third-generation antiepileptic drug, in the treatment of epilepsy in patients with malignant cerebral gliomas. It has been shown that perampanel not only effectively controls seizures in patients with malignant cerebral gliomas but also suppresses tumor progression. Perampanel can dose-dependently enhance apoptosis and disrupt cell migration in malignant glioma cell lines. A synergistic effect of perampanel in combination with temozolamide has been identified. During chemoradiation therapy, perampanel exerts a protective effect on healthy peritumoral tissues. Adverse drug reactions associated with perampanel use are infrequent and mild. Further research is needed to investigate the anticonvulsant and antitumor efficacy of perampanel for the treatment of epilepsy in patients with malignant brain tumors.

Extraneural metastases of a cerebral glioma in a child: case report with literature review

Extraneural metastases of a cerebral glioma in a child: case report with literature review

Correction to: Recent Update on PET/CT Radiotracers for Imaging Cerebral Glioma

Correction to: Recent Update on PET/CT Radiotracers for Imaging Cerebral Glioma

The landscape of cancer-associated transcript fusions in adult brain tumors: a longitudinal assessment in 140 patients with cerebral gliomas and brain metastases.

Oncogenic fusions of neurotrophic receptor tyrosine kinase NTRK1, NTRK2, or NTRK3 genes have been found in different types of solid tumors. The treatment of patients with TRK fusion cancer with a first-generation TRK inhibitor (such as larotrectinib or entrectinib) is associated with high response rates (>75%), regardless of tumor histology and presence of metastases. Due to the efficacy of TRK inhibitor therapy of larotrectinib and entrectinib, it is clinically important to identify patients accurately and efficiently with TRK fusion cancer. In this retrospective study, we provide unique data on the incidence of oncogenic NTRK gene fusions in patients with brain metastases (BM) and gliomas. 140 samples fixed and paraffin-embedded tissue (FFPE) of adult patients (59 of gliomas [17 of WHO grade II, 20 of WHO grade III and 22 glioblastomas] and 81 of brain metastasis (BM) of different primary tumors) are analyzed. Identification of NTRK gene fusions is performed using next-generation sequencing (NGS) technology using Focus RNA assay kit (Thermo Fisher Scientific). We identified an ETV6 (5)::NTRK3 (15) fusion event using targeted next-generation sequencing (NGS) in one of 59 glioma patient with oligodendroglioma-grade II, IDH-mutated and 1p19q co-deleted at incidence of 1.69%. Five additional patients harboring TMPRSS (2)::ERG (4) were identified in pancreatic carcinoma brain metastasis (BM), prostatic carcinoma BM, endometrium BM and oligodendroglioma (grade II), IDH-mutated and 1p19q co-deleted. A FGFR3 (17)::TACC3 (11) fusion was identified in one carcinoma breast BM. Aberrant splicing to produce EGFR exons 2-7 skipping mRNA, and MET exon 14 skipping mRNA were identified in glioblastoma and pancreas carcinoma BM, respectively. This study provides data on the incidence of NTRK gene fusions in brain tumors, which could strongly support the relevance of innovative clinical trials with specific targeted therapies (larotrectinib, entrectinib) in this population of patients. FGFR3 (17)::TACC3 (11) rearrangement was detected in breast carcinoma BM with the possibility of using some specific targeted therapies and TMPRSS (2)::ERG (4) rearrangements occur in a subset of patients with, prostatic carcinoma BM, endometrium BM, and oligodendroglioma (grade II), IDH-mutated and 1p19q co-deleted, where there are yet no approved ERG-directed therapies.

Non-Invasive Detection of the IDH-1 Gene Mutation in Cerebral Gliomas Based on Proton MR Spectroscopy

Non-Invasive Detection of the IDH-1 Gene Mutation in Cerebral Gliomas Based on Proton MR Spectroscopy

Involvement of the Supraventricular Zone of the Brain in the Development of Cerebral Glioma

Involvement of the Supraventricular Zone of the Brain in the Development of Cerebral Glioma

Efficacy of Operative Ultrasonography Plus Neuronavigation for Brain Glioma Surgery: 2 – Year Single Center Experience in a Developing Country

Background: preoperative MRI data has been the gold standard for the diagnosis and therapy of malignant gliomas for decades, and operative ultrasonography for the management of patients with neurological pathologies that require surgical treatment has been also used for many years as it provides additional image guidance for surgical procedure to neuronavigation techniques. The main objective of this study is to find out if the use of operative ultrasonography in glioma surgery could give greater benefit in the total resection of brain gliomas and how improvement influences the degree of neoplastic resection on the survival of patients. Methods: prospective case-control study that was performed at the ISSEMyM Licenciado Arturo Montiel Rojas Medical Center, of patients with a histopathological diagnosis of cerebral glioma treated by the neurosurgery service in the period between January 2018 and December 2020. Results: Thirty - two patients were included, with 13 patients (40.6%) with grade IV astrocytoma. Operative USG + NNV was used in 17 patients and a subtotal or total resection was achieved in 75% of the patients, with a significantly lower postoperative volumetry in patients operated on by NNV + USG (5.6mm3 + 2.5), compared to NNV alone (8mm3 + 2.8) However, these results did not affect tumor-free time, which was comparable between both groups. Conclusions: Surgical treatment of brain gliomas with USG + NNV has a good degree of tumor resection compared to those treated with NNV only, but the main factor affecting survival is the hystophatological grade of the tumor.

Application value of intraoperative electrophysiological monitoring in cerebral eloquent area glioma surgery: a retrospective cohort study

IntroductionSurgery for gliomas involving eloquent areas is a very challenging microsurgical procedure. Maximizing both the extent of resection (EOR) and preservation of neurological function have always been the focus of attention. Intraoperative neurophysiological monitoring (IONM) is widely used in this kind of surgery. The purpose of this study was to evaluate the efficacy of IONM in eloquent area glioma surgery.MethodsSixty-eight glioma patients who underwent surgical treatment from 2014 to 2019 were included in this retrospective cohort study, which focused on eloquent areas. Clinical indicators and IONM data were analysed preoperatively, two weeks after surgery, and at the final follow-up. Logistic regression, Cox regression, and Kaplan‒Meier analyses were performed, and nomograms were then established for predicting prognosis. The diagnostic value of the IONM indicator was evaluated by the receiver operating characteristic (ROC) curve.ResultsIONM had no effect on the postoperative outcomes, including EOR, intraoperative bleeding volume, duration of surgery, length of hospital stay, and neurological function status. However, at the three-month follow-up, the percentage of patients who had deteriorated function in the monitored group was significantly lower than that in the unmonitored group (23.3% vs. 52.6%; P < 0.05). Logistic regression analysis showed that IONM was a significant factor in long-term neurological function (OR = 0.23, 95% CI (0.07–0.70). In the survival analysis, long-term neurological deterioration indicated worsened overall survival (OS) and progression-free survival (PFS). A prognostic nomogram was established through Cox regression model analysis, which could predict the probability 3-year survival rate. The concordance index was 0.761 (95% CI 0.734–0.788). The sensitivity and specificity of IONM evoked potential (SSEP and TCeMEP) were 0.875 and 0.909, respectively. In the ROC curve analysis, the area under the curve (AUC) for the SSEP and TCeMEP curves was 0.892 (P < 0.05).ConclusionsThe application of IONM could improve long-term neurological function, which is closely related to prognosis and can be used as an independent prognostic factor. IONM is practical and widely available for predicting postoperative functional deficits in patients with eloquent area glioma.

Can the metabolic characteristics of diffuse glioma on &lt;sup&gt;11&lt;/sup&gt;C-methionine PET/CT serve as a marker of its IDH status? Cross sectional study

INTRODUCTION: Since 2016, molecular markers, in particular, mutations in isocitrate dehydrogenase (IDH) 1 and 2, have been introduced as a classifying feature of cerebral gliomas that provided superior prognostication. The search for non-invasive biomarkers of the molecular profile of gliomas is necessary to improve the quality of preoperative diagnostics, identify patients with good and poor prognosis and determine treatment tactics.OBJECTIVE: Was to study the relationship between the IDH genotype of diffuse cerebral gliomas and metabolic biomarkers according to the results of PET/CT with [11C]methionine.MATERIALS AND METHOD: The results of PET/CT with 11C-methionine were identified to a retrospective analysis of 260 patients aged 18 to 75 years (median 40 years) with untreated cerebral glioma. Based on histological and molecular genetic studies of the surgical material including the determination of a mutation in the isocitrate dehydrogenase 1 (IDH1132H) gene, diffuse gliomas were classified according to the 2016 WHO classification of CNS tumors. Metabolic biomarkers included the calculation of tumor-to-brain ratio of 11С-methionine (TBRmax, TBRpeak and TBRmean) as well as the metabolic tumor volume (MTV). Statistics. Non-parametric tests were performed to compare the differences among patient groups. ROC curve analysis was performed to screen the optimal parameter and its best cutoff value for the discrimination of glioma genotype. All data analyses were performed using “Statistica 10,0” and “MedCalc” ststistical software. p-values less than 0.05 were considered statistically significant.RESULTS: According to the 2016 WHO classification astrocytic and oligodendroglial tumors of the adult type were divided into three groups: astrocytic gliomas with a mutation in the IDH1 gene (IDH1 mut) (n=95), astrocytic gliomas without a mutation in the IDH1 gene (IDH1 wild type — IDH1 wt) (n=103), and IDH1-mutant oligodendrogliomas (n=62). Significant differences in all ratios between the three molecular groups of gliomas were established. TBRmax cutoff of 2.27 differentiated between IDH1 wt and IDH1 mut gliomas with a sensitivity of 61% and a specificity of 77% (area under curve — AUC 0.752). When considering subgroups of gliomas that are homogeneous in terms of the IDH1 status or Grade, the dependence of TBR on the glioma histotype and grading was additionally established. In IDH1 mut oligodendrogliomas, TBR was significantly higher than in mutant astrocytomas, and in IDH1 wt astrocytomas, significant differences in TBR were established between Grade 2 and Grade 3–4. TBRmax was not a predictor of glioma type according to the WHO 2016 classification due to significant overlap of individual of TBR values. But TBRmax allowed diagnosing a cluster of malignant gliomas, including glioblastoma and astrocytoma Grade 3 IDH wt, as well as oligodendroglioma Grade 3 IDH1 mut, with a sensitivity of 65% and a specificity of 89% (AUC 0.848) at a cutoff of TBR=2.7. A strong correlation between the three tumor-to-brain ratios allows any ratio to be used in diagnostics. There were no significant differences in MTV between molecular types of gliomas.DISCUSSION: Distinguishing glioma types based on the 2016 WHO classification of the CNS tumors on the basis of 11Cmethionine uptake seems to be not reliable due to many factors that affect its uptake. In astrocytomas high TBR is associated with malignant grade and wild type IDH1 gene. However, the lack of differences in TBR between these astrocytomas and Grade 3 IDH1-mutant oligodendrogliomas does not allow one to predict the IDH1 status of the tumor in the absence of other radiological signs of the glioma histotype. The absence of differences in TBR between Grade 2 and Grade 3 astrocytomas IDH1 mut supports the view that they are considered as a single subgroup of lower grade gliomas. CONCLUSION: PET/CT with 11C-methionine has limited potential to assess the IDH status of diffuse gliomas. High TBR is associated with malignant glioma with wild-type IDH1 gene or oligodendroglial structure.

Awake Craniotomy for Gliomas in the Non-Dominant Right Hemisphere: A Comprehensive Review.

Awake surgery has become a standard practice for managing diffuse low-grade gliomas (LGGs), particularly in eloquent brain areas, and is established as a gold standard technique for left-dominant-hemisphere tumors. However, the intraoperative monitoring of functions in the right non-dominant hemisphere (RndH) is often neglected, highlighting the need for a better understanding of neurocognitive testing for complex functions in the right hemisphere. This article aims to comprehensively review the current literature on the benefits of awake craniotomy in gliomas of the non-dominant right hemisphere. A systematic review was conducted using the PubMed and ScienceDirect databases with keywords such as "right hemisphere", "awake surgery", "direct electrical brain stimulation and mapping", and "glioma". The search focused on anatomical and surgical aspects, including indications, tools, and techniques of awake surgery in right cerebral hemisphere gliomas. The literature search identified 74 sources, including original articles, books, monographs, and review articles. Two papers reported large series of language assessment cases in 246 patients undergoing awake surgery with detailed neurological semiology and mapping techniques, while the remaining studies were predominantly neuroradiological and neuroimaging in nature. Awake craniotomy for non-dominant-hemisphere gliomas is an essential tool. The term "non-dominant" should be revised, as this hemisphere contributes significantly to essential cognitive functions in the human brain.

Homeostatic status of thyroid hormones and brain water movement as determinant factors in biology of cerebral gliomas: a pilot study using a bioinformatics approach.

The expression and localization of the water channel transporters, aquaporins (AQPs), in the brain are substantially modified in gliomas during tumorigenesis, cell migration, edema formation, and resolution. We hypothesized that the molecular changes associated with AQP1 and AQP4 in the brain may potentially be anticancer therapeutic targets. To test this hypothesis, a bioinformatics analysis of publicly available data from international consortia was performed. We used RNA-seq as an experimental strategy and identified the number of differential AQP1 and AQP4 transcript expressions in glioma tissue compared to normal brain tissue. AQPs genes are overexpressed in patients with glioma. Among the glioma subtypes, AQP1 and AQP4 were overexpressed in astrocytoma (low-grade glioma) and classical (high-grade glioma). Overall survival analysis demonstrated that both AQP genes can be used as prognostic factors for patients with low-grade glioma. Additionally, we observed a correlation between the expression of genes involved in the tyrosine and thyroid hormone pathways and AQPs, namely: PNMT, ALDH1A3, AOC2, HGDATP1B1, ADCY5, PLCB4, ITPR1, ATP1A3, LRP2, HDAC1, MED24, MTOR, and ACTB1 (Spearman's coefficient = geq 0.20 and p-value = ≤ 0.05). Our findings indicate that the thyroid hormone pathways and AQPs 1 and 4 are potential targets for new anti-tumor drugs and therapeutic biomarkers for malignant gliomas.

Selective DRD2 antagonist and ClpP agonist ONC201 in a recurrent non-midline H3 K27M-mutant glioma cohort.

Diffuse midline glioma, H3 K27-altered (H3 K27M-altered DMG) are invariably lethal, disproportionately affecting the young and without effective treatment besides radiotherapy. The 2016 World Health Organization (WHO) Central Nervous System (CNS) Tumors Classification defined H3 K27M mutations as pathognomonic but restricted diagnosis to diffuse gliomas involving midline structures by 2018. Dordaviprone (ONC201) is an oral investigational small molecule, DRD2 antagonist, and ClpP agonist associated with durable responses in recurrent H3 K27M-mutant DMG. Activity of ONC201 in non-midline H3 K27M-mutant diffuse gliomas has not been reported. Patients with recurrent non-midline H3 K27M-mutant diffuse gliomas treated with ONC201 were enrolled in 5 trials. Eligibility included measurable disease by Response Assessment in Neuro-Oncology (RANO) high-grade glioma, Karnofsky/Lansky performance score ≥60, and ≥90 days from radiation. The primary endpoint was overall response rate (ORR). Five patients with cerebral gliomas (3 frontal, 1 temporal, and 1 parietal) met inclusion. One complete and one partial response were reported by investigators. Blinded independent central review confirmed ORR by RANO criteria for 2, however, 1 deemed nonmeasurable and another stable. A responding patient also noted improved mobility and alertness. H3 K27M-mutant diffuse gliomas occasionally occur in non-midline cerebrum. ONC201 exhibits activity in H3 K27M-mutant gliomas irrespective of CNS location.

Atypical Presentation of a Pilocytic Astrocytoma at the Regional Hospital of Ségou in Mali country

Introduction: Pilocytic astrocytoma is the most common cerebral glioma in pediatric age, preferentially located in the posterior cerebral fossa. Atypical presentations have rarely been described in the literature. Clinical Case: We report a case of pilocytic astrocytoma whose appearance on CT scan is unusual. It concerns a young boy of 9 years old, who presented convulsive seizures since the age of 6 years old, followed by general practitioners with irregular treatment based on gardenal. 2 months ago the seizures became more frequent and this prompted a specialist consultation with the neurologist, after a brain scan he referred the patient to us. The neurological examination was unremarkable today. Brain CT with contrast showed a right parietal lesion. It was a lesion with a double cystic and fleshy component associated with calcifications with heterogeneous enhancement which amputated the posterior horn of the lateral ventricle. The radiological appearance was in favor of a low-grade oligodendroglioma. The patient underwent surgery with complete macroscopic excision of the lesion. Histological examination revealed a pilocytic astrocytoma (grade I). Conclusion: The usual radiological appearance of pilocytic astrocytoma combines a cystic part and a highly contrasting mural nodule. It rarely presents in the form of a supratentorial lesion with calcifications. This form of presentation is rare and can lead to confusion with other gliomas. We can achieve healing for the patient with total excision.

Menthol-modified paclitaxel multifunctional cationic liposomes cross the blood-brain barrier and target glioma stem cells for treatment of glioblastoma

Glioblastoma is the most malignant glioma of the central nervous system, as the presence of cerebral glioma stem cells and the blood-brain barrier hamper its treatment. Menthol can improve blood-brain barrier permeability. Cationic liposomes can interact with negatively charged macromolecules on tumor neovascular endothelial cells to produce passive targeting. Ginsenoside Rh2 can replace cholesterol to make liposomes more stable. Paclitaxel has an excellent antitumor effect. Therefore, in this study, menthol-modified paclitaxel cationic liposomes were constructed to cross the blood-brain barrier and targeted the tumor, to achieve safe and effective treatment of glioblastoma. We discovered that the addition of DC-chol liposomes can enhance the uptake of C6 glioma stem cells, promote the apoptosis of C6 glioma stem cells and inhibit the proliferation of tumor cells in vitro. We found that targeted liposomes could cross the blood-brain barrier and target tumor sites to induce tumor cell apoptosis in vivo. In brief, menthol-modified paclitaxel cationic liposomes offer a safer approach to the treatment of glioblastoma.

Effect of high-field iMRI guided resection in cerebral glioma surgery: A randomized clinical trial

BackgroundExtent of resection (EOR) in glioma contributes to longer survival. The purpose of NCT01479686 was to prove whether intraoperative magnetic resonance imaging (iMRI) increases EOR in glioma surgery and benefit survival. MethodsPatients were randomized (1:1) to receive the iMRI (n = 161) or the conventional neuronavigation (n = 160). The primary endpoint was gross total resection (GTR); secondary outcomes reported were progression-free survival (PFS), overall survival (OS), and safety. Results188 high-grade gliomas (HGGs) and 133 low-grade gliomas (LGGs) were enrolled. GTR was 83.85% in the iMRI group vs. 50.00% in the control group (P < 0.0001). In 321 patients, the median PFS (mPFS) was 65.12 months in the iMRI group and 61.01 months in the control group (P = 0.0202). For HGGs, mPFS was improved in the iMRI group (19.32 vs. 13.34 months, P = 0.0015), and a trend of superior OS compared with control was observed (29.73 vs. 25.33 months, P = 0.1233). In the predefined eloquent area HGG subgroup, mPFS, and mOS were 20.47 months and 33.58 months in the iMRI vs. 12.21 months and 21.16 months in the control group (P = 0.0098; P = 0.0375, respectively). From the exploratory analyses of HGGs, residual tumor volume (TV) < 1.0 cm3 decreased the risk of survival (mPFS: 18.99 vs. 9.43 months, P = 0.0055; mOS: 29.77 vs. 18.10 months, P = 0.0042). LGGs with preoperative (pre-OP) TV > 43.1 cm3 and postoperative (post-OP) TV > 4.6 cm3 showed worse OS (P= 0.0117) ConclusionsIt showed that iMRI significantly increased EOR and indicated survival benefits for HGGs, particularly eloquent HGGs. Residual TV in either HGGs or LGGs is a prognostic factor for survival.

Fully automated MR-based virtual biopsy of primary CNS lymphomas.

Primary central nervous system lymphomas (PCNSL) pose a challenge as they may mimic gliomas on magnetic resonance imaging (MRI) imaging, compelling precise differentiation for appropriate treatment. This study focuses on developing an automated MRI-based workflow to distinguish between PCNSL and gliomas. MRI examinations of 240 therapy-naive patients (141 males and 99 females, mean age: 55.16 years) with cerebral gliomas and PCNSLs (216 gliomas and 24 PCNSLs), each comprising a non-contrast T1-weighted, fluid-attenuated inversion recovery (FLAIR), and contrast-enhanced T1-weighted sequence were included in the study. HD-GLIO, a pre-trained segmentation network, was used to generate segmentations automatically. To validate the segmentation efficiency, 237 manual segmentations were prepared (213 gliomas and 24 PCNSLs). Subsequently, radiomics features were extracted following feature selection and training of an XGBoost algorithm for classification. The segmentation models for gliomas and PCNSLs achieved a mean Sørensen-Dice coefficient of 0.82 and 0.80 for whole tumors, respectively. Three classification models were developed in this study to differentiate gliomas from PCNSLs. The first model differentiated PCNSLs from gliomas, with an area under the curve (AUC) of 0.99 (F1-score: 0.75). The second model discriminated between high-grade gliomas and PCNSLs with an AUC of 0.91 (F1-score: 0.6), and the third model differentiated between low-grade gliomas and PCNSLs with an AUC of 0.95 (F1-score: 0.89). This study serves as a pilot investigation presenting an automated virtual biopsy workflow that distinguishes PCNSLs from cerebral gliomas. Prior to clinical use, it is necessary to validate the results in a prospective multicenter setting with a larger number of PCNSL patients.

Role of perfusion weighted imaging in the differential diagnosis of intracranial space occupying lesions

Introduction. Magnetic Resonance Imaging (MRI) is a well-established modality for identifying intracranial space-occupying lesions (ICSOLs). However, conventional MRI has limitations in the cerebral glioma accurate grading. Advanced techniques, like Diffusion-Weighted Imaging (DWI), Perfusion MRI, and Magnetic Resonance Spectroscopic Imaging (MRS), have been introduced to address these limitations. Aims and objective. The primary objective of this research is to assess the significance of perfusion-weighted imaging (PWI) in distinguishing intracranial space-occupying lesions (ICSOLs), with a specific emphasis on its capacity to refine diagnostic accuracy and advance the classification of cerebral gliomas. Materials and methods. A prospective observational research involving 38 patients having ICSOLs used a Philips Multiva 1.5 Tesla MRI system. The protocol included DWI, ADC (Apparent Diffusion Coefficient) analysis, and perfusion imaging. Results. The study population (n=38) had a diverse age range (22-70 years), with a majority in the 30-40 age group. High-grade gliomas constituted 43.2% of all the cases. Significant differences in rCBF, rCBV, and MTT have been observed among HGGs &amp; LGGs. Specific cut-off values were used to predict glioma grades. Discussion. Comparisons with existing studies validated these findings, emphasizing the utility of advanced physiological techniques in enhancing diagnostic precision. Discrepancies with certain studies have highlighted the need for a comprehensive approach to lesion characterization. Conclusion. Intracranial lesion diagnosis, especially for meningiomas, demonstrated comparable efficacy between conventional and advanced techniques. While conventional MRI can differentiate lower-grade from higher-grade gliomas to a limited extent, the combination of advanced physiological approaches significantly improves specificity in tumor categorization.

Evaluation of the effectiveness of multicomponent treatment in the progression of primary low-grade brain gliomas. Own experience

BACKGROUND: Despite the improved results of treatment of brain tumors achieved over the past decade, most patients experience relapses of the disease 1–2 years after treatment. Numerous clinical studies have made it possible to obtain standard protocols for the treatment of primary brain tumors; however, protocols for the treatment of recurrent tumors have not been developed. The choice of treatment usually includes reoperation, systemic chemotherapy, and reirradiation alone or in combination. However, the treatment of recurrent glial tumors is challenging given the lack of effective treatment options and the lack of randomized controlled trials on which to base therapy.&#x0D; AIM: To determine the most important prognostic factors, as well as the most effective treatment option in patients with continued growth of primary low-grade gliomas of the brain.&#x0D; METHODS: This study included 40 patients with a confirmed diagnosis of progression of low-malignant glial brain tumors, who underwent inpatient treatment at the Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine from 2007 to 2022. The ratio of men and women: 1:1.5. The mean age was 45.6±11.5 years. Patients with grade I astrocytomas predominated (n=23), oligodendroglioma was diagnosed in 8 patients.&#x0D; Reoperation was performed in 11 patients as the first stage of progression treatment. In 7 cases, monochemotherapy with temozolomide was performed. Repeated radiation therapy was performed in 29 patients, of which: 9 patients received a course of combined photon-neutron therapy; 9 patients — stereotactic radiation therapy (was performed on the CyberKnife device); 11 patients — external beam radiation therapy.&#x0D; RESULTS: The median overall survival (OS) for all patients with continued growth of low-grade cerebral gliomas after treatment was 120 months. 1-year OS — 97.3%; 3-year — 86.8%; 5-year — 78.2%. Median OS after relapse treatment was 36 months. The median OS was higher in the age group under 50 compared to the older age group: 120 and 95 months (p 0.05).&#x0D; The best results of treatment were noted in patients who underwent reoperation followed by a course of radiation therapy or chemotherapy with temozolomide for 48 months and 36 months respectively (p 0.05). When analyzing the results of treatment after a course of repeated radiation therapy in an independent variant, there were undoubted advantages in patients who underwent stereotactic radiation therapy and photon-neutron therapy for 60 months and 24 months respectively (p 0.05).&#x0D; CONCLUSIONS: The optimal approach to the treatment of patients with continued growth of primary low-grade glioma brain tumors is to perform a second operation, followed by radiation therapy or chemotherapy. The method of choice for a repeat course of radiotherapy may be photon-neutron therapy or stereotactic radiation therapy.

Platelets as delivery vehicles for targeted enrichment of NO· to cerebral glioma for magnetic resonance imaging

Using a magnetic resonance imaging (MRI) contrast agent, MRI has made substantial contributions to glioma diagnosis. Metal-free MRI agents, such as the nano free radical nitric oxide (NO·) micelle, can overcome the inherent toxicity of metal-based agents in certain patient populations. However, the low spatial resolution of nano NO· micelle in MRI limits its clinical development. In this study, we pretreated platelets (PLTs) and loaded them with nano NO· micelles to synthesize NO·@PLT, which can overcome the low contrast and poor in vivo stability of nitroxide-based MRI contrast agents. The PLTs can serve as potential drug carriers for targeting and delivering nano NO· micelles to gliomas and thus increase the contrast in T1-weighted imaging (T1WI) of MRI. This drug carrier system uses the unique tumor-targeting ability of PLTs and takes advantage of the high signal presentation of steady nano NO· micelles in T1WI, thereby ultimately achieving signal amplification of glioma in T1WI. With the effect of PLTs-tumor cell adhesion, NO·@PLT has per-nitroxide transverse relativities of approximately 2-fold greater than those of free NO· particles. These features allow a sufficient NO·@PLT concentration to accumulate in murine subcutaneous glioma tumors up from 5 min to 2.5 h (optimum at 1.5 h) after systemic administration. This results in MRI contrast comparable to that of metal-based agents. This study established a promising metal-free MRI contrast agent, NO·@PLT, for glioma diagnosis, because it has superior spatial resolution owing to its high glioma-targeting ability and has significant translational implications in the clinic.

11 C-Acetate PET/CT for Reactive Astrogliosis Outperforms 11 C-Methionine PET/CT in Glioma Classification and Survival Prediction.

11 C-acetate (ACE) PET/CT visualizes reactive astrogliosis in tumor microenvironment. This study compared 11 C-ACE and 11 C-methionine (MET) PET/CT for glioma classification and predicting patient survival. In this prospective study, a total of 142 patients with cerebral gliomas underwent preoperative MRI, 11 C-MET PET/CT, and 11 C-ACE PET/CT. Tumor-to-contralateral cortex (TNR MET ) and tumor-to-choroid plexus ratios (TNR ACE ) were calculated for 11 C-MET and 11 C-ACE. The Kruskal-Wallis test and Bonferroni post hoc analysis were used to compare the differences in 11 C-TNR MET and 11 C-TNR ACE . The Cox proportional hazards regression analysis and classification and regression tree models were used to assess progression-free survival (PFS) and overall survival (OS). The median 11 C-TNR MET and 11 C-TNR ACE for oligodendrogliomas (ODs), IDH1 -mutant astrocytomas, IDH1 -wildtype astrocytomas, and glioblastomas were 2.75, 1.40, 2.30, and 3.70, respectively, and 1.40, 1.20, 1.77, and 2.87, respectively. The median 11 C-TNR MET was significantly different among the groups, except between ODs and IDH1 -wildtype astrocytomas, whereas the median 11 C-TNR ACE was significantly different among all groups. The classification and regression tree model identified 4 risk groups ( IDH1 -mutant with 11 C-TNR ACE ≤ 1.4, IDH1 -mutant with 11 C-TNR ACE > 1.4, IDH1 -wildtype with 11 C-TNR ACE ≤ 1.8, and IDH1 -wildtype with 11 C-TNR ACE > 1.8), with median PFS of 52.7, 44.5, 25.9, and 8.9 months, respectively. Using a 11 C-TNR ACE cutoff of 1.4 for IDH1 -mutant gliomas and a 11 C-TNR ACE cutoff of 2.0 for IDH1 -wildtype gliomas, all gliomas were divided into 4 groups with median OS of 52.7, 46.8, 27.6, and 12.0 months, respectively. Significant differences in PFS and OS were observed among the 4 groups after correcting for multiple comparisons. 11 C-ACE PET/CT is better for glioma classification and survival prediction than 11 C-MET PET/CT, highlighting its potential role in cerebral glioma patients.