High-grade Gliomas Research Articles

Case Report: Clinical awareness about the effect of laser interstitial thermal therapy on pediatric high-grade brain tumors after radiotherapy

The use of magnetic resonance-guided laser interstitial thermal therapy (LITT) for the treatment of brain tumors and epileptic lesions has increased in the field of pediatric neurosurgery. However, very little is known about the effect of LITT on pediatric high-grade tumors that have been previously treated with radiotherapy. We report on two cases of children with an unexpected rapid brain tumor progression after LITT. The first case was an 11-year-old boy with a periventricular metastasis of a recurrent anaplastic ependymoma treated with proton-therapy and radiosurgery. The second case was a 6-year-old girl with a Lynch-syndrome and a recurrence of a mesio-temporo-occipital high-grade glioma admitted to gross total resection, proton-therapy, chemotherapy, bevacizumab and immune checkpoint inhibitor. Due to evidence of tumor progression in both cases, a decision was made to perform LITT. Shortly after the laser ablation, we observed a significant tumor growth along the trajectory of the LITT catheters, accompanied by clinical deterioration. The effect of LITT on pediatric ependymoma and high-grade glioma recurrence after radiotherapy is still unclear. The tumor expansion following LITT in these two patients should drive a deeper awareness of the effect of radiation and LITT on the tumor-environment. The breakage of the morphogenetic boundaries of the neuromeres, to which each tumor was initially confined, through the placement of the LITT catheters should be considered while trying to understand the disease spread mechanisms. Based on the experience of our center, we advise a careful implementation of this technique on pediatric high-grade central nervous system tumors, particularly in recurrent tumors that were previously treated with radiotherapy, until the underlying pathophysiologic mechanism has been better understood.

Concurrent RB1 and P53 pathway disruption predisposes to the development of a primitive neuronal component in high-grade gliomas depending on MYC-driven EBF3 transcription

Concurrent RB1 and P53 pathway disruption predisposes to the development of a primitive neuronal component in high-grade gliomas depending on MYC-driven EBF3 transcription

Pediatric high-grade gliomas with concomitant RB1 and SETD2 alterations and Li-Fraumeni syndrome

Pediatric high-grade gliomas with concomitant RB1 and SETD2 alterations and Li-Fraumeni syndrome

Diagnostic and Prognostic Values of miRNAs in High-Grade Gliomas: A Systematic Review

Background Gliomas, particularly glioblastomas, have grim prognoses, necessitating early diagnostic and prognostic indicators. MicroRNAs (miRNAs), influential in cancer research, show potential as glioma biomarkers. This systematic review aimed to examine the efficacy of miRNAs in the diagnosis and prognosis of high-grade glioma. Methods A comprehensive search was conducted of PubMed, EMBASE, Cochrane Library, and Web of Science for studies published from 2013 to 2023. The eligibility criteria included high-grade glioma, histopathological confirmation, miRNA samples from cerebrospinal fluid or plasma, and relevant outcome data. Studies were excluded if they were experimental or reviews and not in English. Results Of the 1120 initial results, 8 studies involving 660 subjects met the inclusion criteria. Several studies have assessed miRNA expression and its association with diagnosis and prognosis of high-grade gliomas. Overexpression of miR-221, miR-222, miR-210, miR-21, miR-125b, and miR-223 and under-expression of miR-15b and miR-124-3p showed significant potential in differentiating high-grade glioma patients from controls. Additionally, miRNAs are associated with distinct tumorigenic pathways. Conclusion Elevated or depressed expression levels of specific circulating miRNAs hold significant promise as noninvasive biomarkers for the diagnosis and prognosis of high-grade glioma. These miRNAs offer valuable insights into disease progression and patient outcome. Further validation through extensive clinical trials and in-depth mechanistic studies is essential to realize their full clinical utility.

Characterization of NOD-like receptor-based molecular heterogeneity in glioma and its association with immune micro-environment and metabolism reprogramming

Background and purposeThe characteristics and role of NOD-like receptor (NLR) signaling pathway in high-grade gliomas were still unclear. This study aimed to reveal the association of NLR with clinical heterogeneity of glioblastoma (GBM) patients, and to explore the role of NLR pathway hub genes in the occurrence and development of GBM.MethodsTranscriptomic data from 496 GBM patients with complete prognostic information were obtained from the TCGA, GEO, and CGGA databases. Using the NMF clustering algorithm and the expression profiles of NLR genes, these 496 GBM patients were classified into different clinical subtypes. The pathway activity of NLR and the immune micro-environment characteristics were then compared between these subtypes. A novel and accurate NLR expression profile-based prognostic marker for GBM was developed using LASSO and COX regression analysis.ResultsBased on the NLR gene expression profile, GBM patients were accurately divided into two clinical subtypes (C1 and C2) with different clinical outcomes. The two groups of patients showed different immune microenvironment characteristics and metabolic characteristics, which might be the potential reason for the difference in prognosis. Differential expression and enrichment analyzes revealed intrinsic gene signature differences between C1 and C2 subtypes. Based on the differential expression profiles of C1 and C2, prognostic molecular markers related to NLR were developed. The AUC value of the 3-year ROC curve ranged from 0.601 to 0.846, suggesting its potential clinical significance. Single-cell sequencing analysis showed that the NLR gene was mainly active in myeloid cells within GBM. The random forest algorithm identified the crucial role of TRIP6 gene in NLR pathway. Molecular biology experiments confirmed that TRIP6 was abnormally overexpressed in GBM. Knockdown of TRIP6 gene can significantly inhibit the proliferation and migration ability of GBM cells.ConclusionThe NLR signaling pathway plays a critical role in regulating immune microenvironment and metabolism reprogramming of GBM. TRIP6 is a potential hub gene within the NLR pathway and affects the malignant biological behavior of GBM cells.

Therapeutic Manipulation and Bypass of the Blood Brain Barrier: Powerful Tools in Glioma Treatment

Abstract The blood brain barrier (BBB) remains an obstacle for delivery of chemotherapeutic agents to gliomas. High grade and recurrent gliomas continue to portend a poor prognosis. Multiple methods of bypassing or manipulating the BBB have been explored, including hyperosmolar therapy, convection enhanced delivery (CED), laser guided interstitial thermal therapy (LITT), and Magnetic Resonance Guided Focused Ultrasound (MRgFUS) to enhance delivery of chemotherapeutic agents to glial neoplasms. Here, we review these techniques, currently ongoing clinical trials to disrupt or bypass the BBB in gliomas, and results of completed trials.

Gastrin-Releasing Peptide Receptor Targeting PET/CT With 68Ga-NOTA-RM26 in the Assessment of Glioma and Combined Multiregional Biopsies.

The aim of this study was to investigate the value of 68Ga-NOTA-RM26 (68Ga-RM26), a gastrin-releasing peptide receptor-targeting antagonist labeled with the radionuclide 68Ga, in the diagnosis of high-grade gliomas and in combination with multiregional biopsies using PET/CT. After institutional review board approval and informed consent, a total of 35 patients with suspected glioma lesions were enrolled in this study. All patients underwent 68Ga-RM26 PET/CT scans within 2 weeks before surgery. There were 8 grade II gliomas, 6 grade III gliomas, and 18 grade IV gliomas in a total of 32 glioma lesions. 68Ga-RM26 PET/CT diagnosed 74.4% of lesions (27/32) of all glioma tumor types, and almost all high-grade gliomas were successfully diagnosed (23/24, 95.8%). Among the 9 negative glioma lesions, there were 8 low-grade gliomas (grade II). There was a significantly higher SUVmax, SUVmean, and the lesion-to-background ratio (T/B ratio) in high-grade gliomas compared with low-grade gliomas (P < 0.001). In addition, there was a high correlation between the immunohistochemical staining score of gliomas and parameters (SUVmax, SUVmean, and T/B ratio) on 68Ga-RM26 PET/CT (P < 0.001), and verified by immunohistochemical staining on multiple-point samples of glioma lesions guided by 68Ga-RM26 PET/CT. 68Ga-RM26 could noninvasively diagnose high-grade gliomas and be a promising PET tracer for predicting glioma grading before surgery. This pilot study indicated that the uptake of 68Ga-RM26 correlates with WHO grade in glioma, and preoperative 68Ga-RM26 PET/CT may be helpful to guide multiple-point biopsy of gliomas.

Advancements in targeted and immunotherapy strategies for glioma: toward precision treatment

In recent years, significant breakthroughs have been made in cancer therapy, particularly with the development of molecular targeted therapies and immunotherapies, owing to advances in tumor molecular biology and molecular immunology. High-grade gliomas (HGGs), characterized by their high malignancy, remain challenging to treat despite standard treatment regimens, including surgery, radiotherapy, chemotherapy, and tumor treating fields (TTF). These therapies provide limited efficacy, highlighting the need for novel treatment strategies. Molecular targeted therapies and immunotherapy have emerged as promising avenues for improving treatment outcomes in high-grade gliomas. This review explores the current status and recent advancements in targeted and immunotherapeutic approaches for high-grade gliomas.

Utilizing Diffusion Tensor Imaging to Differentiate High-Grade Gliomas and Solitary Brain Metastases

Abstract Background Brain tumors, encompassing a spectrum of neoplastic disorders, significantly impact patient morbidity and mortality. Distinguishing between high-grade gliomas (HGGs) and solitary brain metastases (SBMs) is crucial for tailored clinical management. Conventional structural magnetic resonance imaging (MRI) faces challenges in this differentiation, leading to the exploration of advanced imaging modalities such as diffusion tensor imaging (DTI). Materials and Methods In this prospective study, 41 patients with solitary enhancing brain lesions underwent total or subtotal resection, confirmed by histopathology. Imaging involved a 3-Tesla MRI scanner, and DTI data were analyzed for metrics including mean diffusivity, fractional anisotropy (FA), axial diffusivity, radial diffusivity, as well as planar, spherical, and linear (CL) anisotropy coefficients. Results Peritumoral FA and CL exhibited significant differences (p = 0.0217 and p = 0.039, respectively) between HGG and SBM. The area under the curve for peritumoral FA and CL in differentiating HGG and SBM were 0.2791 and 0.6984, respectively. No significant differences were observed in the other diffusion metrics. Conclusion This study contributes to understanding DTI-derived metrics for HGG and SBM differentiation. Peritumoral FA and CL show promise as potential discriminators, offering insights for enhanced clinical decision-making and treatment planning in brain tumor patients. Future research with larger cohorts and advanced diffusion imaging techniques could further refine these findings.

An Intratumoral Phaeohyphomycotic Abscess in a Chemotherapy-Naive IDH-Mutant Glioma: A Mere Coincidence?

Phaeohyphomycotic agents causing central nervous system (CNS) infection is rare and is known to affect immunocompetent individuals. We present a patient with a CNS phaeohyphomycotic abscess that had developed within a temporal lobe glioma. Magnetic resonance imaging (MRI) performed two months prior to the surgery showed only the presence of a neoplasm. However, a repeat MRI in the immediate pre-operative period revealed an additional, likely fungal, lesion. During this interval of 2 months, the patient had received a short course of steroids for suspected encephalitis. The steroid therapy and the CNS tropism of the fungi could have contributed to the CNS mycosis. The intratumoral localization of the fungi could be attributed either to the altered tumour vasculature or to a mere coincidence. Occurrence of CNS mycosis within a high grade glioma is exceedingly rare. A majority of such patients reported in the literature had received chemotherapy for the glioma.

Development of a brief screening measure of unmet supportive care needs (SCNS-P&C-6) in caregivers of people with high-grade glioma

PurposeInformal caregivers of people with high grade glioma (HGG) often have high levels of unmet support needs. Routine screening for unmet needs can facilitate appropriate and timely access to supportive care. We aimed to develop a brief screening tool for HGG caregiver unmet needs, based on the Supportive Care Needs Survey—Partners & Caregivers (SCNS-P&C).MethodsSecondary analysis was performed on responses to the SCNS-P&C from 188 HGG caregivers, who participated in the Care-IS trial. SCNS-P&C items were assessed against four criteria: factor loadings; prevalence; variation in domain score; diagnostic accuracy. Supplementary analysis was conducted at two timepoints (T1 & T2) on the final selected items to identify caregivers indicating no needs on the screening items but reported a need on the original SCNS-P&C, suggesting they would be “missed” by the screening items.ResultsSix items performed best against psychometric criteria, capturing two domains: Cancer impact needs and Information and communication needs. Supplementary analysis showed screening items failed to identify only 7.4% (14/188) of caregivers with other unmet needs at T1 and 11.4% (18/158) at T2. Of those missed at T1, only four were missed again at T2.ConclusionsWe identified six-items for inclusion in a brief screening tool, the SCNS-P&C-6, demonstrating good sensitivity in detecting unmet needs of caregivers of people with HGG. Use of this tool in clinical practice has the potential to improve access to care and the cancer experience for both the caregiver and person with brain tumor.

Establishing a living biobank of pediatric high-grade glioma and ependymoma suitable for cancer pharmacology.

Brain tumors are the deadliest solid tumors in children and adolescents. Most of these tumors are glial in origin and exhibit strong heterogeneity, hampering the development of effective therapeutic strategies. In the past decades, patient-derived tumor organoids (PDT-O) have emerged as powerful tools for modeling tumoral cell diversity and dynamics, and they could then help defining new therapeutic options for pediatric brain tumors. Through an integrative approach based on our expertise and a careful review of the literature about glioblastoma 3D primary cultures, we set-up a standardized methodological pipeline for the establishment, characterization and biobanking of PDT-O through direct 3D in vitro culture of the deadliest pediatric glial brain tumors. To assess PDT-O fidelity and validate their pre-clinical relevance, we performed comprehensive histological, molecular and drug-response analyses. Our methodological pipeline allowed the rapid and efficient generation of PDT-O recapitulating their parental tumor features, including intra-tumoral heterogeneity, even after several passages and cryopreservation/revival as 3D cultures. Moreover, we successfully performed pre-clinical test responses on these PDT-O to standard-of-care therapies and new therapeutic options. Finally, we identified ONC201 as a selective drug for pediatric glial tumor types not restricted to H3K27M-mutant glioma, as well as combination strategies to increase the therapeutic response to ONC201. Hence, we describe a fast and robust process to biobank PDT-O for pediatric glial brain tumors. These PDT-O models have the potential for patient-specific modeling even after long-term expansion in vitro and we established the proof-of-concept of their usefulness to support powerful pre-clinical studies.

The correlation histopathological and conventional/advanced MRI techniques in glial tumors.

We aimed to elucidate the histopathological pre-diagnosis of cranial gliomas with magnetic resonance imaging (MRI) techniques in gliomas. A total of 82 glioma patients were enrolled to our study. Pre-operative conventional MRI images (non-contrast T1/T2/flair/contrast-enhanced T1) and advanced MRI images (DAG and ADC mapping, MRI spectroscopy and perfusion MRI [PMRI]) were analyzed. Conventional MRI alone is useful in radiological pre-evaluation in low-grade glioma in 54.8% and 86.3% in high-grade glioma. Additional advanced MRI techniques were beneficial in comparing low-grade gliomas in 98% and 83.9% in high-grade glioma. On ROC analysis, ADC cutoff value 0.905 mm2/s (p = 0.001), rCBV cutoff value 1.77 (p = 0.001), Cho/NAA cut-off value 2.20 (p = 0.001), and Cho/Cr cutoff value 2.01 (p = 0.001) were achieved. Significant results were obtained when ADC, Cho/NAA, and Cho/Cr were analyzed into four histopathologically grade groups besides (p = 0.001). NAA/Cr values were not significant in pathological grading. rCBV measurements were statistically significant between Grades I and IV and between II and IV. Using additional advanced MRI techniques such as PMRI, magnetic resonance spectroscopy, and DWI with conventional MRI could enhance the accuracy of histopathological grading in cranial glioma.

Levetiracetam and valproic acid in glioma: antiseizure and potential antineoplastic effects.

Seizures are a frequent complication in glioma. Incidence of brain tumor-related epilepsy (BTRE) in high-grade glioma (HGG) is an estimated > 25% and in low-grade glioma (LGG) is approximately 72%. Two first-line antiseizure medications (ASMs) for BTRE include levetiracetam (LEV) and valproic acid (VPA). Use of VPA has decreased because of a broader side effect profile, potential interaction with chemotherapeutic drugs, and availability of newer generation agents. In refractory BTRE, LEV and VPA may be prescribed together to enhance seizure control. VPA and LEV have gained attention for their purported antineoplastic effects and synergistic role with temozolomide. VPA is suggested to modulate anticancer activity in vitro through multiple mechanisms. In addition, retrospective studies indicate increased overall survival in patients with epileptogenic HGGs who are managed with LEV or VPA rather than other ASMs. However, these studies have numerous limitations. It is also reported that patients with glioma and a seizure history have a longer survival. This extended survival, if one exists, may be only observed in certain gliomas with corresponding patient characteristics. We provide a brief overview of the management of BTRE, VPA and LEV as anticonvulsants and antineoplastics, and the factors that may be associated with survival in epileptogenic glioma.

Clinical and Imaging Features of Head and Neck Metastasis of High-Grade Glioma: A Single-Center Case Series.

High-grade gliomas are the most frequent primary brain tumors, yet extraneural metastasis is exceedingly rare. This is in part secondary to the relatively poor survival of these patients and likely the shielding effect of the blood-brain barrier. Given the rarity of extraneural metastasis, the pathophysiology and imaging appearance of extraneural metastasis is under-reported and poorly understood. In this case series we present 6 patients with pathology-confirmed high-grade glioma and extraneural head and neck metastasis. We highlight imaging features of metastasis on CT, MRI, and PET/CT. We also explore potential correlations and pathophysiology of high-grade glioma metastasis to the head and neck region.

Noninvasive blood-brain barrier integrity mapping in patients with high-grade glioma and metastasis by multi-echo time-encoded arterial spin labeling.

In brain tumors, disruption of the blood-brain barrier (BBB) indicates malignancy. Clinical assessment is qualitative; quantitative evaluation is feasible using the K2 leakage parameter from dynamic susceptibility contrast MRI. However, contrast agent-based techniques are limited in patients with renal dysfunction and insensitive to subtle impairments. Assessing water transport times across the BBB (Tex) by multi-echo arterial spin labeling promises to detect BBB impairments noninvasively and potentially more sensitively. We hypothesized that reduced Tex indicates impaired BBB. Furthermore, we assumed higher sensitivity for Tex than dynamic susceptibility contrast-based K2, because arterial spin labeling uses water as a freely diffusible tracer. We acquired 3T MRI data from 28 patients with intraparenchymal brain tumors (World Health Organization Grade 3 & 4 gliomas [n = 17] or metastases [n = 11]) and 17 age-matched healthy controls. The protocol included multi-echo and single-echo Hadamard-encoded arterial spin labeling, dynamic susceptibility contrast, and conventional clinical imaging. Tex was calculated using a T2-dependent multi-compartment model. Areas of contrast-enhancing tissue, edema, and normal-appearing tissue were automatically segmented, and parameter values were compared across volumes of interest and between patients and healthy controls. Tex was significantly reduced (-20.3%) in contrast-enhancing tissue compared with normal-appearing gray matter and correlated well with |K2| (r = -0.347). Compared with healthy controls, Tex was significantly lower in tumor patients' normal-appearing gray matter (Tex,tumor = 0.141 ± 0.032 s vs. Tex,HC = 0.172 ± 0.036 s) and normal-appearing white matter (Tex,tumor = 0.116 ± 0.015 vs. Tex,HC = 0.127 ± 0.017 s), whereas |K2| did not differ significantly. Receiver operating characteristic analysis showed a larger area under the curve for Tex (0.784) than K2 (0.604). Tex is sensitive to pathophysiologically impaired BBB. It agrees with contrast agent-based K2 in contrast-enhancing tissue and indicates sensitivity to subtle leakage.

Does Personality Influence the Quality of Life of Patients with Brain Tumors Treated with Radiotherapy?

Background: Understanding the role of personality traits in shaping treatment outcomes is crucial given the multifaceted challenges posed by brain tumors and the significant adverse impact of radiotherapy (RT) on patients' well-being. Purpose: This study aimed to provide insights into how personality traits affect psychosocial well-being and quality of life during RT in patients with high-grade malignant brain tumors. Methods: Personality traits in patients with high-grade glioma were assessed using the Eysenck Personality Questionnaire-Revised (EPQ-R). Quality of life was analyzed using EORTC questionnaires: the Questionnaire-Core 30 (QLQ-C30) and the Brain Cancer Module (QLQ-BN20). Patients were evaluated before RT, immediately after 6 weeks of RT, and 3 months post-RT. Results: Neuroticism predicted emotional function only three months post-RT. Extraversion decreased quality of life in global health status (third assessment), role function (second assessment), and emotional function (second and third assessments) but improved cognitive (first assessment) and social function (second assessment). The trait associated with lying was linked to a better quality of life in all domains except physical and cognitive function. Anxiety predicted a lower quality of life in brain tumor patients across all domains at various stages of RT treatment. Conclusions: This study advances our understanding of the psychosocial aspects of brain tumor care by highlighting the influence of personality traits on quality-of-life outcomes during RT. Identifying high-grade glioma patients at greater risk of a diminished quality of life based on personality profiles allows healthcare professionals to tailor interventions to address specific psychosocial needs, ultimately enhancing patient outcomes and holistic care during oncological treatment.

Frequency and Impact of Constitutional Mismatch Repair Deficiency in Patients With High-Grade Glioma, a Retrospective Analysis of 7 Years in Pakistan: an IRRDC Study.

Constitutional mismatch repair deficiency (CMMRD) is a genetic cancer predisposition syndrome among children and young adults. This study aimed to evaluate the frequency of CMMRD among patients with pediatric high-grade glioma (pHGG) in a single tertiary care center in Pakistan, a country with high consanguinity rates. We reviewed the data of patients age <18 years with pHGG, anaplastic astrocytoma, and diffuse midline glioma (DMG) with CMMRD testing between 2016 and 2023. CMMRD testing was done using the Aronson et al criteria. A few patients were sent to Sick Kids, Toronto, to review the mismatch repair protein stains via multigene panels. Forty-seven patients were identified, with a median age of 11 years (IQR, 8-16). Headache (89.4%) was the most common symptom. Thirty-seven patients had hemispheric tumors; 12.8% and 8.5% had posterior fossa and midline tumors, respectively. Histopathology revealed 70.2% glioblastoma, 23.4% anaplastic astrocytoma, and 6.4% DMG. CMMRD was positive in 15 of 47 patients (31.9%). Eight patients had loss of PMS2. Three had loss of PMS2 and MLH1; two had loss of MSH6, one had loss of MSH6 and MSH2, and only one patient had loss of MSH2. Consanguinity and family history of malignancy correlated with CMMRD (P = .009, P = .031, respectively). Two-year overall survival of all patients was 23.4% (median follow-up, 0.59 years [95% CI, 0.000 to 1.171]). Two-year overall survival of mismatch repair deficiency-positive patients was 20% (median follow-up, 0.910 years [95 CI, 0.380 to 1.440]). We found a high frequency of CMMRD among patients with pHGG, particularly with positive consanguinity. Our study highlights the significance of genetic testing and surveillance. It is essential to develop low and middle income country-tailored protocols due to limited access and financial constraints associated with using immune checkpoint inhibitors.

Brain-Derived Neurotrophic Factor (BDNF) as a Potential Biomarker in Brain Glioma: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis evaluates peripheral and CNS BDNF levels in glioma patients. Following PRISMA guidelines, we systematically searched databases for studies measuring BDNF in glioma patients and controls. After screening and data extraction, we conducted quality assessment, meta-analysis, and meta-regression. Eight studies were included. Meta-analysis showed significantly reduced plasma BDNF levels in glioma patients versus controls (SMD: -1.0026; 95% CI: [-1.5284, -0.4769], p = 0.0002). High-grade gliomas had lower plasma BDNF (p = 0.0288). Tissue BDNF levels were higher in glioma patients (SMD: 1.9513; 95% CI: [0.7365, 3.1661], p = 0.0016) and correlated with tumor grade (p = 0.0122). Plasma BDNF levels negatively correlated with patient age (p = 0.0244) and positively with female percentage (p = 0.0007). BDNF is a promising biomarker in glioma, showing significant changes in plasma and tissue levels correlating with tumor grade, patient age, and gender.

Development and Validation of a Prognostic Molecular Phenotype and Clinical Characterization in Grade III Diffuse Gliomas Treatment with Radio-Chemotherapy.

The relationship between molecular phenotype and prognosis in high-grade gliomas (WHO III and IV, HGG) treated with radiotherapy and chemotherapy is not fully understood and needs further exploration. The HGG patients following surgery and treatment with radiotherapy and chemotherapy. Univariate and multivariate Cox analyses were used to assess the independent prognostic factors. The nomogram model was established, and its accuracy was determined via the calibration plots. A total of 215 and 88 patients had grade III glioma and grade IV glioma, respectively. Grade III oligodendroglioma (OG-G3) patients had the longest mPFS and mOS than other grade III pathology, while grade III astrocytoma (AA-G3) patients were close to IDH-1 wildtype glioblastoma (GBM) and had a poor prognosis. The IDH-1 mutant group had a better mPFS and mOS than the IDH-1 wildtype group in all grade III patients, OG-G3 and AA-G3 patients. Furthermore, 1p/19q co-deletion group had a longer mPFS and mOS than 1p/19q non-deletion group in all grade III patients. IDH-1 mutation and 1p/19q co-deletion patients had the best prognosis than other molecular types. Also, the MGMT methylation and IDH-1 mutation or 1p/19q co-deletion group had a longer mPFS and mOS than the MGMT unmethylation and IDH-1 wildtype or 1p/19q non-codeletion of grade III patients. In addition, the low Ki-67 expression group had a better prognosis than high Ki-67 expression group in grade III patients. Univariate and multivariate COX showed that 1p/19q co-deletion and MGMT methylation were the independent prognostic factors for mPFS and mOS. The calibration curve showed that the established nomogram could well predict the survival based on these covariates. The AA-G3 with IDH-1 wildtype, MGMT unmethylation or 1p/19q non-codeletion patients was resistant to radiotherapy and chemotherapy, has a poor prognosis and needs a more active treatment.