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Management of primary thalamic low-grade glioma in pediatric patients: results of the multicenter treatment studies HIT-LGG 1996 and SIOP-LGG 2004.

ABSTRACT: Background:Thalamic low-grade glioma (LGG) poses a special therapeutic challenge, as complete resection is often not possible. To determine the survival outcomes of mono- and bithalamic LGG, we analyzed a large cohort of pediatric patients. Methods:From 1996 until 2012, 2618 patients were registered in the HIT-LGG 1996 and the SIOP-LGG 2004 studies. A total of 102 of these 2618 patients (3.9%) were diagnosed with a thalamic LGG with a median age at diagnosis of 8.0 years (range, 0.4-17.5 years); 87 patients (85%) had monothalamic and 15 patients (15%) had bithalamic LGG. Results:Ninety patients received at least one surgical procedure. Thirty-one patients received radiotherapy and 24 patients received chemotherapy as a first-line, nonsurgical treatment indicated by radiological tumor progression or severe/progressive clinical symptoms. Patients with monothalamic tumors showed a 10-year overall survival (OS) rate of 91%, whereas patients with bithalamic tumors only reached 65% (P = .001). Bithalamic tumors more frequently showed diffuse histology than monothalamic tumors. Patients with diffuse astrocytoma had a lower 10-year OS (68%) than those with pilocytic astrocytoma (93%). The 10-year progression-free survival rate after the start of first nonsurgical treatment was 53% in the radiotherapy group and 34% in the chemotherapy group. Conclusions:Thalamic glioma was manageable using a strategy that included surgery, observation, chemotherapy, and/or radiotherapy. Radiotherapy could be successfully deferred or obviated in a number of patients. Survival was high in among patients with monothalamic tumors. The worse prognosis associated with bithalamic tumors correlates with the higher rate of diffuse histology in this subgroup, precluding total or near-total resection.

SUBMITTER: Boesten T

PROVIDER: S-EPMC6655541 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Management of primary thalamic low-grade glioma in pediatric patients: results of the multicenter treatment studies HIT-LGG 1996 and SIOP-LGG 2004.

Boesten Tineke T Gerber Nicolas U NU Kandels Daniela D Azizi Amedeo A AA Schmidt Rene R Warmuth-Metz Monika M Pietsch Torsten T Kortmann Rolf-Dieter RD Gnekow Astrid A Grotzer Michael A MA

Neuro-oncology practice 20161209 1

<h4>Background</h4>Thalamic low-grade glioma (LGG) poses a special therapeutic challenge, as complete resection is often not possible. To determine the survival outcomes of mono- and bithalamic LGG, we analyzed a large cohort of pediatric patients.<h4>Methods</h4>From 1996 until 2012, 2618 patients were registered in the HIT-LGG 1996 and the SIOP-LGG 2004 studies. A total of 102 of these 2618 patients (3.9%) were diagnosed with a thalamic LGG with a median age at diagnosis of 8.0 years (range, 0 ...[more]

PMID: 31385995

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Project description:IntroductionGlioma is the most common primary tumor in the brain.Integrin beta 2(ITGB2) is a member of the leukocyte integrin family (leukocyte integrin), participating in lymphocyte recycling and homing, cell adhesion, and cell surface-mediated signal transduction. However, few studies on ITGB2 in gliomas have been reported yet.This study first discussed the relationship between ITGB2 expression and clinical characterization of glioma and the prognostic significance of its methylation in low-grade glioma.MethodsWe collected Clinical data and transcription of glioma patients from TCGA, CGGA, and Rembrant datasets to analyze the differential expression of ITGB2 mRNA in glioma tissues and normal tissues. The box polts to evaluated the expression patterns of ITGB2 in different molecular subtypes. Receiver operating characteristic curve (ROC) were used to evaluate and verify the reliability of the model. Kaplan-Meier survival curves to evaluated the relationship between the level of ITGB2 mRNA expression and overall survival (OS). Using cox regression analysis to verify the ability of ITGB2 as an independent predictor of OS in glioma patients. We use TIMER to analyze and visualize the association between immune infiltration levels and a range of variables. The methylation of GBMLGG patients were obtained from the TCGA database through the biological portal.ResultsITGB2 can be a potential marker for mesenchymal molecular subtype gliomas. COX regression analysis shows that ITGB2 is an independent predictive marker of OS in malignant glioma patients. Biological processes show that ITGB2 has involved glioma immune-related activities, especially closely related to B cells, CD4+Tcells, macrophages, neutrophils, and dendritic cells. ITGB2 is negatively regulated by ITGB2 methylation, resulting in low expression in LGG tissues. Low expression of ITGB2 and high methylation indicate good OS in patients with LGG. The ITGB2 methylation risk score (ITMRS) obtained from the ITGB2 methylation CpG site can better predict the OS of LGG patients. We used univariate and multivariate cox regression analysis of methylationsites, used the R language predict function to obtain the risk score of these ITGB2 methylation sites(ITMRS).DiscussionITGB2 can be used as a potential marker of mesenchymal molecular subtypes of gliomas and as an independent predictive marker of OS in patients with malignant gliomas. The ITMRS we established can be used as an independent prognostic factor for LGG and provide a new idea for the diagnosis and treatment of LGG.

Project description:Abstract BACKGROUND There is a lack of treatment options for HGG and LGG patients. BRAFV600E mutations are uncommon in glioma, with a poor long-term prognosis. Combined BRAF/MEK inhibition extends progression-free survival (PFS) and overall survival (OS) in BRAF V600E–mutated melanoma, non small-cell lung cancer, and anaplastic thyroid cancer. METHODS This phase 2, open-label trial (NCT02034110) evaluated dabrafenib (BRAF inhibitor, 150mg BID) plus trametinib (MEK inhibitor, 2mg QD) in patients with BRAF V600E mutations in 9 rare tumor types, including HGG and LGG. Eligible patients had histologically-confirmed recurrent or progressive glioma (LGG:WHO grade 1 or 2; HGG:WHO grade 3 or 4), with HGG patients required to have received radiotherapy and first-line chemotherapy, or concurrent chemoradiation. Treatment continued until unacceptable toxicity, disease progression, or death. Primary endpoint was investigator-assessed objective response rate (ORR) using RANO criteria. Secondary endpoints included duration of response (DOR), PFS, OS, and safety. RESULTS Interim analysis (IA) #14 (data cutoff: April 2, 2018) reported additional 3 months follow-up, with 49 patients enrolled (HGG, n=39; LGG, n=10) and 3 patients not evaluable for response. In HGG patients, ORR was 27% (10/37; 95%CI: 13.8%-44.1%), including CR (n=1), PR (n=9), and SD (n=11), with 16 patients currently ongoing treatment. In LGG patients, ORR was 56% (5/9; 95%CI: 26.8%-79.3%), including PR (n=5) and SD (n=4), with 6 patients currently ongoing treatment. OS, PFS, and DOR will be presented (IA#15). In HGG patients, adverse events (AEs) included fatigue (33%), headache (31%), rash (28%), and pyrexia (23%); grade 3/4 AEs included neutropenia (8%) and fatigue (5%). In LGG patients, AEs included headache (70%), fatigue, pyrexia (60% each), nausea, and arthralgia (50% each); grade 3/4 AEs included fatigue (20%). CONCLUSIONS Dabrafenib plus trametinib demonstrated promising efficacy in patients with recurrent or refractory BRAF V600E?mutated HGG or LGG, with manageable AEs and no new safety signals.

Project description:Serine Incorporator 2 (SERINC2) is a transmembrane protein that incorporates serine into membrane lipids. The function of SERINC2 in tumors has been reported, but the role of SERINC2 in gliomas is not fully understood. RNA-sequencing data from The Cancer Genome Atlas (TCGA) (530 cases of low-grade glioma (LGG) and 173 cases of glioblastoma multiforme (GBM)) and microarray data from Gene Expression Omnibus (GEO) (Accession No. GSE16011, 284 cases gliomas were included) were acquired. Bioinformatics analysis was performed as the primary method to examine the function of SERINC2 and its correlated genes in glioma. SERINC2 was highly expressed in GBM compared with LGG and normal brain tissues. Elevated SERINC2 expression predicted shorter 5-, 10-, and 15-year overall survival (OS) of LGG patients and isocitrate dehydrogenase-1 (IDH-1) mutation-type LGG patients but had no effect on the OS of GBM patients. Cox regression analysis showed that SERINC2 was an independent factor in LGG OS. Methylation analysis found that 13 CpG methylation sites (methylation450k) correlated with SERINC2 expression in LGG. The mRNA expression level of SERINC2 was significant lower in the DNA deletion group than in the intact and amplification groups. A total of 390 copositive and 244 conegative correlation genes with SERINC2 were obtained from LGG in TCGA-LGG and GSE16011. Gene ontology (GO) category and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the copositive correlation genes were primarily enriched in the mitotic process and cell cycle. Combining the results from the protein-protein interaction (PPI) network of SERINC2 correlation genes and CytoHubba led to the selection of 10 hub genes (CDC20, FN1, AURKB, AURKA, KIF2C, BIRC5, CCNB2, UBE2C, CCNA2, and CENPE). OncoLnc analysis confirmed that high expression levels of these hub genes were associated with poor OS in LGG. Our results suggested that aberrant SERINC2 expression existed in glioma and that its expression might be a potential prognostic marker in LGG patients. CDC20, FN1, AURKB, AURKA, KIF2C, BIRC5, CCNB2, UBE2C, CCNA2, and CENPE may be potential biomarkers and therapeutic targets for LGG.

Dataset Information

Management of primary thalamic low-grade glioma in pediatric patients: results of the multicenter treatment studies HIT-LGG 1996 and SIOP-LGG 2004.

Publications

Management of primary thalamic low-grade glioma in pediatric patients: results of the multicenter treatment studies HIT-LGG 1996 and SIOP-LGG 2004.

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