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2022 ◽  
Author(s):  
Nayan Lamba ◽  
Malia McAvoy ◽  
Vasileios K Kavouridis ◽  
Timothy R Smith ◽  
Mehdi Touat ◽  
...  

Abstract Background The optimal chemotherapy regimen between temozolomide and procarbazine, lomustine, and vincristine (PCV) remains uncertain for W.H.O. grade 3 oligodendroglioma (Olig3) patients. We therefore investigated this question using national data. Methods Patients diagnosed with radiotherapy-treated 1p/19q-codeleted Olig3 between 2010-2018 were identified from the National Cancer Database. The OS associated with first-line single-agent temozolomide vs. multi-agent PCV was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression. Results 1,596 radiotherapy-treated 1p/19q-codeleted Olig3 patients were identified: 88.6% (n=1,414) treated with temozolomide and 11.4% (n=182) with PCV (from 5.4% in 2010 to 12.0% in 2018) in the first-line setting. The median follow-up was 35.5 months (interquartile range [IQR] 20.7-60.6 months) with 63.3% of patients alive at time of analysis. There was a significant difference in unadjusted OS between temozolomide (5yr-OS 58.9%, 95%CI: 55.6-62.0) and PCV (5yr-OS 65.1%, 95%CI: 54.8-73.5; p=0.04). However, a significant OS difference between temozolomide and PCV was not observed in the Cox regression analysis adjusted by age and extent of resection (PCV vs. temozolomide HR 0.81, 95%CI: 0.59-1.11, p=0.18). PCV was more frequently used for younger Olig3s, but otherwise was not associated with patient’s insurance status or care setting. Conclusions In a national analysis of Olig3s, first-line PCV chemotherapy was associated with a slightly improved unadjusted short-term OS compared to temozolomide; but not following adjustment by patient age and extent of resection. There has been an increase in PCV utilization since 2010. These findings provide preliminary data while we await the definitive results from the CODEL trial.


2022 ◽  
Vol 11 ◽  
Author(s):  
Junhong Li ◽  
Huanhuan Fan ◽  
Xingwang Zhou ◽  
Yufan Xiang ◽  
Yanhui Liu

The urokinase-type plasminogen activator(PLAU) and its receptor PLAUR participate in a series of cell physiological activities on the extracellular surface. Abnormal expression of PLAU and PLAUR is associated with tumorigenesis. This study aims to evaluate the prognostic value of PLAU/PLAUR transcription expression in glioma and to explore how they affect the generation and progression of glioma. In this study, online databases are applied, such as Oncomine, GEPIA, CGGA, cBioPortal, and LinkedOmics. Overexpression of PLAU/PLAUR was found to be significantly associated with clinical variables including age, tumor type, WHO grade, histology, IDH-1 mutation, and 1p19q status. PLAU and PLAUR had a high correlation in transcriptional expression levels. High expression of PLAU and PLAUR predicted a poor prognosis in primary glioma and recurrent glioma patients, especially in lower grade gliomas. Cox regression analysis indicated that high expression of PLAU and PLAUR were independent prognostic factors for shorter overall survival in glioma patients. In gene co-expression network analysis PLAU and PLAUR and their co-expression genes were found to be involved in inflammatory activities and tumor-related signaling pathways. In conclusion, PLAU and PLAUR could be promising prognostic biomarkers and potential therapeutic targets of glioma patients.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Kosuke Nakajo ◽  
Takehiro Uda ◽  
Toshiyuki Kawashima ◽  
Yuzo Terakawa ◽  
Kenichi Ishibashi ◽  
...  

AbstractThis study aimed whether the uptake of amino tracer positron emission tomography (PET) can be used as an additional imaging biomarker to estimate the prognosis of glioma. Participants comprised 56 adult patients with newly diagnosed and untreated World Health Organization (WHO) grade II–IV astrocytic glioma who underwent surgical excision and were evaluated by 11C-methionine PET prior to the surgical excision at Osaka City University Hospital from July 2011 to March 2018. Clinical and imaging studies were retrospectively reviewed based on medical records at our institution. Preoperative Karnofsky Performance Status (KPS) only influenced progression-free survival (hazard ratio [HR] 0.20; 95% confidence interval [CI] 0.10–0.41, p < 0.0001), whereas histology (anaplastic astrocytoma: HR 5.30, 95% CI 1.23–22.8, p = 0.025; glioblastoma: HR 11.52, 95% CI 2.27–58.47, p = 0.0032), preoperative KPS ≥ 80 (HR 0.23, 95% CI 0.09–0.62, p = 0.004), maximum lesion-to-contralateral normal brain tissue (LN max) ≥ 4.03 (HR 0.24, 95% CI 0.08–0.71, p = 0.01), and isocitrate dehydrogenase (IDH) status (HR 14.06, 95% CI 1.81–109.2, p = 0.011) were factors influencing overall survival (OS) in multivariate Cox regression. OS was shorter in patients with LN max ≥ 4.03 (29.3 months) than in patients with LN max < 4.03 (not reached; p = 0.03). OS differed significantly between patients with IDH mutant/LN max < 4.03 and patients with IDH mutant/LN max ≥ 4.03. LN max using 11C-methionine PET may be used in prognostic markers for newly identified and untreated WHO grade II–IV astrocytic glioma.


Author(s):  
Theo F. J. Kraus ◽  
Christoph Schwartz ◽  
Lukas Machegger ◽  
Barbara Zellinger ◽  
Dorothee Hölzl ◽  
...  

AbstractHere, we report on a patient presenting with two histopathologically distinct gliomas. At the age of 42, the patient underwent initial resection of a right temporal oligodendroglioma IDH mutated 1p/19q co-deleted WHO Grade II followed by adjuvant radiochemotherapy with temozolomide. 15 months after initial diagnosis, the patient showed right hemispheric tumor progression and an additional new left frontal contrast enhancement in the subsequent imaging. A re-resection of the right-sided tumor and resection of the left frontal tumor were conducted. Neuropathological work-up showed recurrence of the right-sided oligodendroglioma with features of an anaplastic oligodendroglioma WHO Grade III, but a glioblastoma WHO grade IV for the left frontal lesion. In depth molecular profiling revealed two independent brain tumors with distinct molecular profiles of anaplastic oligodendroglioma IDH mutated 1p/19q co-deleted WHO Grade III and glioblastoma IDH wildtype WHO grade IV. This unique and rare case of a patient with two independent brain tumors revealed by in-depth molecular work-up and epigenomic profiling emphasizes the importance of integrated work-up of brain tumors including methylome profiling for advanced patient care.


2022 ◽  
Vol 10 (1) ◽  
Author(s):  
Azadeh Ebrahimi ◽  
Andrey Korshunov ◽  
Guido Reifenberger ◽  
David Capper ◽  
Joerg Felsberg ◽  
...  

AbstractPleomorphic xanthoastrocytoma (PXA) in its classic manifestation exhibits distinct morphological features and is assigned to CNS WHO grade 2 or grade 3. Distinction from glioblastoma variants and lower grade glial and glioneuronal tumors is a common diagnostic challenge. We compared a morphologically defined set of PXA (histPXA) with an independent set, defined by DNA methylation analysis (mcPXA). HistPXA encompassed 144 tumors all subjected to DNA methylation array analysis. Sixty-two histPXA matched to the methylation class mcPXA. These were combined with the cases that showed the mcPXA signature but had received a histopathological diagnosis other than PXA. This cohort constituted a set of 220 mcPXA. Molecular and clinical parameters were analyzed in these groups. Morphological parameters were analyzed in a subset of tumors with FFPE tissue available. HistPXA revealed considerable heterogeneity in regard to methylation classes, with methylation classes glioblastoma and ganglioglioma being the most frequent mismatches. Similarly, the mcPXA cohort contained tumors of diverse histological diagnoses, with glioblastoma constituting the most frequent mismatch. Subsequent analyses demonstrated the presence of canonical pTERT mutations to be associated with unfavorable prognosis among mcPXA. Based on these data, we consider the tumor type PXA to be histologically more varied than previously assumed. Histological approach to diagnosis will predominantly identify cases with the established archetypical morphology. DNA methylation analysis includes additional tumors in the tumor class PXA that share similar DNA methylation profile but lack the typical morphology of a PXA. DNA methylation analysis also assist in separating other tumor types with morphologic overlap to PXA. Our data suggest the presence of canonical pTERT mutations as a robust indicator for poor prognosis in methylation class PXA.


2022 ◽  
Author(s):  
Jinyang Ma ◽  
Lei Wang ◽  
Youdong Zhou ◽  
Changtao Fu ◽  
Song Huang ◽  
...  

Abstract Backgroud: Discovering effective immune-related biomarkers is vital to ensure efficient immunotherapy for glioma patients. Integrin Alpha L(ITGAL), essential to inflammatory and immune responses, have not been studied in gliomas, systematically. Methods RNA‑seq data and corresponding clinical information of glioma patients were collected from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA), and mRNA data of normal brain tissues were obtained in Genotype-Tissue Expression (GTEx) project. Wilcoxon test was performed to analyze the correlation of ITGAL expression and glioma subtypes. Univariate and multivariate cox proportional hazards regression, receiver operating characteristic (ROC) curves and Kaplan-Meier plots were used to evaluate the prognostic value of ITGAL in glioma. Functional enrichment analyses and immune infiltration analysis were performed to investigate the potential function in mediating the immune response in the tumor microenvironment. Finally, we evaluated the ability of ITGAL for predicting the efficacy of ICB treatment for patients. Results We found the up-regulation of ITGAL may predict a poor prognosis for glioma patients, the expression level increased with the increasing of WHO grade and 1p19q co-deletion status and IDH mutation status. The total methylation level and copy number variation of ITGAL were moderately correlated with its mRNA expression in LGG samples (P < 0.05). Furthermore, ITGAL was correlated with the immunosuppressive tumor microenvironment for the strong correlation with M2 macrophages and Tregs. Finally, GSEA showed the upregulation of ITGAL was mainly involved in the signal recognition and regulation between immune cells, and Toll-like receptor signaling pathway. Conclusion ITGAL is a novel tumor-related and immune-associated biomarker, which could predict the prognosis and effect of ICB therapy for glioma patients.


2022 ◽  
Vol 11 ◽  
Author(s):  
Louise Carstam ◽  
Alba Corell ◽  
Anja Smits ◽  
Anna Dénes ◽  
Hanna Barchéus ◽  
...  

BackgroundWhile molecular insights to diffuse lower-grade glioma (dLGG) have improved the basis for prognostication, most established clinical prognostic factors come from the pre-molecular era. For instance, WHO grade as a predictor for survival in dLGG with isocitrate dehydrogenase (IDH) mutation has recently been questioned. We studied the prognostic role of WHO grade in molecularly defined subgroups and evaluated earlier used prognostic factors in the current molecular setting.Material and MethodsA total of 253 adults with morphological dLGG, consecutively included between 2007 and 2018, were assessed. IDH mutations, codeletion of chromosomal arms 1p/19q, and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions were analyzed.ResultsThere was no survival benefit for patients with WHO grade 2 over grade 3 IDH-mut dLGG after exclusion of tumors with known CDKN2A/B homozygous deletion (n=157) (log-rank p=0.97). This was true also after stratification for oncological postoperative treatment and when astrocytomas and oligodendrogliomas were analyzed separately. In IDH-mut astrocytomas, residual tumor volume after surgery was an independent prognostic factor for survival (HR 1.02; 95% CI 1.01–1.03; p=0.003), but not in oligodendrogliomas (HR 1.02; 95% CI 1.00–1.03; p=0.15). Preoperative tumor size was an independent predictor in both astrocytomas (HR 1.03; 95% CI 1.00–1.05; p=0.02) and oligodendrogliomas (HR 1.05; 95% CI 1.01–1.09; p=0.01). Age was not a significant prognostic factor in multivariable analyses (astrocytomas p=0.64, oligodendrogliomas p=0.08).ConclusionOur findings suggest that WHO grade is not a robust prognostic factor in molecularly well-defined dLGG. Preoperative tumor size remained a prognostic factor in both IDH-mut astrocytomas and oligodendrogliomas in our cohort, whereas residual tumor volume predicted prognosis in IDH-mut astrocytomas only. The age cutoffs for determining high risk in patients with IDH-mut dLGG from the pre-molecular era are not supported by our results.


Author(s):  
Mohamed Saied Abdelgawad ◽  
Mohamed Hamdy Kayed ◽  
Mohamed Ihab Samy Reda ◽  
Eman Abdelzaher ◽  
Ahmed Hafez Farhoud ◽  
...  

Abstract Background Non-neoplastic brain lesions can be misdiagnosed as low-grade gliomas. Conventional magnetic resonance (MR) imaging may be non-specific. Additional imaging modalities such as spectroscopy (MRS), perfusion and diffusion imaging aid in diagnosis of such lesions. However, contradictory and overlapping results are still present. Hence, our purpose was to evaluate the role of advanced neuro-imaging in differentiation between low-grade gliomas (WHO grade II) and MR morphologically similar non-neoplastic lesions and to prove which modality has the most accurate results in differentiation. Results All patients were classified into two main groups: patients with low-grade glioma (n = 12; mean age, 38.8 ± 16; 8 males) and patients with non-neoplastic lesions (n = 27; mean age, 36.6 ± 15; 19 males) based on the histopathological and clinical–radiological diagnosis. Using ROC curve analysis, a threshold value of 0.93 for rCBV (AUC = 0.875, PPV = 92%, NPV = 71.4%) and a threshold value of 2.5 for Cho/NAA (AUC = 0.829, PPV = 92%, NPV = 71.4%) had 85.2% sensitivity and 83.3% specificity for predicting neoplastic lesions. The area under the curve (AUC) of ROC analysis was good for relative cerebral blood volume (rCBV) and Cho/NAA ratios (> 0.80) and fair for Cho/Cr and NAA/Cr ratios (0.70–0.80). When the rCBV measurements were combined with MRS ratios, significant improvement was observed in the area under the curve (AUC) (0.969) with improved diagnostic accuracy (89.7%) and sensitivity (88.9%). Conclusions Evaluation of rCBV and metabolite ratios at MRS, particularly Cho/NAA ratio, may be helpful in differentiating low-grade gliomas from non-neoplastic lesions. The combination of dynamic susceptibility contrast (DSC) perfusion and MRS can significantly improve the diagnostic accuracy and can help avoiding the need for an invasive biopsy.


2022 ◽  
pp. 197140092110674
Author(s):  
Bettina L Serrallach ◽  
Brandon H Tran ◽  
David F Bauer ◽  
Carrie A Mohila ◽  
Adekunle M Adesina ◽  
...  

Primary spinal cord high-grade gliomas, including those histologically identified as glioblastoma (GBM), are a rare entity in the pediatric population but should be considered in the differential diagnosis of intramedullary lesions. Pediatric spinal cord high-grade gliomas have an aggressive course with poor prognosis. The aim of this case report is to present a 15-year-old female adolescent with histopathologically confirmed spinal cord GBM with H3F3A K27 M mutation consistent with a diffuse midline glioma (DMG), H3 K27-altered, CNS WHO grade 4 with leptomeningeal seeding on initial presentation. As imaging features of H3 K27-altered DMGs are non-specific and may mimic more frequently encountered neoplastic diseases as well as demyelinating disorders, severe neurological deficits at presentation with short duration, rapid progression, and early leptomeningeal seeding should however raise the suspicion for a pediatric-type diffuse high-grade glioma like DMG, H3 K27-altered.


Author(s):  
Jiabo Li ◽  
Xuya Wang ◽  
Lulu Chen ◽  
Jinhao Zhang ◽  
Yiming Zhang ◽  
...  

AbstractGlioblastoma is the most common primary intracranial malignant tumor in adults and has high morbidity and high mortality. TMEM158 has been reported to promote the progression of solid tumors. However, its potential role in glioma is still unclear. Here, we found that TMEM158 expression in human glioma cells in the tumor core was significantly higher than that in noncancerous cells at the tumor edge using bioinformatics analysis. Cancer cells in patients with primary GBMs harbored significantly higher expression of TMEM158 than those in patients with WHO grade II or III gliomas. Interestingly, regardless of tumor grading, human glioma samples that were IDH1-wild-type (IDH1-WT) exhibited higher expression of TMEM158 than those with IDH1-mutant (IDH1-Mut). We also illustrated that TMEM158 mRNA expression was correlated with poor overall survival in glioma patients. Furthermore, we demonstrated that silencing TMEM158 inhibited the proliferation of glioma cells and that TMEM158 overexpression promoted the migration and invasion of glioma cells by stimulating the EMT process. We found that the underlying mechanism involves STAT3 activation mediating TMEM158-driven glioma progression. In vivo results further confirmed the inhibitory effect of the TMEM158 downregulation on glioma growth. Collectively, these findings further our understanding of the oncogenic function of TMEM158 in gliomas, which represents a potential therapeutic target, especially for GBMs.


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