IDH mutation is associated with higher risk of malignant transformation in low-grade glioma

ObjectivesTo review the risk factors and patterns of progression/recurrence of low grade glioma (LGG).DesignSystematic review of the published literature.SubjectsInclusion criteria were peer reviewed publications of cohort studies of recurrent/progressive LGG. Studies of wider populations were included if relevant LGG data could be analysed separately.MethodsMedline and Cochrane databases were searched using MeSH and non-MeSH terms, including ‘glioma’, ‘astrocytoma’, ‘oligoastrocytoma’, ‘diffuse glioma’, ‘oligodendroglioma’, ‘low grade’ and ‘disease recurrence’ by two independent reviewers.ResultsOverall, 917 studies were screened, of which 57 studies met the inclusion criteria. The most frequently described risk factor for recurrent LGG was suboptimal extent of resection (EOR) of the initial tumour (in 20 studies); recurrence was also associated with the patient’s age (2), tumour location (4), neurological status (3), tumour volume (6), bihemispherical tumour (3) and astrocytic histology (6). IDH mutation was associated with recurrence in 1 out of 3 studies, but TP53 mutation (2 of 4) and MGMT methylation status (4) were not. Malignant transformation was associated with TP53 mutations (3), IDH mutation (1) and EOR (1). Favourable progression free survival (PFS) and/or overall survival (OS) were associated with greater EOR (16), oligodendroglioma histology (2 of 4), initial KPS (3) and the use of adjuvant therapies (9 of 14). IDH mutation was associated with improved PFS and OS (3 of 4). TP53 mutation improved PFS in 1 of 3 studies. MGMT methylation and 1 p/19q codeletion may predict treatment response but their effects on survival are unclear.ConclusionsAstrocytoma histology, IDH and TP53 mutation statuses and surgical treatment (EOR) are essential in determining the time to recurrence or progression in LGG.

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Multi Omics Profiling and Clustering Low Grade Glioma Based on Integrated Stress Status

10.21203/rs.3.rs-139591/v1 ◽

2021 ◽

Author(s):

Xiaolin Ren ◽

Xin Chen ◽

Chen Zhu ◽

Anhua Wu

Keyword(s):

Stress Response ◽

High Risk ◽

Malignant Transformation ◽

Immune Cell ◽

High Risk Group ◽

Low Grade Glioma ◽

The Cancer Genome Atlas ◽

Low Grade ◽

Integrated Stress Response ◽

Genome Atlas

Abstract Background: Although the prognosis of low-grade glioma (LGG) is better than that of glioblastoma (GBM), there are still some patients who will develop into high-grade glioma. Integrated stress response contributed to the malignant transformation of tumor. As there is few research focus on the integrated stress status in LGG, it is urgent to profile and re-classify LGG based on integrated stress response (ISR). Methods: Glioma patients were obtained from the Chinese Glioma Genome Atlas ( the Cancer Genome Atlas (TCGA) and GSE16011 cohorts. Statistical 8 analyses were conducted by GraphPad Prism and R language. Results: We quantified four types of integrated stress response respectively. The relationship between the four stress states and the clinical characteristics of LGG was analyzed. Then we re-classified the patients based on these four scores, we found that cluster 1 had the worst prognosis, whereby cluster 3 had the best prognosis. We also established an accurate ISR risk signature to predicting cluster 1. We found that immune response and suppressive immune cell components were more enriched in the high-risk group. We also profiled the genomic difference between low and high risk groups, including the non-missense mutation of drivel genes and the condition of copy number variation (CNV). Conclusion: LGG patients could be divided into four clusters based on the integrated stress status, cluster 1 exhibited malignant transformation trends. ISR signature could reflect the traits of cluster 1 well, high ISR score indicated worse prognosis and enriched inhibitory immune microenvironments.

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Malignant Transformation of Molecularly Classified Adult Low-Grade Glioma

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2019.08.025 ◽

2019 ◽

Vol 105 (5) ◽

pp. 1106-1112 ◽

Cited By ~ 2

Author(s):

Martin C. Tom ◽

Deborah Y.J. Park ◽

Kailin Yang ◽

C. Marc Leyrer ◽

Wei Wei ◽

...

Keyword(s):

Malignant Transformation ◽

Low Grade Glioma ◽

Low Grade

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PATH-57. MOLECULAR DETERMINANTS OF RECURRENCE AND MALIGNANT TRANSFORMATION IN DIFFUSE LOW GRADE GLIOMA

Neuro-Oncology ◽

10.1093/neuonc/noy148.711 ◽

2018 ◽

Vol 20 (suppl_6) ◽

pp. vi171-vi171

Author(s):

Ko-Ting Chen ◽

Ian Chang ◽

Tai-Wei Erich Wu

Keyword(s):

Malignant Transformation ◽

Low Grade Glioma ◽

Low Grade ◽

Molecular Determinants

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AT-42 * FACTORS ASSOCIATED WITH MALIGNANT TRANSFORMATION OF LOW-GRADE GLIOMA

Neuro-Oncology ◽

10.1093/neuonc/nou237.41 ◽

2014 ◽

Vol 16 (suppl 5) ◽

pp. v17-v18

Author(s):

K. Moriya ◽

M. Nitta ◽

T. Maruyama ◽

T. Saito ◽

S. Ikuta ◽

...

Keyword(s):

Malignant Transformation ◽

Low Grade Glioma ◽

Low Grade ◽

Factors Associated

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Malignant Transformation of Adult Low Grade Glioma: Risk Factors and Outcomes in the Molecular Era

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2019.06.140 ◽

2019 ◽

Vol 105 (1) ◽

pp. S143 ◽

Cited By ~ 1

Author(s):

M.C. Tom ◽

D.Y.J. Park ◽

W. Wei ◽

C.M. Leyrer ◽

K. Yang ◽

...

Keyword(s):

Risk Factors ◽

Malignant Transformation ◽

Low Grade Glioma ◽

Low Grade ◽

Glioma Risk

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Predictors of early, recurrent, and intractable seizures in low-grade glioma

Neuro-Oncology Practice ◽

10.1093/nop/npaa054 ◽

2020 ◽

Author(s):

Jasmin Jo ◽

Kathryn Nevel ◽

Ryan Sutyla ◽

Mark Smolkin ◽

M Beatriz Lopes ◽

...

Keyword(s):

Low Grade Glioma ◽

World Health ◽

Rank Test ◽

Molecular Testing ◽

Low Grade ◽

Idh Mutation ◽

Who Grade ◽

Intractable Seizures ◽

Significant Difference ◽

Male Sex

Abstract Background Seizures are common among patients with low-grade glioma (LGG) and can significantly affect morbidity. We sought to determine the association between the clinical and molecular factors with seizure incidence and refractoriness in LGG patients. Methods We conducted a retrospective review at the University of Virginia in patients with LGG (World Health Organization, WHO Grade II) evaluated between 2002 and 2015. Descriptive statistics were calculated for variables of interest, and the Kaplan-Meier method was used to estimate survival curves, which were compared with the log-rank test. Results A total of 291 patients were included; 254 had molecular testing performed for presence of an isocitrate dehydrogenase (IDH) mutation and/or 1p/19q codeletion. Sixty-eight percent of patients developed seizures prior to LGG diagnosis; 41% of all patients had intractable seizures. Using WHO 2016 integrated classification, there was no significant difference in seizure frequency during preoperative and postoperative periods or in developing intractable seizures, though a trend toward increased preoperative seizure incidence among patients with the IDH mutation was identified (P = .09). Male sex was significantly associated with higher seizure incidence during preoperative (P < .001) and postoperative periods (P < .001); men were also more likely to develop intractable seizures (P = .01). Conclusions Seizures are common among patients with LGG. Differences in preoperative or postoperative and intractable seizure rates by WHO 2016 classification were not detected. Our data showed a trend toward higher seizure incidence preoperatively in patients with IDH-mutant LGG. We describe a unique association between male sex and seizure incidence and intractability that warrants further study.

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