NI-40 * MR IMAGING AND SPECTROSCOPY PROVIDES INSIGHT INTO MALIGNANT TRANSFORMATION AND IDH-MUTATION STATUS IN DIFFUSE LOW-GRADE GLIOMA

Abstract BACKGROUND Tumour Protein 53 (TP53) is a tumour suppressor gene that is mutated in at least 50% of human malignancies. The prevalence of TP53 mutation is much higher in astrocytomas with reports of up to 75% TP53 mutant cases. Rare cases of TP53 mutation also exist in oligodendroglial tumours (10–13%). P53 pathway is therefore an important factor in low-grade glioma tumorigenesis. Although the prognostic impact of TP53 mutations has been studied previously, no concrete concordance were reached between the studies. In this study, we investigated the prognostic effects of TP53 mutation in astrocytoma and oligodendroglioma. MATERIAL AND METHODS A cohort of 65 matched primary and recurrent fresh frozen tumours were sequenced to identify hotspot exons of TP53 mutation. Exons 1 to 10 were sequenced and pathogenic mutations were mostly predominant between Exons 4 and 8. The cohort was further expanded with 78 low grade glioma fresh frozen tissues and hotspot exons were sequenced. Selecting only the primary tumour from 65 matched tumours, a total of 50 Astrocytoma cases and 51 oligodendroglioma cases were analysed for prognostic effects of TP53. Only pathogenic TP53 mutations confirmed through COSMIC and NCBI databases were included in the over survival and progression-free survival analysis. RESULTS 62% (31/50) of astrocytomas and 16% (8/51) of oligodendrogliomas harboured pathogenic TP53 mutations. Pathogenic hotspot mutations in codon 273 (c.817 C>T and c.818 G>A) was prevalent in astrocytoma with 58% (18/31) of tumours with these mutations. TP53 mutation status was maintained between primary and recurrent tumours in 93% of cases. In astrocytoma, overall survival of TP53 mutant patients was longer compared to TP53 wild-type patients (p<0.01) but was not significant after adjusting for age, gender, grade and IDH1 mutation status. In contrast, astrocytoma patients with specific TP53 mutation in codon 273 showed significantly better survival compared to other TP53 mutant and TP53 wild-type patients combined (p<0.01) in our multivariate analysis. Time to first recurrence (progression-free survival) of TP53 mutant patients was significantly longer than TP53 wild-type patients (p<0.01) after adjustments were made, while TP53 mutation in codon 273 was not prognostic for progression-free survival. In oligodendroglioma patients, TP53 mutations did not significantly affect overall survival and progression-free survival. CONCLUSION In agreement with others, TP53 mutation is more prevalent in Astrocytoma and mutations in codon 273 are significantly associated with longer survival.

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Classification of Brain Tumor IDH Status using MRI and Deep Learning

10.1101/757344 ◽

2019 ◽

Author(s):

Sahil Nalawade ◽

Gowtham Murugesan ◽

Maryam Vejdani-Jahromi ◽

Ryan A. Fisicaro ◽

Chandan Ganesh Bangalore Yogananda ◽

...

Keyword(s):

Deep Learning ◽

Classification Accuracy ◽

Test Accuracy ◽

Low Grade ◽

Idh Mutation ◽

Validation Data ◽

Mutation Status ◽

Radiologic Imaging ◽

Address Data

AbstractIsocitrate dehydrogenase (IDH) mutation status is an important marker in glioma diagnosis and therapy. We propose a novel automated pipeline for predicting IDH status noninvasively using deep learning and T2-weighted (T2w) MR images with minimal preprocessing (N4 bias correction and normalization to zero mean and unit variance). T2w MRI and genomic data were obtained from The Cancer Imaging Archive dataset (TCIA) for 260 subjects (120 High grade and 140 Low grade gliomas). A fully automated 2D densely connected model was trained to classify IDH mutation status on 208 subjects and tested on another held-out set of 52 subjects, using 5-fold cross validation. Data leakage was avoided by ensuring subject separation during the slice-wise randomization. Mean classification accuracy of 90.5% was achieved for each axial slice in predicting the three classes of no tumor, IDH mutated and IDH wild-type. Test accuracy of 83.8% was achieved in predicting IDH mutation status for individual subjects on the test dataset of 52 subjects. We demonstrate a deep learning method to predict IDH mutation status using T2w MRI alone. Radiologic imaging studies using deep learning methods must address data leakage (subject duplication) in the randomization process to avoid upward bias in the reported classification accuracy.

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RTHP-31. LOW GRADE GLIOMA MALIGNANT TRANSFORMATION (MT): CLINICAL OUTCOMES AND PROGNOSTIC FACTORS IN TEMOZOLOMIDE ERA

Neuro-Oncology ◽

10.1093/neuonc/now212.756 ◽

2016 ◽

Vol 18 (suppl_6) ◽

pp. vi180-vi180 ◽

Cited By ~ 1

Author(s):

Erin Murphy ◽

C. Marc Leyrer Leyrer ◽

Michael Parsons ◽

John Suh ◽

Samuel Chao ◽

...

Keyword(s):

Prognostic Factors ◽

Clinical Outcomes ◽

Malignant Transformation ◽

Low Grade Glioma ◽

Low Grade

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Low grade glioma patients with IDH mutation and 1p19q codeletion: What to do after surgery?

Annals of Oncology ◽

10.1093/annonc/mdx366.003 ◽

2017 ◽

Vol 28 ◽

pp. v110

Author(s):

E. Franceschi ◽

A. Mura ◽

A. Mandrioli ◽

S. Minichillo ◽

A. Tosoni ◽

...

Keyword(s):

Low Grade Glioma ◽

Low Grade ◽

Idh Mutation ◽

1P19q Codeletion

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WP1-18 Risk factors and patterns of recurrence of low grade glioma: a systematic review

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-abn.19 ◽

2019 ◽

Vol 90 (3) ◽

pp. e6.3-e6

Author(s):

V Narbad ◽

JP Lavrador ◽

A Elhag ◽

S Acharya ◽

J Hanrahan ◽

...

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Tp53 Mutation ◽

Methylation Status ◽

Low Grade Glioma ◽

Low Grade ◽

Diffuse Glioma ◽

Idh Mutation ◽

Mgmt Methylation ◽

Inclusion Criteria

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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First intraoperative, shared-resource, ultrahigh-field 3-Tesla magnetic resonance imaging system and its application in low-grade glioma resection

Journal of Neurosurgery ◽

10.3171/2009.3.jns081139 ◽

2010 ◽

Vol 112 (1) ◽

pp. 57-69 ◽

Cited By ~ 63

Author(s):

M. Necmettin Pamir ◽

Koray Özduman ◽

Alp Dinçer ◽

Erdem Yildiz ◽

Selçuk Peker ◽

...

Keyword(s):

Mr Imaging ◽

Mr Spectroscopy ◽

Imaging System ◽

Low Grade Glioma ◽

Low Grade ◽

Imaging Protocol ◽

Proton Mr Spectroscopy ◽

Shared Resource ◽

Ultrahigh Field ◽

And Diffusion

Object The authors describe the first shared-resource, 3-T intraoperative MR (ioMR) imaging system and analyze its impact on low-grade glioma (LGG) resection with an emphasis on the use of intraoperative proton MR spectroscopy. Methods The Acibadem University ioMR imaging facility houses a 3-T Siemens Trio system and consists of interconnected but independent MR imaging and surgical suites. Neurosurgery is performed using regular ferromagnetic equipment, and a patient can be transferred to the ioMR imaging system within 1.5 minutes by using a floating table. The ioMR imaging protocol takes < 10 minutes including the transfer, and the authors obtain very high–resolution T2-weighted MR images without the use of intravenous contrast. Functional sequences are performed when needed. A new 5-pin headrest–head coil combination and floating transfer table were specifically designed for this system. Results Since the facility became operational in June 2004, 56 LGG resections have been performed using ioMR imaging, and > 19,000 outpatient MR imaging procedures have been conducted. First-look MR imaging studies led to further resection attempts in 37.5% of cases as well as a 32.3% increase in the number of gross-total resections. Intraoperative ultrasonography detected 16% of the tumor remnants. Intraoperative proton MR spectroscopy and diffusion weighted MR imaging were used to differentiate residual tumor tissue from peritumoral parenchymal changes. Functional and diffusion tensor MR imaging sequences were used both pre- and postoperatively but not intraoperatively. No infections or other procedure-related complications were encountered. Conclusions This novel, shared-resource, ultrahigh-field, 3-T ioMR imaging system is a cost-effective means of affording a highly capable ioMR imaging system and increases the efficiency of LGG resections.

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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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Pharmacoresistant seizures and IDH mutation in low grade gliomas

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab146 ◽

2021 ◽

Author(s):

Carlos Eduardo Correia ◽

Yoshie Umemura ◽

Jessica R Flynn ◽

Anne S Reiner ◽

Edward K Avila

Keyword(s):

Tumor Resection ◽

Incidence Rates ◽

P Value ◽

Low Grade ◽

Idh Mutation ◽

Wild Type ◽

Mutation Status ◽

Low Grade Gliomas ◽

Idh1 R132h ◽

Idh Mutations

Abstract Purpose Many low-grade gliomas (LGG) harbor isocitrate dehydrogenase (IDH) mutations. Although IDH mutation is known to be epileptogenic, the rate of refractory seizures in LGG with IDH mutation vs wild-type had not been previously compared. We therefore compared seizure pharmacoresistance in IDH-mutated and wild-type LGGs. Methods Single-institution retrospective study of patients with histologic proven LGG, known IDH mutation status, seizures, and ≥ 2 neurology clinic encounters. Seizure history was followed until histological high-grade transformation or death. Seizures requiring ≥ 2 changes in anti-epileptic drugs were considered pharmacoresistant. Incidence rates of pharmacoresistant seizures were estimated using competing risks methodology. Results Of 135 patients, 25 patients (19%) had LGGs classified as IDH wild-type. Of those with IDH mutation, 104 (94.5%) were IDH1 R132H; only six were IDH2 R172K. 120 patients (89%) had tumor resection and 14 (10%) had biopsy. Initial post-surgical management included observation (64%), concurrent chemoradiation (23%), chemotherapy alone (9%), and radiotherapy alone (4%). Seizures became pharmacoresistant in 24 IDH-mutated patients (22%) and in 3 IDH wild-type patients (12%). The 4-year cumulative incidence of intractable seizures was 17.6% (95% CI: 10.6%-25.9%) in IDH-mutated and 11% (95% CI: 1.3%-32.6%) in IDH wild-type LGG (Gray’s P-value= 0.26). Conclusions 22% of the IDH-mutated patients developed pharmacoresistant seizures, compared to 12% of the IDH wild-type tumors.The likelihood of developing pharmacoresistant seizures in patients with LGG-related epilepsy is independent to IDH mutation status, however, IDH-mutated tumors were approximately twice as likely to experience LGG-related pharmacoresistant seizures.

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