scholarly journals The molecular biology of WHO Grade II gliomas

2013 ◽  
Vol 34 (2) ◽  
pp. E1 ◽  
Author(s):  
Nicholas F. Marko ◽  
Robert J. Weil
Keyword(s):  
Molecular Biology ◽  
Tumor Biology ◽  
Molecular Characteristics ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Who Grade ◽  
Low Grade Gliomas ◽  
Molecular Features ◽  
Grade Ii ◽  
Who Grade Ii Gliomas

The WHO grading scheme for glial neoplasms assigns Grade II to 5 distinct tumors of astrocytic or oligodendroglial lineage: diffuse astrocytoma, oligodendroglioma, oligoastrocytoma, pleomorphic xanthoastrocytoma, and pilomyxoid astrocytoma. Although commonly referred to collectively as among the “low-grade gliomas,” these 5 tumors represent molecularly and clinically unique entities. Each is the subject of active basic research aimed at developing a more complete understanding of its molecular biology, and the pace of such research continues to accelerate. Additionally, because managing and predicting the course of these tumors has historically proven challenging, translational research regarding Grade II gliomas continues in the hopes of identifying novel molecular features that can better inform diagnostic, prognostic, and therapeutic strategies. Unfortunately, the basic and translational literature regarding the molecular biology of WHO Grade II gliomas remains nebulous. The authors' goal for this review was to present a comprehensive discussion of current knowledge regarding the molecular characteristics of these 5 WHO Grade II tumors on the chromosomal, genomic, and epigenomic levels. Additionally, they discuss the emerging evidence suggesting molecular differences between adult and pediatric Grade II gliomas. Finally, they present an overview of current strategies for using molecular data to classify low-grade gliomas into clinically relevant categories based on tumor biology.

Molecular Alterations in Pediatric Low-Grade Gliomas That Led to Death

2021 ◽  
Author(s):  
Jared T Ahrendsen ◽  
Claire Sinai ◽  
David M Meredith ◽  
Seth W Malinowski ◽  
Tabitha M Cooney ◽  
...  
Keyword(s):  
Braf V600e ◽  
Molecular Characteristics ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Term Survival ◽  
Pten Loss ◽  
Low Grade Gliomas ◽  
Molecular Alterations ◽  
Idh1 R132h ◽  
Poor Outcomes

Abstract Pediatric low-grade gliomas (PLGGs) have excellent long-term survival, but death can occasionally occur. We reviewed all PLGG-related deaths between 1975 and 2019 at our institution: 48 patients were identified; clinical data and histology were reviewed; targeted exome sequencing was performed on available material. The median age at diagnosis was 5.2 years (0.4–23.4 years), at death was 13.0 years (1.9–43.2 years), and the overall survival was 7.2 years (0.0–33.3 years). Tumors were located throughout CNS, but predominantly in the diencephalon. Diagnoses included low-grade glioma, not otherwise specified (n = 25), pilocytic astrocytoma (n = 15), diffuse astrocytoma (n = 3), ganglioglioma (n = 3), and pilomyxoid astrocytoma (n = 2). Recurrence occurred in 42/48 cases, whereas progression occurred in 10. The cause of death was direct tumor involvement in 31/48 cases. Recurrent drivers included KIAA1549-BRAF (n = 13), BRAF(V600E) (n = 3), NF1 mutation (n = 3), EGFR mutation (n = 3), and FGFR1-TACC1 fusion (n = 2). Single cases were identified with IDH1(R132H), FGFR1(K656E), FGFR1 ITD, FGFR3 gain, PDGFRA amplification, and mismatch repair alteration. CDKN2A/B, CDKN2C, and PTEN loss was recurrent. Patients who received only chemotherapy had worse survival compared with patients who received radiation and chemotherapy. This study demonstrates that PLGG that led to death have diverse molecular characteristics. Location and co-occurring molecular alterations with malignant potential can predict poor outcomes.

scholarly journals The Role of Extent of Resection in IDH1 Wild-Type or Mutant Low-Grade Gliomas

Neurosurgery ◽  
2017 ◽  
Vol 82 (6) ◽  
pp. 808-814 ◽  
Author(s):  
Toral Patel ◽  
Evan D Bander ◽  
Rachael A Venn ◽  
Tiffany Powell ◽  
Gustav Young-Min Cederquist ◽  
...  
Keyword(s):  
Cox Regression ◽  
Extent Of Resection ◽  
World Health ◽  
Low Grade ◽  
Wild Type ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Low Grade Gliomas ◽  
Grade Ii ◽  
The Impact

Abstract BACKGROUND Maximizing extent of resection (EOR) improves outcomes in adults with World Health Organization (WHO) grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs. OBJECTIVE To assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS) in mtIDH and wtIDH LGGs. METHODS We performed a retrospective review of 74 patients with WHO grade II gliomas and known IDH mutational status undergoing resection at a single institution. EOR was assessed with quantitative 3-dimensional volumetric analysis. The effect of predictor variables on MPFS and OS was analyzed with Cox regression models and the Kaplan–Meier method. RESULTS Fifty-two (70%) mtIDH patients and 22 (30%) wtIDH patients were included. Median preoperative tumor volume was 37.4 cm3; median EOR of 57.6% was achieved. Univariate Cox regression analysis confirmed EOR as a prognostic factor for the entire cohort. However, stratifying by IDH status demonstrates that greater EOR independently prolonged MPFS and OS for wtIDH patients (hazard ratio [HR] = 0.002 [95% confidence interval {CI} 0.000-0.074] and HR = 0.001 [95% CI 0.00-0.108], respectively), but not for mtIDH patients (HR = 0.84 [95% CI 0.17-4.13] and HR = 2.99 [95% CI 0.15-61.66], respectively). CONCLUSION Increasing EOR confers oncologic and survival benefits in IDH1 wtLGGs, but the impact on IDH1 mtLGGs requires further study.

Interstitial radiosurgery of low-grade gliomas

1995 ◽  
Vol 82 (3) ◽  
pp. 418-429 ◽  
Author(s):  
Friedrich W. Kreth ◽  
Michael Faist ◽  
Peter C. Warnke ◽  
Reinhard Roβner ◽  
Benedikt Volk ◽  
...  
Keyword(s):  
Ct Scan ◽  
Tumor Recurrence ◽  
Survival Rates ◽  
Low Grade ◽  
Who Grade ◽  
Content Type ◽  
Low Grade Gliomas ◽  
Interstitial Radiosurgery ◽  
Grade Ii ◽  
Fine Print

✓ The treatment of patients with low-grade gliomas remains a subject of controversy, especially with respect to new treatment modalities such as interstitial radiosurgery (brachytherapy), radiosurgery, and stereotactic radiotherapy. In a retrospective analysis conducted between 1979 and 1991, the authors studied the results of interstitial radiosurgery in 455 patients with low-grade gliomas (World Health Organization (WHO) Grade I + WHO Grade II) with regard to survival time, quality of life, the risk of malignant transformation, and the risk profile of the treatment concept. Interstitial radiosurgery with iodine-125 was performed using permanent (1979–1985) or temporary implants (after 1985) with low-dose rates (≤ 10 cGy/hr) and a reference dose of 60 to 100 Gy calculated to the outer rim of the tumor. The 5- and 10-year survival rates in patients with pilocytic astrocytomas (97 patients) were 84.9% and 83%, and in patients with WHO Grade II astrocytomas (250 patients) 61% and 51%, respectively. Five-year survival rates for patients with oligoastrocytomas (60 patients), oligodendrogliomas (27 patients), and gemistocytic astrocytomas (21 patients) were 49%, 50%, and 32%, respectively. In the group with WHO Grade II gliomas, young age and a good performance status were associated with a better prognosis. Unfavorable factors were midline shift, enhancement on computerized tomography (CT) scan, and tumor recurrence after previous radiotherapy or surgery. Tumor location had no influence on the prognosis (247 patients in this series had deep-seated tumors). Malignant transformation was the major cause of death. Important risk factors for malignancy were the patient's age, tumor enhancement in CT scan, and tumor recurrence after previous surgery or radiotherapy. Perioperative mortality was 0.9% and perioperative morbidity was 1.7%. Radiogenic complications were observed in 2.7% of all patients, most often in larger tumors and after using permanent implants. The authors conclude that interstitial radiosurgery represents a specific treatment modality for selected patients with unifocal circumscribed low-grade gliomas with a diameter of less than 4 cm in any location. The efficacy of this treatment lies in the same range as the best results after surgery and radiotherapy.

scholarly journals Prognostic significance of clinical parameters in patients with cerebral low-grade glioma

2020 ◽  
pp. 85-85
Author(s):  
Milos Jokovic ◽  
Radovan Mijalcic ◽  
Vladimir Bascarevic ◽  
Nemanja Jovanovic
Keyword(s):  
Overall Survival ◽  
Tumor Biology ◽  
Prognostic Significance ◽  
Extent Of Resection ◽  
Categorical Variables ◽  
Low Grade ◽  
Clinical Parameters ◽  
Site Location ◽  
Who Grade ◽  
Low Grade Gliomas

Introduction/Objective. Low-grade gliomas (LGG) affect younger adults and carry a favorable prognosis. We aim to describe clinical patterns of low-grade gliomas as well as prognosis in different groups of patients. Our intention was to determine clinical parameters that may affect prognosis, and whether a greater extent of resection would increase the long-term progression-free or overall survival of patients with low-grade gliomas. Methods. We analyzed data obtained from the files of the patients with a diagnosis of WHO grade II gliomas. The relationships among categorical variables were analyzed using standard statistical tools and a 95% confidence interval (CI). Results. We analyzed 118 patients with median age of 34 years. Over 57% were male and the primary site location was the cerebrum. All these patients were operated on and some of them received radiation and/or chemotherapy. Median overall survival was 9.6 years and better prognosis is associated with younger age, frontal and noneloquent zone location, seizures as the first symptom of disease and gross total resection of the tumor. Indications for early surgery are increased intracranial pressure, preoperative neurologic deficit, tumor size larger than 6 cm with contrast enhancement and older age. Conclusion. Tumor location, 1p/19q co-deletion and age were the main determinants of treatment received and overall survival, likely reflecting tumor biology differences. Any form of treatment was preferred over watchful waiting. This study found that a greater extent of resection could significantly increase the overall survival of patients with low-grade gliomas.

scholarly journals Long-term outcome of stereotactic brachytherapy with temporary Iodine-125 seeds in patients with WHO grade II gliomas

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Juliana Watson ◽  
Alexander Romagna ◽  
Hendrik Ballhausen ◽  
Maximilian Niyazi ◽  
Stefanie Lietke ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Low Grade ◽  
Toxicity Profile ◽  
Who Grade ◽  
Low Grade Gliomas ◽  
Stereotactic Brachytherapy ◽  
Grade Ii ◽  
Iodine 125

Abstract Background This long-term retrospective analysis aimed to investigate the outcome and toxicity profile of stereotactic brachytherapy (SBT) in selected low-grade gliomas WHO grade II (LGGII) in a large patient series. Methods This analysis comprised 106 consecutive patients who received SBT with temporary Iodine-125 seeds for histologically verified LGGII at the University of Munich between March 1997 and July 2011. Investigation included clinical characteristics, technical aspects of SBT, the application of other treatments, outcome analyses including malignization rates, and prognostic factors with special focus on molecular biomarkers. Results For the entire study population, the 5- and 10-years overall survival (OS) rates were 79% and 62%, respectively, with a median follow-up of 115.9 months. No prognostic factors could be identified. Interstitial radiotherapy was applied in 51 cases as first-line treatment with a median number of two seeds (range 1–5), and a median total implanted activity of 21.8 mCi (range 4.2–43.4). The reference dose average was 54.0 Gy. Five- and ten-years OS and progression-free survival rates after SBT were 72% and 43%, and 40% and 23%, respectively, with a median follow-up of 86.7 months. The procedure-related mortality rate was zero, although an overall complication rate of 16% was registered. Patients with complications had a significantly larger tumor volume (p = 0.029). Conclusion SBT is a minimally invasive treatment modality with a favorable outcome and toxicity profile. It is both an alternative primary treatment method as well as an adjunct to open tumor resection in selected low-grade gliomas.

scholarly journals PO-0995: Estimation of radiobiology parameters of infiltrative low-grade gliomas WHO Grade II

2017 ◽  
Vol 123 ◽  
pp. S549 ◽  
Author(s):  
S. Milyukov ◽  
Y. Lysak ◽  
G. Panshin ◽  
N. Kharchenko ◽  
Z. Tsallagova ◽  
...  
Keyword(s):  
Low Grade ◽  
Who Grade ◽  
Low Grade Gliomas ◽  
Grade Ii

364 Tumor Compression Effect on White Matter Pathways Revealed by Local Connectome Fingerprint

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 284-285
Author(s):  
Pinar Celtikci ◽  
David Tiago Fernandes Cabral ◽  
Yeh Fang-Cheng ◽  
Sandip S Panesar ◽  
Juan Carlos Fernandez-Miranda
Keyword(s):  
White Matter ◽  
Density Measurement ◽  
High Angular Resolution ◽  
Imaging Method ◽  
Low Grade ◽  
Who Grade ◽  
Low Grade Gliomas ◽  
Compression Effect ◽  
Human Connectome Project ◽  
Grade Ii

Abstract INTRODUCTION Low-grade gliomas (LGGs) are slow growing tumors that often cause infiltration and/or compression of the white matter pathways. Regular imaging modalities are no capable of revealing such a pathologic condition. Furthermore, up-to-date there is no reliable noninvasive imaging method to address this issue. Here we report that the local connectome fingerprint, an along track density measurement derived from diffusion MRI (dMRI), is capable of revealing the tumor compression effect on the surrounding white matter pathways. METHODS We acquired high angular resolution dMRI data on 16 patients diagnosed of LGG (WHO grade II). Peritumoral fiber tracts underwent qualitative and quantitative evaluation. Contralateral hemisphere counterparts were used for comparison. The local connectome fingerprint of peritumoral tract segment and their ratio to healthy side were visualized and calculated in comparison with 842 normal subjects from the Human Connectome Project. RESULTS >Our results showed significant increase in the ratios to the normal side among displaced tracts and decreases among the infiltrated tracts when compared to their healthy counterpart. Qualitative analysis of 65 peritumoral tracts revealed 9 (13.8%) unaffected, 24 (36.9%) displaced, 13 (20%) infiltrated and 19 (29.2%) tracts with a combination of displacement and infiltration. There were no disrupted tracts. The along tracks local connectome fingerprint further localizes the track segments with compression effect caused by the tumor mass. This feature cannot be observed in conventional tensor and diffusivity analysis. CONCLUSION The unique capability of local connectome fingerprint in revealing the compression and infiltration effect can provide potential diagnostic and prognostic applications in clinical intervention of patients with WHO grade-II low-grade gliomas.

scholarly journals Association of the FGFR1 mutation with spontaneous hemorrhage in low-grade gliomas in pediatric and young adult patients

2020 ◽  
pp. 1-9 ◽  
Author(s):  
Yukitomo Ishi ◽  
Shigeru Yamaguchi ◽  
Kanako C. Hatanaka ◽  
Michinari Okamoto ◽  
Hiroaki Motegi ◽  
...  
Keyword(s):  
Young Adult ◽  
Univariate Analysis ◽  
Genetic Alterations ◽  
Adult Patients ◽  
World Health ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Who Grade ◽  
Low Grade Gliomas ◽  
Spontaneous Hemorrhage

OBJECTIVEThe authors aimed to investigate genetic alterations in low-grade gliomas (LGGs) in pediatric and young adult patients presenting with spontaneous hemorrhage.METHODSPatients younger than 30 years of age with a pathological diagnosis of World Health Organization (WHO) grade I or II glioma and who had undergone treatment at the authors’ institution were retrospectively examined. BRAF V600E, FGFR1 N546/K656, IDH1 R132, IDH2 R172, and KIAA1549-BRAF (K-B) fusion genetic alterations were identified, and the presence of spontaneous tumoral hemorrhage was recorded.RESULTSAmong 66 patients (39 with WHO grade I and 27 with grade II tumors), genetic analysis revealed K-B fusion in 18 (27.3%), BRAF V600E mutation in 14 (21.2%), IDH1/2 mutation in 8 (12.1%), and FGFR1 mutation in 4 (6.1%). Spontaneous hemorrhage was observed in 5 patients (7.6%); 4 of them had an FGFR1 mutation and 1 had K-B fusion. Univariate analysis revealed a statistically significant association of an FGFR1 mutation and a diencephalic location with spontaneous hemorrhage. Among 19 diencephalic cases including the optic pathway, hypothalamus, and thalamus, an FGFR1 mutation was significantly associated with spontaneous hemorrhage (p < 0.001). Four FGFR1 mutation cases illustrated the following results: 1) a 2-year-old female with pilomyxoid astrocytoma (PMA) harboring the FGFR1 K656E mutation presented with intraventricular hemorrhage (IVH); 2) a 6-year-old male with PMA harboring FGFR1 K656E and D652G mutations presented with intratumoral hemorrhage (ITH); 3) a 4-year-old female with diffuse astrocytoma harboring FGFR1 K656M and D652G mutations presented with IVH; and 4) a young adult patient with pilocytic astrocytoma with the FGFR1 N546K mutation presented with delayed ITH and IVH after 7 years of observation.CONCLUSIONSAlthough the mechanism remains unclear, the FGFR1 mutation is associated with spontaneous hemorrhage in pediatric and young adult LGG.

scholarly journals P04.10 IDH-wildtype low grade gliomas: overall survival and prognostic indicators

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii30-iii31
Author(s):  
G Berzero ◽  
A Di Stefano ◽  
S Ronchi ◽  
C Villa ◽  
Y Marie ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Genetic Alterations ◽  
Biological Behavior ◽  
Low Grade ◽  
Rare Tumor ◽  
Who Grade ◽  
Grade Ii ◽  
Chromosome 9P ◽  
Who Grade Ii Gliomas

Abstract BACKGROUND IDH-wildtype WHO grade II diffuse gliomas represent a rare subgroup of low grade tumors characterized by poor prognosis. The clinical and molecular profile associated with these tumors has not been fully elucidated yet, and the ongoing uncertainties regarding their biological behavior hamper to establish a standard of treatment. The aim of this study is to define the median overall survival and the main prognostic factors associated with this rare tumor entity. MATERIALS AND METHODS We performed a retrospective research in our center for all patients diagnosed with diffuse WHO grade II and III gliomas from 1976 to 2018. WHO grade II and III gliomas were divided into three molecular subgroups according to the IDH1/2 mutation and the 1p/19q codeletion status (1: IDH-mutant, 1p/19q codeleted; 2: IDH-mutant, 1p/19q non codeleted; 3: IDH-wildtype). We analyzed the clinical and molecular characteristics of the three subgroups, and then the clinical, radiological, histological and molecular features of IDH-wildtype WHO grade II gliomas. RESULTS We identified 445 patients with diffuse WHO grade II gliomas, including 59 IDH1/2-wildtype tumors. IDH-wildtype grade II gliomas affected more frequently male (75% vs. 55%, p = 0.004) and older (mean age: 50.0 vs. 39.6 years, p<0.0001) patients, had frequent fronto-temporo-insular location (41%) and commonly underwent biopsy (53%) rather than resection. We found TERT promoter mutations (18/42, 43%), chromosome 7q gains (12/30, 40%), chromosome 10q losses (12/44, 27%), chromosome 9p losses (7/47, 15%), EGFR amplifications (5/51, 10%) and p16 deletions (4/50, 8%) but no P53 (0/16) mutations. Median overall survival was 46 months (vs. 98 for IDH-mutant non codeleted and 175 for IDH-mutant codeleted WHO grade II gliomas (p<0.0001); vs. 20 months for IDH-wildtype WHO grade III gliomas (p = 0.001)). Survival was not significantly influenced by age, preoperative KPS, tumor location, extent of resection or adjuvant treatment schemes. Chromosome 9p loss had a strong negative impact on overall survival (p=0.002). CONCLUSION The median overall survival associated with IDH-wildtype WHO grade II gliomas does not exceed 4 years from diagnosis. As some genetic alterations seem to have a strong prognostic impact, an exhaustive genetic assessment can be helpful in this rare tumor group for purposes of prognostic stratification and treatment decision.

scholarly journals Gene Expression Profiling in Human High-Grade Astrocytomas

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Zhongyu Liu ◽  
Zhiqiang Yao ◽  
Chao Li ◽  
Yicheng Lu ◽  
Chunfang Gao
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Anaplastic Astrocytoma ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Who Grade ◽  
Grade Ii ◽  
Who Grade Iii ◽  
Grade Iii

Diffuse astrocytoma of (WHO grade II) has a tendency to progress spontaneously to anaplastic astrocytoma (WHO grade III) and/or glioblastoma (WHO grade IV). However, the molecular basis of astrocytoma progression is still poorly understood. In current study, an essential initial step toward this goal is the establishment of the taxonomy of tumors on the basis of their gene expression profiles. We have used gene expression profiling, unsupervised (hierarchal cluster (HCL) and principal component analysis (PCA)) and supervised (prediction analysis for microarrays (PAM)) learning methods, to demonstrate the presence of three distinct gene expression signatures of astrocytomas (ACMs), which correspond to diffuse or low-grade astrocytoma (WHO grade II), Anaplastic astrocytoma (WHO grade III) and Glioblastoma multiforme (WHO grade IV). We also demonstrate a 171 gene-based classifier that characterize the distinction between these pathologic/molecular subsets of astrocytomas. These results further define molecular subtypes of astrocytomas and may potentially be used to define potential targets and further refine stratification approaches for therapy. In addition, this study demonstrates that combining gene expression analysis with detailed annotated pathway and gene ontology (GO) category resources was applied to highly enriched normal and tumor population; it can yield an understanding of the critical biological mechanism of astrocytomas.

Sign in / Sign up

Export Citation Format

Share Document