scholarly journals ACT-5 Prognosis of IDH-mut lower-grade gliomas in Hokkaido University Hospital

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi10-vi10
Author(s):  
Shigeru Yamaguchi ◽  
Yukitomo Ishi ◽  
Michinari Okamoto ◽  
Ryousuke Sawaya ◽  
Hiroaki Motegi ◽  
...  
Keyword(s):  
Primary Treatment ◽  
University Hospital ◽  
Treatment Intensity ◽  
Low Grade ◽  
Lower Grade ◽  
High Grade ◽  
Who Grade ◽  
Idh Mutations ◽  
Histological Malignancy ◽  
Grade 3

Abstract Background: WHO grade 2 and 3 adult gliomas are nowadays getting together as lower-grade gliomas (LrGGs), but we had been recognized grade 3 (G3) tumors as high-grade and grade 2 (G2) tumors as low-grade. In this report, we investigate the treatment and prognosis of the patients with LrGG harboring IDH mutations in our institutions. Methods:We retrospectively review primary treatments and their prognosis for LrGG patients with IDH mutation since 2003. They categorized as astrocytomas and oligodendrogliomas according to 1p/19q loss-of-heterozygosity status. Prognosis were evaluated by overall survival. Postoperative primary treatments applied chemo-radiotherapy (CRT), radiotherapy only (RT), chemotherapy only (CT), and observation (Ob). Results: 36 astrocytomas and 60 oligodendrogliomas were identified. In astrocytomas, the patients with G3 (N=16) were treated by CRT (N=14) or CT (N=2), and the patients with G2 (N=20) were treated by CRT (N=2), RT (N=3), CT (N=3), or Ob (N=12). In oligodendrogliomas, the patients with G3 (N=34) were treated by CRT (N=32) or CT (N=2), and the patients with G2 (N=26) were treated by CRT (N=3), RT (N=1), CT (N=5), or Ob (N=17). 10-year survival rate (10yOS) of astrocytomas and oligodendrogliomas are 54% and 90%, respectively (p=0.002). According to histological malignancy, 10yOS of G3 and G2 astrocytomas were 54% and 54%, respectively (p=0.97) and that of G3 and G2 oligodendrogliomas were 86% and 100%, respectively (p=0.64). In both group, there are no different of prognosis according to histological malignancy. Discussion: There was no prognostic different between G2 and G3 astrocytomas in our institution. Since the treatment intensity for G2 and G3 astrocytomas were clearly different, the primary treatment for G2 astrocytomas might be insufficient. On the other hand, there were no prognostic different between G2 and G3 oligodendrogliomas in our institution, as with recent reports, so the primary treatment intensity for oligodendrogliomas should be appropriate.

TMOD-06. CREATION OF PATIENT-DERIVED LOWER GRADE GLIOMA ORGANOID MODELS FOR PERSONALIZED TREATMENT RESPONSE ASSESSMENT

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi216-vi217
Author(s):  
Kalil Abdullah ◽  
Joseph Buehler ◽  
Cylaina Bird ◽  
MIlan Savani ◽  
Alex Sternisha ◽  
...  
Keyword(s):  
Treatment Response ◽  
Genetic Alterations ◽  
Lower Grade ◽  
High Grade ◽  
Who Grade ◽  
Oncology Research ◽  
Genetically Engineered Mice ◽  
Lower Grade Glioma ◽  
Idh Mutations

Abstract Creating in vitro models of lower grade glioma represents a major challenge in neuro-oncology research. There are few such models that are tractable and widely used, which has hindered understanding of the biology of these tumors. Recently, substantial progress has been made in generating patient-derived in vitro organoid models of high grade glioma, but modeling lower grade disease remains difficult. Based on our experience creating neurosphere cultures of lower grade astrocytomas from genetically engineered mice, we hypothesized that modifying patient-derived organoid generation protocols to incorporate physiological oxygen levels would allow establishment and propagation of lower grade glioma organoids. In this study, we show that this approach supports efficient organoid model generation from primary glioma specimens across all histological subtypes and tumor grades (WHO Grade I-IV, n = 20). These organoid models retain key characteristics of their respective parental tumors, including IDH mutations and other genetic alterations, metabolite profiles, intratumoral heterogeneity, cellular composition, and cytoarchitectural features. Importantly, lower grade glioma organoids can be cultured for months and reanimated after biobanking. Our high success rate ( >90%) in establishing organoid models from primary lower grade glioma tissue samples further highlighted opportunities for treatment response assessments. To perform longitudinal measurements of therapy-induced changes in glioma organoid viability, we designed a novel, non-invasive imaging assay (termed rapid apex imaging) to determine real-time treatment response in low and high grade gliomas. We evaluated longitudinal responses of glioblastoma and IDH1 R132H-positive Grade II astrocytoma organoids to temozolomide and olaparib with and without radiation treatment. We quantified topological changes in organoid structure by building a bioinformatics tool to translate imaging data into a cellularity metric as a biomarker of organoid response. Our work unveils an effective new method to create in vitro, personalized models of lower grade glioma that supports elucidation of treatment sensitivity profiles.

IDH mutations as an early and consistent marker in low-grade astrocytomas WHO grade II and their consecutive secondary high-grade gliomas

2012 ◽  
Vol 108 (3) ◽  
pp. 403-410 ◽  
Author(s):  
Tareq A. Juratli ◽  
Matthias Kirsch ◽  
Katja Robel ◽  
Silke Soucek ◽  
Kathrin Geiger ◽  
...  
Keyword(s):  
Low Grade ◽  
High Grade ◽  
Who Grade ◽  
Idh Mutations ◽  
Grade Ii ◽  
High Grade Gliomas

scholarly journals CAPTEM in Metastatic Well-Differentiated Intermediate to High Grade Neuroendocrine Tumors: A Single Centre Experience

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Arvind Sahu ◽  
Michael Jefford ◽  
Julia Lai-Kwon ◽  
Alesha Thai ◽  
Rodney J. Hicks ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neuroendocrine Tumors ◽  
Functional Imaging ◽  
Low Grade ◽  
Significant Activity ◽  
High Grade ◽  
Who Grade ◽  
Well Differentiated ◽  
Grade 3 ◽  
Imaging Response

Introduction. Capecitabine-temozolomide (CAPTEM) has significant activity in patients (pts) with metastatic low grade pancreatic neuroendocrine tumors (NETs). However, there is limited data regarding its activity in pts with metastatic well-differentiated intermediate and high grade pancreatic and nonpancreatic NETs. The objective of this study was to assess the functional imaging response, survival, and tolerability of CAPTEM in this population.Methods. A retrospective audit of pts with metastatic well-differentiated intermediate (WHO grade 2) or high grade (WHO grade 3) NETs treated at Peter MacCallum Cancer Centre between March 2013 and March 2017. Pts received capecitabine 750 mg/m2orally twice daily (bd) from days1 to 14 and temozolomide 100 mg/m2bd from days 10 to 14 every 28 days. Data regarding functional imaging response, progression-free and overall survival, and toxicities was collected.Results. Thirty-two pts received a median of 6 cycles (range: 2-16) of CAPTEM for grade 2 (n=21, 66%) or grade 3 (n=11, 34%), Ki67 <55% (n= 7, 21.9%) or Ki67 ≥55% (n= 4, 12.5 %) NET. Primary site included gastroenteropancreatic (n= 17, 53%), lung (n= 12, 37.5%), and unknown origin (n = 3, 9.4%). Twenty-two percent received CAPTEM as first-line therapy. After a median of 31 months of follow-up, the two-year overall survival (OS) was 42%, with a median OS of 24 months. There was a trend towards improved median progression-free survival (PFS) in pts with low grade 3 (Ki67<55%) versus high grade 3 (Ki67 ≥55%) NETs (15 vs 4 months, p= 0.11). Ten (31.3%) experienced grade 3/4 toxicity, with nausea (15.6%), thrombocytopaenia (12.5%), and fatigue (9.4%) the most common toxicities reported.Conclusion. CAPTEM has significant activity in patients with metastatic grades 2 and 3 NETs with manageable toxicity. The PFS benefit observed in the grade 3 subgroup with Ki67<55% warrants further evaluation in a larger randomized trial.

scholarly journals Trace Amine-Associated Receptor 1 (TAAR1) Is a Positive Prognosticator for Epithelial Ovarian Cancer

2021 ◽  
Vol 22 (16) ◽  
pp. 8479
Author(s):  
Tilman L. R. Vogelsang ◽  
Aurelia Vattai ◽  
Elisa Schmoeckel ◽  
Till Kaltofen ◽  
Anca Chelariu-Raicu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Tnm Classification ◽  
Rank Correlation ◽  
University Hospital ◽  
Cancer Tissue ◽  
Low Grade ◽  
High Grade ◽  
Trace Amine

Trace amine-associated receptor 1 (TAAR1) is a Gαs- protein coupled receptor that plays an important role in the regulation of the immune system and neurotransmission in the CNS. In ovarian cancer cell lines, stimulation of TAAR1 via 3-iodothyronamine (T1AM) reduces cell viability and induces cell death and DNA damage. Aim of this study was to evaluate the prognostic value of TAAR1 on overall survival of ovarian carcinoma patients and the correlation of TAAR1 expression with clinical parameters. Ovarian cancer tissue of n = 156 patients who were diagnosed with epithelial ovarian cancer (serous, n = 110 (high-grade, n = 80; low-grade, n = 24; unknown, n = 6); clear cell, n = 12; endometrioid, n = 21; mucinous, n = 13), and who underwent surgery at the Department of Obstetrics and Gynecology, University Hospital of the Ludwig-Maximilians University Munich, Germany between 1990 and 2002, were analyzed. The tissue was stained immunohistochemically with anti-TAAR1 and evaluated with the semiquantitative immunoreactive score (IRS). TAAR1 expression was correlated with grading, FIGO and TNM-classification, and analyzed via the Spearman’s rank correlation coefficient. Further statistical analysis was obtained using nonparametric Kruskal-Wallis rank-sum test and Mann-Whitney-U-test. This study shows that high TAAR1 expression is a positive prognosticator for overall survival in ovarian cancer patients and is significantly enhanced in low-grade serous carcinomas compared to high-grade serous carcinomas. The influence of TAAR1 as a positive prognosticator on overall survival indicates a potential prognostic relevance of signal transduction of thyroid hormone derivatives in epithelial ovarian cancer. Further studies are required to evaluate TAAR1 and its role in the development of ovarian cancer.

scholarly journals CTIM-06. DENDRITIC CELL VACCINE STUDY FOR RECURRENT, HIGH-GRADE GLIOMA: TISSUE-BASED RNA SEQUENCING AND SERUM CYTOKINE LEVELS AS POTENTIAL BIOMARKERS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii33-ii34
Author(s):  
Macarena De La Fuente ◽  
Tulay Koru-Sengul ◽  
Deborah Heros ◽  
Feng Miao ◽  
Alain Fernandez Marrero ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Rna Sequencing ◽  
Tumor Antigens ◽  
High Grade Glioma ◽  
Treatment Discontinuation ◽  
Sequencing Analysis ◽  
High Grade ◽  
Who Grade ◽  
Cytokine Levels ◽  
Grade 3

Abstract BACKGROUND Glioblastoma is the most common primary malignant brain tumor. Despite multimodality treatment approach, median progression-free survival (PFS) is only 8 months, median overall-survival (OS) 14 months and 5-year survival rate of under 10%. Dendritic cells (DCs) are the professional antigen presenting cells of the immune system. The rationale for sensitizing dendritic cells to a pool of non-selected tumor antigens is based on the marked heterogeneity present within glioblastoma tumor cells. METHODS Phase 1/feasibility study of DC vaccine for recurrent high-grade glioma was conducted. Pooled, non-selected tumor antigens collected via tumor cell lysate were used for DC sensitization. RNA sequencing analysis was performed on all tumor samples. Cytokine levels in serum were detected using a Luminex cytokine panel. RESULTS A total of 20 patients were enrolled onto this study (median age 58yrs, range: 39–74, 65% male). Pathology showed WHO grade IV glioblastoma in 14 (70%) and grade III anaplastic astrocytoma in 6 (30%) patients. IDH wild type in 19 (95%) patients. Treatment emergent adverse events (all grades, regardless of attribution) occurred in more than 15% of the patients (20% fatigue, 15% dizziness, 15% headache, none leading to treatment discontinuation). There were five grade 3–4 and none grade 5 events. One grade 4 event (seizure) probable related to investigational treatment leading to treatment discontinuation. Four grade 3 events (dysphasia, possible related; intracranial hemorrhage unrelated; muscle weakness, unlikely related and hematoma, unrelated). Median PFS was 3.8 months. Median OS was 11 months. RNA sequencing in tumor samples and correlation with cytokine levels in serum is currently been analyzed. CONCLUSION Tumor lysate pulsed DC vaccination demonstrates acceptable safety and tolerability in high-grade glioma patients. Evaluations of integrating molecular profiling RNA sequencing information and cytokine levels to identify potential subset of patients with significant clinical benefit will be provided.

CASE STUDY ON CIRCUMSCRIBED GLIOMAS, THEIR CLINICOPATHOLOGICAL CORRELATION IN A TERTIARY CARE CENTER

2021 ◽  
pp. 42-45
Author(s):  
Esther Alffi Papang ◽  
K. Rama
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tertiary Care ◽  
Biological Behavior ◽  
Low Grade ◽  
Lower Grade ◽  
Who Grade ◽  
Primary Tumors ◽  
Short Period ◽  
The Impact

The histogenesis and biological behavior of primary tumors of the central nervous system(CNS) are very diverse. The majority of present gliomas as benign, slow growing lesions classied as by the WHO classicati grade I or II (Low grade gliomas) on of CNS tumors. However, a signicant fraction of gliomas develop over a short period of time and progress rapidly and are therefore classied as WHO grade III or IV(High grade gliomas). Astrocytomas are primary central nervous system tumours that can develop in adults or in children. They arise from the Astrocytes. They can be divided into diffuse that generally have a higher grade and poorer prognosis and those that are localised that tend to be of a lower grade and have a better prognosis. In this study, we outline the basic histological spectrum and features, epidemiological aspects and grade of circumscribed gliomas (localised) or other Astrocytic tumours according to WHO classication . These are the Pilocytic Astrocytoma, Pilomyxoid Astrocytoma, Subependymal giant cell Astrocytoma, Pleomorphic xanthoastrocytoma and Anaplastic astrocytoma . The knowledge of these tumours are important as they are one of the commonest cause of mortality and morbidity in both the young and old, accounting for about 60% of the glial tumours. Therefore neuropathological diagnosis and tumour characteristics will therefore profoundly inuence the impact of treatment strategies.

scholarly journals Study the activity of P53 & Bcl-2 genes in the biopsies of inflamed colon from patients of ulcerative colitis

2010 ◽  
Vol 4 (1) ◽  
pp. 34-43
Author(s):  
Zainab M. T. Jafer ◽  
Esmail K. Shubber
Keyword(s):  
Ulcerative Colitis ◽  
Intermediate Stage ◽  
Hybridization Technique ◽  
Low Grade ◽  
High Grade ◽  
Colonic Tissue ◽  
Grade 3 ◽  
Apoptosis Gene ◽  
Tumor Gene

The study has been done on 36 samples of biopsies which drawn from patients suffered from ulcerative colitis, the samples were taken from female & male of different ages. The goal was to observe the gene expression of the suppresser tumor gene P53, & the suppresser apoptosis gene Bcl-2, by using in situ hybridization technique. The results showed that there were relationships between both genes (P53 & Bcl-2) in patients suffered from ulcerative colitis compared with healthy individuals. The suppresser gene P53 gave 63% in the high grade(3) , 29 % in the intermediate stage (2) & 8% in the low grade (1) .While for the suppresser apoptosis gene Bcl-2 , the results showed increasing in the activity of this gene , which gave 66% in the high grade(3) , 27% in the intermediate stage (2) , & 7% in the low grade (1) . These results indicate accumulated mutations in the gene P53 & increase in the activity of gene Bcl-2 in inflamed colonic tissue of chronic ulcerative colitis. This gave an indication of early detection for diagnostic, therapeutic and monitoring purposes.

scholarly journals Redefining Stage I Endometrial Cancer: Incorporating Histology, a Binary Grading System, Myometrial Invasion, and Lymph Node Assessment

2013 ◽  
Vol 23 (9) ◽  
pp. 1620-1628 ◽  
Author(s):  
Joyce N. Barlin ◽  
Robert A. Soslow ◽  
Megan Lutz ◽  
Qin C. Zhou ◽  
Caryn M. St. Clair ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Myometrial Invasion ◽  
Staging System ◽  
Stage I ◽  
Low Grade ◽  
List Type ◽  
High Grade ◽  
High Grade Carcinoma ◽  
Concordance Probability ◽  
Grade 3

ObjectiveWe propose a new staging system for stage I endometrial cancer and compare its performance to the 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) systems.MethodsWe analyzed patients with 1988 FIGO stage I endometrial cancer from January 1993 to August 2011. Low-grade carcinoma consisted of endometrioid grade 1 to grade 2 lesions. High-grade carcinoma consisted of endometrioid grade 3 or nonendometrioid carcinomas (serous, clear cell, and carcinosarcoma). The proposed system is as follows:IA. Low-grade carcinoma with less than half myometrial invasionIA1: Negative nodesIA2: No nodes removedIB. High-grade carcinoma with no myometrial invasionIB1: Negative nodesIB2: No nodes removedIC. Low-grade carcinoma with half or greater myometrial invasionIC1: Negative nodesIC2: No nodes removedID. High-grade carcinoma with any myometrial invasionID1: Negative nodesID2: No nodes removedResultsData from 1843 patients were analyzed. When patients were restaged with our proposed system, the 5-year overall survival significantly differed (P < 0.001): IA1, 96.7%; IA2, 92.2%; IB1, 92.2%; IB2, 76.4%; IC1, 83.9%; IC2, 78.6%; ID1, 81.1%; and ID2, 68.8%. The bootstrap-corrected concordance probability estimate for the proposed system was 0.627 (95% confidence interval, 0.590–0.664) and was superior to the concordance probability estimate of 0.530 (95% confidence interval, 0.516–0.544) for the 2009 FIGO system.ConclusionsBy incorporating histological subtype, grade, myometrial invasion, and whether lymph nodes were removed, our proposed system for stage I endometrial cancer has a superior predictive ability over the 2009 FIGO staging system and provides a novel binary grading system (low-grade including endometrioid grade 1–2 lesions; high-grade carcinoma consisting of endometrioid grade 3 carcinomas and nonendometrioid carcinomas).

Management for Different Glioma Subtypes: Are All Low-Grade Gliomas Created Equal?

2019 ◽  
pp. 133-145 ◽  
Author(s):  
Martin C. Tom ◽  
Daniel P. Cahill ◽  
Jan C. Buckner ◽  
Jörg Dietrich ◽  
Michael W. Parsons ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
World Health ◽  
Low Grade ◽  
Lower Grade ◽  
Future Directions ◽  
Molecular Alterations ◽  
Lower Grade Glioma ◽  
Grade 3 ◽  
Health Organization

Following the identification of key molecular alterations that provided superior prognostication and led to the updated 2016 World Health Organization (WHO) Central Nervous System (CNS) Tumor Classification, the understanding of glioma behavior has rapidly evolved. Mutations in isocitrate dehydrogenase (IDH) 1 and 2 are present in the majority of adult grade 2 and 3 gliomas, and when used in conjunction with 1p/19q codeletion for classification, the prognostic distinction between grade 2 versus grade 3 is diminished. As such, the previously often used term of “low-grade glioma,” which referred to grade 2 gliomas, has now been replaced by the phrase “lower-grade glioma” to encompass both grade 2 and 3 tumors. Additional molecular characterization is ongoing to even further classify this heterogeneous group of tumors. With such a colossal shift in the understanding of lower-grade gliomas, management of disease is being redefined in the setting of emerging molecular-genetic biomarkers. In this article, we review recent progress and future directions regarding the surgical, radiotherapeutic, chemotherapeutic, and long-term management of adult lower-grade gliomas.

scholarly journals A Comparison of Death Domain-Associated Protein 6 in Different Endometrial Carcinomas Histotypes

2019 ◽  
Vol 14 ◽  
pp. 117727191986489
Author(s):  
Cao Jin ◽  
Sean Hacking ◽  
Miglena K Komforti ◽  
Mansoor Nasim
Keyword(s):  
Clear Cell ◽  
Point Mutations ◽  
Low Grade ◽  
Nuclear Staining ◽  
High Grade ◽  
Death Domain ◽  
Gynecology And Obstetrics ◽  
Grade 3 ◽  
Histologic Types ◽  
Endometrial Carcinomas

Background: Death domain-associated protein 6 (DAXX) is involved in regulating apoptosis via subcellular localization. The presence of DAXX point mutations correlates well with loss of nuclear expression on immunohistochemistry (IHC). In this study, we sought to determine (1) whether DAXX expression pattern is the same across different uterine carcinoma subtypes, and (2) which uterine carcinomas show loss of nuclear DAXX IHC. Design: We studied 65 uterine carcinomas of the following histologic types: 30 endometrioid (12 FIGO [The International Federation of Gynecology and Obstetrics] grade 1, 12 FIGO grade 2, and 6 FIGO grade 3), 8 serous, 14 clear cell, and 13 undifferentiated/dedifferentiated type (UEC/DDEC). Nuclear DAXX IHC was assessed in each tumor and was graded semi-quantitatively as follows: 0% to 50%, 50% to 75%, and greater than 75% of lesional cells react. Results: A total of 61% (25/41) of high-grade carcinomas (FIGO grade 3, serous, clear cell, and UEC/DDEC]) showed retained DAXX nuclear staining in >75% of lesional cells, compared with only 4.2% (1/24) of the low-grade carcinomas (FIGO grades 1 and 2) ( P = .0001), where DAXX expression was cytoplasmic. In addition, in the 11 DDEC cases, all the differentiated components showed loss of nuclear DAXX compared with the undifferentiated components which retained nuclear DAXX expression. Conclusions: We demonstrate that loss of nuclear DAXX is present in low-grade endometrial carcinomas and the differentiated components in UEC/DDEC, but not in high-grade ones, suggesting DAXX’s role in tumor progression and its potential as a therapeutic target in high-grade endometrial carcinomas.

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