scholarly journals P14.43 Histone H3F3A and HIST1H3B K27M mutations in pediatric high-grade gliomas: the Florentine experience

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii76-iii77
Author(s):  
M Guidi
Keyword(s):  
Meta Analysis ◽  
Histone H3 ◽  
Histone Variants ◽  
Statistical Correlation ◽  
High Grade ◽  
K27m Mutation ◽  
High Grade Gliomas ◽  
The Difference ◽  
Low Incidence ◽  
Line Of Therapy

Abstract Background Pediatric high- grade gliomas (HGGs) represent a malignancy with a poor survival. The genetic analysis of these entities has identified useful mutations for an improved prognostic framing. The research of mutations in all H3 histone variants (HIST1H3B and H3F3A) could be usefull to define tumors with different prognosis and phenotypes inasmuch they seems to drive two distinct oncogenic programmes. MATERIALS E METHODS We performed a retrospective analysis of pediatric HGGs. We evaluated the type of histone H3 mutated and we performed a meta-analysis comparing our results with literature data. RESULTS We evaluated 41 cases of pediatric HGGs (median age of patients: 7 years old, range: 0–32):): 32 anaplastic astrocytoma (78,5%), 9 glioblastoma multiforme (25,9%), We have researched the K27M mutations in the distinct histone H3 variants (i.e. HIST1H3B and H3F3A). The mutation H3F3A K27M was found in 6 patients instead HIST1H3B K27 mutations was found in a single patient with GBM. All the patients with H3F3A K27M mutation had a progression disease but without statistical correlation (p:0,07). They had a worse prognosis with a median overall survival of 15,5 months (p: 0.0014) versus wild type patients (not reached). H3.3K27M mutation status is a significant predictor of OS with a hazard ratio of 4.499 (p = 0.0001). The patient with HIST1H3B K27 mutation died after first line of therapy. Conclusions Due to the low incidence of the mutation HIST1H3B in our series we can’t define the difference with two variants. However, the research of K27M mutation in HGGs has diagnostic and prognostic role. The role of histone H3 mutated could predict the outcome in HGGs patients and it could give us more informations compared to the clinic and radiological characteristic of the tumors.

scholarly journals Low-Grade Gemistocytic Morphology in H3 G34R-Mutant Gliomas and Concurrent K27M Mutation: Clinicopathologic Findings

2020 ◽  
Vol 79 (10) ◽  
pp. 1038-1043
Author(s):  
Meaghan Morris ◽  
Meghan Driscoll ◽  
John W Henson ◽  
Charles Cobbs ◽  
LiQun Jiang ◽  
...  
Keyword(s):  
Histone H3 ◽  
Low Grade ◽  
High Grade ◽  
K27m Mutation ◽  
Gemistocytic Astrocytoma ◽  
First Case ◽  
Clinicopathologic Findings ◽  
Tumor Phenotype ◽  
High Grade Gliomas ◽  
H3 K27m Mutations

Abstract Mutations in histone H3 are key molecular drivers of pediatric and young adult high-grade gliomas. Histone H3 G34R mutations occur in hemispheric high-grade gliomas and H3 K27M mutations occur in aggressive, though histologically diverse, midline gliomas. Here, we report 2 rare cases of histologically low-grade gliomas with gemistocytic morphology and sequencing-confirmed histone H3 G34R mutations. One case is a histologically low-grade gemistocytic astrocytoma with a G34R-mutation in H3F3A. The second case is a histologically low-grade gemistocytic astrocytoma with co-occurring K27M and G34R mutations in HIST1H3B. Review of prior histone H3-mutant gliomas sequenced at our institution shows a divergent clinical and immunohistochemical pattern in the 2 cases. The first case is similar to prior histone H3 G34R-mutant tumors, while the second case most closely resembles prior histone H3 K27M-mutant gliomas. These represent novel cases of sequencing-confirmed histone H3 G34R-mutant gliomas with low-grade histology and add to the known rare cases of G34R-mutant tumors with gemistocytic morphology. Although K27M and G34R mutations are thought to be mutually exclusive, we document combined K27M and G34R mutations in HIST1H3B and present evidence suggesting the K27M-mutation drove tumor phenotype in this dual mutant glioma.

scholarly journals Against the Resilience of High-Grade Gliomas: The Immunotherapeutic Approach (Part I)

2021 ◽  
Vol 11 (3) ◽  
pp. 386
Author(s):  
Alice Giotta Lucifero ◽  
Sabino Luzzi
Keyword(s):  
Monoclonal Antibodies ◽  
Natural Killer ◽  
Immune Escape ◽  
Meta Analysis ◽  
Treatment Options ◽  
High Grade Glioma ◽  
High Grade ◽  
Future Challenges ◽  
Genetic Landscape ◽  
High Grade Gliomas

The resilience of high-grade gliomas (HGGs) against conventional chemotherapies is due to their heterogeneous genetic landscape, adaptive phenotypic changes, and immune escape mechanisms. Innovative immunotherapies have been developed to counteract the immunosuppressive capability of gliomas. Nevertheless, further research is needed to assess the efficacy of the immuno-based approach. The aim of this study is to review the newest immunotherapeutic approaches for glioma, focusing on the drug types, mechanisms of action, clinical pieces of evidence, and future challenges. A PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis)-based literature search was performed on PubMed/Medline and ClinicalTrials.gov databases using the keywords “active/adoptive immunotherapy,” “monoclonal antibodies,” “vaccine,” and “engineered T cell.”, combined with “malignant brain tumor”, “high-grade glioma.” Only articles written in English published in the last 10 years were selected, filtered based on best relevance. Active immunotherapies include systemic temozolomide, monoclonal antibodies, and vaccines. In several preclinical and clinical trials, adoptive immunotherapies, including T, natural killer, and natural killer T engineered cells, have been shown to be potential treatment options for relapsing gliomas. Systemic temozolomide is considered the backbone for newly diagnosed HGGs. Bevacizumab and rindopepimut are promising second-line treatments. Adoptive immunotherapies have been proven for relapsing tumors, but further evidence is needed.

Does Topical Antibiotic Prophylaxis Reduce Post—Tympanostomy Tube Otorrhea?

1994 ◽  
Vol 103 (1) ◽  
pp. 54-58 ◽  
Author(s):  
Philip Garcia ◽  
George A. Gates ◽  
Kenneth B. Schechtman
Keyword(s):  
Antimicrobial Agents ◽  
Antimicrobial Prophylaxis ◽  
Meta Analysis ◽  
Tympanostomy Tube ◽  
Continued Use ◽  
The Difference ◽  
Prophylactic Use ◽  
Low Incidence ◽  
Topical Antimicrobial ◽  
Patient Studies

Purulent otorrhea is the most common complication of tympanostomy tube (TT) insertion. It may occur in the postoperative period or at any time during the sojourn of the tube. The efficacy of topical antimicrobial prophylaxis against purulent postoperative otorrhea (PPO) has been examined in 5 prospective, randomized studies; all demonstrated a reduction in PPO from topical antimicrobial prophylaxis, but in only 1 study was the difference statistically significant. Because the 5 studies used 2 different experimental designs — By-patient, and by-ear — a single meta-analysis could not be done. However, the by-patient studies met the criteria for meta-analysis, which demonstrated a combined odds ratio of 0.12 (95% confidence interval 0.04 to 0.37, p = .0002). This represents an 85% reduction in otorrhea, which is judged to be clinically as well as statistically significant. We conclude from the available evidence that prophylactic use of topical antimicrobial agents following TT insertion consistently reduces the rate of PPO. However, the low incidence of PPO and the heterogeneity of the published studies prevent making a final judgment for or against the continued use of these agents. Therefore, given that these potentially ototoxic agents are frequently administered to prevent postoperative otorrhea, further study of this subject is warranted. In the meantime, we recommend judicious use of these agents following TT insertion in those cases at higher risk for PPO, namely those with mucoid or purulent effusion.

scholarly journals Incidence of Tumour Progression and Pseudoprogression in High-Grade Gliomas: a Systematic Review and Meta-Analysis

2017 ◽  
Vol 28 (3) ◽  
pp. 401-411 ◽  
Author(s):  
Abdul W. Abbasi ◽  
Henriette E. Westerlaan ◽  
Gea A. Holtman ◽  
Kamal M. Aden ◽  
Peter Jan van Laar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Tumour Progression ◽  
Meta Analysis ◽  
High Grade ◽  
High Grade Gliomas

Increased risk of liver toxicity secondary to nivolumab therapy in the treatment of cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14559-e14559 ◽  
Author(s):  
Kevin Zarrabi ◽  
Shenhong Wu
Keyword(s):  
Liver Toxicity ◽  
Meta Analysis ◽  
High Grade ◽  
Careful Monitoring ◽  
Laboratory Markers ◽  
Increased Risk ◽  
Melanoma Patients ◽  
Low Incidence ◽  
Grade 3

e14559 Background: Nivolumab, a humanized immunotherapy targeting PD-1, is approved for the treatment of a number of solid and liquid cancers and is associated with liver toxicity. This meta-analysis was conducted to determine the overall risk of hepatotoxicity with nivolumab therapy in cancer patients. Methods: An analysis from all phase I, II, and II clinical trials up to December 2016 examining the role of nivolumab in a variety of cancers was conducted. Eligible trials included those in which patients received nivolumab. Data on all-grade and high-grade (grade 3 and 4) elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were extracted from the safety profiles of each clinical trial. Incidence and relative risk (RR) were calculated using random - or fixed - effect models with 95% confidence intervals. Results: The data from 27 eligible trials were included for analysis. A total of 5,287 patients were evaluated (Nivolumab: n = 3515, Control: n = 1772). The incidences of all-grade and high-grade elevations in AST were 5.4% (95% CI: 3.2% - 9.1%) and 1.60% (95% CI: 0.9% - 3.0%), respectively. The incidences of all-grade and high-grade elevations in ALT were 4.9% (95% CI: 2.9% - 8.2%) and 1.5% (95% CI: 0.9% - 3.1%), respectively. Elevations of both laboratory markers were significantly increased when compared to control (P < 0.001). Nivolumab increased the RR of AST/ALT elevations; RR of all-grade AST elevations was 1.58 (95% CI: 1.1 - 2.2), all-grade ALT elevations was 1.62 (95% CI: 1.2 - 2.3). Subgroup analysis of all-grade AST elevations revealed melanoma patients exhibited a significantly higher rate compared to other solid tumors with an incidence of 8.7% (95% CI: 4.3 - 18.2%). All-grade ALT elevations in melanoma patients revealed the same incidence rate. Of note, renal cell carcinoma patients exhibited a particularly low incidence of all-grade transaminitis with AST 1.6% (95% CI: 0.6 - 11.1%) and ALT 1.8% (95% CI: 0.6 - 14.6%). Conclusions: Nivolumab is associated with significantly increased risk of all-grade and high-grade elevations in AST and ALT. Therapy should include careful monitoring of hepatotoxicity.

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