scholarly journals Prevalence of BRAF V600 in primary gliomas: a systematic review

2021 ◽  
Vol 23 (Supplement_4) ◽  
pp. iv13-iv14
Author(s):  
Lily Andrews ◽  
Zak Thornton ◽  
Samir Saincher ◽  
Sarah Dawson ◽  
Vincent Cheng ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pleomorphic Xanthoastrocytoma ◽  
Subependymal Giant Cell Astrocytoma ◽  
Diffuse Astrocytoma ◽  
Who Guidelines ◽  
Braf Inhibitors ◽  
Desmoplastic Infantile Astrocytoma ◽  
Primary Glioma ◽  
Epithelioid Glioblastoma ◽  
Braf V600 Mutation

Abstract Aims Glioma is a fatal disease that causes significant years of life lost to an individual. Mutations in the driver gene BRAF, such as the V600 alteration, may contribute to gliomagenesis in adults and children through abnormal signaling causing uncontrolled cell proliferation. The use of BRAF-inhibitor drugs including Vemurafenib and Dabrafenib have shown a favorable response in 48% and 50% of melanoma patients with BRAF V600 mutations respectively. BRAF inhibitors and MEK inhibitors have shown efficacy in certain paediatric gliomas in the recurrent setting. Despite the potential benefit of BRAF inhibitors, the prevalence of BRAF V600 within primary gliomas is not fully discovered. Some studies identify the prevalence to be over 50%, while others find the prevalence to be around 1%. We performed a comprehensive systematic review to determine the prevalence of BRAF V600 within the adult and paediatric glioma population in different diagnostic groups. Method A systematic literature search was performed using Ovid MEDLINE and Embase from genesis to the 22nd October 2020. Studies were not restricted by language. Studies were eligible if patients were histologically diagnosed according to WHO guidelines as a primary glioma evaluating the prevalence of BRAF V600 and included ≥ 10 primary glioma patients. The review protocol was registered in PROSPERO (CRD42019127704). Search results were managed using Endnote. Two independent reviewers assessed the eligibility of the publications using Rayyan, conflicts were evaluated by a third reviewer. Included articles were extracted by one reviewer and confirmed by a second reviewer. Risk of bias assessments were conducted using Hoy et al’s risk of bias tool. Results were synthesized using “metaprop” in R. The meta-analysis was carried out in R which produced forest plots. Results Our cohort included 182 studies with a total of 13669 adult and paediatric glioma patients classified diagnostically according to WHO guidelines. Among 48 glioma entities, BRAF V600 was identified most commonly in epithelioid glioblastoma with a prevalence of 69% (95% confidence interval (CI): 45-89%), followed by pleomorphic xanthoastrocytoma with a prevalence of 56% (95% CI: 48-64%), anaplastic pleomorphic xanthoastrocytoma with a prevalence of 38% (95% CI: 23-54%), ganglioglioma with a prevalence of 40% (95% CI: 33-46%), and anaplastic ganglioglioma with a prevalence of 46% (95% CI: 18-76%). Other glioma entities were found to have a prevalence of BRAF V600, these include astroblastoma (24%), desmoplastic infantile astrocytoma (16%), subependymal giant cell astrocytoma (8%), dysembryoplastic neuroepithelial tumour (3%), diffuse astrocytoma (3%), and pilocytic astrocytoma (3%). Conclusion To our knowledge, this is the largest systematic review examining the prevalence of BRAF V600 in adult and paediatric glioma classified according to diagnostic WHO criteria. However, there were some limitations in this review. The sample sizes of some studies were very small, and the method of mutational analysis for BRAF V600 varied between papers. We found BRAF V600 in a significant prevalence of epithelioid glioblastoma, pleomorphic xanthoastrocytoma, anaplastic pleomorphic xanthoastrocytoma, ganglioglioma, and anaplastic ganglioglioma. Of interest, BRAF V600 mutation was found in a lower prevalence of astroblastoma, desmoplastic infantile astrocytoma, subependymal giant cell astrocytoma, dysembryoplastic neuroepithelial tumour, diffuse astrocytoma, and pilocytic astrocytoma. Consideration of assessment of BRAF V600 mutation may enable further treatment options with BRAF and/or MEK inhibitors in these particular diagnostic entities.

scholarly journals HGG-02. ADOLESCENT AND YOUNG ADULT (AYA) GLIOMA WITH BRAF V600E-MUTANTATION

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii344-iii344
Author(s):  
Yui Kimura ◽  
Yukitomo Ishi ◽  
Yuko Watanabe ◽  
Yoshiko Nakano ◽  
Shigeru Yamaguchi ◽  
...  
Keyword(s):  
Braf Inhibitor ◽  
Clinical Information ◽  
Early Recurrence ◽  
Pleomorphic Xanthoastrocytoma ◽  
Adolescent And Young Adult ◽  
Braf V600e ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Genetic Features ◽  
Epithelioid Glioblastoma

Abstract BACKGROUND Biological features of pediatric glioma differ significantly from those of adult glioma, and limited data are available on those of AYA patients. Here, we focused on AYA patients with glioma, especially those harboring BRAF V600E mutation, and investigated their clinical and genetic features. METHOD: We retrospectively analyzed AYA patients with brain tumors harboring BRAF V600E, who were treated in two hospitals in Japan. RESULTS Clinical information was available for 14 patients. The median age at diagnosis was 25 years (range: 15–38). Five patients were diagnosed with glioblastoma (GBM), including one epithelioid type. These patients were over 25. Although one patient with GBM died of the disease 6.9 years after initial diagnosis, the remaining patients were alive. Two patients were alive without recurrence at 38 and 51 months after the treatment. The patient with epithelioid glioblastoma experienced early recurrence. The remaining nine patients (64%) were diagnosed with low-grade glioma, including ganglioglioma, pilocytic astrocytoma, diffuse astrocytoma, oligodendroglioma, pleomorphic xanthoastrocytoma, and polymorphous low-grade neuroepithelial tumor of the young. No patients died of the disease, and four patients are alive without recurrence after initial operation without adjuvant treatment. Two patients are (epithelioid glioblastoma and ganglioglioma) currently undergoing treatment with a BRAF inhibitor for recurrent tumors. DISCUSSION Although the number of this study is limited, our study suggested that the prognosis of AYA patients with BRAF-V600E positive GBM may not be as dismal as that of children or adults.

Frequency and Topography of AstrocyticTumor: Experience of 567 Cases at Referral Neuroscience Hospital in Bangladesh

2020 ◽  
Vol 6 (2) ◽  
pp. 91-95
Author(s):  
Md Nowfel Islam ◽  
Naila Haq ◽  
Md Badius Salam ◽  
Monsur Ahmed ◽  
Sk Muhammad Ekramullah ◽  
...  
Keyword(s):  
Pilocytic Astrocytoma ◽  
Anaplastic Astrocytoma ◽  
Pleomorphic Xanthoastrocytoma ◽  
Subependymal Giant Cell Astrocytoma ◽  
Diffuse Astrocytoma ◽  
Female Ratio ◽  
Glial Tumors ◽  
The Mean ◽  
Male To Female ◽  
Good Number

Background: Glioma is the most commonly occurring malignant brain tumor that varies by age, sex, race or ethnicity. A very few number of records on CNS tumors are available in Bangladesh. National Institute of Neurosciences and Hospital (NINS), Dhaka has a good number of CNS surgeries. Regularly both tumorous and non-tumorous ICSOL samples are examined here. Objective: The aim of the study was to see the subtypes, frequency and topography of Astrocytic tumors at NINS setting. Methodology: Data from the department of Neuropathology department of NINS since January 2013 to June 2019 were evaluated. Tissue were fixed in formalin, paraffin embedded, stained with H&E. Histomorphology and WHO 2007 CNS tumor classification were used. Result: From 3945 routine sample 567 cases were sorted out as Astrocytic tumor. Total male were 61% (346) and female 39% (221), male to female ratio was 1.6:1. The mean age was 32.64 and ranged from 1 to 80 years. Sixty six percent (66%) tumors were in supratentorial compartment, 15% infratentorial, 6.3% spinal and 9.7% in midline areas like thalamus, hypothalamus and seller region. In this study 34.6% (196) cases were Glioblastoma, followed by Anaplastic Astrocytoma 8.3%(47), Diffuse Astrocytoma 29% (165), Pilocytic Astrocytoma 26.6% (151), Pilomyxoid Astrocytoma 0.4% (2), Subependymal giant cell Astrocytoma 0.9% (5) and Pleomorphic Xanthoastrocytoma 0.1 (0.1). Topographically 66% glial tumors are supratentorial. Among the glial tumors 34.6% is Glioblastoma, 8.3% Anaplastic Astrocytoma, 29% Diffuse Astrocytoma and 26.6% Pilocytic astrocytoma. Common age group of Glioblastoma is 41-60 (52%) years, diffuse astrocytoma is 21-40 years 60.60 and Pilocytic Astrocytoma is 1-20 years (66.88). Glioblastoma, Anaplastic Astrocytoma and Diffuse astrocytoma are more common in male than female. Conclusion: There is no gender difference in case of Pilocytic Astrocytoma. Journal of National Institute of Neurosciences Bangladesh, 2020;6(2): 91-95

scholarly journals Effectiveness of BRAF inhibitors in patients with BRAF V600 mutation positive glioma: a systematic review

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv14-iv14
Author(s):  
Ian Yao ◽  
Sarah Dawson ◽  
Julian Higgins ◽  
Luke McGuinness ◽  
Alexandra McAleenan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Objective Response ◽  
Braf Inhibitor ◽  
High Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
Braf Inhibitors ◽  
Duration Of Treatment ◽  
Braf V600 Mutation

Abstract Background BRAF inhibitor treatment with vemurafenib and dabrafenib have produced significant increases in median overall survival for BRAF V600 mutation-positive melanoma patients and are in wide clinical use. BRAF inhibitors have also been used in an ad hoc fashion in BRAF V600 mutation-positive glioma in a number of glioma subtypes with varying prognoses. Methods An electronic search was performed on MEDLINE and Embase on February 1, 2019 to identify studies of any design that reported the outcome of patients with BRAF V600 mutation-positive glioma treated with BRAF inhibitors. Data was collected for demographic information, tumour information (type and grading), BRAF mutation type, prior treatment regimens, type of BRAF inhibitor, dose and duration of treatment, best objective response, progression free survival (PFS), overall survival (OS), glioma specific symptomatic relief and adverse events. Preliminary Results Seventy-nine case reports, case series and single arm cohort studies with a total of 286 patients were included. Duration of treatment was available for 197 patients and varied from 0.1 to 54 months, with 104 patients still undergoing treatment at the time of publication. Progression occurred in 158 patients (including both low-grade and high-grade glioma) at between 0.805 and 36 months following the start of treatment. 34 people died, at between 0.329 and 40.1 months following the start of treatment. Conclusions Our systematic review shows varying clinical effectiveness of BRAF inhibitors in BRAF V600 mutation-positive glioma depending on low-grade or high-grade glioma. This evidence may inform future trials of BRAF inhibitors for glioma patients.

scholarly journals Drugs Associated With the Development of Palmoplantar Keratoderma: A Systematic Review

2021 ◽  
pp. 120347542110045
Author(s):  
Sara Mirali ◽  
Abrahim Abduelmula ◽  
Asfandyar Mufti ◽  
Muskaan Sachdeva ◽  
Jensen Yeung
Keyword(s):  
Systematic Review ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Complete Resolution ◽  
Kinase Inhibitors ◽  
Healthcare Providers ◽  
Latency Period ◽  
Braf Inhibitors ◽  
Palmoplantar Keratoderma ◽  
Drug Induced

Background Palmoplantar keratoderma (PPK) are a heterogenous group of hereditary and acquired disorders that are characterized by excessive epidermal thickening of the palms and/or soles. PPK has been described as a rare adverse event for some medications. The aim of this systematic review was to summarize outcomes in PPK associated with various medications. This data will assist dermatologists and other healthcare providers treating patients with drug-induced PPK. Methods EMBASE and MEDLINE databases were searched in accordance with PRISMA guidelines using the keyword “palmoplantar keratoderma.” 40 studies met the inclusion criteria. Results A total of 247 patients (mean age: 57.0 years) were included in the analysis. Among patients whose sex was reported, 60.3% ( n = 35/58) were male. PPK most frequently developed after treatment with BRAF inhibitors (73.7%, n = 182/247), BRAF inhibitors combined with MEK1/2 inhibitors (15.4%, n = 38/247), tyrosine kinase inhibitors (TKIs) (3.2%, n = 8/247), or chemotherapy (2.4%, n = 6/247). The mean latency period between initiation of the drug and onset of PPK was 7.6 months (range: 0.25-90 months). Improvement of PPK was reported in 24 cases, with 50% ( n = 12/24) achieving complete resolution and 50% ( n = 12/24) achieving partial resolution. All patients who achieved complete resolution stopped the suspected drug, with a mean resolution period of 2.4 months (range: 2 weeks-6 months). The most common treatments for PPK were keratolytic treatments ( n = 10) and topical corticosteroids ( n = 4). Conclusions PPK was most frequently associated with targeted kinase inhibitors, specifically BRAF, MEK1/2, and tyrosine kinase inhibitors.

scholarly journals Radiological characteristics study on epithelioid glioblastoma, a rare subtype of GBM

2019 ◽  
Author(s):  
Xiaojuan Deng ◽  
Qingya Luo ◽  
Xiaolin Tang ◽  
Youqiang Chen ◽  
Chengyi Mao ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Diffusion Weighted Imaging ◽  
Braf V600e ◽  
Diffuse Astrocytoma ◽  
Peritumoral Edema ◽  
1H Mrs ◽  
Radiological Features ◽  
Epithelioid Glioblastoma ◽  
Intracerebral Tumor ◽  
Immunohistological Staining

Abstract Purpose Epithelioid glioblastoma (eGBM) is rare and a newly recognized subtype of GBM. Given the short of studies focusing on radiological characteristics of these tumors, we aimed to report the radiological features of eGBM deriving from six patients. Methods Six patients with pathologically diagnosed as eGBM were enrolled in this retrospective study. CT and pre-operative MR examinations with conventional and advanced sequences, such as diffusion weighted imaging and so on were analyzed. Immunohistological staining and mutation analysis of BRAF V600E was also explored. Results Only case 6 showed a co-locating tumor which was verified to be a diffuse astrocytoma (WHO II), other cases demonstrated single intracerebral tumor. Majority of the tumors originated in cerebral cortex, two cases involved corpus callosum. Tumors demonstrated iso-, hypo- or mixed intensity on T1WI, hyper- or mixed intensity on T2WI and FLAIR, heterogeneous enhancement on post-contrasted imaging. Involvement of leptomeninge, which appeared as leptomenigeal thickening and abnormal enhancing was discovered in 4 cases. Peritumoral edema (4/6) and hemorrhage (3/6) was common, calcium was only seen in case 5. Notable restrictive diffusion and consequently decreased rADC was found in solid component in 5 cases. Most cases demonstrated increased Cho and Lac/Lip value on 1H-MRS, and promoted rCBV value on PWI. The cases with CT examination showed an ill-defined mass with mixed density. Conclusions Although there are some overlaps between typical GBM and eGBM, some radiological characteristics, such as location (often in cerebral cortex), involvement of leptomeninge and intratumoral calcium, may support the diagnosis of eGBM.

Efficacy and safety of dabrafenib‐trametinib in the treatment of unresectable or metastatic melanoma with BRAF V600 mutation: A systematic review and network meta‐analysis

2020 ◽  
Author(s):  
Nathaly Garzón‐Orjuela ◽  
Laura Prieto‐Pinto ◽  
Pieralessandro Lasalvia ◽  
Daniel Herrera ◽  
Johanna Castrillón ◽  
...  
Keyword(s):  
Systematic Review ◽  
Metastatic Melanoma ◽  
Meta Analysis ◽  
Efficacy And Safety ◽  
Braf V600 Mutation

scholarly journals Epithelioid glioblastoma presenting as multicentric glioma: A case report and review of the literature

2020 ◽  
Vol 11 ◽  
pp. 8 ◽  
Author(s):  
Daisuke Kohno ◽  
Akihiro Inoue ◽  
Mana Fukushima ◽  
Tomoharu Aki ◽  
Shirabe Matsumoto ◽  
...  
Keyword(s):  
Surgical Excision ◽  
World Health ◽  
Preoperative Imaging ◽  
Diffuse Astrocytoma ◽  
Isocitrate Dehydrogenase 1 ◽  
Multicentric Glioma ◽  
Parietal Lobes ◽  
Short Period ◽  
Epithelioid Glioblastoma ◽  
The Right

Background: Epithelioid glioblastoma is a rare aggressive variant of glioblastoma multiforme (GBM), which was formally recognized by the World Health Organization classification of the central nervous system in 2016. Clinically, epithelioid GBMs are characterized by aggressive features, such as metastases and cerebrospinal fluid dissemination, and an extremely poor prognosis. A rare case of epithelioid GBM that was discovered as a multicentric glioma with different histopathology is reported. Case Description: A 78-year-old man was admitted to our hospital with mild motor weakness of the right leg. Neuroimaging showed small masses in the left frontal and parietal lobes on magnetic resonance imaging. The abnormal lesion had been increasing rapidly for 3 weeks, and a new lesion appeared in the frontal lobe. 11C-methionine positron emission tomography (PET) showed abnormal uptake corresponding to the lesion. To reach a definitive diagnosis, surgical excision of the right frontal mass lesion was performed. Histological findings showed diffuse astrocytoma. Only radiotherapy was planned, but the left frontal and parietal tumors progressed further within a short period. Therefore, it was thought that these tumors were GBM, and a biopsy of the left parietal tumor was performed. The histological diagnosis was epithelioid GBM. Immunohistochemistry showed that most tumor cells were negatively stained for p53 and isocitrate dehydrogenase 1. BRAF V600E mutations were not identified, but TERT promoter mutations were identified. Immediately after surgery, the patient was given chemotherapy using temozolomide, extended local radiotherapy and then bevacizumab. After 6 months, he showed no signs of recurrence. Conclusion: Epithelioid GBM is one of the rarest morphologic subtypes of GBM and has a strongly infiltrative and aggressive nature. Therefore, careful identification of preoperative imaging studies and detailed evaluation of genetic studies are necessary to select the appropriate treatment for epithelioid GBM.

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