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.

A case of an epithelioid glioblastoma with the BRAF V600E mutation colocalized with BRAF intact low-grade diffuse astrocytoma

2015 ◽  
Vol 36 (2) ◽  
pp. 181-186 ◽  
Author(s):  
Jun-Ichiro Kuroda ◽  
Sumihito Nobusawa ◽  
Hideo Nakamura ◽  
Hideaki Yokoo ◽  
Ryuta Ueda ◽  
...  
Keyword(s):  
Braf V600e Mutation ◽  
Braf V600e ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Epithelioid Glioblastoma

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 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.

scholarly journals LGG-26. DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT) IN CHILDREN: DIFFERENT CLINICAL PRESENTATIONS AND OUTCOMES

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii371-iii371
Author(s):  
Andge Valiakhmetova ◽  
Ludmila Papusha ◽  
Ludmila Yasko ◽  
Alexander Druy ◽  
Alexander Karachunsky ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Braf Inhibitor ◽  
Complete Response ◽  
Mek Inhibitor ◽  
Braf V600e ◽  
Glioneuronal Tumor ◽  
Low Grade ◽  
Conventional Chemotherapy ◽  
Diffuse Leptomeningeal Glioneuronal Tumor ◽  
Braf Fusion

Abstract Diffuse leptomeningeal glioneuronal tumor (DLGNT) is an extremely rare disease, newly recognized in the 2016 WHO classification of tumors of the CNS. Most DLGNTs are low-grade neuroepithelial tumors with variable elements of neuronal/neurocytic and glial differentiation, have diffuse leptomeningeal enhancement on MRI, and typically harbor KIAA1549-BRAF fusions. Other alterations, such as the BRAF V600E substitution, are less common. Here, we present three cases of DLGNT with different presentations and outcomes. The first patient is a 2yr-old male with KIAA1549-BRAF fusion, and was treated with Carbo/VCR chemotherapy after a biopsy, with resultant ongoing stable disease for 3.5 years. The second patient, an 8yr-old male had the BRAF V600E point mutation and was treated with conventional chemotherapy (VCR/carboplatin). On progression, he received the BRAF inhibitor vemurafenib, achieving a complete response which last 14 month. The third patient, a 27 month old male, harbored a KIAA1549-BRAF fusion and was treated at diagnosis with the MEK inhibitor trametinib. The tumor has been radiographically stable in the context of clinical improvement for 21 months since the treatment initiation, ongoing 24 month. In summary, we present further evidence of MAPK pathway alterations in children with DLGNT. We describe a range of molecular presentations and clinical outcomes, including one patient treated with conventional chemotherapy with further stabilization of disease during 3.5 years and two patients who were successfully treated with targeted therapy.

scholarly journals Outcomes of BRAF V600E Pediatric Gliomas Treated With Targeted BRAF Inhibition

2020 ◽  
pp. 561-571 ◽  
Author(s):  
Liana Nobre ◽  
Michal Zapotocky ◽  
Vijay Ramaswamy ◽  
Scott Ryall ◽  
Julie Bennett ◽  
...  
Keyword(s):  
Objective Response ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Homozygous Deletion ◽  
Braf V600e ◽  
Rapid Progression ◽  
Low Grade ◽  
Term Survival ◽  
Braf Inhibition ◽  
Poor Outcomes

PURPOSE Children with pediatric gliomas harboring a BRAF V600E mutation have poor outcomes with current chemoradiotherapy strategies. Our aim was to study the role of targeted BRAF inhibition in these tumors. PATIENTS AND METHODS We collected clinical, imaging, molecular, and outcome information from patients with BRAF V600E–mutated glioma treated with BRAF inhibition across 29 centers from multiple countries. RESULTS Sixty-seven patients were treated with BRAF inhibition (pediatric low-grade gliomas [PLGGs], n = 56; pediatric high-grade gliomas [PHGGs], n = 11) for up to 5.6 years. Objective responses were observed in 80% of PLGGs, compared with 28% observed with conventional chemotherapy ( P < .001). These responses were rapid (median, 4 months) and sustained in 86% of tumors up to 5 years while receiving therapy. After discontinuation of BRAF inhibition, 76.5% (13 of 17) of patients with PLGG experienced rapid progression (median, 2.3 months). However, upon rechallenge with BRAF inhibition, 90% achieved an objective response. Poor prognostic factors in conventional therapies, such as concomitant homozygous deletion of CDKN2A, were not associated with lack of response to BRAF inhibition. In contrast, only 36% of those with PHGG responded to BRAF inhibition, with all but one tumor progressing within 18 months. In PLGG, responses translated to 3-year progression-free survival of 49.6% (95% CI, 35.3% to 69.5%) versus 29.8% (95% CI, 20% to 44.4%) for BRAF inhibition versus chemotherapy, respectively ( P = .02). CONCLUSION Use of BRAF inhibition results in robust and durable responses in BRAF V600E–mutated PLGG. Prospective studies are required to determine long-term survival and functional outcomes with BRAF inhibitor therapy in childhood gliomas.

scholarly journals Recurrent copy number alterations in low-grade and anaplastic pleomorphic xanthoastrocytoma with and without BRAF V600E mutation

2017 ◽  
Vol 28 (2) ◽  
pp. 172-182 ◽  
Author(s):  
Rachael A. Vaubel ◽  
Alissa A. Caron ◽  
Seiji Yamada ◽  
Paul A. Decker ◽  
Jeanette E. Eckel Passow ◽  
...  
Keyword(s):  
Copy Number ◽  
Pleomorphic Xanthoastrocytoma ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Low Grade ◽  
Copy Number Alterations

Concurrent TERT promoter and BRAF V600E mutation in epithelioid glioblastoma and concomitant low-grade astrocytoma

2016 ◽  
Vol 37 (1) ◽  
pp. 58-63 ◽  
Author(s):  
Nozomi Matsumura ◽  
Nozomi Nakajima ◽  
Tatsuya Yamazaki ◽  
Takuro Nagano ◽  
Kaie Kagoshima ◽  
...  
Keyword(s):  
Braf V600e Mutation ◽  
Braf V600e ◽  
Low Grade ◽  
Tert Promoter ◽  
Epithelioid Glioblastoma

scholarly journals HGG-06. REMARKABLE RESPONSE TO BRAF INHIBITOR IN AN INFANT WITH DISSEMINATED DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii345-iii345
Author(s):  
Le Le Aung
Keyword(s):  
Braf Inhibitor ◽  
Braf V600e ◽  
Proliferation Index ◽  
Glioneuronal Tumor ◽  
Low Grade ◽  
Braf Inhibitors ◽  
Visual Contact ◽  
Ki 67 ◽  
Low Grade Gliomas ◽  
Diffuse Leptomeningeal Glioneuronal Tumor

Abstract INTRODUCTION Diffuse Leptomeningeal Glioneuronal Tumor (DLGNT) are rare CNS tumors and in infants, they can be lethal. There are several anecdotal reports in infants with low grade gliomas (LGG) with treated with BRAF inhibitors. METHODS A six-month old baby girl presented with a 2-week history of absent visual contact and vomiting. Imaging revealed a large 4.7 X 4.2 X 2.8 cm suprasellar charismatic region mass and multiple small extra-axial plaques in spinal canal. The child developed significant ascites post VP shunt requiring shunt externalization, extensive protein infusion support and hospitalization for six weeks. Immunohisto-chemical staining revealed Olig-2 and S-100, GFAP and synaptophysin positive. EMA showed patchy cytroplasmic reactivity in stromal cells and CD99 showed diffuse reactivity in stromal and lesional cells. INI-1, IDH-1, and CD117 were negative. Ki-67 proliferation index was 8–10%. PCR for BRAF V600E/E2/D was detected and KIAA1549-BRAF fusion as negative. This was confirmed by Genome Wide Next Generation Sequencing. While waiting for GNS testing results, the baby received one dose of Vinblastine. However, within seven days of initiating Debrafenib, significant clinical and radiological responses were observed. CONCLUSION The baby continues safely on Debrafenib with continued dramatic radiological response. This suggest that there may be a role in early initiation of targeted therapy such as BRAF inhibitors rather than giving standard chemotherapy such as Vinblastine or Carboplatin-Vincristine in extremely ill infants with low grade gliomas.

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