scholarly journals Pleomorphic Xanthoastrocytoma, Anaplastic Pleomorphic Xanthoastrocytoma, and Epithelioid Glioblastoma: Case Series with Clinical Characteristics, Molecular Features and Progression Relationship

2021 ◽  
Author(s):  
Zhiying Lin ◽  
Runwei Yang ◽  
Haojie Zheng ◽  
Zhiyong Li ◽  
Guozhong Yi ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Case Series ◽  
Pleomorphic Xanthoastrocytoma ◽  
Braf V600e ◽  
Tumour Tissue ◽  
Tissue Samples ◽  
Chromosome 1P ◽  
Molecular Features ◽  
Epithelioid Glioblastoma ◽  
Next Generation Sequencing Ngs

Abstract Background: Pleomorphic xanthoastrocytoma (PXA), anaplastic pleomorphic xanthoastrocytoma (A-PXA), and epithelioid glioblastoma (E-GBM) show overlapping features. However, little is known about their clinical characteristics, molecular features and relationship with progression. Methods: Fourteen patients diagnosed at Nanfang Hospital from 2016 to 2019 were enrolled, including eleven PXA patients, two A-PXA patients, and one E-GBM patient. All tumour tissue samples of the fourteen patients were examined by immunohistochemical staining (MGMT, VEGF, BRAF-V600E, etc.). The recurrent tumour tissue of the patient with E-GBM arising from A-PXA was screened to detect 11 glioma markers (MGMT, BRAF-V600E, etc.) and chromosome 1p/19q by next-generation sequencing (NGS).Results: The mean age of 13 patients with PXA or A-PXA was 25.4 years; twelve of these patients had tumours at supratentorial regions. VEGF positivity was detected in the tumour samples of 13 patients, MGMT positivity in 10 patients, and BRAF-V600E positivity in 7 patients. For the tumour sample of the E-GBM patient who survived for up to 10 years after the fourth resection, BRAF V600E was wild type in the sample obtained from the first surgery, while it was mutant in the second, third, and fourth surgeries. In contrast, the promoter status of MGMT in the four surgeries was unmethylated. The NGS results showed that the mutation frequencies of BRAF V600E in the second, third and fourth surgeries were 14.06%, 9.13% and 48.29%, respectively.Conclusions: Collectively, the results suggest that patients with A-PXA may relapse multiple times and eventually progress to E-GBM with the BRAF-V600E mutation.

scholarly journals Pleomorphic Xanthoastrocytoma, Anaplastic Pleomorphic Xanthoastrocytoma, and Epithelioid Glioblastoma: Case Series with Clinical Characteristics, Molecular Features and Progression Relationship

2021 ◽  
Author(s):  
Zhiying Lin ◽  
Runwei Yang ◽  
Haojie Zheng ◽  
Zhiyong Li ◽  
Guozhong Yi ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Case Series ◽  
Pleomorphic Xanthoastrocytoma ◽  
Braf V600e ◽  
Tumour Tissue ◽  
Tissue Samples ◽  
Chromosome 1P ◽  
Molecular Features ◽  
Epithelioid Glioblastoma ◽  
Next Generation Sequencing Ngs

Abstract Background: Pleomorphic xanthoastrocytoma (PXA), anaplastic pleomorphic xanthoastrocytoma (A-PXA), and epithelioid glioblastoma (E-GBM) show overlapping features. However, little is known about their clinical characteristics, molecular features and relationship with progression. Methods: Fourteen patients diagnosed at Nanfang Hospital from 2016 to 2019 were enrolled, including eleven PXA patients, two A-PXA patients, and one E-GBM patient. All tumour tissue samples of the fourteen patients were examined by immunohistochemical staining (MGMT, VEGF, BRAF-V600E, etc.). The recurrent tumour tissue of the patient with E-GBM arising from A-PXA was screened to detect 11 glioma markers (MGMT, BRAF-V600E, etc.) and chromosome 1p/19q by next-generation sequencing (NGS).Results: The mean age of 13 patients with PXA or A-PXA was 25.4 years; twelve of these patients had tumours at supratentorial regions. VEGF positivity was detected in the tumour samples of 13 patients, MGMT positivity in 10 patients, and BRAF-V600E positivity in 7 patients. For the tumour sample of the E-GBM patient who survived for up to 10 years after the fourth resection, BRAF V600E was wild type in the sample obtained from the first surgery, while it was mutant in the second, third, and fourth surgeries. In contrast, the promoter status of MGMT in the four surgeries was unmethylated. The NGS results showed that the mutation frequencies of BRAF V600E in the second, third and fourth surgeries were 14.06%, 9.13% and 48.29%, respectively.Conclusions: Collectively, the results suggest that patients with A-PXA may relapse multiple times and eventually progress to E-GBM with the BRAF-V600E mutation.

scholarly journals Pleomorphic Xanthoastrocytoma, Anaplastic Pleomorphic Xanthoastrocytoma, and Epithelioid Glioblastoma: Case Series With Clinical Characteristics, Molecular Features and Progression Relationship

2020 ◽  
Author(s):  
Zhiying Lin ◽  
Runwei Yang ◽  
Haojie Zheng ◽  
Zhiyong Li ◽  
Guozhong Yi ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Tumor Tissue ◽  
Case Series ◽  
Pleomorphic Xanthoastrocytoma ◽  
Braf V600e ◽  
Tissue Samples ◽  
Chromosome 1P ◽  
Molecular Features ◽  
Epithelioid Glioblastoma ◽  
Next Generation Sequencing Ngs

Abstract Background: Pleomorphic xanthoastrocytoma (PXA), anaplastic pleomorphic xanthoastrocytoma (A-PXA), and epithelioid glioblastoma (E-GBM) show overlapping features. However, little is known about their clinical characteristics, molecular features and progression relationship. Methods: Fourteen patients diagnosed at Nanfang Hospital from 2016 to 2019 were enrolled, including eleven PXA patients, two A-PXA patients, and one E-GBM patient. All tumor tissue samples of fourteen patients were examined by immunohistochemistry staining (MGMT, VEGF, BRAF-V600E, etc.). The recurred tumor tissue of the E-GBM patient arising from A-PXA was detected for 11 glioma markers (MGMT, BRAF-V600E, etc.) and chromosome 1p/19q by next generation sequencing (NGS). Results: The mean age of 13 patients with PXA or A-PXA was 25.4 years, twelve of whom were burdened with tumors at supratentorial regions. VEGF showed positive expression in the tumor samples of 13 patients, MGMT positive in 10 patients, and BRAF-V600E positive in 7 patients. As for the tumor sample of the E-GBM patient survived for up to 10 years after the fourth resections, BRAF V600E was wild-type in the sample obtained from the first surgery while it was mutant in the second, third, and fourth surgery. In the contrast, the promoter status of MGMT in four operations were unmethylated. The NGS results showed that the mutation frequencies of BRAF V600E in the second surgery, the third surgery and the fourth surgery were 14.06%, 9.13% and 48.29% respectively. Conclusions: Collectively, the results suggest that patients with A-PXA may relapse multiple times and eventually progress to E-GBM with BRAF-V600E mutation.

scholarly journals HGG-35. PEDIATRIC PLEOMORPHIC XANTHOASTROCYTOMA WITH ANAPLASIA TREATED WITH SURGERY AND ADJUVANT CHEMOTHERAPY: A CASE SERIES OF 3 LONG-TERM SURVIVORS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii350-iii350
Author(s):  
Rebecca Ronsley ◽  
Christopher Dunham ◽  
Stephen Yip ◽  
Juliette Hukin ◽  
Sylvia Cheng
Keyword(s):  
Case Series ◽  
Complete Response ◽  
Pleomorphic Xanthoastrocytoma ◽  
Braf V600e ◽  
Pediatric Tumor ◽  
Molecular Features ◽  
End Of Treatment ◽  
Genetic Landscape ◽  
Long Term Survivors

Abstract OBJECTIVE Pleomorphic xanthoastrocytoma (PXA) with anaplasia is a rare histological subtype of central nervous system astrocytoma and generally treated as high grade gliomas. The optimal extent of therapy required is unknown. Here we report on 3 pediatric cases of PXA with anaplasia. We also describe molecular features and methylation profile of PXA with anaplasia compared to age-matched PXA without anaplasia. METHODS Our institutional database was queried for cases of PXA since 1998 and 3 cases with anaplasia were identified and records reviewed. RESULTS 2/3 patients were male and all were aged 12 at diagnosis. All underwent a gross total resection (GTR), where the diagnosis of PXA with anaplasia was made. Immunohistochemistry demonstrated that two cases were BRAF V600E positive and two were CD34 positive. Methylation profiling revealed unique pattern of CpG methylation/unmethylation. All patients underwent 5400cGy radiation to the surgical bed. 2/3 patients received concurrent temozolamide with radiation followed by maintenance chemotherapy with temozolamide and lomustine for 6 cycles as per the Children’s Oncology Group Protocol ACNS0423. These two patients had a continued complete response. The third patient received temozolamide following radiation and subsequently had recurrent disease at the end of treatment and went on to have a re-resection GTR and achieved complete response after 6 cycles of lomustine, vincristine and procarbazine. All are alive with no evidence of disease at more than 2 years post treatment completion (OS=100%,EFS=67%). CONCLUSIONS This rare pediatric tumor is not well understood. The genetic landscape may be informative for optimizing treatment and prognosis.

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.

Dual BRAF/MEK therapy in BRAF V600E-mutated primary brain tumors: a case series showing dramatic clinical and radiographic responses and a reduction in cutaneous toxicity

2020 ◽  
Vol 133 (6) ◽  
pp. 1704-1709 ◽  
Author(s):  
Aaron Bernstein ◽  
Oliver D. Mrowczynski ◽  
Amrit Greene ◽  
Sandra Ryan ◽  
Catherine Chung ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Pilocytic Astrocytoma ◽  
Case Series ◽  
Mek Inhibitor ◽  
Pleomorphic Xanthoastrocytoma ◽  
Inhibitor Therapy ◽  
Braf V600e ◽  
Dual Inhibitor ◽  
Cutaneous Toxicity ◽  
Primary Brain Tumors

OBJECTIVEBRAF V600E is a common oncogenic driver in a variety of primary brain tumors. Dual inhibitor therapy using dabrafenib (a selective oral inhibitor of several mutated forms of BRAF kinase) and trametinib (a reversible inhibitor of MEK1 and MEK2) has been used successfully for treatment of metastatic melanoma, anaplastic thyroid cancer, and other tumor types, but has been reported in only a few patients with primary brain tumors and none with pleomorphic xanthoastrocytoma. Here, the authors report on the substantial clinical response and reduction in cutaneous toxicity in a case series of BRAF V600E primary brain cancers treated with dual BRAF/MEK inhibitor therapy.METHODSThe authors treated 4 BRAF V600E patients, each with a different type of primary brain tumor (pilocytic astrocytoma, papillary craniopharyngioma, ganglioglioma, and pleomorphic xanthoastrocytoma) with the combination of dabrafenib and trametinib.RESULTSThe patients with pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and papillary craniopharyngioma experienced near-complete radiographic and complete clinical responses after 8 weeks of therapy. A substantial partial response (by RANO [Response Assessment in Neuro-Oncology] criteria) was observed in the patient with ganglioglioma. The patient with craniopharyngioma developed dramatic, diffuse verrucal keratosis within 2 weeks of starting dabrafenib. This completely resolved within 2 weeks of adding trametinib.CONCLUSIONSDual BRAF/MEK inhibitor therapy represents an exciting treatment option for patients with BRAF V600E primary brain tumors. In addition to greater efficacy than single-agent dabrafenib, this combination has the potential to mitigate cutaneous toxicity, one of the most common and concerning BRAF inhibitor–related adverse events.

BRAF V600E, TERT, and IDH2 Mutations in Pleomorphic Xanthoastrocytoma: Observations from a Large Case-Series Study

2018 ◽  
Vol 120 ◽  
pp. e1225-e1233 ◽  
Author(s):  
Chengxin Ma ◽  
Rui Feng ◽  
Hong Chen ◽  
N.U.Farrukh Hameed ◽  
Abudumijit Aibaidula ◽  
...  
Keyword(s):  
Case Series ◽  
Pleomorphic Xanthoastrocytoma ◽  
Braf V600e ◽  
Case Series Study ◽  
Large Case Series ◽  
Series Study ◽  
Large Case

Epithelioid glioblastoma arising from pleomorphic xanthoastrocytoma with the BRAF V600E mutation

2014 ◽  
Vol 31 (3) ◽  
pp. 172-176 ◽  
Author(s):  
Shingo Tanaka ◽  
Mitsutoshi Nakada ◽  
Sumihito Nobusawa ◽  
Satoshi O. Suzuki ◽  
Hemragul Sabit ◽  
...  
Keyword(s):  
Pleomorphic Xanthoastrocytoma ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Epithelioid Glioblastoma

scholarly journals A case series of pediatric survivors of anaplastic pleomorphic xanthoastrocytoma

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Rebecca Ronsley ◽  
Christopher Dunham ◽  
Stephen Yip ◽  
Lindsay Brown ◽  
Jeffrey A Zuccato ◽  
...  
Keyword(s):  
Case Series ◽  
Immunohistochemical Analysis ◽  
Copy Number Variations ◽  
Pleomorphic Xanthoastrocytoma ◽  
Braf V600e ◽  
Adjuvant Chemoradiotherapy ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Pediatric Tumor ◽  
Genetic Landscape

Abstract Background Anaplastic pleomorphic xanthoastrocytoma (APXA) is a rare subtype of CNS astrocytoma. They are generally treated as high-grade gliomas; however, uncertainty exists regarding the optimal therapy. Here, we report on 3 pediatric cases of APXA. Methods Our institutional database was queried for cases of APXA and 3 cases were identified. Surgical samples were processed for methylation profiling and chromosomal microarray analysis. Methylation data were uploaded to the online CNS tumor classifier to determine methylation-based diagnoses to determine copy number variations (CNVs). Results Two patients were male, 1 female, and all were aged 12 years at diagnosis. All underwent a gross total resection (GTR) and were diagnosed with an APXA. Immunohistochemical analysis demonstrated that 2 cases were BRAF V600E positive. Methylation-based tumor classification supported the APXA diagnosis in all cases. CNV analyses revealed homozygous CKDN2A deletions in all and chromosome 9p loss in 2 cases. All patients received radiation therapy (54 Gy in 30 fractions) with concurrent temozolomide. Two patients received maintenance chemotherapy with temozolomide and lomustine for 6 cycles as per the Children’s Oncology Group ACNS0423. The third patient recurred and went on to receive a second GTR and 6 cycles of lomustine, vincristine, and procarbazine. All are alive with no evidence of disease >4 years post-treatment completion (overall survival = 100%, event free survival = 67%). Conclusions The natural history and optimal treatment of this rare pediatric tumor are not well understood. This case series supports the use of adjuvant chemoradiotherapy in the treatment of APXA. The genetic landscape may be informative for optimizing treatment and prognosis.

scholarly journals Clinical Characteristics and Molecular Patterns of RET-Rearranged Lung Cancer in Chinese Patients

2019 ◽  
Vol 27 (5) ◽  
pp. 575-582 ◽  
Author(s):  
Kai Zhang ◽  
Huajun Chen ◽  
Ye Wang ◽  
Lin Yang ◽  
Chengzhi Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Clinical Characteristics ◽  
Progression Free Survival ◽  
Chinese Patients ◽  
Lung Cancers ◽  
Lung Cancer Patients ◽  
Molecular Features ◽  
Molecular Patterns ◽  
Next Generation Sequencing Ngs

RET rearrangement has been proven as an oncogenic driver in patients with lung cancer. However, the prevalence, clinical characteristics, molecular features, and therapeutic options in RET-rearranged patients remain unclear, especially in Chinese lung cancer patients. We retrospectively collected 6,125 Chinese lung cancer patients who have been profiled using next-generation sequencing (NGS). The clinical demographics and molecular features of RET rearrangement-positive patients were analyzed. RET rearrangements were identified in 84 patients with a proportion of 1.4% in our cohort. The median age at diagnosis was 58 years, and it mainly occurred in females with adenocarcinoma histology. KIF5B-RET was the most frequent fusion type and accounted for 53.8% (57/106) of all RET fusions identified, with K15-R12 as the most frequent variant (71.9%). Among 47 RET+ patients profiled with larger panels, 72.3% (34/47) harbored concurrent alterations. TP53 ranked as the most common concurrent alteration, and concomitant EGFR oncogenic alterations were identified in seven patients. Moreover, an adenocarcinoma patient harboring concurrent RET fusion and EGFR L858R responded to combinatorial treatment of cabozantinib and osimertinib, with a progression-free survival of 5 months. Our study improved knowledge of clinical characteristics and molecular features of RET-rearranged lung cancers in China. It might be helpful to guide clinicians for more effective personalized diagnostic and therapeutic approaches.

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