P14.65 Anaplastic pleomorphic xanthoastrocytoma: literature review& case report

Abstract

Abstract Pleomorphic xanthoastrocytoma (PXA) is a rare glial brain tumor. 9% to 30% cases have anaplastic features which determine poor prognosis. Anaplastic features may be found either in primary tumor or in recurrent PXA in any time frame. According to WHO 2016 Brain Tumor Classification, anaplastic pleomorphic xanthoastrocytoma (aPXA) was reclassified as grade III tumor (previously grade II). Characteristic features for aPXA are mitotic index of 5% or higher and worse 5-year survival rates in comparison with PXA: 57.1% and 90.4%, respectively. About 6% cases have TP53 gene mutation. About 60–78% tumors are BRAF-mutated, which is a potential target for therapy. Currently there are ongoing clinical trials to determine efficacy of BRAF and MEK inhibitors in pediatric patients with high-grade glioma with BRAF mutation. There is a number of publications showing positive outcome of targeted therapy both in children and adults. Treatment protocol for aPXA has not been defined. Case report Patient N. 14-y.o. female. MRI showed tumor of left occipital lobe. 02.03.2016 stereotactic biopsy was performed. Histological examination revealed diffuse astrocytic glioma WHO grade III-IV. Radiation therapy was performed, after which patient’s condition abruptly deteriorated with back pain, patient became almost unable to walk, however control MRI showed no signs of spinal dissemination. 01.12.2016 surgery to remove left occipital lobe tumor was performed. 07.12.2016 MRI showed contrast enhancing lesions throughout entire length of the spinal cord. Histological examination revealed aPXA gr. III, Ki-67 up to 8%. From December to June 2017 patient received 6 cycles of chemotherapy with temozolomide. Molecular testing discovered BRAF V600 mutation in exon 15. Chemotherapy regimen was thereby changed to vemurafenib 1920 mg/day from July 2017. After a month of treatment patient developed cutaneous toxicity and the dose was lowered to 960 mg/day. Patient’s condition improved: back pain syndrome regressed, lower extremity muscle strength increased, patient became able to walk. MRI 03.12.2017 revealed an increase of contrast enhancing lesion and T2-FLAIR hyperintense signal area in left occipital lobe, no progression in spinal cord. Methionine PET/CT was performed, the findings were evaluated as a combination of radiation necrosis and glioma growth. In view of MRI and PET/CT findings, amount of time passed after radiation therapy, we decided to include bevacizumab 400 mg every 2 weeks in the regimen. Since January 2018 patient is receiving vemurafenib 960 mg/day and bevacizumab 400 mg every 2 weeks. There is a marked positive dynamic in clinical findings and imaging data (MRI and PET/CT). We report the patient with aPXA and prolonged response to targeted therapy. The presence of the BRAF V600E mutation was possibility of treatment which led to successful results.