Abstract BACKGROUND BRAF mutations are drivers of oncogenesis in a variety of tumors and they can be successfully targeted with small molecule inhibitors. In primary central nervous system tumors, BRAFV600E mutations are most frequently found in pleomorphic xanthoastrocytoma, ganglioglioma, pilocytic astrocytoma and epithelioid glioblastoma. Dabrafenib is a potent and selective inhibitor of BRAF-mutant kinase that was approved, as monotherapy or in combination with trametinib (mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor), for unresectable or metastatic BRAF-mutated melanoma, advanced non-small cell lung cancer and anaplastic thyroid cancer harboring BRAFV600E mutation. MATERIAL AND METHODS In February 2016, a 21-year-old female was admitted to our Unit for seizures. A brain magnetic resonance imaging (MRI) revealed a frontal contrast enhanced lesion. Neurosurgical resection was performed. The histological analysis diagnosed anaplastic pleomorphic xanthoastrocytoma (PXA) WHO grade III. A volumetric modulated radiotherapy course was delivered for a total dose of 59,4 Gy in 33 fractions with concomitant and adjuvant temozolomide therapy (Stupp protocol). In October 2017, a brain MRI showed relapsing disease. Six courses of chemotherapy with procarbazine, lomustine and vincristine (PCV) were administered, and then neurosurgical partial removal and carmustine wafer implantation were performed. The histological analysis confirmed BRAF V600E mutated anaplastic PXA. RESULTS In April 2019 the 24-year-old female patient with BRAF mutated anaplastic PXA started her third-line therapy with dabrafenib. The well-known tumor residue was less evident on the subsequent MRIs performed every three/four months. Given the literature data of the most effectiveness and the best control of the side effects, in August 2020 the patient was put on combined treatment with dabrafenib plus trametinib. Since December 2021 the residual tumor has not been longer visible. Last MRI evaluation, performed on January 26th 2023, showed no recurrence of the disease, four years after BRAF inhibitor treatment beginning. CONCLUSION Dabrafenib plus trametinib is a promising new therapy for patients affected by BRAFV600E-mutant glioma, with high overall response and manageable toxicity. Due to very poor prognosis, there are a few described cases of high-grade glioma (HGG) patients in third-line therapy, showing complete response and for such a long time. The emergence of optimized sequencing strategies and targeted agents, including multimodal treatment and systemic therapy with dabrafenib plus trametinib, will continue to broaden personalized therapy in HGG and to improve patient outcomes.
INTRODUCTION: Pediatric high-grade gliomas (pHGGs) are represented primarily by anaplastic astrocytomas (AA, WHO-grade III) and glioblastomas (GBM, WHO-grade IV). Despite advances in treatments, the outcome is similar between children and adults, with a 5-year OS less than 20%. Consolidated treatment includes surgery, followed by radiotherapy and chemotherapy associated with temozolomide. MATERIALS AND METHODS: We considered 19 HGG patients admitted to our department to receive therapy between May 2012 and December 2014. Patients were enrolled in a temozolomide/vinorelbine chemotherapy protocol consisting of focal radiotherapy and concomitant chemotherapy (6 weeks) with vinorelbine (20 mg/sqm i.v weekly) and temozolomide (75 mg/sqm i.o daily). The adjuvant phase consisted in 12 months of treatment with chemotherapy with vinorelbine 30 mg/sqm i.v. days 1 and 14 and temozolomide 150 mg/sqm i.o. days 1–5 every 28 days. RESULTS: The median age at diagnosis was 10 years. Six patients (31,6%) had GBM and thirteen (68,4%) an AA. According to localization, 15 tumors (78.9%) were sovratentorial e and 4 (21.1%) were infratentorial. Radical surgery was performed in seven patients. Six patients (26,3%) had a disease progression during the adjuvant phase. One patient died after radiotherapy. One patient was lost during follow-up. Median follow-up was 41.1 months. At time of analysis 11 patients were still alive and without evidence of disease. CONCLUSION: The combination of vinorelbine/temozolomide seems to be safe, without significant adverse events for treatment of aggressive gliomas of pediatric age. Adjuvant chemotherapy is crucial for a better outcome. At 50 months of follow-up 6 patients are alive and without evidence of disease. There is no significant difference, either in PFS than in OS, between AA and GBM.
Poster: ECR 2019 / C-0739 / Radiologic-pathologic correlation of Lesions of Uncertain Malignant Potential on Core Biopsy (B3 lesions). by: R. M. Lorente Ramos , F. J. Azpeitia Arman, C. Oliva Fonte, J. M. LOPEZ ARCAS CALLEJA, J. M. Garcia Gomez, M. T. Rivera Garcia; Madrid/ES
Abstract INTRODUCTION Chemotherapy remains the cornerstone in case of incompletely resected pedatric Low Grade Glioma (pLGGs) and for recurrent tumors in unfavorable locations. Based on previous cisplatin etoposide regimen (INT Milan strategy), we tried to reduce toxicity and achieve a similar tumor control using a modified regimen composed of CBCDA-etoposide. METHODS From August 2012 to December 2023 we treated 79 pLGGS (45 F (57%), 34 M (43%)) with carboplatin (400 mg/m2 day 1) and etoposide (100 mg/2 day 1-3) at 4-6 weeks interval with 10 cycles in one year or until disease progression. Median age at diagnosis is 7 years. Seventeen patients were affected by neurofibromatosis type 1 (21.5%). 28 pLGGS affected visual pathway (35.4%). Treatment was delivered for clinical symptoms and/or radiological evidence of progression. RESULTS According to RAPNO criteria, on brain magentic resonance imaging (MRI) at the end of treatment 40 patients had stable disease (50.6%), 10 had partial response (12.7%), 7 had major response (8.9%), 5 had minor response (6.3%), 2 presented complete remission (2.5%), 13 patient had disease progression (16.5%). 2 patients are undergoing treatment (2.5%). Acute toxicity was unremarkable. During follow up (median time 59,5 months) 9 children (11,4%) developed audiological alterations but 2 of them also received radiotherapy. 14 patients presented hematological toxicity CTCAE grade 3 or 4 (17,7%). During follow up 30 patients developed a progressive disease (38%) and require further treatments and only one patients died because of progressive disease. Overall survival was 98,7% (78/79). CONCLUSIONS The combination of low doses CBCDA-etoposide seems equally effective with a lower hematological and audiological toxicity compared to other regimens.