LGG-23. INHIBITORS IN THE TREATMENT OF LOW GRADE GLIOMAS- A SINGLE CENTER EXPERIENCE, BRATISLAVA, SLOVAKIA

Abstract

Abstract BACKGROUND Pediatric LGGs are the most common CNS tumors in children. They are a very heterogeneous group of tumors of different histological types, according to the WHO classification of grade 1- 2. The major molecular pathway affected in these tumors is the mitogen-activated protein kinase (MAPK) signaling cascade. The frequency of MAPK pathway activation makes this pathway an attractive candidate for targeted therapy, and direct inhibition via BRAF and/or MEK inhibitors is emerging as a clinically relevant strategy. METHODS We performed a retrospective analysis of patients treated with inhibitors at the Department of Pediatric Hematology and Oncology in Bratislava since 03/2020. Currently 9 patients, 5 boys and 4 girls, are treated with inhibitors. They are pLGG patients, two of them with concomitant genetically confirmed neurofibromatosis type 1. Six patients are treated with the MEK inhibitor trametinib in monotherapy and three patients with BRAF V600-mutated LGG with a combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib. In our cohort with a small number of patients, with a median follow-up of 13 months, we did not observe disease progression in even one patient on inhibitor therapy. Tolerance to treatment is reasonable. CONCLUSIONS In recent years, our understanding of the molecular biology of pediatric brain tumors has improved significantly. Alterations in the mitogen-activated protein kinase (MAPK) pathway are generally the most common molecular alterations in cancer, and dysregulation of this pathway also dominates the development of pediatric LGGs. The introduction of targeted drugs not only allows to improve the disease prognosis and survival of children with CNS tumors, to improve their quality of life on treatment, but also to reduce toxicity caused by e.g. radiotherapy, and at the same time to reduce the incidence of late sequelae of treatment.