Targeted therapy of hemispheric infant gliomas

Abstract

Infant high grade gliomas (HGG) are the most frequent tumors of the central nervous system in children below 1 year of age. Standard therapy involves surgical resection and chemotherapy. Prognosis in infant HGG is better than in older patients, however, the absence of effective regimens of anti-recurrence therapy and the impossibility of radiation therapy implementation predetermine a negative prognosis in the group of infant gliomas in case of disease progression. In most patients with infant HGG of hemispheric localization, gene rearrangements of receptor tyrosine kinases – NTRK1/2/3 (24%), ALK (41%), ROS1 (28%), MET (7%) are described. The results of tyrosine kinase inhibitor administration show high efficacy and safety in the treatment of patients with NTRK-positive gliomas. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The paper presents two examples of the successful use of targeted therapy in patients with infant HGG lacking the efficacy of the standard chemotherapy. In both cases, a persistent response was obtained: in the first case, a complete response to therapy was achieved, the duration of treatment is currently 1 year, in the second case – there is no progression of the disease during 20 weeks of therapy. Of the adverse events (AE) of targeted therapy in patients, only transitory neutropenia was noted in the first case, in the second case, AEs were not detected. In order to expand therapeutic options and prescribe targeted therapy drugs, a molecular genetic investigation of tumor tissue is mandatory for patients with hemispheric infant gliomas. The parents of the patients agreed to use the information, including photos of children, in scientific research and publications.