HGG-12. INFANT HEMISPHERIC GLIOMA: CLINICAL AND MOLECULAR CHARACTERISTICS AND RESULTS OF TARGETED THERAPY

Abstract

Abstract We analyzed an infant cohort consisting of 14 patientswith hemispheric gliomas (hHGG, n=10 and DIGG, n=4) diagnosed at D. Rogachev Center between 2017and 2022. The hHGG cohort included nine females and one male ranging in age from one week to 22 months. RTK-fusions were detected in all (ROS1 - 4, ALK - 2,NTRK1 – 2, NTRK3 - 1, and EGFR - 1). In one of thesecases, the diagnosis was made retrospectively in a patient initially diagnosed with anaplastic ependymoma who died during treatment. Out of the nine remaining hHGG patients, four (ROS1 - 3, NTRK3-1) experienced rapid progressive disease (PD) duringconventional chemotherapy and one pt (ROS1) after RT. These five pts received targeted therapy with entrectinib with initial good responses in all cases (CR-2, PR-3); one of these patients (ROS1) experienced PD after 7 months of targeted therapy and died of disease. Molecular genetic analysis after the second operationin this case revealed an acquired ROS1 G2032R mutation. Treatment-related adverse events on entrectinib therapy were detected in two patients and included bone fractures and neutrophil count decrease in one case and decrease left ventricular ejection fraction in another patient. Median duration of targeted therapy was 7 months (range, 3-33). From those pts who received only chemotherapy – 2 pts are alive with CR and 1 pt died from complication of CT. All patients with DIGG are alive without signs of progression after surgery alone. Median follow-up time is 19 months (range, 5-64). Molecular genetic analysis revealed MAPK-pathway alterations in each case (rearrangements of NTRK1-1, ROS-1, RAF1-1, BRAF-1), respectively. Patients with infant hHGG demonstrate an aggressive course on conventional therapy, especially in cases with ROS1-positive tumors. Targeted therapy may be an effective treatment option but required close monitoring for toxicity and resistance.