287 Belzutifan Reduces Intracranial Von-Hippel Lindau-Associated Hemangioblastoma Burden in a Rapid and Sustained Manner: A Volumetric Analysis

INTRODUCTION: Hemangioblastomas frequently arise in the nervous system of Von-Hippel Lindau (VHL) patients and are a significant cause of morbidity and mortality. These are benign, highly vascularized lesions that induce symptoms through mass effect. Historically, VHL patients have required frequent surgeries to reduce tumor burden as hemangioblastomas become symptomatic. Belzutifan, an HIF-2α inhibitor, received FDA approval in August 2021 as the first medication for VHL-associated CNS hemangioblastomas. METHODS: VHL patients with CNS hemangioblastomas =3 mm in diameter who received belzutifan were included in this study. Tumor volumes were manually segmented (Elements Smartbrush, Brainlab A/G, Munich, Germany) on all available MRIs from three years before beginning belzutifan treatment through the present day. Lesion location, presence of peritumoral edema, and cystic morphology were determined on each image. RESULTS: We followed 21 VHL patients (13 female, 62%) with 65 tumors. The average age at belzutifan initiation was 40.9±14.7 years, and the average duration of belzutifan treatment at last imaging was 662±477 days. Tumors were in the cerebellar hemispheres (n=40, 62%), vermis (n=14, 22%) and brainstem (n=11, 17%). Mean time to maximum response was 368±320 days and tumors shrank by 72±26%. Twelve tumors had complete resolution (18.5%), while five tumors (8%) grew during belzutifan treatment. All tumors were smaller at last imaging than at treatment initiation. The percentage of all tumors with cyst (34% vs 62% without cyst, p=0.036) and peritumoral edema decreased (74% pre-belzutifan vs 53% post-belzutifan, p=0.0001). CONCLUSIONS: Belzutifan reduces tumor volume in VHL-associated hemangioblastoma. It offers strong therapeutic value as a non-surgical alternative for patients with this disease.