Belzutifan as a possible novel treatment for sporadic central nervous system hemangioblastoma: a report of two cases and focused review of the literature

Objective To provide a review of hemangioblastoma treatment and to report a new treatment option for sporadic, non-von Hippel-Lindau (VHL) associated central nervous system hemangioblastomas (CNS-HBs). Background Belzutifan is FDA-approved for the treatment of VHL associated cancers including renal cell carcinoma, pancreatic neuroendocrine tumors and CNS-HBs as a hypoxia-inducible factor-2α inhibitor. The efficacy of belzutifan is unclear for sporadic, non-vHL associated CNS-HBs, a disease entity with limited systemic options. Discussion A 23-year-old female presented with a posterior fossa hemangioblastoma which was then resected. At initial recurrence, she completed fractionated radiation therapy with a positive radiographic response. She had multiple symptomatic radiographic recurrences that underwent additional resection. After her fourth recurrence, surgery as well as radiation were not felt to be a reasonable option. Belzutifan 120 mg daily was started. Two months later, she had radiographic improvement with reduction in size of the posterior fossa hemangioblastoma, which has been maintained after 24 months of treatment. A second case is a 33-year-old male with a C7-T1 non-vHL hemangioblastoma that was resected and radiated at recurrence. Nine years later, the patient had radiographic progression that was not amenable to surgery or radiation. Belzutifan was started, which resulted in radiographic and subjective symptomatic improvement. Conclusion We present two cases of sporadic recurrent hemangioblastoma with radiographic improvement to belzutifan, along with a review of hemangioblastoma treatment. To the best of our knowledge, these are the first two cases of radiographic improvement in sporadic, non-VHL associated CNS-HB from the use of belzutifan.