Belzutifan, a hypoxia-inducible factor-2α (HIF-2α) inhibitor approved for von Hippel–Lindau (VHL) disease–related tumors, induces radiological responses in hemangioblastomas, but the timing and extent of early changes are not well defined. A 9-year-old girl was admitted with nausea, vomiting, and ataxia. Brain MRI showed a cystic cerebellar mass, which was fully resected; histology and genetic testing confirmed VHL. Follow-up revealed a small stable cerebellar residual. Two years later, she developed multiple retinal hemangioblastomas (RH) with major visual decline and new cerebellar nodules. Argon laser photocoagulation provided no lasting benefit, prompting initiation of belzutifan. The drug was well tolerated over the first six months, with only grade 1 anemia. Psychological assessments documented excellent adaptation, preserved quality of life, stable daily routines, and regular school attendance. MRI demonstrated a marked reduction in two of the three cerebellar nodules as early as day 15 of cycle 1, followed by progressive shrinkage and stabilization by cycle 4. No new RH emerged, and visual acuity improved within eight weeks of treatment and then remained stable. This case highlights an unusually rapid radiological response of VHL-associated cerebellar and retinal hemangioblastomas shortly after belzutifan initiation, suggesting that imaging performed soon after treatment onset may detect changes earlier than commonly reported. A slight but measurable improvement in visual acuity was also observed, despite the overall structural stability of the retinal hemangioblastomas. These findings support the potential value of early radiological and functional assessment in selected patients receiving HIF-2α inhibition.
Pagliara et al. (2026) studied this question.