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The outcome of central nervous system hemangioblastomas in Von Hippel-Lindau (VHL) disease treated with belzutifan: a single-institution retrospective experience

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Abstract

Purpose

Belzutifan is a Hypoxia Inducible Factor 2-alpha inhibitor approved in 2021 by the FDA for the treatment of renal cell carcinoma (RCC) in patients with Von-Hippel Landau (VHL) disease. These patients can also present with central nervous system (CNS) hemangioblastomas (HBs). We aim to study the effectiveness and adverse effects of belzutifan for CNS HBs, by reporting our preliminary institutional experience.

Methods

We present a series of VHL patients with CNS HBs undergoing treatment with belzutifan for RCC. All the included patients met the RECIST inclusion criteria. The clinical and radiological outcome measures included: Objective response rate (ORR), time-to-response (TTR), adverse events (AE), and patient response. Patient response was classified as partial response (PR), complete response (CR), progressive disease (PD), or stable disease (SD).

Results

Seven patients with 25 HBs were included in our study. A belzutifan dose of 120 mg/day PO was administered for a median of 13 months (range 10–17). Median follow up time was 15 months (range 10–24). An ORR of 71% was observed. The median TTR was 5 months (range: 1–10). None of the patients showed CR, while 5 patients (71.4%) showed PR and 2 (28.5%) showed SD. Among patients with SD the maximum tumor response was 20% [increase/decrease] of the lesion diameter. All the patients experienced decreased hemoglobin concentration, fatigue, and dizziness. None of the patients experienced severe anemia (grade 3–4 CTCAE).

Conclusion

Belzutifan appears to be an effective and safe treatment for CNS hemangioblastoma in VHL patients. Further clinical trials to assess the long-term effectiveness of the medication are required.

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Authors and Affiliations

  1. Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Aroosa Zamarud, Neelan J. Marianayagam, David J. Park, Ulas Yener, Kelly H. Yoo, Antonio Meola & Steven D. Chang

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  1. Aroosa Zamarud
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  2. Neelan J. Marianayagam
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  3. David J. Park
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  4. Ulas Yener
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  5. Kelly H. Yoo
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  6. Antonio Meola
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  7. Steven D. Chang
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Contributions

The list of authors and their individual contributions are listed below:Aroosa Zamarud: Collected the data, made the box plot and spaghetti chart, and drafted the manuscript. Approved the final manuscript.Neelan J. Marianayagam: Editted the manuscript after the initial draft. Helped with the figures. Approved the final manuscript.David J. Park: Critically reviewed the manuscript and provided suggestions. Approved the final manuscript.Ulas Yener: Critically reviewed the manuscript and provided suggestions. Approved the final manuscript.Kelly H. Yoo: Critically reviewed the manuscript and provided suggestions. Approved the final manuscript.Antonio Meola: Contributed to the central idea of the project, critically reviewed the manuscript and provided suggestions. Approved the final manuscript.Steven D. Chang: Provided the central idea for the project and edited and improved the manuscript after the initial draft.Approved the final manuscript.

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Correspondence to Steven D. Chang.

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Zamarud, A., Marianayagam, N.J., Park, D.J. et al. The outcome of central nervous system hemangioblastomas in Von Hippel-Lindau (VHL) disease treated with belzutifan: a single-institution retrospective experience. J Neurooncol 165, 373–379 (2023). https://doi.org/10.1007/s11060-023-04496-z

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