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Toxicity and outcomes of melanoma brain metastases treated with stereotactic radiosurgery: the risk of subsequent symptomatic intralesional hemorrhage exceeds that of radiation necrosis

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Abstract

Purpose

We aimed to assess the outcomes and patterns of toxicity in patients with melanoma brain metastases (MBM) treated with stereotactic radiosurgery (SRS) with or without immunotherapy (IO).

Methods

From a prospective registry, we reviewed MBM patients treated with single fraction Gamma Knife SRS between 2008 and 2021 at our center. We recorded all systemic therapies (chemotherapy, targeted therapy, or immunotherapy) administered before, during, or after SRS. Patients with prior brain surgery were excluded. We captured adverse events following SRS, including intralesional hemorrhage (IH), radiation necrosis (RN) and local failure (LF), as well as extracranial disease status. Distant brain failure (DBF), extracranial progression-free survival (PFS) and overall survival (OS) were determined using a cumulative Incidence function and the Kaplan–Meier method.

Results

Our analysis included 165 patients with 570 SRS-treated MBM. Median OS for patients who received IO was 1.41 years versus 0.79 years in patients who did not (p = 0.04). Ipilimumab monotherapy was the most frequent IO regimen (30%). In the absence of IO, the cumulative incidence of symptomatic (grade 2 +) RN was 3% at 24 months and remained unchanged with respect to the type or timing of IO. The incidence of post-SRS g2 + IH in patients who did not receive systemic therapy was 19% at 1- and 2 years compared to 7% at 1- and 2 years among patients who did (HR: 0.33, 95% CI 0.11–0.98; p = 0.046). Overall, neither timing nor type of IO correlated to rates of DBF, OS, or LF. Among patients treated with IO, the median time to extracranial PFS was 5.4 months (95% IC 3.2 – 9.1).

Conclusion

The risk of g2 + IH exceeds that of g2 + RN in MBM patients undergoing SRS, with or without IO. IH should be considered a critical adverse event following MBM treatments.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Princess Margaret Cancer Centre, University Health Network, Toronto, Canada

    Paola A. Jablonska, Normand Laperriere, Barbara-Ann Millar, Tatiana Conrad & David B. Shultz

  2. Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada

    Thiago Muniz, Mauricio Ribeiro & Marcus Butler

  3. Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, ON, M5G 2M9, Canada

    Zhihui Amy Liu & Xiang Y. Ye

  4. Department of Medical Science, University of Toronto Institute and Princess Margaret Cancer Research Tower, Toronto, Canada

    Kaviya Devaraja

  5. Department of Neurosurgery, Toronto Western Hospital, Toronto, Canada

    Paul Kongkham

  6. 700 University Avenue, 7Th Floor (Room 7-401), Toronto, ON, M5G 1Z5, Canada

    David B. Shultz

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  1. Paola A. Jablonska
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Paola Anna Jablonska, David Shultz, Xiang Y. Ye, and Kaviya Devaraja. The first draft of the manuscript was written by Paola Anna Jablonska and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to David B. Shultz.

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Jablonska, P.A., Muniz, T., Ribeiro, M. et al. Toxicity and outcomes of melanoma brain metastases treated with stereotactic radiosurgery: the risk of subsequent symptomatic intralesional hemorrhage exceeds that of radiation necrosis. J Neurooncol 164, 199–209 (2023). https://doi.org/10.1007/s11060-023-04404-5

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