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Published on: August 2, 2022
Evolving treatment paradigms for melanoma brain metastases: A systematic review of current modalities
Krista-Gaie Grant1, Yasmine Gillespie1, Armin Karamian2
1University of Florida, College of Medicine, Gainesville, FL, United States.
Background:
Melanoma brain metastases (MBM) affect up to 60 % of advanced melanoma cases and are associated with poor prognosis and significant neurologic morbidity. Recent advancements include immune checkpoint inhibitors (ICIs), BRAF/MEK-targeted inhibitors, stereotactic radiosurgery (SRS), and combination strategies, but optimal integration of these modalities remains unclear.
Methods:
We conducted a systematic review of studies published from 2009 to 2024 across PubMed, Scopus, and Web of Science. Included studies reported outcomes such as overall survival (OS), progression-free survival (PFS), intracranial response rate (IRR), and adverse events (AEs) in patients receiving systemic therapies, radiotherapy, surgery, or combination regimens. Risk of bias was assessed using the Cochrane, Newcastle-Ottawa, and Joanna Briggs Institute (JBI) tools.
Results:
70 studies met inclusion criteria. ICIs demonstrated durable responses, especially in asymptomatic patients not requiring corticosteroids. Nivolumab and pembrolizumab offered superior response rates and OS versus chemotherapy. Targeted therapies like dabrafenib and vemurafenib produced rapid intracranial control but less durable responses. SRS improved local control with low neurotoxicity and showed synergy when combined with ICIs. Triple-modality strategies (surgery+SRS+systemic therapy) showed the most promising survival outcomes in selected patients. Median OS (mOS) ranged from 5.3 to 15.9 months, depending on treatment and patient selection.
Conclusion:
Management of MBM is shifting toward multimodal approaches integrating local and systemic therapies. ICIs, particularly when paired with SRS, remain central to treatment. Prospective, biomarker-driven studies are needed to clarify treatment sequencing, maximize intracranial control, and improve quality of life (QoL).
Insights
Treatment for melanoma brain metastases (MBM) is evolving towards multimodal strategies. Immune checkpoint inhibitors (ICIs) combined with stereotactic radiosurgery (SRS) show promise for improving survival and intracranial control in MBM patients.
Area of Science:
- Oncology
- Neurology
- Medical Research
Background:
- Melanoma brain metastases (MBM) present a significant challenge in advanced melanoma, leading to poor prognosis and neurological deficits.
- Optimal integration of emerging treatments like immune checkpoint inhibitors (ICIs), targeted therapies, and stereotactic radiosurgery (SRS) for MBM remains unclear.
Purpose of the Study:
- To systematically review and synthesize evidence on current treatment modalities for melanoma brain metastases.
- To evaluate the efficacy and safety of systemic therapies, radiotherapy, surgery, and combination regimens for MBM.
Main Methods:
- A systematic review of studies published between 2009 and 2024 from PubMed, Scopus, and Web of Science.
- Inclusion of studies reporting overall survival (OS), progression-free survival (PFS), intracranial response rate (IRR), and adverse events (AEs).
- Risk of bias assessment using established tools (Cochrane, Newcastle-Ottawa, JBI).
Main Results:
- Immune checkpoint inhibitors (ICIs) demonstrated durable responses, particularly in asymptomatic patients.
- Targeted therapies offered rapid intracranial control, while SRS improved local control with low toxicity and synergistic effects with ICIs.
- Triple-modality strategies (surgery+SRS+systemic therapy) showed the most promising survival outcomes in selected patients, with median OS ranging from 5.3 to 15.9 months.
Conclusions:
- The management of MBM is increasingly adopting multimodal approaches integrating local and systemic therapies.
- Immune checkpoint inhibitors (ICIs) combined with stereotactic radiosurgery (SRS) are central to current treatment paradigms.
- Further prospective, biomarker-driven research is essential to optimize treatment sequencing, maximize intracranial control, and enhance patient quality of life (QoL).
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