Management of newly diagnosed melanoma brain metastases

The approach to brain metastases assumes that the most likely diagnosis is metastatic melanoma, or that the diagnosis has been confirmed pathologically. However, not all new tumors or mass lesions in patients with melanoma are metastases, and alternative diagnoses should be considered before treating empirically, particularly for single masses and in the absence of systemic metastatic disease. Surgery may be indicated in such situations before proceeding with additional therapy, even for relatively small or asymptomatic tumors.

CNS: central nervous system; SRS: stereotactic radiosurgery; RT: radiation therapy; PD-1: programmed cell death receptor 1.
* Locoregional CNS therapy includes surgical resection, SRS, and/or RT.
¶ Optimal patients have limited comorbidities, appropriate performance status, and extracranial involvement.
Δ Some patients may be candidates for systemic therapy following locoregional CNS therapy.
◊ Patients with a single brain metastasis are candidates for surgical resection. SRS may be an option for patients who are not candidates for surgery, have multiple brain metastases, and/or have lesions that are surgically inaccessible or in eloquent areas.
§ Postoperative RT to the surgical cavity may be deferred in selected patients. Refer to UpToDate topics on melanoma brain metastases. Close monitoring for disease recurrence with periodic neuroimaging is appropriate regardless of treatment approach.
¥ This approach may be offered to patients with a short life expectancy, in whom systemic therapy is unlikely to offer substantial benefit, and/or large intracranial tumor burden.
‡ In patients who have previously received prior immunotherapy and BRAF/MEK inhibitors, the choice and sequence of definitive CNS therapy depends primarily on the number, size, and location of brain metastases, as well as the extent of CNS symptoms and overall performance status.
† Combined BRAF/MEK inhibition is an alternative option to combined immunotherapy in patients with BRAF V600 mutations requiring rapid extracranial disease response or in patients who are ineligible for immunotherapy.
** If BRAF/MEK inhibition is offered as subsequent treatment after immunotherapy for progressive intracranial disease, use should be limited to patients with small and minimally symptomatic brain metastases.
¶¶ For patients with prior exposure to a single-agent PD-1 inhibitor, some experts offer combination immunotherapy with nivolumab plus ipilimumab, although data are limited for this approach. Clinical trials evaluating immunotherapy in this setting are encouraged.

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Management of newly diagnosed melanoma brain metastases