What are the management options and prognosis for an adult patient with a history of melanoma, now presenting with metastasis to the brain, a clot in the superior sagittal vein, and a larger brain bleed in the left temporal lobe around the melanoma metastasis?

Management of Melanoma Brain Metastasis with Superior Sagittal Sinus Thrombosis and Intratumoral Hemorrhage

This patient requires urgent multidisciplinary neurosurgical evaluation for potential resection of the hemorrhagic metastasis, followed by systemic immunotherapy with anti-PD-1 agents (pembrolizumab or nivolumab), as checkpoint inhibitors can be safely used in patients with symptomatic brain metastases and have shown significant efficacy in this setting. 1, 2, 3

Immediate Management Priorities

Neurosurgical Considerations

• Surgical resection should be strongly considered as first-line therapy for this solitary symptomatic brain metastasis with hemorrhage, as surgery alleviates symptoms, provides local disease control, and offers potential for long-term survival when followed by adjuvant immunotherapy 1, 4, 5
• The presence of hemorrhage and mass effect from the temporal lobe lesion makes this patient a candidate for craniotomy rather than stereotactic radiosurgery 1, 6
• Complete (R0) resection should be the surgical goal, as incomplete resection changes the treatment paradigm 1, 4

Management of Superior Sagittal Sinus Thrombosis

• Systemic anticoagulation for the venous sinus thrombosis is safe and should be initiated despite the brain metastasis and hemorrhage 7
• A retrospective study of 74 melanoma patients with brain metastases and venous thromboembolism found that anticoagulation did not significantly increase intracranial hemorrhage risk (4% vs 0%, P=1.00) and showed a trend toward improved survival (4.2 vs 1.2 months, P=0.06) 7
• The hemorrhage around the metastasis is likely tumor-related rather than anticoagulation-related, and withholding anticoagulation poses greater mortality risk from pulmonary embolism 7

Post-Surgical Systemic Therapy

First-Line Immunotherapy After Resection

• Following complete resection, adjuvant nivolumab (240 mg IV every 2 weeks or 480 mg IV every 4 weeks for up to 1 year) or pembrolizumab should be initiated 4
• Anti-PD-1 monotherapy is the preferred approach based on ASCO guidelines, demonstrating superior efficacy compared to ipilimumab alone 2, 3
• BRAF mutation testing should be performed on the resected tumor specimen, as this will guide future treatment decisions if disease progresses 1, 3

Alternative if Surgery Not Feasible

• If the patient is not a surgical candidate due to location, comorbidities, or patient preference, stereotactic radiosurgery combined with systemic immunotherapy is the next best option 1
• For symptomatic brain metastases, the combination of ipilimumab plus nivolumab has shown significant efficacy with response rates of approximately 70%, though toxicity is substantially higher than monotherapy 1, 3
• Stereotactic radiosurgery is strongly preferred over whole-brain radiotherapy to preserve neurocognitive function 1

Prognosis and Expected Outcomes

Survival Expectations

• Historical median survival for melanoma brain metastases is 4-6 months with supportive care alone 6, 5
• With aggressive multimodal treatment (surgery + immunotherapy), selected patients can achieve long-term disease control and potential cure 4, 8
• The presence of hemorrhage does not preclude good outcomes if the lesion is resected and systemic therapy is effective 7, 8

Factors Affecting Prognosis

• Good performance status (ECOG 0-1) is essential for aggressive treatment and improved outcomes 1, 4
• Solitary brain metastasis has better prognosis than multiple lesions 1, 6
• Control of extracranial disease with systemic therapy is critical for overall survival 1

Critical Management Considerations

Multidisciplinary Team Approach

• All decisions must be made in an interdisciplinary tumor board with neurosurgery, medical oncology, radiation oncology, and neuroradiology representation 1, 3, 4
• Treatment at centers with extensive melanoma brain metastasis experience is strongly recommended 1, 3

Monitoring Requirements

• Brain MRI should be performed every 3 months for the first 2 years, then every 6 months for years 3-5 1, 4
• Monitor closely for immune-related adverse events including colitis, hepatitis, pneumonitis, endocrinopathies, and severe infections (particularly tuberculosis) 2, 3, 4
• Neurological assessment should accompany each imaging study 1

Common Pitfalls to Avoid

• Do not delay neurosurgical consultation - hemorrhagic brain metastases can deteriorate rapidly and require urgent intervention 1
• Do not withhold anticoagulation due to fear of hemorrhage, as the thrombosis poses greater mortality risk and anticoagulation is safe in this population 7
• Do not use whole-brain radiotherapy as initial treatment - it compromises neurocognitive function without survival benefit and should be reserved for multiple unresectable lesions 1
• Do not delay immunotherapy initiation after surgery, as prompt treatment optimizes outcomes 2, 3
• Do not use high-dose interleukin-2 in patients with active brain involvement, as it is contraindicated and may worsen cerebral edema 1

Second-Line Options if Disease Progresses

• If progression occurs on anti-PD-1 monotherapy, switch to ipilimumab plus nivolumab combination (21% response rate, 55% 12-month survival) 3
• For BRAF-mutated melanoma, BRAF/MEK inhibitor combinations (dabrafenib/trametinib) are options after immunotherapy failure 1, 3
• Repeat stereotactic radiosurgery can be considered for limited progressive lesions (<5-10 lesions, <3 cm each) 1
• Clinical trial enrollment should be prioritized given the rapidly evolving treatment landscape 2, 3, 4