Treatment for Brain Metastases

Surgery may be offered for patients with brain metastases, considering the following factors: Patients with suspected brain metastases without a primary cancer diagnosis may benefit from surgery to attain a diagnosis and undergo tumor removal.

• Patients with large tumors with mass effect likely benefit from surgery.
• Patients with multiple brain metastases and/or uncontrolled systemic disease are less likely to benefit from surgery unless the remaining disease is controllable via other measures.

Where surgery is considered, no recommendation regarding the method of resection (piecemeal vs. en bloc) can be made.

No recommendation can be made for or against LITT.

Patients with symptomatic brain metastases should be offered local therapy (radiosurgery/radiation therapy and/or surgery) as recommended in this guideline regardless of the systemic therapy used for the systemic disease.

For patients with asymptomatic brain metastases, local therapy should not be deferred unless deferral is specifically recommended in Recommendations 2.3 through 2.7 of this guideline. The decision to defer local therapy should be based on a multi-disciplinary discussion (neuro or medical oncology, neurosurgery, and radiation oncology) of the potential benefits and harms the patient may experience.

Osimertinib or icotinib may be offered to patients with asymptomatic brain metastases from EGFR-mutant NSCLC. If these agents are used, local therapy may be delayed until there is evidence of intracranial progression.

Alectinib, brigatinib, or ceritinib may be offered to patients with asymptomatic brain metastases from ALK-rearranged NSCLC. If these agents are used, local therapy may be delayed until there is evidence of intracranial progression.

Pembrolizumab may be offered to patients with asymptomatic brain metastases from immunotherapy-naive PD-L1 expressing NSCLC who are also receiving pemetrexed and a platinum agent.

Ipilimumab plus nivolumab (for all patients regardless of BRAF status) or dabrafenib plus trametinib (for patients with BRAF-V600E mutation) may be offered to patients with asymptomatic brain metastases from melanoma. If these agents are used, local therapy may be delayed until there is evidence of intracranial progression.

The combination of tucatinib, trastuzumab, and capecitabine may be offered to patients with HER2 positive metastatic breast cancer who have asymptomatic brain metastases and have progressed on previous trastuzumab, pertuzumab, and/or trastuzumab emtansine-based therapy. If these agents are used, local therapy may be delayed until there is evidence of intracranial progression.

Radiation therapy should not be offered to patients with asymptomatic brain metastases who have:

1. Performance status KPS ≤50 or less, OR
2. Performance status KPS <70 and no systemic therapy options.

SRS alone (as opposed to WBRT or combination of WBRT and SRS) should be offered to patients with 1 to 4 unresected brain metastases, excluding small cell carcinoma.

SRS alone should be offered to patients with 1 to 2 resected brain metastases if the surgical cavity can be safely treated and considering the extent of remaining intracranial disease.

SRS, WBRT, and the combination of SRS plus WBRT are all reasonable options for patients with more than 4 unresected or more than 2 resected brain metastases and better performance status (e.g., KPS ≥70). SRS may be preferred for patients with better prognosis or where systemic therapy that is known to be active in the central nervous system is available.

Memantine and hippocampal avoidance should be offered to patients who will receive WBRT and have no hippocampal lesions and 4 months or more expected survival.

Radiation sensitizing agents should not be offered to patients.

For patients who will receive both radiation therapy and surgery, no recommendation regarding the specific sequence of therapy can be made.