How should multiple brain metastases (mts) be treated?

From the Guidelines

Treatment of multiple brain metastases should be individualized, but for patients with numerous metastases, whole brain radiation therapy (WBRT) may be recommended, typically delivered as 30 Gy in 10 fractions or 20 Gy in 5 fractions, as suggested by the most recent and highest quality study 1.

Key Considerations

• The decision to treat multiple brain metastases involves a multidisciplinary approach, considering the patient's overall condition, primary cancer type, number and location of metastases, and symptoms.
• Stereotactic radiosurgery (SRS) is often preferred for patients with limited metastases (typically 1-4), delivering precise, high-dose radiation to the tumors while sparing surrounding brain tissue.
• Surgical resection is considered for large symptomatic lesions (>3 cm), those causing significant mass effect, or when a tissue diagnosis is needed.
• Systemic therapy options depend on the primary cancer type and may include chemotherapy, targeted therapy, or immunotherapy.
• Supportive care with corticosteroids and anticonvulsants helps manage cerebral edema and symptoms.

Treatment Options

• WBRT: 30 Gy in 10 fractions or 20 Gy in 5 fractions for patients with numerous metastases.
• SRS: for patients with limited metastases, delivering 15-24 Gy in a single fraction.
• Surgery: for large symptomatic lesions or those causing significant mass effect.
• Systemic therapy: depending on the primary cancer type, such as chemotherapy, targeted therapy, or immunotherapy.

Recent Guidelines

• The 2022 ASCO-SNO-ASTRO guideline recommends SRS alone for patients with one to four unresected brain metastases, excluding small-cell lung carcinoma 1.
• The 2022 ASCO guideline update recommends WBRT plus memantine and hippocampal avoidance for patients with diffuse disease and/or extensive metastases and a more favorable prognosis 1.

From the FDA Drug Label

The baseline demographic and disease characteristics of the overall trial population were: median age 62 years (range: 20-90 years), ≥75 years old (15%), female (64%), White (32%), Asian (65%), never smoker (68%), WHO performance status 0 or 1 (100%) Fifty-four percent (54%) of patients had extra-thoracic visceral metastases, including 34% with central nervous system (CNS) metastases (including 11% with measurable CNS metastases) and 23% with liver metastases. In a supportive analysis of PFS according to BICR, median PFS was 11 months in the TAGRISSO arm compared to 4.2 months in the chemotherapy arm (HR 0.28; 95% CI: 0.20,0. 38). Of 419 patients, 205 (49%) had baseline brain scans reviewed by BICR; this included 134 (48%) patients in the TAGRISSO arm and 71 (51%) patients in the chemotherapy arm. Assessment of CNS efficacy by RECIST v1. 1 was performed in the subgroup of 46/419 (11%) patients identified by BICR to have measurable CNS lesions on a baseline brain scan.

Treatment of Multiple Brain Metastases:

• The provided drug labels do not directly address the treatment of multiple brain metastases.
• However, the labels mention that 34% of patients had CNS metastases, including 11% with measurable CNS metastases, and that assessment of CNS efficacy was performed in a subgroup of patients with measurable CNS lesions.
• The labels also mention that TAGRISSO demonstrated a statistically significant improvement in PFS compared to chemotherapy in patients with metastatic EGFR T790M mutation-positive NSCLC.
• No conclusion can be drawn on how multiple brain metastases should be treated based on the provided information 2 2.

From the Research

Treatment Options for Multiple Brain Metastases

• Whole-brain radiation therapy (WBRT) is often used to treat multiple brain metastases, but it can cause cognitive impairment in patients who are expected to live longer than 6 months 3.
• Stereotactic radiosurgery (SRS) is a recommended treatment option for patients with oligometastases (one to three metastases) or multiple lesions less than 3 to 4 cm, especially if the primary tumor is considered radiotherapy resistant 3, 4.
• SRS can also be used to treat extensive brain metastases (>10-15 metastases), and clinical trials are currently comparing WBRT with SRS for extensive disease 5.
• Surgical resection with or without postoperative WBRT should be considered for patients with brain metastases greater than 4 cm 3.

Comparison of WBRT and SRS

• A nonrandomized controlled trial found no significant difference in overall survival (OS) and intracranial progression-free survival (iPFS) between patients treated with SRS and those treated with WBRT for 4-10 brain metastases 6.
• SRS may allow for an increased risk of radiation necrosis or leptomeningeal disease dissemination after treatment, but preoperative SRS and multifraction radiotherapy can decrease this risk 5.
• Combining SRS with immune checkpoint inhibitors may improve patient outcomes 5.

Systemic Therapy and Supportive Care

• Systemic therapy, including targeted therapy and immunotherapy, is effective against brain metastases and may be an early choice, especially in patients with sensitive primary tumors 3.
• Corticosteroids or antiepileptic medications can be helpful in symptomatic patients, regardless of treatment goals 3.
• Best supportive care may be appropriate for patients with progressive systemic disease, limited treatment options, and poor performance status 3.