Is local therapy recommended?

Local Therapy for Brain Metastases: Recommendations and Approach

Local therapy should be offered to patients with brain metastases, particularly those who are symptomatic, as it significantly impacts morbidity, mortality, and quality of life outcomes. 1

When Local Therapy is Indicated

Symptomatic Brain Metastases

• Patients with symptomatic brain metastases should always be offered local therapy (radiosurgery, radiation therapy, and/or surgery) regardless of the systemic therapy being used 1
• This recommendation is based on high-quality evidence and carries a strong recommendation strength 1
• Local therapy should not be deferred in symptomatic patients even when systemic therapy has CNS activity

Asymptomatic Brain Metastases

• For patients with asymptomatic brain metastases, local therapy should generally not be deferred unless specific exceptions apply 1
• Deferral of local therapy may only be considered in specific circumstances:
  • When there is compelling evidence of CNS activity for the specific systemic therapy being used
  • When the patient has certain tumor types with targeted therapies (e.g., ALK-rearranged NSCLC treated with alectinib, brigatinib, or ceritinib) 1
  • When a multidisciplinary discussion has occurred involving neuro/medical oncology, neurosurgery, and radiation oncology

Decision-Making Algorithm for Local Therapy

1. Assess symptom status:

   • If symptomatic → Proceed with local therapy immediately
   • If asymptomatic → Continue to next step

2. Evaluate tumor characteristics:

   • Determine tumor type, location, size, and number of metastases
   • Consider intracerebral location (eloquent vs. non-eloquent brain regions)
   • Assess for specific genetic markers that might predict response to systemic therapy

3. Consider systemic therapy context:

   • Is the patient receiving a therapy with proven CNS activity?
   • Does the patient have a tumor type specifically mentioned in recommendations 2.3-2.7 of the ASCO-SNO-ASTRO guideline? 1
   • If not, local therapy should not be deferred

4. Multidisciplinary discussion:

   • Any decision to defer local therapy must involve multidisciplinary input
   • Weigh potential benefits and harms the patient may experience

Pitfalls and Caveats

• Lack of formal definition of "symptomatic": Clinical judgment is required to determine what constitutes symptomatic disease 1
• Monitoring requirements: If local therapy is deferred, close monitoring for progression is crucial to ensure local therapy can be offered when most valuable 1
• Evidence limitations: Evidence for deferring local therapy is often from smaller, non-randomized studies 1
• Location considerations: Even asymptomatic metastases in critical brain regions may benefit from local therapy to prevent future neurologic deficits 1

Special Considerations

• Some patients with mild symptoms controlled with supportive therapy (e.g., steroids) may reasonably defer local therapy while receiving a CNS-active systemic therapy 1
• The evidence regarding systemic therapy for brain metastases is constantly evolving, and recommendations may change as CNS activity is demonstrated for other agents 1
• Patient preferences should be considered, but the evidence strongly supports local therapy for most patients with brain metastases to improve mortality and quality of life outcomes

The decision to use local therapy should be guided by the strongest evidence available, with a focus on improving survival and quality of life for patients with brain metastases.