What is the best approach for managing symptoms in patients with leptomeningeal (leptomeningeal metastases) metastases during the dying process?

Managing the Dying Process in Patients with Leptomeningeal Metastases

For patients with leptomeningeal metastases and life expectancy less than 1 month, the focus should be on best supportive care and palliative measures rather than disease-directed therapy. 1

Prognosis and Treatment Decision Framework

The most critical factor determining management approach is estimated life expectancy:

• Life expectancy < 1 month: Best supportive care is the primary recommendation, with consideration of palliative radiotherapy only if symptomatic benefit clearly outweighs treatment-related toxicities 1
• Median survival with leptomeningeal metastases: Even with aggressive treatment, survival ranges from 2-6 months in controlled trials, with breast cancer patients achieving 6-7 months in some series 1, 2, 3
• Untreated patients: Median survival of only 2-6 weeks 2, 4

Symptom-Directed Palliative Management

For Symptomatic Relief

Whole brain radiotherapy (WBRT) with memantine may be offered for symptomatic brain leptomeningeal metastases if there is reasonable expectation of symptomatic improvement that outweighs acute toxicities including fatigue and neurocognitive decline 1

• Standard palliative dose: 30-36 Gy in 10-12 daily fractions to symptomatic sites 1
• Radiotherapy provides more rapid symptom relief than chemotherapy 1
• Consider focal radiotherapy for specific symptomatic areas (cranial neuropathies, spinal cord compression) rather than craniospinal irradiation in end-stage patients 1

For Elevated Intracranial Pressure and Hydrocephalus

CSF drainage procedures can rapidly alleviate symptoms related to increased intracranial pressure:

• Symptoms include headache, nausea, vomiting, and mental status changes 1
• Lumboperitoneal shunt is less invasive than ventriculoperitoneal shunt and may be appropriate for frail end-stage patients with symptomatic hydrocephalus 5
• Adjustable pressure valves allow symptom management as clinical status changes 5
• Shunting should be performed for symptomatic communicating hydrocephalus that does not clear rapidly with treatment 1

Corticosteroids

Dexamethasone for best supportive care to reduce cerebral edema and inflammation 6

Disease-Directed Therapy Considerations (Only if Life Expectancy ≥ 1 Month)

If performance status is reasonable (KPS ≥ 70) and life expectancy exceeds 1 month, limited disease-directed therapy may be considered 1, 6:

Intrathecal Chemotherapy

• Not recommended in the dying process when life expectancy is < 1 month 1
• Primarily effective for small leptomeningeal deposits and floating tumor cells, not bulky disease 2
• Requires adequate performance status and CSF flow without obstruction 1, 2

Systemic Therapy

• May be considered only if patient has good performance status and effective systemic options available 1
• High-dose systemic methotrexate or other CNS-penetrating agents may obviate need for intrathecal therapy in select cases 1, 3

Key Prognostic Factors to Guide Decision-Making

Favorable prognostic indicators (if present, may justify more aggressive palliative measures) 6:

• KPS ≥ 70%
• Age ≤ 55 years
• CSF protein < 100 mg/dL
• Mild to moderate neurologic deficits (NFS ≤ 2)
• Absence of CSF flow obstruction
• Availability of effective systemic therapy options

Poor prognostic indicators (favor comfort-focused care only) 6:

• Poor performance status (KPS < 70%)
• Severe neurologic deficits
• CSF flow obstruction
• No available systemic therapy options

Critical Pitfalls to Avoid

• Do not pursue intrathecal chemotherapy in patients with symptomatic hydrocephalus requiring ventriculoperitoneal shunt or with ventricular devices without on/off options 1
• Avoid combined modality therapy (radiotherapy plus chemotherapy) in dying patients due to increased risk of leukoencephalopathy and myelosuppression 1
• Do not administer intrathecal chemotherapy in non-isovolumetric manner, as this can cause herniation 2
• Recognize that radiotherapy to sites of CSF flow obstruction must precede intrathecal therapy if such therapy is being considered 1

Practical Symptom Management Algorithm

1. Assess life expectancy and performance status using KPS and neurologic function scale 1, 6

2. If life expectancy < 1 month or KPS < 70%:

   • Best supportive care with dexamethasone 6
   • Consider CSF drainage for symptomatic hydrocephalus 5
   • WBRT only if clear symptomatic benefit expected and patient/family understand limited goals 1

3. For specific symptoms:

   • Headache/nausea/vomiting: CSF drainage, dexamethasone, consider WBRT 1, 5
   • Cranial nerve palsies: Focal radiotherapy to skull base if life expectancy permits 1
   • Spinal symptoms: Involved-field radiotherapy to symptomatic spinal segments 1
   • Pain: Standard palliative pain management plus dexamethasone 1

4. Discuss goals of care explicitly with patient and family, emphasizing that treatment is palliative and focused on quality of life, not disease control 1