How to manage a patient with leptomeningeal carcinomatosis (cancer that has spread to the membranes surrounding the brain and spinal cord) who has an intracranial bleed?

Management of Intracranial Bleeding in Leptomeningeal Carcinomatosis

If intracranial bleeding is present in a patient with leptomeningeal carcinomatosis, intrathecal chemotherapy must be temporarily withheld, and the treatment approach should shift to supportive care with consideration of focal radiotherapy for symptomatic lesions only. 1

Immediate Management Priorities

Assess Bleeding Severity and Location

• Active intracranial hemorrhage is a contraindication to intrathecal chemotherapy until the bleeding has stabilized and resolved, as the procedure carries risk of worsening hemorrhage and the chemotherapy itself may impair hemostasis 1
• Determine if the bleeding is symptomatic (causing mass effect, increased intracranial pressure, or neurological deficits) versus asymptomatic microbleeds on imaging 2, 3
• Evaluate for CSF flow obstruction, which may require intervention before any chemotherapy can be considered 1

Anticoagulation Decision-Making

• If the patient requires anticoagulation for established VTE, this creates a critical clinical dilemma that requires careful risk-benefit assessment 2, 3
• The presence of intracranial bleeding does NOT automatically mean anticoagulation must be permanently discontinued if there is life-threatening VTE 3
• For patients with brain metastases (which may coexist with leptomeningeal disease), the risk of intracranial hemorrhage with therapeutic anticoagulation is probably not increased compared to baseline 2
• LMWH remains the preferred anticoagulant if anticoagulation is deemed necessary despite bleeding, as it is more controllable than other agents 2, 3

Modified Treatment Algorithm

Radiation Therapy as Primary Modality

• Focal radiotherapy becomes the primary treatment option when intrathecal chemotherapy is contraindicated 1
• Administer 30-36 Gy in 10-12 fractions to symptomatic sites of leptomeningeal disease 1
• Radiation provides faster symptom relief than chemotherapy and does not carry the same bleeding risks as intrathecal administration 1

Systemic Therapy Considerations

• Continue or initiate systemic therapy with CNS penetration, as this does not carry the same hemorrhage risk as intrathecal administration 1
• For HER2+ breast cancer: trastuzumab deruxtecan or tucatinib-based combinations 1
• For EGFR-mutated lung cancer: osimertinib or almonertinib 1
• For BRAF-mutated melanoma: BRAF/MEK inhibitors with CNS penetration 1

Supportive Care Measures

• If CSF flow obstruction with elevated intracranial pressure is present, ventriculoperitoneal shunt placement should be considered for symptom palliation 1
• This intervention can improve quality of life even when definitive cancer treatment is limited 1

Critical Pitfalls to Avoid

• Do NOT administer intrathecal chemotherapy in the presence of active intracranial bleeding - the risk of worsening hemorrhage and neurological deterioration outweighs any potential benefit 1
• Do NOT combine craniospinal radiation with intrathecal chemotherapy if bleeding resolves and both modalities are being considered, as this increases leukoencephalopathy risk 1
• Do NOT place inferior vena cava filters as an alternative to anticoagulation in patients with VTE and intracranial bleeding - they have high failure rates without improved survival 3

Prognosis Modification

• The presence of intracranial bleeding significantly worsens prognosis in leptomeningeal carcinomatosis, as it eliminates the most effective local treatment option (intrathecal chemotherapy) 1, 4
• Without intrathecal chemotherapy, median survival is typically limited to 6-8 weeks even with systemic therapy 1, 4
• If life expectancy is estimated at less than 1 month, the approach should be purely palliative and supportive rather than pursuing aggressive interventions 1

Reassessment Strategy

• Serial neuroimaging should be performed to monitor bleeding resolution 3
• Intrathecal chemotherapy may be reconsidered only after: documented resolution of hemorrhage on repeat imaging, stable neurological examination, and confirmation of unobstructed CSF flow 1
• The decision to resume intrathecal therapy requires weighing the limited survival benefit against the ongoing bleeding risk in this high-risk population 1, 4