Radiation Oncology/Supportive care/Thromboembolism

Brain Metastases

• Brain hemorrhage risk higher with brain mets and anticoagulation
• Treatment is thus a judgment call between risk of brain hemorrhage vs. risk of death/complications from thromboembolism
• MSKCC data suggests <10% risk of significant CNS complications on anticoagulation. Caution with hemorrhagic histologies
• It is important not to reach supratherapeutic levels; LMWH is probably safer from that perspective
• Gamma Knife treatment is not considered a contraindication

• MSKCC, 1994 PMID 8293418 -- "Therapy of venous thromboembolism in patients with brain metastases." (Schiff D, Cancer. 1994 Jan 15;73(2):493-8.)
  • Retrospective. 51 patients, 10 treated with IVC, 39 treated with anticoagulation, 2 not treated (both died of PE)
  • IVCF: 4/10 recurrent nonfatal thromboembolic events (2 PEs, 2 DVTs) -> 3/4 required secondary anticoagulation
  • Anticoagulation: 39 as primary therapy + 3 secondary after IVCF failure. 2/42 patients devastating CNS hemorrhage in the setting of supratherapeutic anticoagulation, 1/42 minor deterioration (overall 7% incidence of CNS complications on anticoagulation). 3/42 asymptomatic with hyperdensity on CT
  • Conclusion: Anticoagulation more effective than IVC. Acceptably safe when maintained within therapeutic range

Review

• Hopkins, 2006 PMID 16525187 -- "Management of venous thromboembolism in patients with primary and metastatic brain tumors." (Gerber DE, J Clin Oncol. 2006 Mar 10;24(8):1310-8.)
  • Anticoagulation can be used safely and effectively for most patients; IC hemorrhage often due to overanticoagulation
  • High risk patients: thrombocytopenia, recent neurosurgery, tumor types prone to bleeding (renal cell, melanoma, choriocarcinoma, thyroid cancer) are relative contraindication
  • Mechanical approaches have high complication rate and high failure rates, but can be used if cannot anti-coagulate
  • Antithrombolytic agents are absolute contraindication
  • Treatment recommendation:
    • High risk (craniotomy within 3-5 days, high risk histology, recent bleeding): IVCF
    • Acute/progressive symptoms: mini-heparin bolus (40 U/kg IV) or full heparin bolus (80 U/kg IV) for 24 hours depending on severity of TE symptoms. Careful monitoring of therapeutic level. Then long-term LMWH or warfarin
    • Standard risk (eg DVT): IV heparin (no bolus) for 24 hours, then long-term LMWH or warfarin

• Paris, 2005 (France) PMID 16224238 -- "Palliative care in patients with brain metastases." (Taillibert S, Curr Opin Oncol. 2005 Nov;17(6):588-92.)
  • Prophylaxis: recommended if decreased mobility, with LMWH
  • Symptomatic DVH: anticoagulation safe; recommend LMWH due to lack of interaction with chemo and convenience
  • Hemorrhagic mets: unless active bleeding, can anticoagulate, but requires strict monitoring
  • Avoid NSAIDs and Vitamin K