Leptomeningeal disease (LMD)

How common is leptomeningeal disease (LMD)? 

LMD is diagnosed in 5% of patients with metastatic cancer. The most common primary tumors associated with the development of LMD are breast, lung, and melanoma.

Which sites are typically affected in leptomeningeal disease ? 

The cerebellar folia, cortical surface and basal cisterns of the brain, as well as the dorsal aspect of the spinal cord (especially the cauda equina).

What tests should be ordered in a person suspected of having leptomeningeal disease? 

MRI of the entire neuroaxis with contrast and a lumbar puncture to send CSF for cytology.

MRI should be performed prior to the lumbar puncture as pachymeningeal enhancement may be seen on imaging following a lumbar puncture.

Are CSF cytology results sensitive for LMD? 

An initial cytology sample has a sensitivity of only around 70%. The sensitivity increases to 86% after two samples and 90% after three samples.

At least 10 mL of CSF should be collected with each sample for cytologic analysis alone. Flow cytometry should also be ordered in hematologic malignancies.

What is the prognosis of leptomeningeal disease

Is there a difference in survival in LMD patients with primary solid versus primary hematologic malignancies? 

Prognosis for patients with LMD is extremely poor.

Patients with solid tumors have a median survival around 2 to 3 months whereas those with hematologic malignancies have a slightly better median survival of around 4 to 5 months.

How are poor-risk versus good-risk patients defined in LMD? 

Poor-risk patients have a low Karnofsky performance status (KPS) <60, severe neurologic deficits, or extensive systemic cancer with limited therapeutic options.

These patients have a poor prognosis, and treatment should be focused on alleviating symptoms with steroids, analgesics, and/or radiation therapy.

Good-risk patients have a KPS of 60 or greater, no major neurologic impairments, little systemic disease, and/or a cancer for which there are treatment options. Good-risk patients receive treatment with radiation to bulky/symptomatic areas of LMD followed by intrathecal chemotherapy.

The three most commonly used intrathecal chemotherapies in patients with LMD. 

  • Methotrexate
  • liposomal cytarabine
  • thiotepa
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