An overview of leptomeningeal disease

Leptomeningeal disease (LMD) is a poor prognosis pattern of disease progression in patients with metastatic malignancy with limited treatment options. Patients may be asymptomatic or present with non-specific neurologic deficits, therefore gadolinium-enhanced magnetic resonance imaging of the brain and spine is critical for establishing a diagnosis. Although the treatment intent is palliative in the context of LMD, a multidisciplinary approach is still important to ensure patients receive a timely diagnosis and appropriate treatment to maximize symptom control and preserve quality of life. Radiotherapy is typically delivered to the whole brain or focal spinal regions for the purposes of treating bulky disease, stabilizing symptoms, or relieving cerebrospinal fluid obstruction. Whole craniospinal irradiation (CSI) is generally avoided given its toxicity profile and should only be considered in carefully selected patients where the potential benefit may outweigh the adverse effects. CSI with proton radiotherapy (oppose to conventional photon radiotherapy) has shown promise with improved toxicity for patients with primary CNS tumors. This may be a preferred option for patients being considered for CSI at centres with the proton therapy capabilities. Focal hypofractionated stereotactic radiotherapy (SRT) to intracranial targets is an emerging approach to LMD that may be useful in select patients with limited disease particularly in the setting of reirradiation. Chemotherapies may be delivered intrathecally, although the evidence supporting its efficacy is limited and heterogeneous in regards to the tumor sites examined. Finally, targeted therapy and novel applications of immune checkpoint inhibitors are promising; however, further research is required to guide the use of these agents.