Management of leptomeningeal metastases in non-small cell lung cancer

ABSTRACT

In leptomeningeal metastasis (LM), malignant lung cancer cells reach the sanctuary site of the leptomeningeal space through haematogenous or lymphatic route and thrive in the leptomeninges because of restricted access of chemotherapeutic agents across the blood brain barrier. The incidence of LM is 3%–5% in non-small cell lung cancer (NSCLC) patients; the incidence is higher in patients with anaplastic lymphoma kinase (ALK) gene rearrangement or epidermal growth factor receptor (EGFR) mutations. However, the real-world burden of undiagnosed cases may be higher. LM diagnosis is based on clinical, radiological, and cytological testing. Disease management remains a challenge because of low central nervous system penetration of drugs. The prognosis of NSCLC patients with LM is poor with an overall survival (OS) of 3 months with contemporary treatment and <11 months with novel therapies. Therapy goals in this patient population are to improve or stabilize neurologic status, improve quality of life, and prolong survival while limiting the toxicity of chemotherapeutic regimens. We reviewed therapeutic options for management of LM in NSCLC patients with or without genetic mutations. Radiotherapy, systemic, or intrathecal chemotherapy, and personalized molecularly targeted therapy prolong the OS in patients with LM. Newer third generation EGFR-tyrosine kinase inhibitors have considerable brain penetration property and have been vital in increasing the OS especially in patients with EGFR mutations. Sequential or combination therapy third generation EGFR agents with radiotherapy or chemotherapy might be effective in increasing the quality of life and overall survival.