Central nervous system (CNS) metastases develop in a substantial portion of patients with epidermal growth factor receptor (EGFR)-mutated metastatic non-small cell lung cancer (mNSCLC) over the disease course, shaping both prognosis and treatment planning.1,2 Because not all systemic therapies penetrate the CNS equally, this is a relevant consideration when initiating first-line treatment in patients with known or suspected brain involvement.1
Leptomeningeal disease represents a particularly difficult subset.2 It carries a poor prognosis, and because these patients have historically been excluded from many clinical trials, treatment approaches after progression on standard therapy remain less well defined.3 Third-generation TKIs show stronger meningeal penetrance than earlier agents and have been associated with improved intracranial response and survival in leptomeningeal disease, though options overall remain limited and further study is needed to define optimal use in this setting.2
Access to neuro-oncology expertise, specialized MRI protocols, and cerebrospinal fluid analysis can vary meaningfully depending on care setting, which may affect how quickly CNS involvement is identified and managed. Emerging liquid biopsy approaches, such as circulating tumor DNA, circulating tumor cells, and extracellular vesicles, have demonstrated promising sensitivity in early studies and may complement conventional CSF cytology, although larger prospective studies are needed to define their clinical role.2
Given how often CNS involvement occurs in this population, baseline brain imaging and follow-up brain imaging should be individualized according to symptoms, disease status, and treatment approach. Early referral to neuro-oncology or radiation oncology may be warranted when CNS disease is identified or suspected, particularly for patients treated outside specialized centers.4
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