This narrative review looks at patients with EGFR-mutant non-small cell lung cancer who develop resistance to tyrosine kinase inhibitors. These patients often face leptomeningeal metastasis, a serious spread of cancer to the lining around the brain and spinal cord. The authors describe a multimodal approach that integrates targeted therapies, intrathecal drug administration, radiotherapy, and intracranial pressure relief devices. This strategy aims to address the unique challenges of treating cancer that has crossed the blood-brain barrier.
The review highlights several important limitations that affect how these treatments are used. There is a lack of standardized protocols, and tumor staging varies widely among patients. Resistance mechanisms differ, and systemic therapies often have limited penetration across the blood-brain barrier. Efficacy can be unpredictable, and logistical challenges complicate the delivery of multidisciplinary care.
The main reason to be cautious is that this is a narrative review, not a clinical trial with a specific sample size or follow-up period. No primary outcomes were reported, and safety data regarding toxicity or discontinuations were not detailed. Readers should understand that this work outlines a clinical decision-making pathway to help physicians optimize and personalize treatment regimens. It does not provide proof that one specific method works better than another. The evidence is limited and should be viewed as a framework for discussion rather than a definitive guide.