Can tailored radiation outsmart Drug-Resistant lung cancer in the brain?

This trial is for people with a specific type of lung cancer (EGFR-mutant non-small cell lung cancer) that has spread to the lining of the brain and spinal cord (leptomeningeal metastasis) and has stopped responding to third-generation targeted pills. The study tests whether a personalized, risk-adaptive consolidation therapy—using proton craniospinal irradiation (a precise type of radiation) with or without low-dose intrathecal pemetrexed (chemotherapy given directly into the spinal fluid)—can delay cancer progression in the brain better than the standard approach of intrathecal pemetrexed alone. Participants first receive induction intrathecal pemetrexed, and their response is measured by a blood-based marker (ctDNA) in the spinal fluid to determine their risk level. Based on this, intermediate- and high-risk patients are randomly assigned to either standard consolidation or the experimental adaptive therapy. The trial aims to see if this tailored strategy improves intracranial progression-free survival and overall survival, while also monitoring safety and quality of life.