Community Access, Future Directions, and Key Takeaways for CNS Disease in EGFR-Mutated NSCLC

Dr. Alder asks how clinicians without access to proton therapy, intrathecal treatment, or specialized neuro-oncology consultation should approach LMD and CNS disease, and what infrastructure changes would most improve outcomes.

Dr. Nagpal emphasizes that maximizing systemic CNS-penetrant therapy is the most broadly applicable strategy. As more drugs accumulate CNS-specific data, community practitioners will be better equipped to provide intracranial protection through systemic treatment choices alone. Intrathecal therapy will remain niche given its substantial burden on both patients and providers, which is time that many patients would prefer to spend with family. Proton CSI remains to be evaluated more broadly before recommending it universally.

The most anticipated near-term developments include CNS data from sacituzumab tirumotecan, and results from an NRG cooperative group study evaluating whether preoperative SRS before brain metastasis resection reduces the rate of subsequent leptomeningeal disease, a practice change that could affect a substantial proportion of patients. CSF liquid biopsy methodology continues to evolve and will provide increasingly actionable information.

Closing key messages include: optimize systemic CNS-penetrant therapy first; refer to neuro-oncology early and freely; clinical trials remain the preferred option at any treatment transition; and patients with LMD now have access to disease-specific support through the Leptomeningeal Cancer Foundation, which is partnering with major lung and breast cancer advocacy organizations. A national leptomeningeal tumor board is forthcoming, representing a meaningful resource for clinicians and patients navigating this challenging diagnosis.