BIOM-76. LEPTOMENINGEAL CARCINOMATOSIS AS A FIRST SIGN OF METASTATIC NSCLC: EXCEPTIONAL OUTCOMES WITH TARGETED THERAPY IN TWO ILLUSTRATIVE CASES

Abstract The median overall survival for patients with non-small cell lung cancer diagnosed with leptomeningeal carcinomatosis is approximately 3 to 5 months with standard therapies. Outcomes improve with targeted therapies and actionable driver mutations, though rare mutations lack extensive documentation. A 53-year-old female nonsmoker presented to the emergency department with progressive headaches and episodes of vision loss. Imaging revealed leptomeningeal enhancement as well as a small lung mass. She initiated systemic therapy with carboplatin, pemetrexed, and pembrolizumab, but declined quickly. She developed symptomatic hydrocephalus which responded to serial lumbar punctures. Whole brain radiation therapy was contemplated but not started. NGS testing was not performed on tumor tissue given inadequate sample size, so liquid biopsy was sent. A RET rearrangement was noted, and she was started on selpercatinib. Within four weeks, she experienced clinical improvement. An MRI of the brain performed 18 weeks later showed that enhancing leptomeningeal disease had fully resolved. She is presently continuing therapy on reduced-dose selpercatinib, and is over 2 years from her diagnosis. Her MRI of the brain shows no abnormal enhancement. A 49 year-old female with prolonged smoking history presented to the emergency department with headaches, dizziness, blurred vision, and mild dyspnea on exertion. Imaging revealed diffuse leptomeningeal enhancement as well as a large right-sided lung mass. Biopsy of the lung mass confirmed lung adenocarcinoma with a KRAS Q61H mutation. She was treated with 3000 cGy of whole brain radiation, then repeat MRI of the brain showed increasing disease burden. She initiated therapy with trametinib. Within eight weeks, enhancing leptomeningeal disease had improved. An MRI of the brain after 9 months of therapy showed no enhancing leptomeningeal disease. She is presently continuing therapy on reduced dose trametinib and is over 2 years from her diagnosis. Her MRI of the brain shows no abnormal enhancement.