P14.26 Leptomeningeal Disease Secondary to Melanoma: Diagnosis, Treatment, and Outcomes at a Single Institution between 2013 and 2019

Abstract

Abstract BACKGROUND Leptomeningeal disease (LMD) is devastating with a median survival of only 8–10 weeks. LMD affects approximately 5% to 25% of melanoma patients. Its pathophysiology remains unknown and effective treatments are virtually non-existent. The aim was to evaluate demographics, validity of Veridex CellSearch® System (VCS) compared to Gold Standard test (i.e., CSF cytology), risk factors for LMD, and treatment outcomes. MATERIALS AND METHODS A retrospective chart review was performed of subjects with suspected LMD from melanoma enrolled in the MCC 19332/19648 studies between 2013 and 2019 at Moffitt Cancer Center. The patients underwent standard of care with different treatments as deemed appropriate by treating physician. CSF samples were obtained from lumbar punctures, surgeries, and Ommaya reservoir, and sent for analysis. Peripheral blood and CSF were evaluated for detection and quantification of CSF circulating tumor cells (CTCs) with the Veridex CellSearch® System, which is adapted to enumerate CTCs from CSF. RESULTS More than 100 patient charts were reviewed. Only patients with melanoma as primary tumor (N=48) were included in the analysis, with ages 29–80. N=28 (58%) met criteria for LMD (median age 59, M:F ratio of 3:1). Within the LMD group, n=26 patients had cutaneous melanoma as primary tumor; BRAF mutant n=17 (V600E n=14; G469E n=1). At the time of diagnosis, median KPS score was 70, with most prevalent symptoms of headaches, encephalopathy, focal weakness, and nausea/vomiting. N=20 (71%) patients were diagnosed radiographically and n=5 (18%) with CSF cytology; n=14 (52%) had positive cytology on first LP, n=18 (67%) on first two LPs. From 25 patients with LMD who underwent CellSearch® to quantify CTCs, n=22 (88%) patients had positive CSF CTCs; n=18 (72%) on first sample sent for analysis, n=20 (80%) on first two samples. The sensitivity and specificity of the Veridex CellSearch® System compared to the Gold Standard CSF cytology were analyzed. Survival in months plotted against the percentage of CSF-CTCs showed a significant value of p=0.0377. CSF analysis i.e., inflammatory markers, and treatments pre-/post-LMD diagnosis will be described. Most patient were managed with Ommaya reservoir placement, radiation therapy, immunotherapy, BRAF +/- MEK inhibitors, IT thiotepa, or IT topotecan. The median survival of those with LMD was 3.15 months. Two patients outlived their counterparts by 21.1 and 39.0 months after the LMD diagnosis, one of them is still alive but with a very poor functional status. CONCLUSION These results indicate the potential value of the VCS as an additional tool to the gold standard in the diagnosis of LMD in patients with high suspicion of the disease. Future directions involve doing prospective studies to further validate this method, and to better understand this patient population to enhance diagnostic tools and management of LMD.