Sdps-47 circulating tumor cell analysis from the cerebrospinal fluid informs early diagnosis, treatment and prognosis in leptomeningeal carcinomatosis

INTRODUCTION Leptomeningeal carcinomatosis (LMC) is an aggressive pattern of recurrence with limited survival. Early detection by traditional CSF (cerebrospinal fluid) cytology is poor. We evaluated CSF circulating tumor cells (CTCs) with a commercially available assay (CNSideTM) and subsequent molecular profiling on captured CTCs, to determine if CTC analysis would lead to early detection, identification of therapeutic targets, and improved treatment outcomes. METHODS We analyzed 58 patients with carcinoma who were referred to Neuro-oncology clinic for evaluation for LMC, and underwent comprehensive work-up with CSF sampling (traditional cytology and CTCs), brain and spine MRI, and neurologic examination, and were followed for survival. RESULTS 28/58 were diagnosed with LMC (breast n=16, Lung n=9, other n=3). 24/28 were female. Median KPS was 80. 15/16 breast cancer patients were HER2- on initial systemic cancer diagnosis. The mean time to LMC from cancer diagnosis was 70 months. In the patients with LMC, CTCs were positive in 96%, compared to traditional cytology, which was positive in 64%. Molecular analysis of the CTCs in 15 patients with HER2- primary tumors detected HER2+ amplification in 3/15 patients. 14/28 patients received first line therapy for LMC with radiation + systemic chemotherapy + intrathecal chemotherapy, and 8/28 received systemic chemotherapy + intrathecal chemotherapy. 6/28 received other combinations. The overall median progression-free survival (PFS) was 5.3 months and the overall survival (OS) was 7.7 months from LMC diagnosis (breast PFS 4.5 months, OS 6.3 months; Lung PFS 5.3 months, OS 23.5 months). CONCLUSION CTC detection had superior sensitivity compared to traditional cytology, allowing for earlier detection of LMC and consequently earlier treatment. Molecular analysis of CTCs can allow for identification of therapeutic targets specific to the CSF, such as intrathecal trastuzumab for HER2+ LMC. PFS and OS in our cohort with this approach suggested improved survival compared to historical controls.