Leptomeningeal carcinomatosis: Retrospective review of a large series.

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e14005 Background: Leptomeningeal carcinomatosis (LMC) remains associated with a poor outcome and effective treatment options are not currently available. Knowledge about risk factors, diagnosis and optimal treatment of LMC is still limited. Methods: We performed a retrospective analysis of all consecutive patients with a solid tumor and LMC confirmed by CSF (cerebrospinal fluid)-positive cytology, diagnosed at our institution between January 2013 and November 2020. Clinical, imaging and cytologic data were collected. We used multivariable Cox regression models adjusted for age and Eastern Cooperative Oncology Group (ECOG) performance status to test the prognostic impact of clinical and treatment-related variables. Results: A total of 73 patients with LMC were identified, 75% female. The most common cancers were breast (51%, n = 37), lung (22%, n = 16), and melanoma (11%, n = 8). Most patients presented with intracranial hypertension (58%, n = 42), followed by cerebellar symptoms (20%, n = 15), radiculopathy (19%, n = 14), cranial nerve palsies (16%, n = 12), seizures (12%, n = 9), and other (4%, n = 3). More than half of patients (56%) had evidence of leptomeningeal involvement only, while 25% of patients (n = 18) had known central nervous system (CNS) metastases and 19% (n = 14) were diagnosed simultaneously with CNS metastases. Median time from primary tumor diagnosis to LMC was 32 months. Median overall survival (mOS) was 1.57 months (95% CI 1.17-2.32 months), with 15% of patients alive at 6 months (95% CI 9-26%). Patients with gynecological (7%, n = 5) and lung cancer had the best mOS (67 and 64 days, respectively), and patients with melanoma had the worst mOS (18 days). mOS in patients with evidence of meningeal involvement by MRI was 41 days, compared to 71.5 days in patients with a negative MRI. Starting a new systemic treatment was associated with a better prognosis (survival hazard ratio (HR) 0.39, 95% CI 0.21-0.75, p = 0.004). Forty patients (55%) received specific treatment for LMC. Neither intrathecal treatment nor radiation were associated with an improved outcome (HR 1.03, 95% CI 0.51-2.10, p = 0.930 and HR 0.60, 95% CI 0.30-1.17, p = 0.130, respectively). Presenting with seizures was significantly associated with a worse prognosis (HR 3.23, 95% CI 1.35-7.76, p = 0.009). In CSF cytology, both pleocytosis (> 5 cells/mm3) and hyperproteinorhachia were individually associated with a worse prognosis (pleocytosis: HR 1.94, 95% CI 1.16-3.26, p = 0.012; hyperproteinorhachia: HR 2.61, 95% CI 1.28-5.32, p = 0.008). Conclusions: In this large series of patients diagnosed with LMC based on positive CSF cytology, the outcome was poor. Absence of leptomeningeal involvement by MRI and switching to a new treatment regimen were associated with a better outcome, likely reflecting tumor burden and patient selection. LMC will likely become more common as systemic treatment options and imaging improve and effective treatment options are an urgent and yet unmet need.