Abstract

Abstract BACKGROUND CSF-CTC testing using the CellSearch® platform is a validated diagnostic tool for leptomeningeal metastases (LM) from solid tumors. CSF-CTCs can also be detected in patients with brain metastases (BM), but their significance is unclear. Our objective was to evaluate the utility of CSF-CTC quantification in predicting outcomes in CNS metastases. METHODS We retrospectively reviewed charts of patients with solid tumors who underwent CSF-CTC measurement between 2016–2019 at Memorial Sloan Kettering Cancer Center. Information on neuroaxis imaging, CSF results, systemic cancer status, tumor molecular profile and survival was collected. LM was diagnosed by MRI and/or CSF cytology. Survival analyses were performed using Cox proportional hazards modeling, and CSF-CTC splits associated with survival were identified through recursive partitioning analysis (RPA). RESULTS A total of 407 patients (38% lung primary, 34% breast, 28% other tumor types) were included; of these, 144 had LM and 233 had BM diagnosed before or around the time of CSF tests (97 had both). For a subgroup of 101 patients with LM diagnosed within 30 days of CSF sampling, mean CSF-CTCs were 127.3/3ml, compared to 44.6/3ml in the overall cohort. CSF-CTCs predicted survival in these patients, with optimal cutoff at 61 CSF-CTCs/3ml, above which the risk of death doubled (HR=2.09, 95% CI: 1.13–3.87, p=0.02). For 53 patients with BM diagnosed 1–6 months prior to CSF tests, CSF-CTCs (mean 54.1/3ml) also determined higher risk of death when above the optimal cutoff of 94 (HR=5.15, 95% CI: 2.08–12.78, p=0.004). For both groups, positive/suspicious cytology was associated with higher risk of death as well, but these results were not statistically significant (LM group: HR=1.79, 95% CI: 0.95–3.35, p=0.07; BM group: HR=1.86, 95%CI: 0.82–4.22, p=0.14). CONCLUSION In newly diagnosed LM and BM, quantification of CSF-CTCs predicts survival. CSF-CTC analysis can be used as a prognostic tool in patients with CNS metastases.

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