Abstract
BACKGROUND
Breast cancer (BC) is the most frequent cause of leptomeningeal metastases (LM). LM diagnosis is confirmed by the detection of tumor cells in the cerebrospinal fluid (CSF) using conventional cytology (gold standard). However, even with optimal CSF sample volume and time to the analysis, the sensitivity of this technique is low, demanding repeated samples. Here, we aimed to evaluate the value of circulating tumor cell (CTC) detection in CSF using the CellSearch® system for LM diagnosis.
MATERIAL AND METHODS
This prospective, monocentric study included adult BC patients with suspected LM (clinical and/or radiological signs). CSF samples from 1–3 lumbar puncture(s) were analyzed: protein level, conventional cytology (60 drops), and CTC detection with the CellSearch® system (60 drops, first lumbar puncture only). Sensitivity (Se) and specificity (Sp) were calculated, using the results of the conventional cytology as the gold-standard.
RESULTS
Forty-nine eligible patients were included (Jan 2017-Jan 2020): median age 51.8, 95.9% women, 20.4% HER2+ BC, 93.8% previously diagnosed with metastatic BC, 89.8% with clinical symptoms. Among them, 40 were evaluable (CTC detection failure: n=8, eligibility criteria failure: n=1). Median sample volume was 3.0 mL for conventional cytology samples (median time to analysis: 22min) and 3.3 mL for CTC samples. Of the 40 evaluable patients, 18 had a positive cytology (on CSF sample n=°1/n°2: n=16/n=2) and were therefore diagnosed with LM using the gold-standard method. Protein level was elevated in 88.2% of these patients, compared with 45.1% of patients with negative CSF cytology (p=0.005). CTCs were detected in these 18 patients (median 5824 CTCs, range 93-45052). CTCs were also detected in 5/22 patients with a negative cytology (median 2 CTCs, range 1–44). Among them, one patient (44 CTCs) was diagnosed with a cytologically-proven LM 9 months later, while there was no further argument for LM in the other 4 patients’ history (1–3 CTC), who died of the extra-cerebral disease after a median time of 5.2 months (range 0.9–25.9). The detection of at least one CTC in CSF was associated with a Se of 100.0% (IC95% 82.4–100) and a Spe of 77.3% (IC95% 64.3–90.3) for the diagnosis of LM.
CONCLUSION
CTCs were detected with the CellSearch® system in all patients diagnosed with a cytologically-proven LM, as well as in a few patients without a cytological confirmation of LM. The prognosis of these patients with CSF cytology-/CTCs+ needs to be further investigated in a larger cohort.
6 Cases of Breast Cancer-Associated Neoplastic Meningitis and Literature Review
