Abstract P3-02-02: Sensitivity and dynamic range of CellSearch based DTC enumeration in the CSF in patients with leptomeningeal metastases (LMM)
Authors: Van Goethem A , Rypens C , Rutten A , Prove A , Van den Mooter T , Erven K , Van Havenbergh T , Van Laere S , Vermeulen P , Dirix L 
Published: May 2019

Improvements in the treatment of patients with MBC and the inefficiency of many drugs in crossing the BBB have led to an increased incidence of symptomatic CNS metastasis. CNS metastases are clinically characterized by two distinct phenotypes, although their combined occurrence is possible. Most patients suffer from solid CNS metastases, but metastatic deposits limited to the leptomeningeal surfaces occur (LMM). In addition to its poor prognosis, neurological impairment in LMM is devastating.

Methods: 27 patients with breast cancer (MBC) were diagnosed with LMM and treated with intrathecal (IT) therapy from 2008 to 2018 in a single centre (GZA Hospitals Antwerp). Clinicopathologic and treatment information were collected. Conventional diagnosis was based on positive cytology on CSF and/or on the combination of clinical signs and neuro-imaging findings. For a subset of patients (n=12), we have enumerated circulating tumor cells (CTCs) and CSF DTCs at time of LMM diagnosis. Whole blood and CSF was processed on the CellSearch platform according to the standard method for CTC enumeration in blood.

Results: The 27 MBC pts diagnosed with LMM had a median time to LMM of 70.5 months (6.5-241) from the diagnosis of BC. Median age at LMM diagnosis was 56 y (36-75). At time of last follow-up, 23 patients (85%) had died. The median OS from LMM diagnosis was 27 months (4.5-128). From the 27 patients, 52% (14/27) were hormone receptor-positive (HR+), 33% (9/27) were HER2 overexpressing and 15% (4/27) were triple-negative. Coexisting brain metastases are present in 37% of patients. In 11 cases (41%), LMM was not accompanied by extra cranial disease at time of diagnosis. The biochemical data matched the classic CSF findings of LMM including a high protein concentration (75%, 9/12) and a low glucose concentration (42%, 5/12) (Table 1.). CSF lactate was elevated (&gt;2.2 mmol/l) in 100% (10/10). In 70% (7/10) CSF lactate was &gt;3.5 mmol/l. Cytologic evaluation of the CSF demonstrated unequivocal malignant cells in 10/12 (83%). DTC enumeration in the CSF of these patients, however, revealed the presence of tumor cells 12/12 (100%). Furthermore, the cell count ranged between 10 to 3523 Epcam-positive cells/mL CSF. Additional evaluation proved these to be cancer cells.

Results off the CSF analysis in 12 patients with LMMPatientWBCGlucoseProteinCTCCytologyDTCVolume mL125&lt;2018566pos21221853422149pos23047317068550pos&gt; 10005413339608neg&gt; 10007.554042280pos114427.56772064410pos63667.5756261211151pos264237.581675161NApos&gt;100039894840pos39311062313200pos191657.511296802.40pos591441225605,113neg7994

Conclusion: Symptomatic LMM has a variable prognosis, with some patients experiencing prolonged survival. LMM occurs in all breast cancer subtypes and can be the sole location (40%). CSF lactate is a sensitive but aspecific marker. DTC enumeration in the CSF is a robust tool to diagnose LMM with apparently a superior sensitivity over conventional cytology. It furthermore has a broad dynamic range rendering it more suitable for treatment effect evaluation. This methodology should be considered in routine workup in MBC patients with suspected LMM.

Citation Format: Van Goethem A, Rypens C, Rutten A, Prove A, Van den Mooter T, Erven K, Van Havenbergh T, Van Laere S, Vermeulen P, Dirix L. Sensitivity and dynamic range of CellSearch based DTC enumeration in the CSF in patients with leptomeningeal metastases (LMM) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-02-02.