CMET-04. CEREBROSPINAL FLUID CIRCULATING TUMOR CELLS (CSF CTC) FOR PATIENT MONITORING AND RESPONSE TO TREATMENT

ABSTRACT: Abstract BACKGROUND The CellSearch system (Janssen Diagnostics, LLC) is an FDA-approved methodology for enumerating CTCs from blood in patients with breast, prostate and colon cancers. It has also been used to evaluate CSF CTC of patients with leptomeningeal metastasis (LM). We explored the use of CSF CTC enumeration over time in patients with LM receiving intrathecal (IT) therapy as a potential biomarker of treatment response. METHODS CSF from patients participating in an IRB-approved phase I/II dose escalation trial of IT trastuzumab for LM in HER2+ cancer (NCT01325207) was evaluated using the CellSearch system. Three ml CSF from a ventricular reservoir was collected for CSF CTC enumeration and cytology at pre-treatment Day 1 of each cycle. CSF was also analyzed for HER2 expression using HER2 antibodies. This was correlated with clinical and radiographic response. LM progression was defined as clinical or radiographic worsening. RESULTS Fifteen patients with HER2+ LM (14 breast, 1 colon) were enrolled; 14 were women. Six patients had baseline positive CSF cytology; the remaining were diagnosed by MRI. Of the 15 patients, 10 had greater than 1 cycle of treatment to be evaluable; 5 patients progressed during cycle 1. Median CSF CTC at baseline was 22 per 3ml (range 0–200); 2 patients had no detectable CSF CTCs. A decrease in CSF CTC was observed in 5 patients after cycle 1 and remained low (mean =9.5, range 0–92) in 2 patients while disease was stable. 3 patients had a rise in CSF CTCs roughly 1 month prior to progression. In the 10 patients with HER2 analysis, number of CTCs correlated with HER 2 expression. CONCLUSION CSF CTC HER2 expression provided further affirmation that CTCs are malignant. Changes in CSF CTC enumeration allow quantitative surveillance of treatment response or as an early biomarker of LM progression and should be further investigated.

SUBMITTER: Malani R 

PROVIDER: S-EPMC5692986 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature