P05.10 Prospective evaluation of cerebrospinal fluid circulating tumor cells (CSF CTC) in patients with HER2 positive cancers and leptomeningeal metastases receiving treatment with intrathecal trastuzumab

ABSTRACT: Abstract Background The validated CellSearch system (Janssen Diagnostics, LLC), utilizing an immunomagnetic CTC selection method based on EPCAM antibody conjugated ferroparticles, is an FDA-approved methodology for enumerating CTC from blood in pts with breast, prostate and colon cancers. The CellSearch system has been used to evaluate CSF CTC of pts with leptomeningeal metastasis (LM) and has demonstrated potential as a diagnostic marker and response to cancer treatment. We explored the use of CSF CTC enumeration in the follow-up of pts with LM from HER2+ cancers receiving intrathecal (IT) therapy, aimed at characterizing changes over time as a potential biomarker of treatment response. Material and Methods CSF from pts participating in an IRB-approved phase I/II dose escalation trial of IT trastuzumab for LM in HER2+ cancer (NCT01325207) was evaluated by CellSearch system. 3 ml CSF from a ventricular reservoir was collected for CSF CTC enumeration at pre-treatment Day 1 of each cycle and correlated with CSF cytology from the same sample, and 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 and should be further investigated.

SUBMITTER: Pentsova E 

PROVIDER: S-EPMC6144227 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature