Dataset Information

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

ACCESS DATA

Similar Datasets

Project description: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.

Project description:ObjectiveThe objective of this research is to investigate the clinical application value of cerebrospinal fluid (CSF) cytology and circulating tumor DNA (ctDNA) in lung adenocarcinoma (LUAD) meningeal metastasis-meningeal carcinomatosis (MC), and to further explore the possible molecular mechanisms and drug treatment targets of LUAD meningeal metastasis by next-generation sequencing (NGS).MethodsWe retrospectively analyzed LUAD with MC in 52 patients. CSF cytology was carried out using the slide centrifugation precipitation method and May-Grüwald-Giemsa (MGG) staining. Tumor tissue, plasma and CSF ctDNA of some MC patients were detected by NGS.ResultsOf the 52 MC patients, 46 (88.46%) were positive for CSF cytology and 34 (65.38%) were positive for imaging, with statistically significant differences in diagnostic positivity (P < 0.05). In 32 of these patients, CSF cytology, cerebrospinal fluid ctDNA, plasma ctDNA and MRI examination were performed simultaneously, and the positive rates were 84.38, 100, 56.25, and 62.50% respectively, the difference was statistically significant (P < 0.001). Analysis of the NGS profiles of tumor tissues, plasma and CSF of 12 MC patients: the mutated gene with the highest detection rate was epidermal growth factor receptor (EGFR) and the detection rate were 100, 58.33, and 100% respectively in tumor tissues, plasma and CSF, and there were 6 cases of concordance between plasma and tissue EGFR mutation sites, with a concordance rate of 50.00%, and 12 cases of concordance between CSF and tissue EGFR mutation sites, with a concordance rate of 100%. In addition, mutations not found in tissue or plasma were detected in CSF: FH mutation, SETD2 mutation, WT1 mutation, CDKN2A mutation, CDKN2B mutation, and multiple copy number variants (CNV), with the most detected being CDKN2A mutation and MET amplification.ConclusionCSF cytology is more sensitive than traditional imaging in the diagnosis of meningeal carcinomatosis and has significant advantages in the early screening and diagnosis of MC patients. CSF ctDNA can be used as a complementary diagnostic method to negative results of CSF cytology and MRI, and CSF ctDNA can be used as an important method for liquid biopsy of patients with MC, which has important clinical significance in revealing the possible molecular mechanisms and drug treatment targets of meningeal metastasis of LUAD.

Dataset Information

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets