In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e21020-e21020
Abstract:
e21020 Background: Circulating tumor cells (CTCs) are promising biomarkers for diagnosis and systemic therapy. However, their infrequent detection rates limit currently their clinical use. Here we tested whether leukapheresis could be a suitable method to increase CTC yields and detection rates by increasing dramatically the analyzed blood volume. Methods: We screened 3x10 6 PBMNCs of 48 historical leukapheresis products harvested from 24 breast cancer patients in the setting of high-dose chemotherapy and from a non-cancer control group (n=10), respectively, with a standard immuno-assay using an anti-cytokeratin antibody (A45/BB3) to detect CTCs. Detected CTCs were isolated, their genomic DNA amplified, and the whole genome screened for chromosomal aberrations using comparative genomic hybridization (CGH) (n=48). To validate the CTC detection frequencies in leukapheresis products, we initiated a prospective pilot-study and performed leukapheresis in 13 cancer patients (breast and pancreatic cancer). 1 mL of the leukapheresis product (total volume: up to 150 ml) was analyzed using the CellSearch® system as well as 7.5 ml peripheral blood taken from the same patients. Results: 44/48 (91.7%) of leukapheresis samples contained CTCs with a median count of 3.0 in 3x10 6 PBMNC (range: 1-35 CTCs). None of the 10 analyzed healthy controls displayed CTCs. We successfully performed single cell CGH of 48 CTCs from 19 patients revealing aberrant CGH profiles in 56% with gains and losses typical for breast cancer. Interestingly, CTCs with high aberration numbers were associated with early metastatic relapse. The validation study using CellSearch® in 13 cancer patients demonstrated in leukapheresis products significantly higher CTC detection frequencies (13/13 vs. 5/13) and CTC numbers (median: 13, range: 1-51 vs. median 0, range: 0-7; p 〈 0.001) compared to the matched peripheral blood samples. Conclusions: Our results indicated that leukapheresis provides CTC detection rates and yields at unprecedented scale. Thus we believe, that leukapheresis will help to exploit the full clinical potential of CTCs as biomarkers for diagnosis and systemic therapy.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.e21020
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
