1175P - Clinical feasibility study of a novel cytometry-based system for the detection of circulating tumor cells in patients with lung cancer

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Lung and other Thoracic Tumours
Translational Research
Presenter Yasuhiro Koh
Authors Y. Koh1, M. Watanabe1, T. Sawada2, Y. Uehara2, Y. Fujimura3, T. Tamura4, F. Koizumi2
  • 1Division Of Drug Discovery And Development, Shizuoka Cancer Center, 411-8777 - Sunto-gun/JP
  • 2Shien-lab, National Cancer Center Hospital, Tokyo/JP
  • 3R&d, On-chip Biotechnologies Co., Ltd, Koganei/JP
  • 4Division Of Thoracic Oncology, National Cancer Center Hospital, Tokyo/JP

Abstract

Background

The presence and number of circulating tumor cells (CTCs) in the peripheral blood of solid tumor patients are predictive of clinical outcome. To date the CellSearch system has been the only FDA-cleared CTCs enumeration system for advanced breast, prostate and colon cancers. However, low prevalence of CTCs and lack of capability as an application platform for molecular analysis have limited the use of CTCs in the clinic. To overcome these shortcomings, innovative and emerging technologies with easier access to further molecular analysis are under development worldwide.

Methods

We have developed a flow cytometry-based CTCs detection system independent of EpCAM expression level of tumor cells with cytokeratin and vimentin-staining after the depletion of CD45-expressing cells. In a preclinical study, various cancer cell lines were spiked into blood from healthy donors and the sensitivity in detection was evaluated at two different sites (Shizuoka Cancer Center and National Cancer Center Tokyo). Then clinical feasibility study was conducted in patients with lung cancer.

Results

Enumeration of the spiked cancer cells (10 to 1000 cells in 4 ml of blood) was linear, with a recovery rate of over 90%. A significantly higher recovery rate was observed with our system (90 to 102%) than that with CellSearch system (0%) particularly when EpCAM-negative PC-14 non-small lung cancer cells were spiked in, suggesting a superior sensitivity of our system in capturing EpCAM-negative tumor cells. In 22 blood samples from lung cancer patients, CTCs were detected with numbers ranging from 0 to 16 CTCs (median, 6.5) per 4 ml of blood with our system and in 72.7% (17/23) of the patients, 4 CTCs or more per 4 ml of blood were detected. On the other hand with CellSearch system, 2 CTCs or more per 7.5 ml of blood were detected in only 27% of the patients.

Conclusions

The preclinical study and the results of the clinical feasibility study suggested superior sensitivity of our flow cytometry-based detection method than CellSearch system. Cell sorting device under development will be combined with this system for isolation and collection of CTCs for molecular analysis with next-generation sequencing.

Disclosure

All authors have declared no conflicts of interest.