Clinical Utility Of Circulating Tumor Cell Monitoring For Therapeutic Response In Gastric Cancer Patients

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Background: Circulating tumor cells (CTCs) in the peripheral blood are considered as a useful biomarker for disease outcome and treatment response because the presence of CTCs is associated with short survival. We previously established the biological imaging system to detect viable CTCs among millions of peripheral blood leukocytes using telomerase-specific replication-selective adenovirus expressing green fluorescent protein (GFP) (Kojima et al, J Clin Invest, 2010). In present study, we demonstrate the clinical potential of our method for monitoring the efficacy of treatment in patients with gastric cancer. Methods: We used a GFP-expressing adenovirus variant, in which the telomerase promoter regulates viral replication (OBP-401), to selectively label human tumor cell with fluorescence. Whole blood cells collected from 7.5ml of peripheral blood were infected OBP-401 after elimination of anti-adenovirus antibodies and incubated at 37 oC. Viruses were inactivated 24 hours after virus-infection and then red blood cells were lysed. The GFP-expressing cells were detected using fluorescence microscopy. Results: A total of 72 blood samples from 39 patients with histologically-confirmed gastric cancer (stage IA to IV) were analyzed. CTCs were detected in 32 of 39 patients (82%, range 1 to 40<) before treatment, however, there was no apparent relationship between the number of CTCs and clinical status. We further assessed the CTC dynamics in 24 patients who were undergoing surgery, chemotherapy or endoscopic submucosal dissection (ESD). In patients with early gastric cancer, 7 patients had decrease in CTC numbers after surgery or ESD, and 6 patients had decreased CTC numbers following temporary increase after treatment. As for advanced cancer, the number of CTCs dropped in 3 patients after complete resection and increased in 2 patients with poor prognosis despite chemotherapy. Conclusion: Our data suggest that patients with early gastric cancer also have CTCs in peripheral blood and the dynamic change of CTCs correlate with treatment response. Although numerous samples and long-term outcome should be analyzed, the enumeration of CTC using this GFP-expressing virus-based method might be useful for monitoring the efficacy of treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3160. doi:10.1158/1538-7445.AM2011-3160