Annals of Surgical Oncology

, Volume 22, Issue 12, pp 3954–3961 | Cite as

Circulating Tumor Cells as an Independent Predictor of Survival in Advanced Gastric Cancer

  • H. OkabeEmail author
  • S. Tsunoda
  • H. Hosogi
  • S. Hisamori
  • E. Tanaka
  • S. Tanaka
  • Y. Sakai
Gastrointestinal Oncology



When the indication for surgery of highly advanced gastric cancer is considered, careful selection of the patients is important. In addition to tumor-node-metastasis factors and peritoneal lavage cytology (CY), which are important predictors of prognosis, detection of circulating tumor cells (CTCs) could be another potential marker.


This study prospectively evaluated CTCs using a semi-automated immunomagnetic separation system (CellSearch) for 136 patients with advanced gastric cancer to determine the frequency of CTC positivity. For 123 patients who also had their CY evaluated, the significance of both CTC and CY, was investigated as a potential biomarker to predict progression-free survival (PFS) or to monitor the therapeutic effect.


In 25 patients (18.4 %), CTCs were positive. Positive CTC counts were more common for tumors with diffuse histologic type and distant metastasis. The PFS of CTC-positive patients was significantly shorter than that of CTC-negative patients (hazard ratio 2.03; P = 0.016). A multivariate analysis of 123 patients showed that CTC and CY as well as performance status and macroscopic distant metastasis were independent factors for PFS. When both CTC and CY were converted to negative values by therapeutic interventions, long-term PFS was achieved.


Detection of CTCs was an independent predictor of a shorter PFS in advanced gastric cancer. For selecting patients who require intensive treatment, CTCs could be a valuable biomarker. The combined status of CTC and CY would be useful in selecting patients for radical surgery. Further investigation with a larger number of patients is necessary to establish the importance of CTCs.


Gastric Cancer Advanced Gastric Cancer Staging Laparoscopy CellSearch System Receive Induction Chemotherapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (JSPS) (Grant numbers 20591568, and 25861183), a research Grant from Shimadzu Science Foundation, and a research Grant from Fujiwara Memorial Foundation.



Supplementary material

10434_2015_4483_MOESM1_ESM.doc (77 kb)
Supplementary material 1 (DOC 77 kb)
10434_2015_4483_MOESM2_ESM.tif (2.4 mb)
Scatter plot of CTC counts in patients with advanced gastric cancer (TIFF 2507 kb)
10434_2015_4483_MOESM3_ESM.tif (1.3 mb)
ROC curve analysis to determine a cut-off value of CTCs (TIFF 1345 kb)
10434_2015_4483_MOESM4_ESM.tif (1.3 mb)
Flow diagram of the treatment course for the 123 patients with advanced gastric cancer (TIFF 1362 kb)
10434_2015_4483_MOESM5_ESM.tif (866 kb)
CTC counts in patients who received chemotherapy before starting treatment (pre-treatment) and after two to three cycles of treatment (post-treatment) (TIFF 866 kb)


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Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  • H. Okabe
    • 1
    Email author
  • S. Tsunoda
    • 1
  • H. Hosogi
    • 1
  • S. Hisamori
    • 1
  • E. Tanaka
    • 1
  • S. Tanaka
    • 2
  • Y. Sakai
    • 1
  1. 1.Division of Gastrointestinal Surgery, Department of SurgeryGraduate School of Medicine Kyoto UniversityKyotoJapan
  2. 2.Division of Breast Surgery, Department of SurgeryGraduate School of Medicine Kyoto UniversityKyotoJapan

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