The Utility of Circulating Tumor Cells in Monitoring the Outcomes in Patients with Biliary Cancer

Abstract

Purpose: Outcomes of patients with biliary cancer are often poor and toxicities of chemotherapy are considerable. Recently the Circulating Tumor Cells (CTC) assay was approved for prognostication in early stage breast cancer (adjuvant therapy) and in metastatic breast, colon and prostate cancer, as their presence has been coorelate with poor progression free and overall survival. This has not been studied with patients with biliary cancer and hence it was undertaken as its validation would help to guide theurapeutic decision making and prognosis in patients with biliary cancer. Methods: Fifteen patients with biliary cancers has 10ml peripheral blood drawn in CellSave Preservative Tubes (Immunicon, Huntingdon Valley, PA) containing EDTA as anticoagulant and a cellular preservative. Blood samples were maintained at room temperature and processed within a maximum of 96 h after blood drawing. The CellSearch system by Veridex that is FDA approved for use in other cancers, was used for the capture, enrichment, identification and enumeration of rare CTCs of epithelial origin in peripheral blood in these patients. The CellSearch assay enumerates only CTC that express the Epithelial Cell Adhesion Molecule (EpCAM) and cytokeratins (CK) 8, 18, and 19. Baseline characteristics and treatment outcomes were correlated with these results. Results: The analysis was done on 13 patients in Roswell Park Cancer Institute in 2008. Patient characteristics were as follows: Median age 64 years (range 45-72 years). Diagnoses were as follows: Intrahepatic cholangiocarcinoma (n=11), Gall bladder cancer (n=2) and extrahepatic cholangiocarcinoma (n=0). Stage at the time of CTC assay: Stage I (n=2), stage II (n=1), stage III (n=4) and stage IV (n=5). All patients had no detectable CTCs, except one patient with an aggressive metastatic gall bladder cancer. The baseline CTC assay showed 4 CTC/7.5 ml whole blood. After 2 cycles of chemotherapy with 5-FU and oxaliplatin (FOLFOX) the assay was repeated and there were no detectable CTCs. The absence of CTC suggested a good response to chemotherapy, even before any clinical improvement had been noted and corresponded to a tumor marker response (CA 19-9 marker which was borderline normal poschemotherapy compared to 54.5 U/mL (high) pretreatment. Subsequently, radiographic confirmation of dramatic partial response and clinical improvement in pain, energy and performance status was seen. Conclusion: This is the first report to our knowledge of the use of this assay in patients with biliary cancer. Further validation in a larger cohort is indicated as our findings suggest that it may be useful for monitoring patients with biliary cancers.