title: Clinico-pathological correlation of serial measurement of circulating tumor cells in 24 metastatic colorectal cancer patients receiving chemotherapy reveals interpatient heterogeneity correlated with CEA levels but independent of KRAS and BRAF mutation.
abstract: BACKGROUND
  The Veridex CellSearch is an FDA-approved technology for enumerating circulating tumor cells in blood samples of metastatic colorectal cancer mCRC) patients and has prognostic value. It is important to understand how counts of circulating tumor cells (CTCs), which are advocated to be tools for "liquid biopsy" of tumors, correlate with clinical and pathologic variables of significance in these patients. In this study, we have attempted to make such correlations along with evaluating how CTC counts change during the course of chemotherapy.
  
  
  METHODS
  Following an IRB-approved protocol, blood samples were collected from 24 patients with mCRC along with relevant clinico-pathological data. Blood was collected at defined time-points both prior to as well as during the course of treatment with combination chemotherapy, and CTC counts were enumerated from 7.5 ml of blood.
  
  
  RESULTS
  Seventeen out of 24 patients with mCRC showed a CTC count of 2 or less cells in 7.5 ml of blood at base-line assessment before chemotherapy while 7 patients showed 3 or more cells in 7.5 ml of blood at that point. A correlation was found between high carcino-embryonic antigen (CEA) levels and high CTC counts (P = 0.018) although it was also found that some patients had elevated CTCs without an elevated CEA. No correlation with the time interval between detection of primary tumor and appearance of secondary (metastatic) tumor(s) was found. CTC counts did not correlate with the presence of lung or liver metastases, i.e. a number of mCRC patients with lung or liver metastases had a count of zero CTCs at baseline. We also noted no correlation between CTC number and the status of KRAS or BRAF mutation. CTC counts dropped immediately after the start of chemotherapy in 11 out of 21 patients, and also reduced from the baseline at the end of chemotherapy in 5 out of 10 patients. Six of 7 patients who started with 3 or more CTCs in 7.5 ml at baseline also showed a final CTC reduction at the end of the therapy assessment.
  
  
  CONCLUSIONS
  Analysis of circulating tumor cells may be of use in monitoring response to therapy in mCRC, either in combination with CEA monitoring or alone when CTCs are elevated but CEA level is not.
authors: a Hematology/Oncology Division; Penn State Hershey Cancer Institute ; Hershey , PA , USA.
authors: Avisnata
authors: A
authors: Das
authors: Miriam
authors: M
authors: Kunkel
authors: Jamal
authors: J
authors: Joudeh
authors: David T
authors: DT
authors: Dicker
authors: Angelique
authors: A
authors: Scicchitano
authors: Joshua E
authors: JE
authors: Allen
authors: Nabeel
authors: N
authors: Sarwani
authors: Zhaohai
authors: Z
authors: Yang
authors: Jussuf
authors: J
authors: Kaifi
authors: Junjia
authors: J
authors: Zhu
authors: Jason
authors: J
authors: Liao
authors: Wafik S
authors: WS
authors: El-Deiry
mesh_terms: D002272:Carcinoembryonic Antigen / Q000097:blood* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics
chemical_list: D002272:Carcinoembryonic Antigen; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins
keywords: BRAF; CEA, carcinoembryonic antigen; CTC, circulating tumor cell; ECOG, Eastern Cooperative Oncology Group; FDA, Food and Drug Administration; IRB, Institutional Review Board; KRAS; biopsy; carcinoembryonic antigen; circulating neoplastic cells; colorectal neoplasms; drug therapy; mCRC, metastatic colorectal cancer; neoplasm metastasis