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Disseminated Tumor Cells in Peripheral Blood: A Novel Marker for Therapy Response in Locally Advanced Rectal Cancer Patients Undergoing Preoperative Chemoradiation

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Diseases of the Colon & Rectum

Purpose

This study was designed to examine whether disseminated tumor cells in peripheral blood of locally advanced rectal cancer patients undergoing preoperative chemoradiation have the potential to serve as a marker for therapy response. Studies suggest that patients with advanced rectal cancer who respond to preoperative chemoradiation most likely benefit from this treatment.

Methods

From advanced rectal cancer patients undergoing preoperative chemoradiation, peripheral blood was obtained at defined times: before, during, and after chemoradiation and during surgery. Patients were divided into histopathologic responders (ypT0-T2) and nonresponders (ypT3-T4). Cytokeratin 20 and carcinoembryonic antigen reverse transcriptase-polymerase chain reaction were performed to detect disseminated tumor cells. A blood sample was deemed positive for disseminated tumor cells if both carcinoembryonic antigen and cytokeratin 20 were detected.

Results

The overall population (n = 26) showed a positivity rate of 32 percent for disseminated tumor cells before initiation of chemoradiation. Of the responders (n = 8), 63 percent were positive for disseminated tumor cells before chemoradiation, whereas only 18 percent of nonresponders (n = 18) were positive (P = 0.026). From initiation of chemoradiation to the end of surgery, a significant decrease was seen in tumor cell positivity in the blood of responders (P = 0.042). Moreover, the responders represented a trend toward a decrease in tumor cell positivity during chemoradiation (P = 0.079). In contrast, there were no noticeable alterations within the treatment course in nonresponders.

Conclusions

This prospective proof of principle study demonstrates that locally advanced rectal cancer with preoperative chemoradiation shows different biologic behavior in terms of tumor cell dissemination in peripheral blood when therapy responders compared with nonresponders.

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Authors and Affiliations

  1. Department of General and Transplant Surgery, Innsbruck Medical University, Anichstrasse 35, A-6020, Innsbruck, Austria

    Matthias Zitt M.D., Hannes M. Müller M.D., Helmut Weiss M.D., Raimund Margreiter M.D., Dietmar Öfner M.D. & Michael Oberwalder M.D.

  2. Tyrolean Cancer Research Institute, Innsbruck, Austria

    Marion Zitt & Albert Amberger Ph.D.

  3. Department of Surgery, Landeskrankenanstalten, Salzburg, Austria

    Adam J. Dinnewitzer M.D.

  4. Department of Radiotherapy and Radiooncology, Innsbruck Medical University, Innsbruck, Austria

    Verena Schwendinger M.D. & Alexander De Vries M.D.

  5. Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria

    Georg Goebel Ph.D.

Authors
  1. Matthias Zitt M.D.
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  2. Marion Zitt
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Corresponding author

Correspondence to Matthias Zitt M.D..

Additional information

Matthias Zitt, M.D., Marion Zitt, and Hannes M. Müller, M.D. contributed equally to this work.

Funded in part by research grants from: Österreichische Nationalbank (ÖNB, Grant number: 10929), Wissenschaftsfond des Landes Tirol, Österreichische Krebshilfe-Krebsgesellschaft Tirol and Chirurgisch-Onkologische Forschungsförderung (COFF).

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Zitt, M., Zitt, M., Müller, H.M. et al. Disseminated Tumor Cells in Peripheral Blood: A Novel Marker for Therapy Response in Locally Advanced Rectal Cancer Patients Undergoing Preoperative Chemoradiation. Dis Colon Rectum 49, 1484–1491 (2006). https://doi.org/10.1007/s10350-006-0673-4

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