Disseminated tumor cells in peripheral blood: a novel marker for therapy response in locally advanced rectal cancer patients undergoing preoperative chemoradiation.
OBJECTIVE
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.
Zitt
Matthias
M
Department of General and Transplant Surgery, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria. matthias.zitt@uibk.ac.at
Zitt
Marion
M
Müller
Hannes M
HM
Dinnewitzer
Adam J
AJ
Schwendinger
Verena
V
Goebel
Georg
G
De Vries
Alexander
A
Amberger
Albert
A
Weiss
Helmut
H
Margreiter
Raimund
R
Ofner
Dietmar
D
Oberwalder
Michael
M
D000230:Adenocarcinoma / Q000097:blood* / Q000235:genetics / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood*; D003131:Combined Modality Therapy; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007633:Keratins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D011446:Prospective Studies; D011878:Radiotherapy; D012004:Rectal Neoplasms / Q000097:blood* / Q000235:genetics / Q000628:therapy; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D007633:Keratins