Zitt Matthias, Zitt Marion, Müller Hannes M, Dinnewitzer Adam J, Schwendinger Verena, Goebel Georg, De Vries Alexander, Amberger Albert, Weiss Helmut, Margreiter Raimund, Ofner Dietmar, Oberwalder Michael
Department of General and Transplant Surgery, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria.
Dis Colon Rectum. 2006 Oct;49(10):1484-91. doi: 10.1007/s10350-006-0673-4.
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.
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.
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.
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.
本研究旨在探讨接受术前放化疗的局部晚期直肠癌患者外周血中的播散肿瘤细胞是否有可能作为治疗反应的标志物。研究表明，对术前放化疗有反应的晚期直肠癌患者最有可能从这种治疗中获益。
从接受术前放化疗的晚期直肠癌患者中，在特定时间采集外周血：放化疗前、放化疗期间、放化疗后及手术期间。患者分为组织病理学反应者（ypT0-T2）和无反应者（ypT3-T4）。进行细胞角蛋白20和癌胚抗原逆转录聚合酶链反应以检测播散肿瘤细胞。如果同时检测到癌胚抗原和细胞角蛋白20，则血样被视为播散肿瘤细胞阳性。
总体人群（n = 26）在放化疗开始前播散肿瘤细胞的阳性率为32%。在反应者（n = 8）中，63%在放化疗前播散肿瘤细胞呈阳性，而无反应者（n = 18）中只有18%呈阳性（P = 0.026）。从放化疗开始到手术结束，反应者血液中的肿瘤细胞阳性率显著下降（P = 0.042）。此外，反应者在放化疗期间肿瘤细胞阳性率有下降趋势（P = 0.079）。相比之下，无反应者在治疗过程中没有明显变化。
这项前瞻性原理验证研究表明，与无反应者相比，接受术前放化疗的局部晚期直肠癌在肿瘤细胞在外周血中的播散方面表现出不同的生物学行为。
