Staritz P, Kienle P, Koch M, Benner A, von Knebel Doeberitz M, Rudi J, Weitz J
Dept. of Medicine, University of Heidelberg, Germany.
J Exp Clin Cancer Res. 2004 Dec;23(4):633-9.
In a pilot study the effect of palliative chemotherapy on the detection rates of circulating tumour cells in peripheral venous blood of stage IV colorectal cancer patients was investigated. The results indicate a recruitment of tumour cells during chemotherapy and suggest a poorer survival for tumour cell positive patients. Circulating tumour cells have been shown to be a potential prognostic factor in patients who undergo curative resection for colorectal cancer. The effect of chemotherapy on the detection rates of disseminated tumour cells in blood has not yet been adequately investigated. Objective of this pilot-study was to analyze circulating tumour cells in peripheral venous blood of colorectal cancer patients undergoing chemotherapy in order to evaluate its potential value as a surrogate-marker for predicting clinical outcome after chemotherapy. Our hypothesis was that chemotherapy results in a reduction of the detection rates of circulating tumour cells in colorectal cancer patients. Forty-two Stage IV patients were examined at three different time points before and during palliative chemotherapy for the presence of disseminated tumour cells, using a previously described RT-PCR-assay for cytokeratin 20. 80.1% of the patients showed disseminated tumour cells at least once. Before chemotherapy, patients with multi-organ metastases were positive in 62.5%, patients with locally limited disease in only 14.3%. After the first chemotherapy, the detection rates in the latter group increased to 62.5%, for all patients in the same time from 46.3% to 57.5%. Clinical therapy responders showed an increase in the detection rates from 28.5% before to 71.4% after chemotherapy. In contrast, chemotherapy had no effect on tumour cell detection rates of patients with progressive disease (57% before vs. 60% after therapy). Patients with detected circulating tumour cells showed a shorter overall survival than patients without circulating tumour cells (83 vs. 53 weeks). Clinical therapy responders on average lived only 3 weeks longer than non-responders. In contrast to the original hypothesis, our data suggest a recruiting of circulating tumour cells during chemotherapy in advanced colorectal cancer. Further investigations are needed to clarify the potential role of circulating tumour cells for monitoring chemotherapy in these patients.
在一项初步研究中,调查了姑息化疗对IV期结直肠癌患者外周静脉血中循环肿瘤细胞检测率的影响。结果表明化疗期间肿瘤细胞会增多,提示肿瘤细胞阳性患者的生存期较短。循环肿瘤细胞已被证明是接受结直肠癌根治性切除患者的潜在预后因素。化疗对血液中播散肿瘤细胞检测率的影响尚未得到充分研究。这项初步研究的目的是分析接受化疗的结直肠癌患者外周静脉血中的循环肿瘤细胞,以评估其作为预测化疗后临床结局替代标志物的潜在价值。我们的假设是化疗会导致结直肠癌患者循环肿瘤细胞检测率降低。42例IV期患者在姑息化疗前和化疗期间的三个不同时间点接受检查,使用先前描述的细胞角蛋白20的逆转录聚合酶链反应检测法检测是否存在播散肿瘤细胞。80.1%的患者至少有一次检测到播散肿瘤细胞。化疗前,多器官转移患者的阳性率为62.5%,局部局限性疾病患者的阳性率仅为14.3%。第一次化疗后,后一组患者的检测率升至62.5%,同期所有患者的检测率从46.3%升至57.5%。临床治疗有反应者的检测率从化疗前的28.5%升至化疗后的71.4%。相比之下,化疗对疾病进展患者的肿瘤细胞检测率没有影响(治疗前为57%,治疗后为60%)。检测到循环肿瘤细胞的患者总生存期比未检测到循环肿瘤细胞的患者短(83周对53周)。临床治疗有反应者平均比无反应者仅多活3周。与原假设相反,我们的数据表明晚期结直肠癌化疗期间循环肿瘤细胞会增多。需要进一步研究以阐明循环肿瘤细胞在监测这些患者化疗中的潜在作用。