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直肠癌患者术前放化疗后循环肿瘤细胞检测率降低:迈向结直肠癌新辅助治疗分子替代标志物的第一步。

Decreased detection rate of disseminated tumor cells of rectal cancer patients after preoperative chemoradiation: a first step towards a molecular surrogate marker for neoadjuvant treatment in colorectal cancer.

作者信息

Kienle Peter, Koch Moritz, Autschbach Frank, Benner Axel, Treiber Martina, Wannenmacher Michael, von Knebel Doeberitz Magnus, Büchler Markus, Herfarth Christian, Weitz Jürgen

机构信息

Division for Molecular Diagnostics and Therapy and Division for Surgical Oncology of the Department of Surgery, University of Heidelberg, Germany.

出版信息

Ann Surg. 2003 Sep;238(3):324-30; discussion 330-1. doi: 10.1097/01.sla.0000086547.27615.e6.

Abstract

OBJECTIVE

To compare the detection rates for rectal cancer cells in blood and bone marrow in patients with or without preoperative chemoradiation.

SUMMARY BACKGROUND DATA

Previous reports have postulated a resistance of disseminated tumor cells to antiproliferative agents because of tumor cell dormancy.

METHODS

Blood samples from 142 patients (pre, intra-, and postoperative samples) and bone marrow samples from 127 patients undergoing resection of rectal adenocarcinoma were analyzed for tumor cells using a cytokeratin (CK) 20-reverse transcription polymerase chain reaction. The results were stratified according to preoperative therapy.

RESULTS

In patients without preoperative chemoradiation, tumor cell detection in blood and bone marrow correlated to tumor stage (Cochran Armitage trend test, P < 0.05). Tumor cells were detected in 34 of 103 (33%) bone marrow and 65 of 117 (55.6%) blood samples of patients without neoadjuvant treatment versus in 4 of 24 (16.7%) bone marrow and in 10 of 25 (40%) blood samples of patients with neoadjuvant treatment. The tumor cell detection rate was significantly lower in the group having undergone chemoradiation (binary logistic regression analysis, P < 0.05). The overall and disease-free survival were significantly worse in patients with tumor cell detection in the bone marrow after neoadjuvant therapy.

CONCLUSIONS

Preoperative chemoradiation is associated with a decreased detection rate of rectal cancer cells in blood and bone marrow. These findings may explain the observed clinical benefit of patients with rectal cancer receiving chemoradiation. This is the first study suggesting that detection of disseminated rectal cancer cells may be useful for assessing the efficacy of neoadjuvant therapy.

摘要

目的

比较术前接受或未接受放化疗的直肠癌患者血液及骨髓中直肠癌细胞的检出率。

总结背景数据

既往报道推测,由于肿瘤细胞休眠,播散性肿瘤细胞对增殖抑制剂具有抗性。

方法

采用细胞角蛋白(CK)20逆转录聚合酶链反应,对142例患者(术前、术中及术后样本)的血样和127例行直肠腺癌切除术患者的骨髓样本进行肿瘤细胞分析。根据术前治疗情况对结果进行分层。

结果

在未接受术前放化疗的患者中,血液及骨髓中的肿瘤细胞检测结果与肿瘤分期相关( Cochr an Armitage趋势检验,P<0.05)。未接受新辅助治疗患者的103份骨髓样本中有34份(33%)及117份血样中有65份(55.6%)检测到肿瘤细胞,而接受新辅助治疗患者的24份骨髓样本中有4份(16.7%)及25份血样中有10份(40%)检测到肿瘤细胞。接受放化疗组的肿瘤细胞检出率显著较低(二元逻辑回归分析,P<0.05)。新辅助治疗后骨髓中检测到肿瘤细胞的患者总生存期及无病生存期明显较差。

结论

术前放化疗与血液及骨髓中直肠癌细胞检出率降低有关。这些发现可能解释了直肠癌患者接受放化疗所观察到的临床获益。这是第一项表明检测播散性直肠癌细胞可能有助于评估新辅助治疗疗效的研究。

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