Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors
Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors
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DOI：
10.1002/ijc.24953
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发表时间：
2010-05-15
影响因子：
6.4
通讯作者：
Cristofanilli, Massimo
中科院分区：
文献类型：
--
作者：
Gazzaniga, Paola;Naso, Giuseppe;Cristofanilli, Massimo
通过CellSearch（TM）技术检测转移性乳腺癌中的循环肿瘤细胞（CTC）的预后价值提出了关于该信息的生物学价值的其他问题。我们假设CTC的耐药谱可以预测癌症患者对化疗的反应，因此可以用于患者选择。105例诊断为癌症的患者参加了一项前瞻性试验。从外周血中分离CTC，并评价阳性样品中参与抗癌药物抗性的一组基因的表达。在24个月的随访中，耐药特征与无病生存期（DFS;辅助治疗患者）和疾病进展时间（TIP;转移性患者）相关。客观反应相关性是次要终点。51%的患者被发现CTC阳性，而来自健康供体的所有血液样本均为阴性。耐药谱与DFS和TTP相关（两者p < 0.001）。测试的灵敏度：能够预测98%患者的治疗反应。检测的特异性：100%;健康受试者的样本中无CTC阳性。阳性和阴性预测值分别为96.5%和100%。我们确定了CTC的耐药谱，这是对化疗反应的预测，与肿瘤类型和疾病阶段无关。这种方法可能代表了癌症患者化疗个体化的第一步。
The prognostic value associated with the detection of circulating tumor cells (CTCs) in metastatic breast cancer by the CellSearch (TM) technology raise additional issues regarding the biological value of this information. We postulated that a drug-resistance profile of CTCs may predict response to chemotherapy in cancer patients and therefore could be used for patient selection. One hundred 5 patients with diagnosis of carcinoma were enrolled in a prospective trial. CTCs were isolated from peripheral blood, and positive samples were evaluated for the expression of a panel of genes involved in anticancer drugs resistance. The drug-resistance profile was correlated with disease-free survival (DFS; patients in adjuvant setting) and time to progression (TIP; metastatic patients) in a 24-months follow-up. Objective response correlation was a secondary end point. Fifty-one percent of patients were found positive for CTCs while all blood samples from healthy donors were negative. The drug-resistance profile correlates with DFS and TTP (p < 0.001 in both). Sensitivity of the test: able to predict treatment response in 98% of patients. Specificity of the test: 100%; no sample from healthy subject was positive for the presence of CTCs. Positive and negative predictive values were found to be 96.5 and 100%, respectively. We identified a drug-resistance profile of CTCs, which is predictive of response to chemotherapy, independent of tumor type and stage of disease. This approach may represent a first step toward the individualization of chemotherapy in cancer patients.