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多中心研究评估循环肿瘤细胞作为转移性乳腺癌治疗反应和总生存期的替代指标。

Multi-center study evaluating circulating tumor cells as a surrogate for response to treatment and overall survival in metastatic breast cancer.

机构信息

Department of Breast Surgical Oncology, St. Luke's International Hospital, Chuo-ku, Tokyo, Japan.

出版信息

Breast Cancer. 2010 Jul;17(3):199-204. doi: 10.1007/s12282-009-0139-3. Epub 2009 Aug 1.

DOI:10.1007/s12282-009-0139-3
PMID:19649686
Abstract

BACKGROUND

Evaluating circulating tumor cells (CTCs) is one way to predict outcome and monitor treatment in patients with MBC. In this prospective study, we evaluated CTCs in predicting treatment efficacy and overall survival (OS) using the CellSearch System (Veridex, LLC, Raritan, NJ).

METHODS

One hundred nineteen patients with MBC with measurable disease were enrolled. Samples of 7.5 ml of blood from 107 eligible patients were tested for CTCs before starting therapy (baseline), after one cycle of therapy (3-4 weeks) and at 12 weeks. We compared CTC levels and imaging at baseline and at 12 weeks. Next, we determined the hazard ratios (HR) by comparing cases with zero CTCs to those with one or more CTCs. Moreover, HR was calculated when comparing cases that had greater than or equal to a certain number of CTCs to those with less than the number of CTCs.

RESULTS

This study shows the incidence of detection of CTCs in patients with metastatic breast cancers. Of the patients, 64.4% (76/118) had one or more CTCs, and 37.3% (44/118) had five or more CTCs. First we set the baseline number of CTCs as 100%. Of the seven cases whose level of CTCs decreased more than 90%, six (85.7%) demonstrated a positive response (complete response and partial response) by imaging after one cycle (3-4 weeks later). For the patients whose CTC levels increased above 100% after one cycle (3-4 weeks later), 7 of 11 (63.6%) had progressive disease (PD). The HR for cases with five to ten CTCs was greater than 1.00 [HR = 2.450; 95% confidence interval (CI) 0.727-8.248]. Statistical significance was observed when comparing patients who had > or =3 CTCs to those with <3 CTCs (P = 0.0273). When comparing cases with > or =5 CTCs to those with <5 CTCs, the hazard ratio was 3.069 (95% CI 1.496-6.295; P = 0.0022).

CONCLUSIONS

Because the change in the number of CTCs was highly correlated with results from imaging before and after therapy, CTCs can be considered a biomarker that may predict the effect of treatment earlier than imaging modalities.

摘要

背景

评估循环肿瘤细胞(CTC)是预测MBC 患者预后和监测治疗的一种方法。在这项前瞻性研究中,我们使用 CellSearch 系统(Veridex,LLC,Raritan,NJ)评估了 CTC 在预测治疗效果和总生存期(OS)方面的作用。

方法

纳入了 119 例可测量疾病的 MBC 患者。107 例合格患者的 7.5ml 血液样本在开始治疗前(基线)、治疗一个周期后(3-4 周)和 12 周时进行 CTC 检测。我们比较了基线和 12 周时的 CTC 水平和影像学结果。然后,我们通过比较零 CTC 病例与一个或多个 CTC 病例来确定风险比(HR)。此外,当比较 CTC 数量大于或等于一定数量的病例与 CTC 数量小于该数量的病例时,我们计算了 HR。

结果

本研究显示了转移性乳腺癌患者中 CTC 检测的发生率。在 118 例患者中,64.4%(76/118)有一个或多个 CTC,37.3%(44/118)有五个或更多的 CTC。首先,我们将基线 CTC 数量设定为 100%。在七个 CTC 水平下降超过 90%的病例中,六个(85.7%)在一个周期(3-4 周后)后通过影像学显示出阳性反应(完全缓解和部分缓解)。对于一个周期(3-4 周后)后 CTC 水平增加超过 100%的患者,11 例中有 7 例(63.6%)发生进展性疾病(PD)。5 到 10 个 CTC 的病例的 HR 大于 1.00[HR=2.450;95%置信区间(CI)0.727-8.248]。与 <3 CTC 的病例相比,比较有 >或=3 CTC 的病例时具有统计学意义(P=0.0273)。当比较 >或=5 CTC 的病例与 <5 CTC 的病例时,风险比为 3.069(95%CI 1.496-6.295;P=0.0022)。

结论

由于 CTC 数量的变化与治疗前后的影像学结果高度相关,因此 CTC 可被视为一种生物标志物,其可能比影像学更早地预测治疗效果。

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