Klinac Dragana, Gray Elin S, Freeman James B, Reid Anna, Bowyer Samantha, Millward Michael, Ziman Melanie
School of Medical Sciences, Edith Cowan University (ECU), 270 Joondalup Drive, Joondalup, Perth, WA 6027, Australia.
BMC Cancer. 2014 Jun 11;14:423. doi: 10.1186/1471-2407-14-423.
New effective treatments for metastatic melanoma greatly improve survival in a proportion of patients. However biomarkers to identify patients that are more likely to benefit from a particular treatment are needed. We previously reported on a multimarker approach for the detection of heterogenous melanoma circulating tumour cells (CTCs). Here we evaluated the prognostic value of this multimarker quantification of CTCs and investigated whether changes in CTC levels during therapy can be used as a biomarker of treatment response and survival outcomes.
CTCs were captured by targeting the melanoma associated markers MCSP and MCAM as well as the melanoma stem cell markers ABCB5 and CD271. CTCs were quantified in 27 metastatic melanoma patients treated by surgery or with vemurafenib, ipilimumab or dacarbazine. Patients were enrolled prospectively and CTC counts performed at baseline (prior to treatment), during and after treatment.
Baseline CTC numbers were not found to be prognostic of overall survival nor of progression free survival. However, a low baseline CTC number was associated with a rapid response to vemurafenib therapy. A decrease in CTCs after treatment initiation was associated with response to treatment and prolonged overall survival in vemurafenib treated patients.
Measuring changes in CTC numbers during treatment is useful for monitoring therapy response in melanoma patients and for providing prognostic information relating to overall survival. Further studies with larger sample sizes are required to confirm the utility of CTC quantification as a companion diagnostic for metastatic melanoma treatment.
转移性黑色素瘤的新型有效治疗方法极大地提高了部分患者的生存率。然而,需要生物标志物来识别更有可能从特定治疗中获益的患者。我们之前报道了一种用于检测异质性黑色素瘤循环肿瘤细胞(CTC)的多标志物方法。在此,我们评估了这种CTC多标志物定量的预后价值,并研究治疗期间CTC水平的变化是否可作为治疗反应和生存结果的生物标志物。
通过靶向黑色素瘤相关标志物MCSP和MCAM以及黑色素瘤干细胞标志物ABCB5和CD271来捕获CTC。对27例接受手术、维莫非尼、伊匹单抗或达卡巴嗪治疗的转移性黑色素瘤患者的CTC进行定量。患者前瞻性入组,并在基线(治疗前)、治疗期间和治疗后进行CTC计数。
未发现基线CTC数量可预测总生存期或无进展生存期。然而,低基线CTC数量与对维莫非尼治疗的快速反应相关。治疗开始后CTC减少与维莫非尼治疗患者的治疗反应和总生存期延长相关。
测量治疗期间CTC数量的变化有助于监测黑色素瘤患者的治疗反应,并提供与总生存期相关的预后信息。需要更大样本量的进一步研究来证实CTC定量作为转移性黑色素瘤治疗伴随诊断的实用性。