英国的一项研究确定了关于循环肿瘤细胞(CTC)对神经内分泌肿瘤患者的预后意义。研究结果在线发表于2012年12月17日的Journal of Clinical Oncology上[全文下载]。

　　这项单中心、前瞻性研究的研究，共纳入了176例存在可测量病灶的转移性神经内分泌肿瘤(NET)患者。循环肿瘤细胞通过使用一项半自动技术进行测定：利用免疫磁性分离方法对上皮细胞粘附的分子表达细胞进行分离。

　　研究结果显示，整体而言，49%的患者在每7.5mL血样中存在≥1个循环肿瘤细胞，42%的患者存在≥2个循环肿瘤细胞，30%的患者存在≥5个循环肿瘤细胞。循环肿瘤细胞的存在与肿瘤负担增加、肿瘤分级提高以及嗜铬粒蛋白A(CgA)水平提高之间存在关联。通过包含90例患者的训练集以及85例患者的验证集，研究者定义了<1个循环肿瘤细胞或≥1个循环肿瘤细胞为无进展存活期(PFS)相关最佳预后阈值点。通过该阈值发现，存在≥1个循环肿瘤细胞与较差的PFS以及较差总生存期(OS)之间存在关联(风险比分别为6.6与8.0；二者P<0.001)。

　　是否检出CTC两组患者的PFS曲线

　　对包括分级、肿瘤负担以及等CgA在内的其他预后指标进行的多变量分析结果显示，循环肿瘤细胞仍为一个显著预后因素。对于各等级肿瘤，根据存在的循环肿瘤细胞可对不良预后的患者亚群进行界定。对于1级肿瘤，PFS风险比为5.0(P =0.017)，OS风险比为7.2(P =0.023)。而对于2级肿瘤，PFS风险比为3.5(P =0.018)，OS风险比为5.2(P =0.036)。

　　由此得出结论，对于转移性神经内分泌癌患者，循环肿瘤细胞是一种有前途的预后指标，应在针对明确肿瘤亚型以及治疗方法的临床试验环境下，进一步对其进行评估。

　　Purpose

　　To determine the prognostic significance of circulating tumor cells (CTCs) in patients with neuroendocrinecancer.

　　Patients and Methods

　　In this single-center prospective study, 176 patients with measurable metastatic neuroendocrinetumors (NETs) were recruited. CTCs were measured using a semiautomated techniquebased on immunomagnetic separation of epithelial cell adhesion molecule-expressing cells.

　　Results

　　Overall, 49% patients had ≥ one CTC, 42% had ≥ two CTCs, and 30% had ≥ five CTCs in 7.5mL blood. Presence of CTCs was associated with increased burden, increased tumor grade,and elevated serum chromogranin A (CgA). Using a 90-patient training set and 85-patientvalidation set, we defined a cutoff of < one or ≥ one as the optimal prognostic threshold withrespect to progression-free survival (PFS). Applying this threshold, the presence of one CTCwas associated with worse PFS and overall survival (OS; hazard ratios [HRs], 6.6 and 8.0,respectively; both P<0.001). In multivariate analysis, CTCs remained significant when otherprognostic markers, grade, tumor burden, and CgA were included. Within grades, presence ofCTCs was able to define a poor prognostic subgroup. For grade 1, HRs were 5.0 forPFS (P=0.017) and 7.2 for OS (P=0.023); for grade 2, HRs were 3.5 for PFS (P=0.018) and5.2 for OS (P=0.036).

　　Conclusion

　　CTCs are a promising prognostic marker for patients with NETs and should be assessed in thecontext of clinical trials with defined tumor subtypes and therapy.
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