Silva Virgílio Souza E, Abdallah Emne Ali, Brito Angelo Borsarelli Carvalho de, Braun Alexcia Camila, Tariki Milena Shizue, de Mello Celso Abdon Lopes, Calsavara Vinicius Fernando, Riechelmann Rachel, Chinen Ludmilla Thomé Domingos
Department of Medical Oncology, A.C. Camargo Cancer Center, São Paulo 01509-900, Brazil.
International Research Center, A.C. Camargo Cancer Center, São Paulo 01508-010, Brazil.
Diagnostics (Basel). 2021 Mar 12;11(3):502. doi: 10.3390/diagnostics11030502.
The discovery of predictive biomarkers in metastatic colorectal cancer (mCRC) is essential to improve clinical outcomes. Recent data suggest a potential role of circulating tumor cells (CTCs) as prognostic indicators. We conducted a follow-on analysis from a prospective study of consecutive patients with mCRC. CTC analysis was conducted at two timepoints: baseline (CTC1; before starting chemotherapy), and two months after starting treatment (CTC2). CTC isolation/quantification were completed by ISET (Rarecells, France). CTC expressions of drug resistance-associated proteins were evaluated. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Seventy-five patients were enrolled from May 2012 to May 2014. A CTC1 cut-off of >1.5 CTCs/mL was associated with an inferior median OS compared to lower values. A difference of CTC2-CTC1 > 5.5 CTCs/mL was associated with a reduced median PFS. By multivariate analysis, CTC1 > 1.5 CTCs/mL was an independent prognostic factor for worse OS. Multi-drug resistance protein-1 (MRP-1) expression was associated with poor median OS. CTC baseline counts, kinetics, and MRP-1 expression were predictive of clinical outcomes. Larger studies are warranted to explore the potential clinical benefit of treating mCRC patients with targeted therapeutic regimens guided by CTC findings.
在转移性结直肠癌（mCRC）中发现预测性生物标志物对于改善临床结局至关重要。近期数据表明循环肿瘤细胞（CTC）作为预后指标具有潜在作用。我们对连续的mCRC患者进行了一项前瞻性研究的后续分析。在两个时间点进行CTC分析：基线（CTC1；开始化疗前）和开始治疗两个月后（CTC2）。通过ISET（法国Rarecells公司）完成CTC分离/定量。评估与耐药相关蛋白的CTC表达。采用Kaplan-Meier法估计无进展生存期（PFS）和总生存期（OS）。2012年5月至2014年5月共纳入75例患者。与较低值相比，CTC1>1.5个/毫升的临界值与较差的中位OS相关。CTC2-CTC1>5.5个/毫升的差异与中位PFS降低相关。通过多变量分析，CTC1>1.5个/毫升是OS较差的独立预后因素。多药耐药蛋白-1（MRP-1）表达与较差的中位OS相关。CTC基线计数、动力学和MRP-1表达可预测临床结局。有必要开展更大规模的研究，以探索根据CTC结果指导mCRC患者接受靶向治疗方案的潜在临床益处。
