该研究的目的是评估持续性 CTC 与术后约 12 个月临床无复发的患者随后复发之间的关联。

循环肿瘤细胞已被提议作为预测胰腺癌存活率的生物标志物。一些患者在术后表现出持续的 CTC，这可能代表最小的残留病灶。

来自先前发表的前瞻性 CLUSTER 试验的患者在术后 12 个月没有临床复发证据，并且在术后 9-15 个月进行了 CTC 检测。上皮细胞 (eCTC) 和移行细胞 (trCTC) 的存在被评估为复发的预测因子。 Kaplan-Meier曲线、对数秩检验和Cox模型用于生存分析。

纳入了 129 名符合条件的患者中的 33 名（CLUSTER 试验）。 trCTC 阳性和阴性患者的临床病理特征平衡良好。 trCTCs 患者的每人每月复发率为 10.3%，而 trCTCs 阴性患者的复发率为 3.1%，中位复发时间分别为 3.9 个月和 27.1 个月。在多变量分析中，trCTCs 阳性与较高的晚期复发风险相关（HR：4.7，95%CI：1.2-18.3，P=0.024）。 14 名 (42.4%) 患者在术后第二年复发。术后 1 年 trCTCs 阳性与第二年较高的复发率相关（OR：13.1，95%CI：1.6-1953.4，P=0.028，AUC=0.72）。将临床病理学特征与 trCTC 相结合将 AUC 增加到 0.80。大多数 trCTCs 阳性患者（N=5, 62.5%）有多部位复发，其次是仅局部（N=2, 25.0%）和仅肝脏（N=1, 12.5%）复发。这与 trCTCs 阴性患者形成鲜明对比，其中大多数（N=6, 66.7%）仅局部复发，其次是仅肝脏（N=2, 22.2%）和多部位（N=1, 11.1%) 复发。在术后 12 个月被认为临床无病的患者中，trCTCs 阳性与更高的随后复发率相关，且复发模式不同。 CTC 可用作推定的生物标志物来指导胰腺癌患者的预后和管理。

Abstract

Objective: The aim of the study was to assess the association between persistent CTCs and subsequent recurrence in patients who were clinically recurrence free approximately 12 months postoperatively.

Background: Circulating tumor cells have been proposed as biomarkers to predict survival in pancreatic cancer. Some patients demonstrate persistent CTCs postoperatively which could represent minimal residual disease.

Methods: Patients from previously published prospective CLUSTER trial without clinical evidence of recurrence 12 months postoperatively and CTC testing performed 9-15 months postoperatively were included. Presence of epithelial (eCTCs) and transitional CTCs (trCTCs) was evaluated as predictor of recurrence. Kaplan-Meier curve, log-rank test, and Cox model were used for survival analysis.

Results: Thirty-three of 129 eligible patients (CLUSTER trial) were included. The trCTC positive and negative patients were well-balanced in clinicopathological features. Patients with trCTCs had a recurrence rate per-person-month of 10.3% compared to 3.1% in trCTCs negative patients with a median time to recurrence of 3.9 versus 27.1 months, respectively. On multivariable analysis trCTCs positivity was associated with higher risk of late recurrence (HR:4.7,95%CI:1.2-18.3, P=0.024). Fourteen (42.4%) patients recurred during the second postoperative year. 1-year postoperative trCTCs positivity was associated with a higher rate of recurrence during the second year (OR:13.1,95%CI:1.6-1953.4,P=0.028, AUC=0.72). Integrating clinicopathological features with trCTCs increased the AUC to 0.80. A majority of trCTCs positive patients (N=5, 62.5%) had multi-site recurrence, followed by local-only (N=2, 25.0%) and liver-only (N=1, 12.5%) recurrence. This was in striking contrast to trCTCs negative patients, where a majority (N=6, 66.7%) had a local-only recurrence, followed by liver-only (N=2, 22.2%) and multi-site (N=1, 11.1%) recurrence.

Conclusion: In patients deemed to be clinically disease free 12 months postoperatively, trCTCs positivity is associated with higher rates of subsequent recurrence with distinct patterns of recurrence. CTCs could be used a putative biomarker to guide patient prognostication and management in pancreatic cancer.

原文链接

https://pubmed.ncbi.nlm.nih.gov/36111892/

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