Prognostic value of CA 19-9, CEA, CRP, LDH and bilirubin levels in locally advanced and metastatic pancreatic cancer: results from a multicenter, pooled analysis of patients receiving palliative chemotherapy
Prognostic value of CA 19-9, CEA, CRP, LDH and bilirubin levels in locally advanced and metastatic pancreatic cancer: results from a multicenter, pooled analysis of patients receiving palliative chemotherapy
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DOI：
10.1007/s00432-012-1371-3
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发表时间：
2013-04-01
影响因子：
3.6
通讯作者：
Boeck, Stefan
中科院分区：
文献类型：
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作者：
Haas, Michael;Heinemann, Volker;Boeck, Stefan
CA 19-9 是唯一已确定的胰腺癌 (PC) 肿瘤标志物； CEA、CRP、LDH 或胆红素等其他血清标志物的预后作用尚未确定。我们汇集了两项德国多中心随机 II 期试验的 CA 19-9、CEA、CRP、LDH 和胆红素水平的治疗前数据以及来自一个大容量德国癌症中心的前瞻性患者数据。在开始晚期 PC 姑息性一线治疗之前和治疗期间连续评估标记物水平（仅适用于 CA 19-9）。通过使用单变量和多变量 Cox 模型，将临床和生物标志物数据（总共 12 个变量）与疗效终点进展时间 (TTP) 和总生存期 (OS) 相关联。来自 291 名患者的数据纳入本次汇总分析； 253 名患者 (87%) 在前瞻性临床试验中接受了治疗。研究队列中的中位 TTP 为 5.1 个月，中位 OS 为 9.0 个月。在单变量分析中，治疗前 CA 19-9 (HR 1.55)、LDH (HR 2.04) 和 CEA (HR 1.89) 水平与 TTP 显着相关。关于 OS，基线 CA 19-9 (HR 1.46)、LDH (HR 2.07)、CRP (HR 1.69) 和胆红素 (HR 1.62) 是重要的预后因素。在多变量分析中，治疗前 log [CA 19-9]（作为 TTP 的连续变量）和 log [胆红素] 以及 log [CRP]（对于 OS）具有独立的预后价值。前两个化疗周期期间 CA 19-9 下降千分之 25% 可预测 TTP 和 OS，与所应用的 CA 19-9 检测无关。一线化疗期间的基线 CA 19-9 和 CA 19-9 动力学可预测晚期 PC。除此之外，发现其他血清标志物如 CRP、LDH 和胆红素也可以提供 TTP 和 OS 的预后信息。
CA 19-9 is the only established tumor marker in pancreatic cancer (PC); the prognostic role of other serum markers like CEA, CRP, LDH or bilirubin has not yet been defined.We pooled pre-treatment data on CA 19-9, CEA, CRP, LDH and bilirubin levels from two German multicenter randomized phase II trials together with prospective patient data from one high-volume German Cancer Center. Marker levels were assessed locally before the start of palliative first-line therapy for advanced PC and serially during treatment (for CA 19-9 only). Clinical and biomarker data (overall 12 variables) were correlated with the efficacy endpoints time-to-progression (TTP) and overall survival (OS) by using uni- and multivariate Cox models.Data from 291 patients were included in this pooled analysis; 253 patients (87 %) received treatment within prospective clinical trials. Median TTP in the study cohort was 5.1 months and median OS 9.0 months. In univariate analysis, pre-treatment CA 19-9 (HR 1.55), LDH (HR 2.04) and CEA (HR 1.89) levels were significantly associated with TTP. Regarding OS, baseline CA 19-9 (HR 1.46), LDH (HR 2.07), CRP (HR 1.69) and bilirubin (HR 1.62) were significant prognostic factors. Within multivariate analyses, pre-treatment log [CA 19-9] (as continuous variable for TTP) and log [bilirubin] as well as log [CRP] (for OS) had an independent prognostic value. A CA 19-9 decline of a parts per thousand yen25 % during the first two chemotherapy cycles was predictive for TTP and OS, independent of the applied CA 19-9 assay.Baseline CA 19-9 and CA 19-9 kinetics during first-line chemotherapy are prognostic in advanced PC. Besides that finding other serum markers like CRP, LDH and bilirubin can also provide prognostic information on TTP and OS.