Haas Michael, Kern Christoph, Kruger Stephan, Michl Marlies, Modest Dominik P, Giessen Clemens, Schulz Christoph, von Einem Jobst C, Ormanns Steffen, Laubender Rüdiger P, Holdenrieder Stefan, Heinemann Volker, Boeck Stefan
Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany,
Tumour Biol. 2015 Apr;36(4):2631-40. doi: 10.1007/s13277-014-2885-x. Epub 2014 Dec 4.
The present prospective single-center study investigated the prognostic role of novel serum biomarkers in advanced pancreatic cancer (PC). Patients (pts) with locally advanced or metastatic PC treated with first-line palliative chemotherapy were included. Among others, the serum markers CYFRA 21-1, haptoglobin, serum-amyloid A (SAA), and 25-OH vitamin D3 were determined at baseline and categorized by pre-defined cut-offs [median values (MV), upper limits of normal (ULN), lower limits of normal (LLN), or the natural logarithm (ln)] and correlated with overall survival (OS). Among the 59 pts included, pre-treatment CYFRA 21-1 levels showed a strong correlation with OS independent of the applied cut-off (MV 4.9 ng/ml-14.2 vs. 4.2 months, HR 0.18, p = 0.001; ULN 3.3 ng/ml-14.2 vs. 4.4 months, HR 0.28, p = 0.003; [ln] CYFRA 21-1-HR 0.77, p = 0.013). Lower values of haptoglobin were additionally associated with an improvement in OS (categorized by LLN of 2.05 g/l-10.4 vs. 5.5 months, HR 0.46, p = 0.023; [ln] haptoglobin-HR 0.51, p = 0.036). Pts with baseline SAA values below the MV of 22 mg/l also had a prolonged OS (10.4 vs. 5.0 months, HR 0.47, p = 0.036). For 25-OH vitamin D3 levels, no significant correlation with OS was found. In multivariate analyses, pre-treatment CYFRA 21-1 levels (categorized by MV-HR 0.15, p = 0.032) as well as [ln] haptoglobin (HR 0.30, p = 0.006) retained their independent prognostic significance for OS. CYFRA 21-1, haptoglobin, and SAA might provide useful prognostic information in advanced PC. An external multicenter validation of these results is necessary.
本前瞻性单中心研究调查了新型血清生物标志物在晚期胰腺癌（PC）中的预后作用。纳入了接受一线姑息化疗的局部晚期或转移性PC患者（pts）。除其他指标外，在基线时测定血清标志物细胞角蛋白19片段（CYFRA 21-1）、触珠蛋白、血清淀粉样蛋白A（SAA）和25-羟基维生素D3，并根据预先定义的临界值[中位数（MV）、正常上限（ULN）、正常下限（LLN）或自然对数（ln）]进行分类，并与总生存期（OS）相关联。在纳入的59例患者中，治疗前CYFRA 21-1水平与OS显示出强相关性，与所应用的临界值无关（MV 4.9 ng/ml - 14.2 vs. 4.2个月，风险比（HR）0.18，p = 0.001；ULN 3.3 ng/ml - 14.2 vs. 4.4个月，HR 0.28，p = 0.003；[ln]CYFRA 21-1 - HR 0.77，p = 0.013）。较低的触珠蛋白值还与OS改善相关（按LLN分类为2.05 g/l - 10.4 vs. 5.5个月，HR 0.46，p = 0.023；[ln]触珠蛋白 - HR 0.51，p = 0.036）。基线SAA值低于MV 22 mg/l的患者OS也延长（10.4 vs. 5.0个月，HR 0.47，p = 0.036）。对于25-羟基维生素D3水平，未发现与OS有显著相关性。在多变量分析中，治疗前CYFRA 21-1水平（按MV分类 - HR 0.15，p = 0.032）以及[ln]触珠蛋白（HR 0.30，p = 0.006）对OS保留其独立的预后意义。CYFRA 21-1、触珠蛋白和SAA可能为晚期PC提供有用的预后信息。这些结果需要进行外部多中心验证。
