Michl M, Koch J, Laubender R P, Modest D P, Giessen C, Schulz Ch, Heinemann V
Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, Ludwig-Maximilians-University of Munich, Marchioninistr 15, D-81377, Munich, Germany,
Tumour Biol. 2014 Oct;35(10):10121-7. doi: 10.1007/s13277-014-2280-7. Epub 2014 Jul 15.
In patients with metastatic colorectal cancer (mCRC), radiological imaging represents the current standard to evaluate the efficacy of chemotherapy. However, with growing knowledge about tumor biology, other diagnostic tools become of interest which can supplement radiology. The aim of the present study was to examine the correlation of tumor and serum markers with radiological imaging in patients with mCRC receiving first-line therapy. Patients were included if tumor (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9)) and serum marker (lactatdehydrogenase (LDH), γ-glutamyltransferase (γGT), alkaline phosphatase (AP), C-reactive protein (CRP), leucocyte count (WBC), hemoglobin (Hb)) levels were available at baseline and at least two times during treatment. The decline and increase of tumor and serum markers over time were approximated for each patient by estimating slopes depending on the radiological assessment. A linear mixed effects multiple regression model for each subject was used to evaluate the intra-class correlation of these slopes modeling tumor and serum marker changes with radiological imaging. Data of 124 patients (41 female, 83 male; median age 62.9 years, range 27-85) who received first-line chemotherapy for mCRC from 11/2007 to 04/2010 were analyzed retrospectively. CEA level slopes (n = 49; slopes = 102) differed between radiologically determined progressive disease (PD) and partial response (PR) (p = 0.005) and between PD and stable disease (SD) (p = 0.042). CA 19-9 level slopes (n = 57; slopes = 127) also showed a significant difference between PD and PR (p = 0.002) and PD and SD (p = 0.058). Furthermore, CRP slopes (n = 62; slopes = 134) differed significantly between PD and PR (p = 0.009). For LDH, ALP, γGT, Hb, and WBC, no correlations were observed. The results indicate the correlation of the tumor markers CEA, CA 19-9, and the serum marker CRP with radiological imaging in patients with mCRC receiving first-line chemotherapy. Further data analyses would be helpful to develop a predictive model for tumor response based on an early tumor marker increase or decrease.
在转移性结直肠癌(mCRC)患者中,放射影像学是评估化疗疗效的当前标准。然而,随着对肿瘤生物学认识的不断增加,其他可补充放射学检查的诊断工具也受到关注。本研究的目的是在接受一线治疗的mCRC患者中,检测肿瘤标志物和血清标志物与放射影像学检查结果之间的相关性。如果患者在基线期以及治疗期间至少两次有肿瘤标志物(癌胚抗原(CEA)、糖类抗原19-9(CA 19-9))和血清标志物(乳酸脱氢酶(LDH)、γ-谷氨酰转移酶(γGT)、碱性磷酸酶(AP)、C反应蛋白(CRP)、白细胞计数(WBC)、血红蛋白(Hb))水平的数据,则纳入研究。根据放射学评估,通过估计斜率来近似每位患者肿瘤标志物和血清标志物随时间的下降和升高情况。使用针对每个受试者的线性混合效应多元回归模型来评估这些斜率的组内相关性,该模型将肿瘤标志物和血清标志物的变化与放射影像学检查结果进行关联。回顾性分析了2007年11月至2010年4月期间接受mCRC一线化疗的124例患者(41例女性,83例男性;中位年龄62.9岁,范围27 - 85岁)的数据。放射学判定的疾病进展(PD)和部分缓解(PR)之间以及PD和疾病稳定(SD)之间,CEA水平斜率(n = 49;斜率 = 102)存在差异(p = 0.005)和(p = 0.042)。CA 19-9水平斜率(n = 57;斜率 = 127)在PD和PR之间以及PD和SD之间也显示出显著差异(p = 0.002)和(p = 0.058)。此外,CRP斜率(n = 62;斜率 = 134)在PD和PR之间存在显著差异(p = 0.009)。对于LDH、ALP、γGT、Hb和WBC,未观察到相关性。结果表明,在接受一线化疗的mCRC患者中,肿瘤标志物CEA、CA 19-9以及血清标志物CRP与放射影像学检查结果具有相关性。进一步的数据分析将有助于基于肿瘤标志物早期的升高或降低情况建立肿瘤反应预测模型。