Haemostatic biomarkers for prognosis and prediction of therapy response in patients with metastatic colorectal cancer

被引:19
|
作者
Moik, Florian [1 ]
Posch, Florian [2 ,3 ]
Grilz, Ella [1 ]
Scheithauer, Werner [4 ]
Pabinger, Ingrid [1 ]
Prager, Gerald [4 ]
Ay, Cihan [1 ,5 ]
机构
[1] Med Univ Vienna, Dept Internal Med 1, Comprehens Canc Ctr Vienna, Clin Div Haematol & Haemostaseol, Vienna, Austria
[2] Med Univ Graz, Div Oncol, Dept Internal Med, Comprehens Canc Ctr Graz, Graz, Austria
[3] Ctr Biomarker Res Med CBmed GesmbH, Graz, Austria
[4] Med Univ Vienna, Dept Internal Med 1, Comprehens Canc Ctr Vienna, Div Clin Oncol, Vienna, Austria
[5] IM Sechenov First Moscow State Med Univ Sechenov, Moscow, Russia
基金
奥地利科学基金会;
关键词
Biomarker; Haemostasis; Metastatic colorectal cancer; Survival; Mortality; D-DIMER LEVELS; PLASMA D-DIMER; VENOUS THROMBOEMBOLISM; VIENNA CANCER; TISSUE FACTOR; RISK-FACTORS; THROMBOSIS; CHEMOTHERAPY; PLATELETS; MECHANISMS;
D O I
10.1016/j.thromres.2020.01.002
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Haemostatic activation and hypercoagulability are frequently observed in patients with metastatic colorectal cancer (mCRC), increase risk of venous thromboembolism (VTE) and have been implicated in tumour proliferation and progression. To date, the association of haemostatic biomarkers with oncologic outcomes including overall survival (OS), progression free survival (PFS) and disease control rate (DCR) is incompletely understood. Methods: Within the framework of the Vienna Cancer and Thrombosis Study, a prospective observational cohort study, we conducted an exploratory analysis to investigate the association of six known biomarkers of haemostasis with oncologic outcomes in 99 patients with mCRC prior to chemotherapy initiation. Results: Patients with high levels of factor VIII activity (FVIII), D-dimer, prothrombin fragment 1 + 2 (F1 + 2) and fibrinogen (defined as levels> 75th percentile) had significantly shorter median OS than patients with lower levels. Elevation of four biomarkers was associated with mortality in multivariable analysis, adjusting for age, sex, number of metastatic sites and VTE (hazard ratio [95% CI] for death per doubling of levels: FVIII: 2.06 [1.28-3.30]; sP-selectin: 1.55 [1.07-2.24]; D-dimer: 1.40 [1.18-1.65]; F1 + 2: 1.64 [1.10-2.46]). Patients with elevated levels had numerically shorter median PFS across all markers and disease control rate (DCR) was significantly smaller in those with high levels of FVIII and F1 + 2 (adjusted odds ratio [95% CI] for DCR per doubling of levels: 0.23 [0.09-0.62] and 0.36 [0.16-0.82]) compared to patients with lower levels. Conclusion: Specific elevated haemostatic biomarkers are associated with higher mortality and partially with worse response to chemotherapy in patients with mCRC.
引用
收藏
页码:9 / 17
页数:9
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