High levels of D-dimer correlated with disease status and poor prognosis of inoperable metastatic colorectal cancer patients treated with bevacizumab

Zhu, Liming; Liu, Bixia; Zhao, Ye; Liu, Luying; Yang, Chen; Yang, Yu‐Guang; Huang, Zhong

doi:10.4103/0973-1482.151451

Cited by 17 publications

(9 citation statements)

References 19 publications

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“…Our results are consistent with previous clinical studies in colorectal cancer that suggested elevated haemostatic biomarkers as markers for shorter OS and time to recurrence in patients after tumour resection in the non-metastatic setting and for worse prognosis and therapy response for patients with unresectable or metastatic disease [17][18][19][20]35,36]. By utilizing a pre-existing dataset of an ongoing prospective, observational study (Vienna Cancer and Thrombosis Study, CATS) and a panel of different biomarkers, we were able to create a cohort that is homogeneous in respect of clinical scenario, as all patients included in the present analysis were initiating systemic chemotherapy due to metastatic disease with high quality of follow up data, due to existing parameters collected within the framework of a prospective observational study and the routine nature of the parameters collected in retrospect.…”

Section: Discussionsupporting

confidence: 92%

“…product reflecting systemic blood coagulation activation, has been investigated as haemostatic biomarker [2,[14][15][16]. In colorectal cancer, Ddimer has been shown to be a predictor for overall survival (OS) and progression free survival (PFS) in inoperable tumours [17]. Changes of D-dimer levels during chemotherapy have been found to be associated with disease progression and OS more accurately than carcinoembryonic antigen, a routine tumour-marker for monitoring of disease [18,19].…”

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confidence: 99%

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

Moik

Posch

Grilz

et al. 2020

Thrombosis Research

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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.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

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

Moik

Posch

Grilz

et al. 2020

Thrombosis Research

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“…Increased D-dimer level was associated with a shorter survival time, and thus many studies have explored the application of D-dimer as a prognostic marker for CRC. 16 , 22 , 23 However, the relationship between plasma D-dimer and distant organ metastasis was seldom reported. Kilic et al 17 enrolled 54 CRC patients with synchronous metastasis, and found that there was a difference in D-dimer values between the metastatic positive group and the metastatic negative group before chemotherapy (373.7 IU/mL vs 603 IU/mL).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, more and more studies find that higher D-dimer levels before operations are correlated with a more advanced CRC tumor stage 10 , 13 – 18 and a poorer prognosis. 14 , 16 , 19 – 23 This is more distinct in the cases of distant organ metastasis, which may result from the increased angiogenesis in the primary tumor as well as the formation of tumor emboli in the circulation. 18 Therefore, we speculate that D-dimer levels might be elevated in CRC patients who develop distant organ metastasis.…”

Section: Introductionmentioning

confidence: 99%

Usefulness of plasma D-dimer level for monitoring development of distant organ metastasis in colorectal cancer patients after curative resection

Guo

Chen

Cui

2018

CMAR

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PurposeTo investigate the usefulness of plasma D-dimer level for monitoring the development of distant organ metastasis in colorectal cancer (CRC) patients after curative resection.Patients and methodsOne hundred and seventy-eight CRC patients after curative resection were enrolled in the study. Ninety-two patients developed distant organ metastasis during follow-up (metachronous metastasis), and blood was collected on the day metastasis was confirmed. Eighty-six patients had no evidence of metastasis yet, and their blood samples were evaluated at last return visit. The levels of D-dimer, carcinoembryonic antigen (CEA), and lactate dehydrogenase (LDH) between two patient groups were compared. The agreement between D-dimer and CEA (or LDH) was examined. The receiver operator characteristic (ROC) curve was used to evaluate the performance of D-dimer, CEA, LDH, and their combination in detection of distant organ metastasis.ResultsThe level of D-dimer in CRC patients with metachronous metastasis was higher than that in non-metastasis patients (P<0.0001). Agreement between D-dimer and CEA was fair (κ=0.416, P<0.0001). D-dimer had a larger area under ROC (AUC) (0.85) compared to CEA (0.72) or LDH (0.68). The specificity of D-dimer (73.3%) was lower than that of CEA (74.4%), but the sensitivity (88.0%) of D-dimer assay was superior to that of CEA assay (65.2%). LDH showed the lowest sensitivity (42.4%) and highest specificity (95.3%) among the three bio-markers. The sensitivity and negative predictive value (NPV) of a combination assay (either D-dimer elevation or CEA elevation) were 94.6% and 91.1%, respectively, and the specificity and positive predictive value of another combination assay (both D-dimer elevation and LDH elevation) were 97.7% and 94.9%, respectively. Parallel test of the three markers improved the sensitivity and NPV to 95.7% and 92.7%, respectively.ConclusionCombining with CEA and/or LDH, D-dimer could be a useful surveillance marker for distant organ metastasis in CRC patients after curative resection.

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“…D-dimer stimulates the growth of malignancies via promoting tumor cell proliferation, adhesion and angiogenesis [6]. Several studies report that the level of D-dimer is increased in breast [7], gastric [8], colorectal [9], lung [10], and nasopharyngeal carcinomas [11], and is correlated with a poor prognosis and decreased response to treatment. However, the relation of D-dimer levels to the survival of patients with endometrial cancer has not been reported.…”

Section: Introductionmentioning

confidence: 99%

The prognostic value of D-dimer levels in endometrial cancer patients treated with intensity-modulated radiation therapy

et al. 2017

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Explain the important role of plasma D-dimer in cancers. Plasma D-dimer is increased in various tumors. However, the predictive value of plasma D-dimer is unclear. This study is aimed to evaluate the prognostic value of the D-dimer level in patients managed with intensity-modulated radiation for endometrial cancer. The D-dimer levels of forty patients with endometrial cancer were assessed before (D1) and after (D2) intensity-modulated radiation therapy (IMRT), respectively. The D-dimer level changes (ΔD) were defined as D2 minus D1. Cox regression and log-rank tests were used to evaluate the D-dimer levels in relation to progression free survival (PFS) and overall survival (OS). The OS and PFS of patients with a low D1 were significantly longer than those with a high D1 (P< 0.001, P< 0.001). We saw the similar correlation between D2, PFS and OS (P< 0.001, P< 0.001). Multivariate survival analyses showed that D-dimer was independently associated with OS and PFS in patients with endometrial cancer. The ΔD level was not related to the OS and PFS in endometrial cancer patients. The levels of D-dimer may be considered as an important predictor of PFS and OS in endometrial cancer patients treated with IMRT.

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High levels of D-dimer correlated with disease status and poor prognosis of inoperable metastatic colorectal cancer patients treated with bevacizumab

Abstract: High levels of plasma baseline D-dimer correlated with high tumor load, advanced disease status and poor prognosis of inoperable mCRC patients treated with bevacizumab. However, clinical research on a much larger cohort of patients will be required to verify these findings.

Cited by 17 publications

References 19 publications

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

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

Usefulness of plasma D-dimer level for monitoring development of distant organ metastasis in colorectal cancer patients after curative resection

The prognostic value of D-dimer levels in endometrial cancer patients treated with intensity-modulated radiation therapy

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