Prognostic significance of blood coagulation tests in lung cancer

Ferrigno, Domenico; Buccheri, Gianfranco; Ricca, Irene

doi:10.1183/09031936.01.17406670

Cited by 73 publications

(83 citation statements)

References 27 publications

(32 reference statements)

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“…7 In addition, changes in the clotting/fibrinolytic system in lung carcinoma patients are common. 3,9,[11][12][13][14][15][16][17] Clinical and experimental evidence supports the idea that the activation of coagulation/fibrinolysis may play an important role in the invasiveness of cancer. 6,7 For example, Kwaan and Keer 6 demonstrated a correlation between coagulation changes and the natural history of malignancies.…”

Section: Discussionmentioning

confidence: 85%

“…16,17 In the earlier study, 16 we reported that several clotting tests were predictive of prognosis, according to both univariate and multivariate models. Univariate tests showed that low values of plasma PT, high values of F, and abnormally elevated concentrations of DD were associated significantly with an adverse outcome.…”

Section: Discussionmentioning

confidence: 99%

“…The multivariate models confirmed the significance of several clotting tests, including DD. The later study 17 assessed the potential prognostic significance of a wider selection of coagulation parameters. Platelet counts and the plasma levels of PT, PTT, antithrombin III (AT-III), F, DD, F-II, Factor VII (F-VII), Factor X (F-X), protein C clotting, plasminogen, and antiplasmin were obtained from 343 consecutive new lung carcinoma patients.…”

Section: Discussionmentioning

confidence: 99%

“…A thrombophilic state often is associated with a large tumor burden, clinical progression, low rates of response to chemotherapy, and a poor prognosis. 3,9,[11][12][13][14][15][16][17] The evidence, however, was derived from several small or medium studies, and no marker of hemostasis was identified, even in the most recent and expert review of lung carcinoma prognosis. 18 The purpose of the current study was to confirm the prognostic significance of hemostatic activation in lung carcinoma patients and to delineate the relationships between markers of hemostasis and other clinical and laboratory characteristics.…”

mentioning

confidence: 99%

“…We limited our attention to the degradation product of fibrin, D-dimer (DD), which is probably the most reliable prognostic indicator of this group. 16,17 …”

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confidence: 99%

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Plasma levels of D‐dimer in lung carcinoma

Buccheri

Torchio

Ferrigno

2003

Cancer

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BACKGROUNDThe activation of the clotting‐fibrinolytic system in cancer patients is common and represents an unfavorable clinical sign. D‐dimer (DD) is a sensitive marker of fibrinolysis.METHODSThe current study comprised 826 new lung carcinoma patients seen consecutively in a single institution over a 10‐year period (1992–2001). For each patient, 31 variables, including DD and survival duration, were available for analysis.RESULTSOnly weak relationships between DD and the other variables were found. The DD variable correlated best with the level of lactate dehydrogenase, performance status, tissue polypeptide antigen, stage of disease, and the number of metastases (rho = 0.33, −0.25, 0.18, 0.18, and 0.15, respectively). The D‐dimer distinguished patients with different prognoses. The median survival periods were 154 days (95% confidence interval [CI], 122–189 days) and 308 days (95% CI, 227–409 days; log rank statistic, 26.56; P < 0.01), respectively, for abnormally elevated and normal values. The difference was greater in patients with adenocarcinoma and in patients presenting with a less advanced disease, especially in patients with pathologic Stage Ia disease. The best multivariate survival model selected 10 significant covariates, including DD.CONCLUSIONSThe authors recommend measuring the plasma level of DD in all new lung carcinoma patients. This measurement may help to formulate individual prognoses and can be used to indicate adjuvant treatment for surgical patients. Cancer 2003;97:3044–52. © 2003 American Cancer Society.DOI 10.1002/cncr.11432

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…We limited our attention to the degradation product of fibrin, D-dimer (DD), which is probably the most reliable prognostic indicator of this group. 16,17 …”

mentioning

confidence: 99%

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Plasma levels of D‐dimer in lung carcinoma

Buccheri

Torchio

Ferrigno

2003

Cancer

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Circulating D‐dimer levels are better predictors of overall survival and disease progression than carcinoembryonic antigen levels in patients with metastatic colorectal carcinoma

Blackwell

Hurwitz

Lieberman³

et al. 2004

Cancer

112

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BACKGROUND Fibrin formation is required for tumor angiogenesis, metastasis, and invasion. D‐dimer, a fibrin degradation product, is produced when crosslinked fibrin is degraded by plasmin. The current study prospectively examined D‐dimer levels in patients with metastatic colorectal carcinoma treated in a Phase II randomized trial comparing bevacizumab (Avastin, Genentech, South San Francisco, CA) plus 5‐fluorouracil/leucovorin (5‐FU/LV) with 5‐FU/LV alone. METHODS At least one circulating D‐dimer level was evaluable in 98 of the 104 previously untreated patients with metastatic colorectal carcinoma in the current trial. Plasma D‐dimer levels were determined using a quantitative immunoassay kit at enrollment, before each treatment, and at the time of trial completion or disease progression. RESULTS At trial enrollment, 86 of 104 patients (88%) had elevated D‐dimer levels (> 20 ng/mL), and 86 of 102 patients (84%) had elevated carcinoembryonic antigen (CEA) levels (> 3 ng/mL). Baseline D‐dimer levels were correlated with the following baseline characteristics: CEA (Pearson coefficient, 0.31; P = 0.002), albumin levels (Pearson coefficient, −0.32; P = 0.002), tumor burden (Pearson coefficient, 0.30; P = 0.003), and number of metastatic sites (Pearson coefficient, 0.21; P = 0.04). At the time of progression, plasma D‐dimer levels reached a maximum postbaseline value in 51 of 61 patients (84%), whereas the CEA level was at its maximum postbaseline value in 39 of 55 patients (71%). Baseline D‐dimer levels were a strong predictor of overall survival on univariate analysis (P = 0.008) and multivariate analysis (P = 0.03). Overall, treatment with bevacizumab (5 mg/kg) and baseline D‐dimer levels were the only predictors of overall survival (P < 0.05). CONCLUSIONS The current study indicates that fibrin remodeling is an important prognostic feature in metastatic colorectal carcinoma. D‐dimer levels should be incorporated into prognostic models, and D‐dimer may represent a useful biomarker for patients treated with antiangiogenic agents. Cancer 2004. © 2004 American Cancer Society.

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F2RL3 methylation, lung cancer incidence and mortality

Zhang

Schöttker

Ordóñez‐Mena

et al. 2015

Intl Journal of Cancer

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Smoking accounts for a large share of lung cancer. F2RL3 methylation was recently identified as a biomarker closely reflecting both current and past smoking exposure. We aimed to assess the associations of F2RL3 methylation with lung cancer incidence and mortality. In a large population-based cohort study, F2RL3 methylation was measured in baseline blood samples of 4,987 participants by MassARRAY. Associations of F2RL3 methylation and smoking with lung cancer incidence/mortality during a median follow-up of 10.9 years were assessed by Cox regression, controlling for potential confounders. The ability of F2RL3 methylation to predict lung cancer was examined by Harrell's C statistics. Hypomethylation at F2RL3 was strongly associated with both lung cancer incidence and mortality, with age-and sex-adjusted hazard ratios (HR; 95% CI) of 9.99 (5.61-17.79) and 16.86 (8.53-33.34), respectively, for participants whose methylation intensity were 0.54 compared with whose methylation intensity were 0.75. Strongly elevated HRs of 2.88 (1.42-5.84) and 5.17 (2.28-11.70) persisted even after controlling for multiple covariates including smoking status and pack-years. With fully adjusted HRs of 9.92 (2.88-34.12) and 16.48 (4.10-66.15), the associations between methylation and the two outcomes were particularly strong among participants 65 years. Combination of F2RL3 methylation and pack-years predicted lung cancer incidence with high accuracy (optimism-corrected Harrell's C statistics 5 0.86 for participants 65 years). These findings suggested that F2RL3 methylation is a very strong predictor of lung cancer risk and mortality, particularly at older age. The potential implications of F2RL3 methylation for early detection, risk stratification and prevention of lung cancer warrant further exploration.With 1.8 million new cases and 1.6 million deaths per year, lung cancer is the most common form of cancer and cause of cancer-related death worldwide. 1 Cigarette smoking is a well-known major risk factor for lung cancer. It is estimated that 80-90% of lung cancer cases and 71% of lung cancer deaths are attributable to smoking. 2,3 Exposure to multiple carcinogens during inhalation of tobacco smoke results in formation of DNA adducts and further induces mutations/ deletions in oncogenes or tumor suppressor genes, such as KRAS, TP53 and P16, which are considered to be involved in the key pathways of lung carcinogenesis. 4,5 Over the last decade, increasing evidence has emerged that epigenetic modifications, in particular aberrant DNA methylation, also play a role in lung tumor initiation and progression, 6,7 primarily

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Prognostic significance of blood coagulation tests in lung cancer

Cited by 73 publications

References 27 publications

Plasma levels of D‐dimer in lung carcinoma

Plasma levels of D‐dimer in lung carcinoma

Circulating D‐dimer levels are better predictors of overall survival and disease progression than carcinoembryonic antigen levels in patients with metastatic colorectal carcinoma

F2RL3 methylation, lung cancer incidence and mortality

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