Tumor response and survival in patients with advanced non-small-cell lung cancer: the predictive value of chemotherapy-induced changes in fibrinogen

Abstract

BackgroundHyperfibrinogenemia is a common problem associated with various carcinomas, and is accompanied by hypercoagulablity. In advanced non-small-cell lung cancer (NSCLC) it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to chemotherapeutic response and prognosis. The purposes of this study were to: 1) analyze the association between chemotherapy-induced changes in plasma fibrinogen level and the chemotherapeutic response after the first two courses of standard first-line platinum-based chemotherapy; and 2) evaluate the prognostic significance of the basal plasma fibrinogen level in patients with advanced NSCLC.MethodsIn this retrospective study, the data from 160 patients with advanced NSCLC were collected. The association between the changes in fibrinogen and the response to chemotherapy, or between the pre-and post-chemotherapy fibrinogen levels and patient clinical characteristics, were analyzed using SPSS software. In addition, the prognostic value of pre-chemotherapy fibrinogen levels was assessed.ResultsThe median pre-chemotherapy plasma fibrinogen level was 4.4 g/L. Pre-chemotherapy plasma fibrinogen levels correlated significantly with gender (p = 0.041). Post-chemotherapy plasma fibrinogen levels correlated with gender (p = 0.023), age (p = 0.018), ECOG (p = 0.002) and tumor response (p = 0.049). Plasma fibrinogen levels markedly decreased after chemotherapy in 98 (61.25 %) patients with pre-chemotherapy hyperfibrinogenemia (p = 0.008); and in this population there was a significant link between the decrease in fibrinogen level, and initial partial response (PR; p = 0.017) and stable disease (SD; p = 0.031). Univariate and multivariate analysis revealed that higher levels of fibrinogen (≥4.4 g/L) and ECOG 1 were positively associated with shorter overall survival (OS). CEA and CA125 also decreased significantly (p =0.015, p =0.000) in DCR group after chemotherapy.ConclusionsThis study showed that the reduction in plasma fibrinogen levels induced by chemotherapy might be as a promising biomarker as CEA and CA125 for evaluating the efficacy of chemotherapy in advanced NSCLC. In addition, basal plasma fibrinogen levels could be used as an independent prognostic parameter for the OS of patients with advanced NSCLC.

Prognostic implications of plasma fibrinogen and serum Creactive protein levels in non-small cell lung cancer resection and survival

“…Unlike this study, a previous study did not demonstrate significant findings between incomplete resection with serum CRP, plasma fibrinogen, or both biomarkers, although a trend towards a higher rate of incomplete resection was observed with increasing levels of these biomarkers. The major difference in these findings is that the previous study used higher cut-off levels for fibrinogen (> 5 g/L) and CRP (> 40 mg/L) to demonstrate increased levels of these biomarkers relative to the current study [14]. …”

“…Moreover, the fibrinogen coating may result in the protection of cancer cells from immune surveillance and extend malignant cell survival [21,22]. These observations are important provided the findings of this study and other investigations that showed a positive correlation between fibrinogen concentration with pathological tumour phase and primary tumour diameter but not with the pathological N stage [14].…”

“…Furthermore, substantial amounts of fibrin and fibrinogen are deposited around solid tumours, implying that fibrinogen induces the development of the tumour stroma [14,20]. Additionally, fibrinogenmediated cellular interactions play a role in cell proliferation, cell migration, apoptosis, inflammatory factor production, and angiogenesis [14,20,21].…”

“…Furthermore, substantial amounts of fibrin and fibrinogen are deposited around solid tumours, implying that fibrinogen induces the development of the tumour stroma [14,20]. Additionally, fibrinogenmediated cellular interactions play a role in cell proliferation, cell migration, apoptosis, inflammatory factor production, and angiogenesis [14,20,21]. Moreover, the development of a platelet-fibrin-tumour cell promotes endothelial adhesion, as well as increased attachment; therefore, fibrinogen forms a layer on the surface of cancer cells to aid in the attachment of growth factors and induce tumour cell dispersion and metastasis [22].…”

“…Hyperfibrinogenemia has been demonstrated in colorectal [11], cervical, oesophageal [12], and pancreatic cancers [13]. In NSCLC, hyperfibrinogenemia is associated with T-stage disease and tumour volume [14]. However, the usefulness of plasma fibrinogen concentrations in evaluating patients with resectable/non-resectable tumours, as well as in predicting the survival of NSCLC patients, is still under debate [15].…”