Cancer-related inflammation as predicting tool for treatment outcome in locally advanced and metastatic non-small cell lung cancer

Abstract

Background: Lung cancer is the leading cause of cancer deaths and the non-small cell lung cancer (NSCLC) represents 80% of all cases. In most cases when diagnosed, it is in locally advanced or metastatic stage, when platinum based doublet chemotherapy is the established therapeutic option for majority of the patients.Predictive factors to filter the patients who will benefit the most from the chemotherapy are not clearly defined. Objective of this study was to explore predictive value of pre-treatment C-reactive protein (CRP), fibrinogen and their interaction, for the response to the frontline chemotherapy.Methods: In this retrospective cohort study 170 patients with locally advanced and metastatic NSCLC were included. Relationship between baseline level of CRP and fibrinogen and response to the frontline chemotherapy was assessed.Results: We found that pre-treatment CRP and fibrinogen values were statistically significantly correlated.Chemotherapy and CRP, fibrinogen, and their interaction were independently significantly associated with disease control rate at re-evaluation. There was statistically significant difference in median pre-treatment CRP level between the patients with disease control or progression at re-evaluation, 13.8 vs. 30.0 mg/L respectively, P=0.026. By Johnson-Neyman technique we found that in patients with initial fibrinogen value below 3.5 g/L, CRP level was significantly associated with disease control or progression of the disease.Above this fibrinogen value the association of CRP and disease control was lost. Conclusions:The findings from this study support the growing evidence of inflammation and cancer relationship, where elevated pre-treatment level of CRP has negative predictive significance on the NSCLC frontline chemotherapy response.

Pre-treatment systemic immune-inflammation represents a prognostic factor in patients with advanced non-small cell lung cancer

“…In addition, NSCLC patients with preoperative thrombocytosis, platelet-to-lymphocyte ratio (PLR), neutrophil/lymphocyte ratio and prognostic nutritional index showed a significantly shorter disease-free survival (DFS) and OS (5)(6)(7). Similarly, elevated platelets count, C-reactive protein and high fibrinogen level were demonstrated as independent poor prognostic factors also in patients with advanced NSCLC (8,9).…”

The relationship of plasma fibrinogen with clinicopathological stages and tumor markers in patients with non-small cell lung cancer

“…Fbg may promote stable adhesion among tumor cells, platelets, and endothelial cells, [3,7,20,21] thereby further protecting the tumor cells from the impact of the immune system, enhancing the ability of cell establishment, deep infiltration, and metastasis. [4,22] Therefore, in our research and early studies, we found the later the N, M, and CS were, the higher the average levels of plasma Fbg were. [19]…”

“…Hyperfibrinogenemia can exist in many patients with malignant tumors including NSCLC and SCLC, which suggests a poor prognosis. [4,5,7,10,19] Fbg, synthesized by liver, is the highest content of coagulation proteins in plasma and can be converted to fiber polymer (insoluble fibrin) by activated thrombin. It plays a vital role in blood coagulation, fibrinolysis, inflammatory response, wound healing, and tumorigenesis.…”

“…[1] Non-small cell lung cancer (NSCLC) accounts for the vast majority of lung cancers, mainly including lung adenocarcinoma and squamous cell carcinoma (SCC). [2–4] When diagnosed, most patients have been already in locally advanced or metastatic stages of cancer. [4,5] The blood of cancer patients often stays in hypercoagulable state, especially in the patients with advanced clinicopathological stages (CS).…”

“…[2–4] When diagnosed, most patients have been already in locally advanced or metastatic stages of cancer. [4,5] The blood of cancer patients often stays in hypercoagulable state, especially in the patients with advanced clinicopathological stages (CS). [6–8] Activation of the coagulation system and procoagulant changes have been relevant to angiogenesis, tumor invasion, cancer progression, and distant metastasis.…”