Correlation Between Commonly Used Coagulation Indexes And Prognosis Of Patients With Lung Cancer

PART 1.Clinical significance of common coagulation indexes in patients with advanced non-small cell lung cancerBackgrounde:Lung cancer is a malignant tumor with high morbidity and mortality.In recent years,with the rapid development of lung cancer treatments,the survival time of lung cancer patients been greatly improved.However,the prognosis of patients with advanced lung cancer is still not optimistic,and hypercoagulabale state is one of the important reasons for the poor prognosis of patients with advanced lung cancer.Because there are no obvious symptoms or signs of hypercoagulabale state associated with lung cancer,they are often overlooked by clinicians and can only be detected by laboratory tests.Purpose:This study made a retrospective analysis to explore the relationship between coagulation-related indicators and the prognosis of patients with advanced non-small cell lung cancer(NSCLC).In order to arouse attention to the hypercoagulabale state of patients with lung cancer and provide suggestions to clinical decision.Methods:In this study,we collected 209 patients with advanced NSCLC in the first affiliated hospital of Soochow university from September 2010 to December 2015.Variants such as gender,age,thrombin time,prothrombin time,activated partial thromboplastin time,Antithrombin Ⅲ,fibrinogen,D-dimer,platelet,c-reactive protein,serum albumin,KPS score and prognostic nutritional index were analyzed.The statistical software packages "survival" and"survminer" of R version 3.6.0(http://www.r-project.org/)be used to establish the original database Relevant data of this study.The relevant data and indicators collected were statistically analyzed.Cox regression model were used for univariate and multivariate analysis.Forest plot were used to show the importance of covariates for prognosis.Harrell’s c-Index,calibration analysis and reclassification tests were used to determine the prognostic ability among other factors.Based on the results of Logistic regression analysis,a nomogram was established for predicting the prognosis by using the R version 3.6.0 "rms" software package.Results:1.C-reactive protein was higher in the non-adenocarcinoma group than in the adenocarcinoma group(11.58(5.61,13.97)vs.9.13(2.25,12.89)),P=0.008.Other indicators such as gender,age,BMI,overall survival,chemotherapy regimens,smoking history,diabetes,hypertension,hyperlipemia,KPS score,thrombin time,prothrombin time,activated partial thromboplastin time,Antithrombin III,fibrinogen,D-dimer,platelet,serum albumin,white blood cells KPS score and prognostic nutritional index was no significant difference between adenocarcinoma and non-adenocarcinoma groups(P>0.05).2.Univariate analysis showed that platinum contained in the chemotherapy regimen(HR=0.11,95%CI[0.02,0.60],P=0.01)was associated with a better prognosis in patients with advanced NSCLC.PT>11.70sec(HR=3.96,95%CI[1.40,11.16],P=0.009),APTT>22.70sec(HR=2.96,95%CI[1.07,8.16],P=0.036)and D-D>lmg/L(HR=2.74,95%CI[1.08,6.97],P=0.035)were associated with poor prognosis.3.We put the variants selected by univariate analysis into multivariate regression model.PT>11.70 sec(HR=2.24,95%CI[0.71,7.12],P=0.17),APTT>22.70 sec(HR=2.96,95%CI[1.07,8.16],P=0.036)and D-D>lmg/L(HR=2.74,95%CI[1.08,6.97],P=0.035)were not independent risk factor for OS in advanced NSCLC patients.Conclusion:Patients with PT>11.70sec、APTT>22.70sec and D-D>1mg/L before treatment maybe predicted poor prognosis.Nomogram based on these three variants could estimate overall survival of these patients and provide suggestions to clinical decision.PART2.Circulating D-dimer and the risk of mortality in patients with Lung Cancer:a systematic review and meta-analysis of 19 clinical cohort studies.Background:Patients with advanced cancer often accompanied by hypercoagulabale state,and D-dimer is an important indicator to detect coagulation function.Previous studies showed the relationship between D-dimer level and the risk of mortality in patients with lung cancer.In the retrospective study of the first part,we also found that D-D was associated with the prognosis of NSCLC patients.However,the link between circulating D-dimer and the risk of mortality in patients with lung cancer varied in different investigations.Purpose:We performed a systematic review and meta-analysis of all available cohort studies regarding the association between baseline circulating D-dimer and mortality in patients with lung cancer.The purpose is to summarize the relationship between D-D and the risk of death in patients with lung cancer,so as to draw clinical attention to D-D detection.Methods:PubMed,Embase as well as Cochrane library databases were searched for relevant cohort studies.Inclusion and exclusion criteria were formulated,the overall hazard ratio for the mortality were extracted.The randomized controlled trial(RCT)used the Cochrance quality assessment standard to evaluate the quality of the literature,while the non-randomized controlled trial used the Newcastle-Ottawa Scale(NOS)to evaluate the quality of the literature.Heterogeneity among the included studies was assessed by I2 statistics,Cochran’s Q Test and p value.A random-effect model or a fixed-effect model was used depending on the heterogeneity.Source of heterogeneity was evaluated via stratified analysis and meta-regression.The publication bias was evaluated by funnel chart,Begg’s test,Egger’s test,and pruning metho.The single-removal method was used for sensitivity analysis.GRADE system was used to evaluate the quality of the results.Results:Among the 19 eligible studies,pooled HR showed that high D-dimer level contributed to lung cancer mortality(HR=1.62,95%CI:1.39-1.88,I2=75.0%).Stratified analysis revealed that higher circulating D-dimer was related to a 1.91times higher risk in advanced lung cancer group(HR=2.91,95%CI:2.24-3.78,I2=6.0%).Fitting other variables,including country,public year,population,follow-up days,design,quality scores and disease status into the meta-regression model,it indicated that disease status was additional sources of heterogeneity(p<0.001).Conclusion:The results of this Meta analysis show that higher serum D-dimer levels indicate a higher risk of long-term death in lung cancer patients.D-dimer may be an important indicator for predicting the prognosis of lung cancer patients.In the future,large-scale prospective cohort studies and even interventional studies are needed to verify this conclusion.