Investigation Of The Relationship Between Cancer-associated Venous Thrombosis And Driver Gene Mutation Status

Objective: Cancer Associated Venous Thromboembolic Disease(VTE)has become the second leading cause of death in cancer patients.In the development background of "precision medicine" and "big data era",the status of gene mutation is increasingly prominent in clinical prognosis and treatment decision-making.So is there a correlation between gene mutation status and cancer-associated VTE,and whether cancer patients with higher risk of thrombosis can be screened according to the gene status,so as to provide theoretical basis for better implementation of prevention and management strategies? The purpose of this study was to explore the relationship between the status of driver gene mutation and the risk of cancer-associated VTE,and to evaluate the incidence of VTE,risk factors and the effects of different treatment regiments on VTE in cancer patients.Methods:We collected clinical data of patients with malignant tumor confirmed by cytology or histopathology and with gene test results who were hospitalized in the department of oncology of the 4th Hospital,Hebei Medical University from January 2016 to January 2019.Relevant imaging examinations and coagulation function tests were performed on all patients to determine whether there was a VTE.1 According to the results of gene test,Patients were divided into mutant group and non-mutant group,and counted the cumulative incidence of VTE in each group.The cumulative VTE incidence of common driver gene epidermal growth factor receptor(EGFR),KRAS,TP53,anaplastic lymphoma kinase(ALK),human epidermal growth factor receptor-2(HER-2)mutant subgroups and non-mutant subgroups were statistically analyzed.2 In the mutant group,according to the treatment situation,the patients were divided into the targeted treatment subgroup and the non-targeted treatment subgroup,and the cumulative incidence of VTE in the two groups was calculated.2.1 In advanced Non-small Cell Lung Cancer(NSCLC),patients were divided into EGFR mutation subgroup and non-mutation subgroup,ALK fusion subgroup and non-fusion subgroup according to their genetic mutations,then calculat the cumulative incidence of VTE for each group.In the EGFR mutation or ALK fusion subgroup,according to the application of Tyrosine kinase inhibitor(TKI)drugs,it was divided into TKI treatment subgroup and non-TKI treatment subgroup,then calculat the cumulative incidence of VTE in each group.2.2 In metastatic colorectal cancer(mCRC)patients,according to KRAS gene mutation,they were divided into KRAS mutation subgroup and non-mutation subgroup,and the cumulative incidence of VTE was observed in the two groups.According to the application of bevacizumab injection,the patients were divided into the beva treatment group and non-beva treatment group,then calculat the cumulative incidence of VTE in the two groups.3 Patients were divided into the thrombotic group and the non-thrombotic group according to whether there was thrombosis at the time of enrollment.According to the Khorana model,the non-thrombotic group was divided into low-risk and medium-risk subgroups,then according to whether prophylactic anticoagulation was given,it was divided into prophylactic anticoagulation subgroup and non-prophylactic anticoagulation subgroup.The observation endpoint was the effective rate of prophylactic anticoagulation.4 Analyze the clinical data of patients in the thrombosis group and the non-thrombosis group,and conduct univariate and multivariate analysis on the risk factors of thrombosis.5 The correlation between the status of driver gene mutation and the status of thrombosis was analyzed to explore whether there was a correlation between the two.Results:1 A total of 301 patients were enrolled in this study,and a total of 42 cases of VTE events occurred,with a cumulative incidence of VTE of 14.0%.The cumulative incidence of VTE in the gene mutation group and non-mutation group was 20.0% and 7.1%,respectively,having no statistical significance(P=0.001).1.1 The cumulative incidence of VTE in the TP53 mutant subgroup and the non-mutant subgroup was 28.8% and 11.6%,respectively,with statistically significant results(OR 3.086,95%CI 1.433-6.649,P=0.003).While the cumulative incidence of in the EGFR,KRAS,TP53,ALK,her-2 mutant subgroup and the non-mutant subgroup was statistically insignificant(P >0.05).2 Among the patients in the mutation group,the cumulative incidence of VTE in the targeted treatment subgroup and non-targeted treatment subgroup was11.0% and 35.0%,respectively,with statistically significant results(OR 0.230,95%CI 0.101-0.522,P=0.000).2.1 Among the patients with advanced NSCLC,the cumulative incidence of VTE in the EGFR?ALK mutation subgroup and non-mutation subgroup was not statistically significant(P>0.05).In the EGFR mutation or ALK fusion subgroup,the cumulative VTE incidence in the TKI treatment subgroup and non-TKI treatment subgroup was 8.3% and 58.3%,respectively,with statistically significant results(OR 0.065,95%CI 0.014-0.302,P=0.000).2.2 Among the mCRC patients,the cumulative incidence of VTE was 18.2%and 6.3% in the KRAS mutation subgroup and non-mutation subgroup,the results were not statistically significant(P=0.277).The cumulative incidence of VTE in the beva treatment group and non-beva treatment groupwas 9.1%and 15.6%,respectively,the results were not statistically significant(P=0.672).3 For the low-risk and intermediate subgroup in the non-thrombotic group,the anticoagulation efficiency of the prophylactic anticoagulation subgroup andthe non-prophylactic anticoagulation subgroup was statistically insignificant(P > 0.05).4 For patients in the thrombosis group,univariate analysis showed that gender,albumin infusion history,hypoalbuminemia,history of using painkiller,gene mutation,D-dimer(D-D),and Performance Status(PS)score had a relationship with thrombosis,with statistical significance(P < 0.05).Multivariate analysis which were selected with P<0.05 by single factor analysis showed that: genetic mutation,gender,D-dimer and history of using painkiller were the independent factors affecting thrombosis.5 Spearman's rho was performed between the status of driver gene mutation and tumor associated VTE,and the result showed that there was a low correlation between the two(rank correlation coefficient:0.186,P=0.001).Conclusions:1.There is a correlation between the status of driver gene mutation and the risk of tumor-associated VTE in patients with malignant tumors,but the correlation is low.2.The TP53 gene mutation will increase the risk of tumor-associated VTE,while EGFR,KRAS,ALK and HER-2 gene mutations are not correlated with the occurrence of tumor-associated VTE.3.For the advanced NSCLC with EGFR gene mutation or ALK fusion mutation,Targeted therapy with TKI alone or in combination with other treatments will reduce the risk of VTE compared to other treatments not including TKI.