Exploration Of High Risk Factors And Prevention Of Anti-tumor Treatment-related Cardiac Toxicity Events In Cancer Patients

Background and Objective:Breast cancer patients are facing a variety of treatment needs,and the central vein catheter has many advantages such as convenience and comfort,which has been paid attention by patients and doctors,and has been widely used in clinical.At the same time,catheter-related complications can lead to treatment interruption,hospitalization time and cost,or even life-threatening.Catheter-related thrombosis(CRT)is one of the common and intractable complications.CRTs has some unique characteristics,such as the type of central venous catheter,the position of catheter tip,etc.whether the risk score based on deep venous thrombosis(such as Khorana Risk Score model)can well predict CRT is unknown.The purpose of this study is to establish a reliable prediction model of catheter-related thrombosis and to provide the basis for the development of individual prevention and control strategies.Materials and Methods:The primary cohort was a retrospective collection of cancer patients with central venous catheterization who were admitted to the National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College from January 1,2015 to December 31,2018(n=3131).The validation cohort 1 of the prediction model was a prospective and independent cohort of cancer patients who underwent central venous catheterization in the National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College from January 1,2019 to August 31,2019(n=685).Validation cohort 2 was a retrospective cohort of Hunan Cancer Hospital(n=61).Discrimination was measured by areas under receiver operating characteristic curves(ROC)curve.Calibration was measured by calibration plots,and Hosmer-Lemeshow(H-L)test.Results:The catheter days in primary cohort is 221,074 days.A total of 397 cases(397/3132,12.7%)of CRT were recorded in primary cohort,with an incidence of 1.80 per 1000 catheter days.The most common site of CRT was subclavian vein,accounting for 52.1%(207/397).In CRT patients,33.8%(134/397)had multiple site thrombosis.Multivariate analysis demonstrated that sex,cancer type,catheter type,position of the catheter tip,chemotherapy status,and antiplatelet/anticoagulation status at baseline were independent risk factors for CRT.A total of 685 patients were enrolled in the validation cohort 1,with catheter days reaching 38,144 days;catheter days in validation cohort 2(n=61)was 5,991 days.According to the maximum Youden index,we divided the high risk and low risk of CRT by 19.6 points.The incidence of CRT in high risk group and low risk group was significantly different(primary cohort:24.5%vs.6.4%;validation cohort 1:26.8%vs.5.6%;validation cohort 2:22.2%vs.8%,p<0.001).The area under receiver operating characteristic(ROC)curve of our prediction model was 0.741(CI:0.715-0.766)in the primary cohort;0.754(CI:0.704-0.803)and 0.658(CI:0.470-0.845)in validation cohorts respectively.At the same time,our model shows good consistency between prediction and actual observation in both primary cohort and validation cohort,which reflects good calibration.Clinical decision analysis also shows that our model has higher clinical net benefit than the traditional Khorana Risk Score model.Conclusions:Our model is a reliable predictor of CRT risk in cancer patients,and can be accurately assign cancer patients into high-risk or low-risk groups accurately.Our model will be valuable for clinicians in the decision making of thromboprophylaxis.Background and Objective:cardiac toxicity adverse events caused by chemotherapy is one of the most common adverse reactions of anti-tumor therapy,which has been widely concerned in recent years.It is generally believed that,the occurrence of cardiac toxicity events is often associated with high cumulative dose of chemotherapy.However,clinical risk factors alone are often insufficient to explain the incidence of early-onset cardiac toxicity events during adjuvant therapy at low cumulative dose of chemotherapy drugs.The purpose of our research is to identify clinical and genetic variants associated with early-onset cardiac toxicity in breast cancer and to establish the ideal predictive risk model.Materials and Methods:A total of 388 recruited patients completed routine blood,liver and kidney function,D-dimer,troponin T(TnT),B-type natriuretic peptide(BNP)or N-terminal prohormone of brain natriuretic peptide(NT-proBNP),electrocardiogram(ECG)and echocardiography(UCG)tests before and after adjuvant chemotherapy.Twenty-five single nucleotide polymorphisms(SNPs)were tested for all patients.Univariable and multivariable analyses were performed to identify independent risk factors.The accuracy and discriminative ability of the predictive models were determined by the area under the receiver operating characteristic(ROC)curve(AUC)and calibration plots.Results:A total of 277 adjuvant chemotherapy-related cardiac toxicity events were recorded in 180 patients(46.4%),and these included an abnormal ECG(145/388,37.4%),an abnormal UCG(36/388,9.3%),an elevated NT-proBNP/BNP(22/388,5.7%),and elevated TnT(1/388,0.3%).Anthracycline-containing chemotherapy(OR,1.698;95%CI,1.118-2.579;p=0.013)and the SLC28A3(rs885004)GG genotype(OR,2.073;95%CI,1.207-3.560;p=0.008)were found to be associated with overall cardiac toxicity.The predictive risk model of cardiac toxicity events in adjuvant chemotherapy for breast cancer consisted of the anthracycline-containing chemotherapy,pathology and genotype of SLC28A3(rs885004).The ROC of the new model was 0.604(95%CI,0.548-0.660),p<0.001.The model shows a good consistency between the prediction and the actual observation,which reflects good calibration.Conclusions:Early-onset cardiac toxicity events are quite common in the real world and should be paid attention to by clinicians.The prediction model based on SNPs and clinical risk factors can better predict the risk of early-onset cardiac toxicity events,and provide important help for the prevention of chemotherapy-related cardiotoxicity in cancer patients.Background and Objective:Breast cancer is the most common cancer in females.The effects of statins on breast cancer prognosis have long been controversial.Therefore,we conducted this study to understand the relationship between different types of statins,duration of treatment,timing of treatment and prognosis of breast cancer.Materials and Methods:We searched the MEDLINE,EMBASE,Cochrane Library,and ISI Web of Knowledge databases.Searches combined the terms "breast cancer" or "breast neoplasms";"statins" or "lipid-lowering drug";"prognosis" or"survival" or "mortality" or "outcome" without time limit for the article to be published.The two authors cross-checked the inclusion criteria and the accuracy of the extracted information.Using Stata/SE 11.0 software,random-effect model was selected for analysis.Results:The initial search identified 503 publications,of which 14 studies met the selection criteria for a total of 302,566 female breast cancer patients.In general,statins can improve cancer-specific mortality and all-cause mortality of breast cancer(cancer-specific mortality:HR,0.78;p<0.001;all-cause mortality:HR,0.77;p<0.001),although the benefit appeared to be constrained by statin's type.Lipophilic statins were associated with decreased breast cancer-specific and all-cause mortality,however,hydrophilic statins improved all-cause mortality but did not improve breast cancer-specific mortality.Duration and timing of intake of statins did not affect the protective effect.Conclusions:Although statins may improve the prognosis of breast cancer,the protective effect depends on the type of statin.The conclusions are helpful to guide the standardized use of statins in breast cancer patients.