| This study is divided into two parts:literature review and clinical research.Firstly,the research progress of traditional Chinese medicine(TCM)in advanced colorectal cancer(CRC)is discussed.Secondly,the application of discriminant analysis in CRC prediction model is described.Clinical research part:in study 1,patients with advanced CRC who received systematic TCM treatment in the oncology department of our hospital were divided into high exposure group and low exposure group according to"whether they received continuous treatment of TCM for 3 months or more".Through the survival analysis and comparison of the two queues,to explore the correlation between the treatment of TCM for more than 3 months and the survival time of patients with advanced CRC.Study 2,on the basis of clinical study 1,the advanced CRC patients who were treated in the outpatient clinic of Professor Yang Yufei were selected from the high exposure groups,and were divided into groups according to the pre-established TCM intervention and treatment dominant population(referred to as TCM dominant population)and non-TCM dominant population grouping criteria,and the characteristics of TCM dominant population were discussed by establishing Logistic regression model.In study 3,the discriminant prediction model of TCM dominant population of advanced CRC was established by discriminant analysis,and the 50%discount cross-validation method was used to test and verify the model to improve the accuracy of the model.Study 4,taking the survival time of TCM intervention treatment as the final evaluation index,screening the factors affecting the choice of TCM intervention treatment as decision variables,based on survival data cost-sensitive learning algorithm to explore the optimal dynamic intervention treatment strategy of advanced CRC patients who received TCM treatment in the outpatient clinic.Study 5,on the basis of clinical study 4,to further explore the rule of using Chinese medicine under different TCM intervention strategies for advanced CRC.Clinical Study 1:Population Characteristics and Curvival Analysis of Patients with Advanced CRC Treated with TCM.Objective:To explore the correlation between the treatment time of TCM intervention and the therapeutic effect of advanced CRC through the survival analysis of high exposure group and low exposure group of TCM.Methods:A retrospective and prospective cohort study was used to collect the information of 686 patients with stage ? colorectal cancer who met the inclusion criteria and received TCM treatment in the outpatient/ward of Professor Yang Yufei in the department of oncology of our hospital from January 1,2013 to October 1,2020 for survival follow-up.The patients were divided into high exposure group(n=459)and low exposure group(n=227)according to whether they had received TCM treatment for 3 consecutive months or more.The KaplanMeier method was used to analyze the survival of the two groups.Results:1.Description of the characteristics of the patientsThe proportion of patients in the left colon was higher than that in the right colon(74.78%VS 25.22%).More than half of the patients had two or more metastases(51.17%).The population of gene mutant type(including KRAS or NRAS or BRAF gene mutation)was higher than that of gene wild type(257 cases VS 217 cases).Most of the patients had been treated with western medicine in the past(63.27%),and most of them sought TCM treatment when western medicine treatment was advanced(44.47%,43.09%).2.Survival analysis of high exposure group and low exposure groupAs of February 20,2020,309 cases in the high exposure group reached the clinical observation end point(67.32%),and 176 cases in the low exposure group reached the clinical observation end point(77.53%).The results of baseline analysis of the two groups showed that the average age of patients in the high exposure group was 62 ± 12 years old,and that in the low exposure group was 62±13 years old.There was no significant difference between the two groups in sex,age,primary location(left colon,right colon),pathological type,metastatic site,whether to receive targeted treatment,the stage of western medicine treatment before the start of TCM treatment,whether the disease was in rapid progression at the beginning of TCM treatment,whether it was complicated with diseases and so on(P>0.05).There was significant difference in gene mutation between the two groups(P<0.001),but the proportion of gene mutation in high exposure group was higher than that in low exposure group(42.05%VS 28.19%).The results of survival analysis showed that the median overall survival time of 686 patients with advanced CRC treated with TCM was 27 months(95%CI:25.3-29.8).The mOS of high exposure group was 33.5 months(95%CI:29.4-36.3),and that of low exposure group was 18.2months(95%CI:15.9-21.3).The difference was statistically significant(P<0.001).Conclusion:1.The patients with advanced CRC treated with TCM have the following characteristics:most of them are over 60 years old,most of them involve metastasis of two or more sites,the proportion of KRAS or NRAS or BRAF gene mutation is high,and most of the patients have been treated with western medicine in the past.2.Patients with advanced CRC receiving high-exposure TCM treatment for three months or more may be associated with longer mOS.Clinical Study 2:Analysis of Dominant Population Characteristics of Traditional Chinese Medicine Intervention in the Treatment of Advanced Colorectal CancerObjective:To explore the characteristics of the dominant population of traditional Chinese medicine in the treatment of advanced colorectal cancer by comparing the characteristics of the dominant population and the non-dominant population in the treatment of advanced colorectal cancer,and to find the advantages of traditional Chinese medicine intervention in the treatment of advanced colorectal cancer.Methods:384 patients were selected from the TCM high exposure group of 459 patients with advanced CRC.According to the grouping criteria established in the previous study,the dominant and non-dominant groups of TCM were divided into two groups.The preponderant population of TCM meets one of the following conditions:?by the time of the patient's death or the last follow-up,the survival time of the whole wild type in the ? stage is>30 months;?the survival time of the KRAS or NRAS gene mutant type ? is>24 months;?The survival time of stage ? in patients with BRAF gene mutation or without gene detection was more than 18 months.Non-TCM advantage group:the remaining population other than the TCM advantage group.Logistic multivariate regression analysis was conducted to explore the characteristics of TCM dominant population in advanced CRC by taking whether the patient was the dominant population treated by TCM as dependent variables(1=yes,0=no),sex,age,site of disease,site of metastasis,genotyping,pathological classification,syndrome differentiation,treatment status of western medicine at first diagnosis,radical operation and other factors as independent variables.Results:A total of 354 cases were included in the study,with an average age of 61±12 years old,including 209 cases of dominant population and 175 cases of non-dominant population.The results of Logistic multivariate regression analysis showed that under the same condition of other factors,women(OR=2.760,P=0.001),ECOG score<2(OR=21.432,P<0.001),pathological classification of adenocarcinoma(OR=2.427,P=0.014),The syndrome differentiation type was non-liver-stagnation and spleen-deficiency type(spleen-kidney deficiency type or lung-kidney deficiency or lung-kidney deficiency or liver-kidney deficiency or liver-kidney deficiency type or liver-stomach disharmony)(OR=30.229,P<0.001),and the western medicine treatment stage was initial treatment or first-line treatment at the first visit(OR=14.783,P<0.001)was significantly positively correlated with whether the patients were TCM advantaged population.Conclusion:The dominant population characteristics of TCM intervention in the treatment of advanced CRC may be female,ECOG score<2,adenocarcinoma,initial treatment at first diagnosis or first-line treatment stage of western medicine.TCM syndrome differentiation type is non-liver depression.Clinical Study 3:Establishment and Verification of Discriminant Prediction Model for TCM Dominant Population of Advanced Colorectal CancerObjective:To establish a discriminant prediction model for the dominant population of TCM in patients with advanced CRC through discriminant analysis,so as to predict whether patients can gain survival benefits from the intervention treatment of TCM,so as to better guide the clinical treatment practice of TCM.Methods:Based on the characteristic results of the dominant population of TCM in the second middle and advanced CRC combined with the clinical practice,gender,pathological classification,ECOG score,site of disease,site ofmetastasis,number of lines treated by western medicine at the first visit,syndrome differentiation and so on were included as independent variables of discriminant analysis.80%of the observed data were taken as dependent variables,and 80%of the observed data were taken as training set.20%was used as the test set to establish four discriminant models,and the 50%discount cross-validation method was used to verify the accuracy of the model.According to the prediction results of the model,the discriminant model with the best prediction effect was selected as the discriminant prediction model for the dominant population of TCM in the final advanced colorectal cancer.Taking the false positive rate of the model as the abscissa and the true positive rate as the ordinate,the receiver operating characteristic curve is drawn,and the classification effect of the model is evaluated by calculating the area under the ROC curve.Results:Among the observed data.there were 209 dominant groups of TCM and 175 cases of non-dominant groups of TCM.Among the four discriminant models,the prediction effect of secondary discriminant analysis model was the best,with an accuracy of 90.79%,a sensitivity of 97.56%and a specificity of 82.86%.Taking the specificity of the model as the abscissa and the sensitivity as the ordinate,the ROC curve is drawn to evaluate the classification of the quadratic discriminant model.The results show that the quadratic discriminant analysis model has a good classification effect,and the AUC reaches 0.9021.Conclusion:The secondary discriminant prediction model of advanced CRC based on sex,location of disease,metastatic site,pathological type,ECOG score,syndrome differentiation and the number of lines treated by western medicine at the first diagnosis in outpatient clinic as independent variables has a good discriminant prediction effect(the accuracy is 90.79%and the AUC is 0.9021).Clinical Study 4:An Exploratory Study on the Optimal Dynamic Intervention Strategy of TCM for Advanced CRC Dased on Professor's Clinical Experience.Objective:To establish the optimal dynamic intervention strategy of TCM for advanced CRC,so as to provide reference for the selection of TCM intervention therapy for advanced CRC.Methods:From the 384 cases of advanced CRC treated in the outpatient clinic of Professor Yang Yufei in the department of oncology of our hospital in Clinical Study ?,197 cases meeting the inclusion criteria were screened out,and the patients were divided into three treatment types according to different TCM intervention treatment strategies,namely pure TCM treatment,auxiliary treatment of western medicine of TCM and equal emphasis on Chinese and western medicine therapy,Chinese medicine intervention treatment time to live for the final evaluation index.The influencing factors such as gender,age,ECOG score,site of onset,site of metastasis,genotyping,and stage of western medicine treatment at the time of initial diagnosis were screened as decision variables,and CSCLSURV algorithm was adopted to treat the patients in two stages strategy,to explore the TCM dynamic intervention treatment strategy for advanced CRC.Results:197 cases were included in the study,152 cases entered the second stage of TCM intervention treatment,of which 114 cases died and 38 cases survived,and 45 cases did not enter the second stage of TCM intervention treatment,of which 32 cases died and 13 cases survived.In this study,there were 126 males and 71 females,with a median age of 63 ± 13years,152cases of left colon and 45 cases of right colon.Most of the patients(70.05%)had metastatic sites that had a high impact on prognosis.The patients with mutant genotype were much higher than those with wild type(45.18%VS 31.98%).More than half of the patients(54.82%)had ECOG score?2.At the time of initial diagnosis,75 cases were in the state of initial treatment,60 cases were treated with first-line treatment,30 cases were treated with second-line treatment,and 32 cases were treated with third-line or more.Taking the survival time of TCM intervention treatment as the evaluation index,the optimal TCM dynamic intervention treatment strategy for advanced colorectal cancer established based on CSCLSurv algorithm can dynamically choose different TCM intervention treatment strategies for advanced CRC according to different decision variables such as sex,age,ECOG score,location of disease,site of metastasis,genotyping,number of treatment lines of western medicine at first diagnosis,etc.Conclusion:the optimal dynamic intervention strategy of TCM for advanced CRC based on CSCLSurv algorithm has a certain clinical hint of TCM,and the prospective and large sample study can be further improved.Clinical Study 5:Exploring the Regularity of the Use of CM in Different TCM Intervention and Treatment StrategiesObjective:To summarize the rules of the use of CM in different TCM intervention schemes,so as to provide reference for the clinical practice of TCM in the treatment of advanced CRC.Methods:The patients with advanced CRC who were treated in the outpatient clinic of Professor in clinical study No.4 were selected as the object of study.Collect and sort out the basic data and diagnosis and treatment information of 1685 prescriptions of 197 patients,based on the methods of frequency statistics and association rule analysis on the basis of study 4 to explore the appropriate TCM intervention treatment schemes for people with different characteristics,to futher summarize the rules of the use of Chinese medicine in different TCM intervention treatment schemes.Results:1.Advanced CRC Syndrome Differentiation Characteristics,Common Symptoms and Commonly Used Drug Examples1.1 Syndrome DifferentiationSyndrome differentiation is mainly characterized by syndrome differentiation of double Zang-fu organs,which is a mixture of deficiency and reality.The frequency of this deficiency syndrome from high to low is:spleen and kidney deficiency,liver depression and spleen deficiency,liver and kidney deficiency,lung and kidney deficiency,lung and spleen deficiency;evil excess syndrome frequency from high to low is:phlegm and blood stasis internal obstruction,phlegm-dampness accumulation,dampness-heat injection,dampness-turbid internal accumulation.1.2 SymptomsSymptoms of patients with advanced CRC include not only tumor-related symptoms such as fatigue,abdominal distension,abdominal pain,cough,hypochondriac pain,but also adverse reactions caused by treatment,such as anorexia,nausea,vomiting,hand and foot syndrome and so on.1.3 Commonly Used Traditional Chinese MedicineThe commonly used TCM are roasted licorice,Poria cocos,fried atracty lodes macrocephala,ligustrum lucidum,codonopsis pilosula,radix astragali,tangerine peel,psoralen,dodder,etc.,as well as Shijianchuan,ghost arrow feather,scutellaria barbata,Ttaxus chinensis var.mairei,etc.2.The Regularity of the Use of Traditional Chinese Medicine in the Treatment of Pure Traditional Chinese MedicineThe 744 prescriptions of TCM of pure Chinese medicine involve 276 kinds of TCM.The combination of Radix Paeoniae Alba,Bupleurum,Codonopsis pilosula,Bran stir-fried Atractylodes macrocephala,Fulongan,Poria,Ghost Arrow Yu,Guizhi,Astragalus,Clematis,Ligustrum lucidum and licorice are more common.Among them,the type of spleen and kidney deficiency is mainly Sijunzi decoction combined with Erzhi Pill;the syndrome of liver depression and spleen deficiency is mainly Sijunzi decoction combined with Bupleurum andErzhi pill;the syndrome of deficiency of liver and kidney is mainly Liuwei Dihuang Pill series;the syndrome of deficiency of lung and spleen is mainly modified by Xiebai San and Sijunzi decoction;for lung and kidney deficiency syndrome,Erzhi pill was added with Astragalus membranaceus,Rhodiola rhodiola and Huangjing.On the basis of syndrome differentiation,if there is lung metastasis,add anti-tumor traditional Chinese medicine such as Ghost Arrow Yu,Shi Jian Chuen,Shi Shangbai,Southern Taxus mairei,Scutellaria barbata,etc;if there is brain metastasis,choose anti-tumor traditional Chinese medicine such as Pleurotus ostreatus,Snake six Gu,Scorpio,etc.The emergence of abdominal and pelvic metastasis selected to add Panax notoginseng powder,grass river car,soil Poria cocos and other anti-tumor traditional Chinese medicine.3.The Regularity of the Use of Traditional Chinese Medicine with Equal Emphasis on Traditional Chinese and wWstern MediclineFour gentlemen soup is commonly used in combination with Ligassum Ligassum,Moxa lotus,dodder,Psoralea fat to supplement the days of this,as appropriate to chicken,fried grain bud,fried malt,fried hawthorn,fried Divine Comic spleen appetizer,digestion lead stagnation;Add peach kernel,safflower,angelica,peony and so on to relieve hand and foot syndrome;Choose to add gastrodia elata,hook rattan,apocynum leaves and other control,prevention of hypertension caused by targeted drugs.At the same time,according to the adverse reactions caused by oral chemotherapeutic drugs or targeted drugs and the strength of the body's tolerance,as appropriate,the Chinese medicine such as Taxus chinensis,Liugu,and Pinellia chinensis is selected to strengthen the anti-tumor effect of chemotherapy drugs.4.The Regularity of the Use of CM in the Treatment Plan of TCM and Western MedicineIn the treatment,strengthening the spleen and tonifying the kidney is the core of the treatment,traditional Chinese medicine is simple Fuzheng,without anti-tumor traditional Chinese medicine or proprietary Chinese medicine.Ginger Pinellia ternata,Codonopsis pilosula,Poria cocos,fried Atractylodes macrocephala,Radix Astragali,Fructus psoraleae,dodder,Ligustrum lucidum,licorice and other combinations are more common.Conclusion:1.Pure TCM treatment:according to syndrome differentiation,disease metastasis site and symptoms of different TCM groups,disease,disease,syndrome trinity,supporting the positive and dispelling evil at the same time,invigorating the spleen and kidney detoxification is the core method of treatment.2.Treatment scheme with equal emphasis on traditional Chinese and western medicine:take invigorating the spleen and tonifying the kidney as the core,add different reducing traditional Chinese medicine according to the different side effects of western medicine treatment,and add anti-tumor traditional Chinese medicine or proprietary Chinese medicine according to the patient's tolerance to the side effects.3.TCM auxiliary western medicine treatment plan:invigorating the spleen and kidney is the treatment method,CM is simple Fuzheng,reduce toxicity and increase efficiency. |
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