Clinical Study On Adjuvant Chemotherapy With Or Without Targeted Therapy Based On Whole Gene Sequence Detection After R0 Radical Resection Of Cholangiocarcinoma

Objective:To evaluate the clinical efficacy of precision targeted therapy combined with traditional chemotherapy by performing standardized R0 radical resection of cholangiocarcinoma plus regional lymph node dissection and complete gene sequence testingMethods:Collected in July 2018 to September 2020 in our hospital within the liver,bile duct carcinoma,perfecting the related magnetic resonance imaging(MRI),ultrasound,portal CT,blood biochemistry,blood cell analysis,tumor markers,such as inspection,assessment is discussed fully with the hospital doctors,a total of 27 patients with selected into the set of standard,metasomatism illness with the patient and family members,communicate,Introduce the surgical method and relevant post-operative treatment,and introduce the specific research protocol of this study as well as the mechanism,expected efficacy and corresponding cost of emerging precision targeted therapy and adjuvant chemotherapy(selected for different types of cholangiocarcinoma according to NCCN Guidelines 2017V2)to patients and their families.Patients were asked if they were willing to participate in this study,and after signing the informed consent,they voluntarily chose postoperative precise targeted therapy with complete gene sequence detection combined with adjuvant chemotherapy(selected according to NCCN guidelines 2017V2 edition).Will collect option with full genetic sequence detection precision guide targeted therapy combined adjuvant chemotherapy in patients with carcinoma tissue to normal after gene sequencing with country’s qualification authentication institutions after related gene sequencing analysis in current medical research have guiding significance of genetic variation of targeted drugs,according to the analysis result accurate choose adjuvant chemotherapy drugs.Patients were divided into targeted group(12 cases)and non-targeted group(15 cases)according to whether they agreed to genetic testing and targeted therapy.To participate in the study of each patient every time returned to the court review chemotherapy are detailed imaging of use,ultrasonics,blood biochemistry,blood cell analysis,a variety of means to monitor the blood coagulation function,and at the same time observation and follow-up study of patients in hospital and daily related adverse reactions(digestive tract symptoms,white,skin symptoms,blood coagulation function to drop,Liver function decline,etc.),and according to the WHO standard of toxic and side effects of chemotherapy.The relapse-free survival(RFS)and median RFS were recorded.The collected data were statistically analyzed.In this experiment,SPSS23.0 was used for data analysis.For counting data,frequency(percentage%)was used to describe,and the chi square analysis method(Fisher exact probability method)was used to analyze the counting data.In the study of RFS,the single-factor Kaplan-Meier analysis method was used firstly,and the log-rank test method was used for comparison of different levels.Then,variables with P value less than 0.05 in the univariate test were included in the subsequent multivariate Cox regression model.For the multivariate classification variables,the appropriate reference layer was selected to establish the multivariate Cox regression model,and the HR value was taken as the risk assessment parameter.P<0.05 was statistically significant.Results:Standardization R0 radical resection+regional lymph node dissection was successfully performed in all patients with cholangiocarcinoma.Among the 27 patients with cholangiocarcinoma,12 cases(44.4%)were in the targeted group and 15 cases(55.6%)were in the non-targeted group.The relapse-free survival time of the 27 patients ranged from 11.8 to 31.8 months,with a median RFS of 22.7±0.322 months[95%CI 22.069 to 23.331 months].The median RFS in the non-targeted group was 21.8±1.932 months[95%CI 18.013-25.587 months],which was significantly longer in the targeted group than in the non-targeted group(31.0±0.789 months[95%CI 29.427-32.519 months]).The difference was statistically significant(P=0.001).Grade 3-4 adverse reactions occurred in 1 patient(3.7%)in the non-targeted group.and the most common adverse reactions were leucopenia(22.2%).Leucopenia and elevated glutamic pyruvic transaminase(25%)were the most common in the targeted group,while leucopenia(20%)were the most common in the non-targeted group,and no drug-related deaths occurred.Univariate KM test analysis showed that different groups(P=0.001)and different types of bile duct carcinoma(P=0.003)had statistically significant effects on RFS.The risk of recurrence outcome in the targeted therapy group[(HR)0.064,95%(CI)0.008--0.495,P=0.008]was 0.936 times higher than that in the control group.The combination of targeted therapy and adjuvant chemotherapy was an independent factor in prolonging relapsed-free survival.Taking intrahepatic cholangiocarcinoma as a reference,the risk of recurrence outcome of distal cholangiocarcinoma[(HR)6.686,95%(CI)1.243--35.962,P=0.027]was 6.686 times higher than that of intrahepatic cholangiocarcinoma,and distal cholangiocarcinoma may be a risk factor for recurrence.Conclusions:In patients with cholangiocarcinoma who have received standardized R0 radical resection+regional lymph node dissection,gene testing combined with targeted therapy combined with adjuvant chemotherapy can significantly improve the patients relapsed-free survival,which is an independent influencing factor for prolonging the relapsed-free survival,and distal cholangiocarcinoma may be a risk factor for recurrence.The most common adverse events in patients receiving targeted therapy combined with adjuvant chemotherapy were leucopenia and alanine aminotransferase elevation,but both were controlled and no drug-related fatal adverse events occurred.