| Part one Comparison of the therapeutic effect of three-dimensionalconformal/intensity modulated radiotherapy alone and the combination therapy with chemothreapy for esophageal carcinoma:a retrospective analysis of propensity score matched analysis.Objective:Retrospective analyzed the esophageal cancer patients who underwent 3D/IMRT radiotherapy in my department in the last 10 years,to evaluate the survival and prognosis for inoperative esophageal cancer patients treated with definitive radiotherapy and chemoradiotherapy,and to find out the best combination of radiotherapy and chemotherapy and to improve the patient’s individualized treatment.Methods:In January 2006 to December 2015,924 esophageal cancer patients treated with 3DCRT/IMRT,not suit for surgery treatment,were analyzed to observe the effect of different combination of radiotherapy with chemotherapy on survival prognosis.The survival was the first analysis objective.Kaplan-meier method was used to calculate the survival rate and log-rank test,Cox model prognostic for multivariate analysis,and PSM method was used to analyze the bias matching group.SPSS19.0 statistical software was used to analyzed.Results:1.The sample sizes in the whole group were 685,257 and 117,respectively.1,3,5 years OS and PFS were 74.2%,33.9%,18.0%and 56.5%,24.8%and 14.2%respectively.The median OS time was 21.82 months(95%CI 19.85~23.79 months),and the median PFS time was 14.7 months(95%CI13.1~16.3 months).Univariate analysis showed that the factors affecting OS and PFS were age,pathology,T stage,N stage,TNM stage,chemotherapy,cycles of chemotherapy,concurrent and sequential chemoradiotherapy,and irradiation field.Multivariate analysis showed that T stage,N stage,irradiation field,chemotherapy cycle number and tumor volume were the factors affecting OS and PFS.2.After the PSM,720 patients were well matched(RT=360,CRT=360).The overall survival rates of 1,3,5-years were 70.8%,30.8%,17.6%and76.1%,38.7%,and 21.0%(P=0.021)respectively in the radiotherapy group and the chemoradiotherapy group.1,3,5 years PFS was 54.4%,24.7%,14.8%and 58.8%,26.6%,16.3%(χ~2=0.973,P=0.324).The OS of the chemotherapeutic group was significantly higher than that of the simple radiotherapy group,and there were statistical differences.Further subgroup analysis showed that in patients with T4,N0/1 and radiotherapy dose of less than 60 Gy,the total survival of the chemotherapeutic group was significantly higher than that of the radiation group,and there was a statistical difference(P=0.035,0.014,0.043).3.In radiation dose≤60 Gy group of 441 esophageal cancer patients,there were 361 cases(RT=214,CRT=147)well balance after PSM.1,3,5 year OS were 71.0%,29.8%,16.0%and 78.9%,41.0%,23.7%(P=0.048),1,3,5years PFS were 50.9%,23.0%,12.9%and 59.9%,26.7%,16.2%(P=0.307),in the radiation group and chemoradiotherapy group,respectively.The OS in the chemoradiotherapy group was obviously higher than that of radiation group,and there are statistically significant.Subgroup analysis showed that in male,T4,N2,squamous carcinoma,the middle and lower part of the esophagus,tumor length>7 cm,tumor size>50cm~3,involved node radiotherapy,traditional Chinese medicine,and the total survival of chemoradiotherapy group was obviously higher than that of radiation group(P=0.005,0.034,0.050,0.034,0.014,0.018,0.013,0.038,0.033).4.In the IFI group of 652 esophageal cancer patients,there were 458cases(RT=229,CRT=229)well balance after PSM.There were no significant differrence between the RT group and CRT group(P=0.419,0.779).There were 280 cases(RT=140,CCRT=140)well balance after PSM.The 1,3,5year OS were 68.6%,31.9%,20.1%and 70.7%,33.9%,18.4%(P=0.885),1,3,5 years PFS was 54.3%,27.5%,19.0%and 50.7%,22.9%and 13.5%,respectively(P=0.486),in the RT group and CCRT group.Survival rate of the RT group compared with CCRT group did not see obvious difference.In the IFI with radiation dose≤60 Gy group of 313 esophageal cancer patients,after PSM(RT=146,CCRT=84),RT group and CRT group of 1,3,5 year OS were67.1%,21.5%,10.0%and 77.4%,38.4%,23.7%(P=0.017),1,3,5 years PFS was 52.1%,17.1%,8.7%and 56.0%,24.4%,15.0%,respectively(P=0.216).CCRT group was obviously higher than that of RT group with statistically significant.Further stratified analysis showed,male,age>66 years old,T4,lower part of the esophagus,tumor volume>50cm~3 of the subgroups of patients,CCRT group was obviously higher than that of RT group,and there were statistically significant(P=0.002,0.011,0.048,0.008,0.008,0.005,0.012).5.To analyze the 564 cases of esophageal cancer treated with radiotherapy alone,age,T stage,N stage,TNM stage,tumor length,tumor size,irradiation range,radiation dose were the factors affecting the prognosis of survival.In the RT group,radiation dose≤60 Gy and dose>60 Gy group of 1,3,5 year overall survival were 71.1%,27.4%,14.0%and 74.8%,34.5%,19.2%(P=0.048),1,3,5 years PFS were 52.6%,21.3%,11.7%and 60.5%,28.4%,and 14.9%(P=0.022),respectively.The survival rate of radiation dose>60 Gy group was obviously higher than that of the group of radiation dose≤60 Gy;Subgroup analysis showed that in the RT using IFI group,the survival of dose>60 Gy group was obviously higher than that of dose≤60Gy(P=0.043),further stratified analysis for N staging,survival rate of dose>60 Gy was significantly higher than that of dose≤60 Gy group in N0 stage(P=0.028).6.Univariate analysis and multivariate analysis were performed on 360esophageal cancer treated with chemoradiotherapy,and the results of univariate analysis showed that T,N,TNM stage,tumor length,tumor size,radiation field,chemotherapy cycles related to the survival prognosis;Multivariate analysis showed that T stage,N stage,irradiation field and chemotherapy cycles were the independent prognostic factors for survival.Summary:1.Patients with esophageal cancer treated with radical 3DCRT/IMRT,T stage,N stage,irradiation field,chemotherapy cycle number and tumor volume were factors affecting OS and PFS.2.The OS in patients with esophageal cancer who were not inoperable received the radiatin combined with chemotherapy were significantly higher than those who received the RT alone,especially those with esophageal cancer who received radiotherapy dose≤60Gy.3.In the group of IFI with dose≤60Gy,the survival rate of patients in concurrent chemoradiotherapy group was significantly higher than that of the patients with radiotherapy group.4.Patients with esophageal cancer treated with radiotherapy alone should have a radiation dose of>60Gy,which is especially applicable to patients with N0 stage of IFI treatment.5.Patients with chemoradiotherapy group,the irradiation field and the number of cycles of chemotherapy are the independent prognostic factors that affect survival.Part two Elective nodal irradiation provides a safe and superiortherapeutic modality for esophageal carcinoma patients versus involved-field irradiation:A retrospective propensity score matched analysisObjective:A retrospective study was conducted to compare the survival of patients with esophageal cancer treated with ENI and IFI,and to determine the prognostic factors affecting the survival through multiple factors and subgroup analysis,and to find the sui Table population for the range of different target areas of the three-dimensional and intensity-modulated radiotherapy.Methods:From January 2006 to December 2015,924 esophageal cancer patients meeting the conditions for the group received radical radiotherapy in our hospital,and clinical data and prognostic survival were analyzed by statistics analysis,and stratified analysis was carried out on the series of related indicators,the main observation indexes are survival rate and prognostic factors.SPSS l9.0 software was used for statistical analysis.Result:1.After propensity score matching,544 cases of patients with good match,1,3,5 year overall survival were 79.0%,43.7%,24.9%and 75.0%,31.8%,17.2%(P=0.003),1,3,5 years progression-free survival(PFS)were 65.3%,31.7%,18.4%and 54.0%,20.9%,12.7%(P=0.001),in the ENI group and IFI group,respectively,and the survival rate of ENI group was obviously higher than that of IFI group;Further stratified analysis showed that men,T1/2/3,N0/1,tumor volume less than 50cm~3 and chemotherapy 1-2 cycles could benefit from ENI treatment.2.In the patients with radiation alone group,the ENI group and the IFI group were well matched(ENI=141,IFI=141)after PSM,and the OS and PFS in the ENI group was similar to that of the IFI group,and there was no statistical difference.Putting the chemoradiotherapy group of patients into propensity score matching,matching is good in 262 patients(ENI=131,IFI=131).1,3,5 year OS and PFS were 83.9%,48.6%,26.8%and 83.9%,34.4%,21.2%in the ENI group.1,3,5 year OS and PFS were 69.5%,31.4%,19.5%and 49.6%,23.2%,16.1%in the IFI group.The OS and PFS of ENI were significantly higher than that of IFI group(P=0.009,0.004).Further stratified analysis,male,age≤66 years,cervical and upper thoracic esophageal cancer,T1/2/3,N0/1,I/II stage,tumor volume≤50 cm~3,tumor length≤7 cm,radiation dose>60 Gy,concurrent chemoradiotherapy patients,can benefit from ENI treatment.3.In the ENI group,it was found that N stage,tumor volume,concurrent or sequential chemoradiotherapy,and chemotherapy cycles were independent prognostic factors for survival.In the patients received chemoradiotherapy with ENI group,1,3,5 year OS were 81.3%,35.6%,16.7%and 35.6%,86.1%,35.6%(P=0.027),1,3,5 years PFS were 59.1%,26.3%,13.6%and 26.3%,76.1%,27.5%(P=0.033)in the sequential chemoradiotherapy and concurrent chemotherapeutic group,respectively.The OS of the concurrent chemotherapeutic group was higher than that of the sequential chemoradiotherapy group,and there was a statistical difference.4.Analyzing involved-node irradiation group,results show that the age≤66 years old,N stage,tumor size≤50 cm~3 is to improve OS and PFS as the independent prognostic factors.For involved-node irradiation and chemotherapy group,analysis shows that patients received dose≤62 Gy with chemotherapy>2 cycles had obviously better survival than other corresponding group,and there was statistically significant(P=0.001).5.After PAM according ENI and IFI groups,the acute hematological toxicity of the ENI group and IFI group was 34(12.5%)and 20(7.4%)respectively,and the difference between the two groups were significant(P=0.045).There was no statistical difference between the two groups of acute radiation esophagitis and radio-pneumonia.There were 37(13.6%)and32(11.8%)cases of radio-pneumonia of the ENI group and the IFI group,respectively(P=0.519).The two groups were 33(12.1%)and 45(16.5%)in the adverse reactions≥3 stages(P=0.142),such as esophageal stenosis,esophageal hemorrhage,esophageal fistula,and advanced radiation lung injury.Summary:1.The clinical outcomes of ENI treatment was significantly better than that of IFI group,especially for patients receiving radiotherapy combined with chemotherapy.2.When patients with esophageal cancer were treated with elective node irradiation,the therapeutic effect of concurrent chemoradiotherapy was better than that of sequential radiotherapy.3.The dose of radiotherapy in involved-node irradiation group should not exceed 62Gy and chemotherapy should be more than 2 cycles,and survival was significantly better than that of other treatment groups.Part three Expression of RNF2 and P-AKT protein in esophagealsquamous cell carcinoma and its relationship with prognosisObjective:By testing RNF2 and P-AKT protein expression in ESCC tissues,analyze its clinical pathological characteristics and the relationship with the survival time after radical radiotherapy,and found out the biological prognosis factors influencing the survival of esophageal squamous carcinoma treated with radical radiotherapy,and provides a new direction for the research.Methods:A total of 99 cases of patients with esophageal squamous carcinoma diagnosed by biopsy in our hospital from January 2010 to December 2013 were collected.All patients received definitive 3DCRT/IMRT radiotherapy.The expression of RNF2 and P-AKT in the esophageal squamous cell carcinoma of the whole group was detected by immunohistochemical technique,and the relationship between RNF2/P-AKT expression and the clinicopathological features and prognosis of patients was analyzed.SPSS l9.0 software was used for statistical analysis.Results:1.Immunohistochemical methods were used to detect RNF2 and P-AKT proteinexpressioninesophagealsquamouscellcarcinoma.Immunohistochemical analysis showed that RNF2 and P-AKT were mainly located in the nucleus of tumor cells.Of the 99 cases of esophageal squamous cell carcinoma,83 were used to analyze the protein expression level of RNF2,85 were used to analyze P-AKT protein expression level,and 80 patients met RNF2/P-AKT group conditions.In 83 cases of esophageal squamous carcinoma tissues,RNF2 negative expression of 9 cases(10.8%);RNF2positive expression in 74 cases(89.2%),in which weakly positive expression of 18 cases(21.7%),moderate positive expression of 36 cases(43.4%),20cases of strong positive expression(24.1%).Of 85 cases of esophageal squamous carcinoma tissues,the P-AKT negative expression of 29 cases(34.1%);P-AKT positive expression of 56 patients(65.9%),in which weakly positive expression of 39 cases(45.9%),moderate positive expression of 16cases(18.8%),1 case(1.2%)of the strong positive expression.80 patients with esophageal carcinoma RNF2/P-AKT expression group,RNF2/P-AKT all negative expression in 5 patients(6.3%),RNF2 positive/P-AKT negative expression of 21 cases(26.3%),RNF2 negative/P-AKT positive expression of4 cases(5%),RNF2/P-AKT positive expression of 50 cases(62.5%).2.Relationship between RNF2/P-AKT and clinical pathological parameters of esophageal squamous cell carcinoma.The moderate/strong positive expression of RNF2 protein in esophageal squamous cell carcinoma was significantly correlated with the N2 and volume(χ~2=4.764,P=0.029;χ~2=4.821,P=0.047).The P-AKT positive protein in the tissues of esophageal squamous cell carcinoma was more related with advanced T,TNM stages than that the weak-positive group(P=0.020,0.044).The positive expression of RNF2/PAKT protein was closely related to the gender and T stage(χ~2=9.132,P=0.003;χ~2=7.240,P=0.065);RNF2 positive/P-AKT negative expression was related to gender and T stage(χ~2=6.432,P=0.011;χ~2=9.377,P=0.025);It was not related to age,N,TNM stage,tumor length and volume(P>0.05).3.Relationship between expression of RNF2/P-AKT and survival prognosis for esophageal squamous cell carcinoma.Kaplan-meier survival analysis showed that the overall survival rate of RNF2(++~+++)positive expression was significantly lower than that of RNF2(-)expression,and the difference was statistically significant.(χ~2=4.893,P=0.027).The overall survival rate of RNF2/P-AKT positive expression was significantly lower than that in the other groups,and there was a statistical difference.(χ~2=4.205,P=0.040).Further multivariate analysis showed that T-stage,RNF2/P-AKT positive expression were the independent prognostic factor affecting survival(P=0.010,0.010).Summary:1.High expression of RNF2 and P-AKT protein in human esophageal squamous cell carcinoma.2.The different expression levels of RNF2 and P-AKT in esophageal squamous cell carcinoma were related to tumor length,volume,N stage and poor prognosis.3.The total survival of RNF2/P-AKT positive expression groups was significantly lower than that in the other group,and RNF2/P-AKT positive expression was an independent prognostic factor affecting the survival rate and expected to be a new prognostic indicator for esophageal squamous cell carcinoma treated with definitive radiotherapy.Conclusions:1.The survival rate of esophageal cancer patients treated with chemoradiotherapy was significantly higher than that of patients received radiotherapy alone,especially when patients were treated with radiation dose≤60Gy.Moreover,the treatment effect of esophageal cancer patients with concurrent chemoradiotherapy was significantly better than that of patients with radiotherapy alone when the radiation dose≤60Gy with IFI irradiation.For patients in the chemoradiotherapy group,irradiation field and the number of cycles of chemotherapy were independent prognostic factors affecting survival.2.For esophageal cancer patients who received radiotherapy alone,the dose should be>60Gy,especially for patients with IFI of N0 stage.3.The effect of ENI treatment was significantly better than that of IFI group for esophageal cancer patients who received chemoradiotherapy.When the patients were treated with ENI,the therapeutic effect of concurrent chemoradiotherapy was significantly better than that of sequential chemoradiotherapy.The radiation dose should not exceed 62Gy at the time of>2 cycle of chemotherapy when the patients treated with IFI.4.RNF2 and P-AKT proteins were highly expressed in the tissues of esophageal squamous cell carcinoma patients.The overall survival of RNF2/PAKT positive expression was significantly lower than that of other groups.RNF2/PAKT positive expression were an independent prognostic factor that affected the survival of esophageal squamous cell carcinoma,which is expected to be a new prognostic index for the definitive radiotherapy of esophageal squamous cell carcinoma. |
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