Analysis Of Preoperative And Postoperative Radiotherapy For Esophageal Squamous Cell Carcinoma

BackgroundEsophageal cancer is one of the most malignant tumors in China.At present,primary treatment of local early(T2-3N0M0)thoracic esophageal cancer is surgery,but there is always controversy on the efficacy of preoperative or postoperative radiotherapy to T2-3N0M0 esophageal cancer.The main aim of this study is to evaluate the efficacy of preoperative radiotherapy and postoperative radiotherapy to T2-3N0M0 stage esophageal squamous cell carcinoma.Part 1:Efficacy of perioperative adjuvant radiotherapy on T2-3N0M0 esophageal cancer based on The Surveillance,Epidemiology,and End Results(SEER)ProgramPurposethis part was designed to analyze the efficacy of preoperative radiotherapy and postoperative radiotherapy to T2-3N0M0 operative esophageal squamous cell carcinoma based on the SEER database.The clinical prognosis factors related to the prognosis of T2-3N0M0 operative esophageal squamous cell carcinoma were also explored here.Methods1.Patients with T2-3N0M0(Ⅱ a,AJCC 6th)stage esophageal squamous cell carcinoma(ESCC)in 2004-2013 were selected from SEER database for this study.All the samples were divided into three groups:Surgery group(S),Radiation therapy+Surgery group(RTS)and Surgery＋Radiation therapy group(SRT).2.Clinical factors including sex,age,race,location,differentiation,T stage,type of adjuvant radiotherapy and Time series data including overall survival(OS)and Cancer specific survival(CSS)were extract for the following analysis.3.The chi-square test was used to compare the difference of clinical data among three groups.4.Kaplan-Meier method was used to calculate the over survival and cancer specific survival of each group,and draw its survival curve.Log-rank test was used to analyze the survival difference of each clinic factor in three groups,and to explored the relevant factors of OS and CSS.5.Cox proportional hazards model was used to analyze prognosis factors of OS and CSS.6.Survival analysis of OS and CSS in T2 and T3 were performed respectively with Cox proportional hazards model.Results1.A total of 318 patients with T2-3N0M0 esophageal squamous cell carcinoma who underwent surgical treatment were selected from the SEER database.2.Baseline data analysis showed that men were over 60%.White patients were over 70%.Age of 50-75 years old accounted for nearly three quarters,the amount of patients who younger than 65 years old and who elder than 65 years old were almost the same.In more than 75%patients,the focal of cancer was in the middle and lower 1/3 part of esophagus,of which,the middle 1/3 part contained 47.8%.The patients with the T3 stage ESCC were 61.6%.The most common treatment was preoperative radiation therapy with surgery(49.7%),next was surgery alone(39.6%),the least was surgery combined with postoperative radiotherapy(10.7%).3.gender and age were significantly associated with the treatment plan of the patients.Young male patients were more likely to receive preoperative radiotherapy combined with surgery for treatment.Factors as race,tumor location,differentiation and T staging were independent with patient treatment regimens.Further analysis showed that young men received the highest proportion of preoperative radiotherapy combined with surgical treatment(23.27%),followed by elder female who receiving surgery alone(12.26%).4.Univariate survival analysis showed that age and radiotherapy were significantly correlated with OS and CSS(P<0.05);T stage was significantly correlated with OS(P<0.05),but a certain related to CSS(0.05<P<0.2).There was also a certain correlation ship between sex,differentiation degree,race factor and OS/CSS(0.05<P<0.2).The relationship between tumor location and OS/CSS were not significant(P>0.2).5.Multivariate survival analysis of OS showed that gender,age,differentiation degree,T stage and radiotherapy were significantly related to OS.Female,patients younger than 65 years old,well differentiated tumor,T2 stage,preoperative radiotherapy can significantly reduce the risk of death and improve overall survival.While race and postoperative radiotherapy has no significant effect on overall survival(P>0.05).Meanwhile,Multivariate survival analysis of CSS showed that gender,age,degree of differentiation and radiotherapy were significantly associated with OS.Female,less than 65 years,well-differentiated tumors,preoperative radiotherapy combined with-surgery could significantly improve CSS(P<0.05).T stage,racial factors and surgery combined with postoperative radiotherapy did not show significant association with CSS(P>0.05).6.Stratified multivariate analysis based on T stage indicated that preoperative radiotherapy or postoperative radiotherapy did not significantly prolonged OS andCSS of patients with T2-stage ESCC,compared with operation alone.Meanwhile,preoperative radiotherapy significantly prolonged the OS(HR 0.304,P<0.001)and CSS(HR 0.204,P<0.001)of patients with T3 stage ESCC,but postoperative radiotherapy did not(P>0.05).Conclusions1.T2-3 stage of operative esophageal squamous cell carcinoma more common in men,50-75 years old,esophageal,middle 1/3,medium and poorly differentiated squamous cell carcinoma,T3 stage patients.2.Sex and age are two important factors influencing the choice of preoperative and postoperative radiotherapy.Young men tend to preoperative radiotherapy combined with surgical treatment.Elderly women are more likely to choose surgery alone.3.Sex,age,differentiation,preoperative radiotherapy have significant correlation with OS and CSS.T staging have significant correlation with OS,but not CSS.4.The efficacy of preoperative or postoperative radiotherapy on ESCC patients concentrate in T3 stage,but not T2 stage.Part 2:A retrospective analysis of the effect of postoperative radiotherapy to T2-3N0M0 esophageal cancerPurposeThis part is to analyze the effect of postoperative radiotherapy to survival in patients with T2-3 stage esophageal squamous cell carcinoma by the data collected from 160 patients treated in our hospital.Prognosis factors of esophageal squamous cell carcinoma were also explore here.Method1.Data of T2-3N0M0 ESCC patients who treated with surgery combined with postoperative radiotherapy or surgery alone were collected.The enrolled patients were divided into two groups:Surgery group(S)and surgery combined with postoperative radiation group(SRT).Difference between two group were compared.2.Propensity Score Matching regression model was used to match surgery group and surgery combined with postoperative radiotherapy group patients,to eliminate possible data bias between groups.The chi-square test was used to compare the difference between clinical factors of two groups and verify the matching effect.3.Kaplan-Meier method was used to calculate the overall survival(OS)and disease-free survival(DFS)and drew survival curve.Log-rank method and Cox proportional hazards model were used for the Univariate and Multivariate analysis of OS and DFS respectively,to find the relevant factors of OS and DFS.4.Stratified Cox proportional hazards model were performed for survival analysis of OS and DFS in T2 and T3 stage respectively.Result1.A total of 349 cases of T2aN0M0 esophageal squamous cell carcinoma(ESCC)were collected between January 2010 and May 2014.269 cases were S group,and the other 80 case were SRT group.Of which,men(87.4%),middle site(81.7%)and well-differentiated(58.5%)and T3 stage(53.3%)were more common.Correlation analysis showed that there were significant difference between the two groups in the differentiation and T stage distribution.The patients with poorly differentiated and T3 stage tumors were more likely to see in the postoperative radiotherapy group.2.By Propensity Score Matching method,individuals matching the clinical data of the samples in SRT group were selected in S group.Eighty patients with surgery alone were selected to match with eighty patients undergoing surgery combined with adjuvant radiotherapy.A total of 160 matched T2-3N0M0 esophageal squamous cell carcinoma patients were enrolled for the following analysis.The chi-square test was performed on the clinical factors such as sex,race,age,disease location,differentiation degree and T stage of two groups.The results showed that there were no difference of these factors between the two groups,All the clinical data of the two groups were with the same distribution.3.Univariate survival analysis showed that differentiation degree and postoperative radiotherapy were significantly correlated with OS and DFS(P<0.01).Age,T stage and tumor location were somewhat correlated with OS and DFS(P<0.2).Sex was not significant correlation with OS and DFS(P>0.05).Based on the preset threshold(P=0.2),four factors including age,differentiation degree,tumor location,T stage and postoperative radiotherapy were selected as potential survival factors for multivariate survival analysis.4.Multivariate survival analysis showed that differentiation degree,T stage,and postoperative radiotherapy were significantly correlated with OS and DFS(P<0.05).Age and tumor location had no significant associate with OS and DFS(P<0.05).5.Stratified multivariate analysis based on T stage showed that adjuvant radiotherapy significantly reduced the risk of death and the risk of recurrence and metastasis in T3 stage ESCC patients.In patients with T2 stage ESCC,postoperative radiotherapy can significantly reduce neither the risk of recurrence or metastasis nor the risk of death.Conclusion1.T stage,differentiation degree and postoperative radiotherapy was significantly related to the choice of postoperative radiotherapy:T3 stage,poorly differentiated patients were more likely to choose postoperative radiotherapy.2.Differentiation degree,T stage,postoperative radiotherapy have a significant correlation with OS and DFS.3.Postoperative radiotherapy was significantly associate with OS and DFS in T3 stage ESCC,but not in T2 stage.