Analysis Of Prognosis And Adverse Events In Esophageal Squamous Cell Cancer Patients Underwent Three-dimensional Radiotherapy

Objective:To investigate the adverse events,efficiency and prognosis of esophageal squamous cell cancer（ESCC）patients underwent three-dimensional radiotherapy（3D-RT）,and analyze the risk factors for adverse events and poor prognosis,which can provide clinical reference for the 3D-RT for treating ESCC.Methods:A total of 373 ESCC patients（male:258;female:115,median age:71 yrs;stageⅠ:71;stageⅡ:196;and stageⅢ:106）admitted to our hospital for radiotherapy using 3D-RT from January 2008 to May 2016 were included in this study.Among these patients,231 received 3D-chemoradiotherapy（3D-CRT）and 142 received intensity modulated radiated therapy（IMRT）.In total,202 patients received radiotherapy only,while the other 171 cases received the CRT.Involved-field irradiation（IFI）was performed in 249 cases,and Extended field irradiation（EFI）was carried out in 124 cases.The number of patients underwent irradiation with a dose intensity of 50-60Gy and 60-70Gy was 60 and 313,respectively.Forty-two cases showed concurrent diabetes mellitus（DM）and the others were non-DM patients.Ninety-nine cases showed concurrent hypertension,while the others were non-hypertension cases.Then we investigated the effects of side effects,efficiency,local control rate,progression-free survival（PSF）rate,overall survival（OS）,non-surgical staging,age,gross tumor volume（GTV）,irradiation scale,dose,combination of chemotherapy,DM or hypertension as well as lymph node metastasis on the prognosis and adverse events.Results:1.The mean dose for the lung(D_mean),and volume of the whole lung receiving a dose of 5 Gy（V5）,10Gy（V10）,15Gy（V15）,20Gy（V20）and 30Gy（V30）were 1114cGy±268c Gy,58.1±14.9%,40.7±11.1%,28.8±8.5%,19.6±6.9%,and10.0±5.2%,respectively.In the IMRT group,the pulmonary V15,V20 and V30 were statistically lower than those of the 3D-CRT group（P<0.05）.No statistical differences were noticed in the V5 and V10 between the two groups（P>0.05）.In the extended field group,the pulmonary D_mean and V20 showed obvious increase（P<0.05）.No statistical differences were noticed in the pulmonary V5,V10,V15 and V30（P>0.05）.The median GTV was 56.6 cm³.Significant increase was noticed in the D_mean,V5,V10,V15,V20 and V30 in the group with GTV of more than 56.6 cm³ compared with those in the group with GTV of less than 56.6 cm³（P<0.05）.Compared with the patients underwent radiotherapy with a dose of 50-60 Gy,significant increase was noticed in the pulmonary V15,V20 and V30 in those with a dose of 60-70Gy（P<0.05）.The pulmonary D_mean,V5 and V10 in the neck was lower than that of the upper/middle/lower chest（P<0.05）.No statistical differences were observed in the V15,V20 and V30 in the neck,upper/middle/lower chest（P>0.05）.The V20 and V30 in the DM patients were lower than the non-DM patients（P<0.05）.In contrast,no statistical differences were observed in the D_mean,V5,V10 and V15 between the DM and non-DM patients（P>0.05）.The V20 and V30 in the hypertension cases were lower than those of the non-hypertension cases（P<0.05）.No statistical differences were noticed in the D_mean,V5,V10 and V15（P>0.05）.The mean cardiac dose was 2056cCy±836cCy.The cardiac V30,V35,V40 and V50 were29.7±17.1%,21.7±13.4%,14.6±9.8%,and 6.7±5.1%,respectively.No statistical differences were noticed in the cardiac D_mean,cardiac V30,V35,V40 and V50 in the patients using different radiation technique,of radiation scale,GTV and radiotherapy dose（P>0.05）.Statistical decrease was noticed in the cardiac D_mean,V30,V35,V40 and V50 in the neck compared with those of the upper/middle/lower chests of cancer patients（P<0.05）.Statistical difference was noticed in the maximal spinal dose between the IMRT group and3D-CRT group（3517cGy±289c Gy vs 3908cGy±311cGy,P=0.048）.2.The prevalence of radiation-induced pulmonary injury was 46.6%,while that for the grade I,II,III and IV was 28.7%,15.8%,2.14%and 0.0%,respectively.The prevalence for the radiation-induced esophageal injury was 86.1%,while that for the grade I,II,III and IV was 46.4%,29.8%,7.0%and 2.9%,respectively.The prevalence of bone marrow depression was 68.4%,while that for the grade I,II,III and IV was 33%,26.8%,6.7%and1.9%,respectively.No statistical difference was noticed in the prevalence of radiation-induced pulmonary and esophageal injuries in the cases with or without chemotherapy（P>0.05）.The prevalence of bone marrow depression（≥grade3）in the patients underwent chemotherapy was significantly higher than that of the counterparts received no chemotherapy（P=0.010）.The prevalence of radiation-induced pulmonary and esophageal injuries（≥grade3）in DM patients was significantly higher than that of the non-DM patients（P<0.05）.The prevalence of radiation-induced pulmonary and esophageal injuries（≥grade3）in hypertension patients was significantly higher than that of the non-hypertension patients（P<0.05）.Hypertension and/or DM caused no effects on the bone marrow depression（P>0.05）.The prevalence of radiation-induced pulmonary injuries showed significant elevation in those with higher pulmonary D_mean,V15,V20 and V30（P<0.05）.3.The total effective rate was 99.2%,including 75.1%of complete response（CR）,24.1%of partial response（PR）.The other cases（0.8%）showed no response（NR）.The T staging,N staging and TNM staging were important factors affecting the efficiency,which was presented by poor efficiency in those of advanced stage（P<0.05）.The age,sex,tumor site,hypertension,DM,radiation technique,target scale,radiotherapy dose,GTV,and concurrent chemotherapy showed no effects on the efficiency（P>0.05）.4.The 1-yr,3-yr and 5-yr OS was 69.4%,33.7%and 22.9%,respectively.The median OS was 22.7 months.The 1-yr,3-yr and 5-yr PFS was 63.8%,32.8%and 22.4%,respectively.The median PFS was 19.2 months.T staging,N staging,TNM staging and GTV could affect the OS and PFS.Those with advanced stages showed larger GTV,and the OS and PFS was poor（P<0.05）.Age,sex,tumor site,hypertension,DM,radiation technique,target scale,radiotherapy dose,GTV,and concurrent chemotherapy showed no effects on OS and PFS（P>0.05）.The 1-yr,3-yr and 5-yr local control rate was 78.8%,66.5%and 38.6%,respectively.The median LC was 32.2 months.T staging,N staging,TNM staging and GTV could affect LC.Those with advanced cancer showed larger GTV and the local control rate was lower（P<0.05）.Age,sex,tumor site,hypertension,DM,radiation technique,target scale,radiotherapy dose,GTV,and concurrent chemotherapy showed no effects on efficiency（P>0.05）.Multi-variate analysis showed that N staging and GTV were independent risk factors for OS and PFS（P<0.05）.5.The 1-yr,3-yr and 5-yr OS in the patients with 1 or 2 sites of lymph nodes was66.7%,32.6%,22.8%,48.5%,13.3%and 0.0%,respectively,which showed statistical differences after comparison（P=0.035）.The 1-yr,3-yr and 5-yr PFS in the patients with 1or 2 sites of lymph nodes was 58.3%,25.9%,20.2%,43.4%,10.3%and 0.0%,respectively,which showed statistical differences after comparison（P=0.041）.6.No statistical difference was noticed in the total recurrence of IFI and EFI（20.9%vs.21.8%,P=0.083）.Besides,no statistical difference was noticed in the recurrence outside of the radiation field in the IFI and EFI（4.8%vs.1.6%,P=0.155）.Conclusions:1.3D-CRT,target scale,tumor volume and site could affect the pulmonary dose parameters in esophageal cancer patients.In patients with esophageal cancer in the cervical part,the radiation dose in the heart was the lowest.Compare with the3D-CRT,IMRT showed protective effects on the spinal cord.2.The combination of chemotherapy and radiotherapy increased the risk of severe bone marrow depression in esophageal cancer patients.DM and/or hypertension were the predisposing factors for radiation-induced esophageal and pulmonary injuries.The pulmonary D_mean,V15,V20 and V30 were closely related to the radiation-induced pulmonary injuries.3.T staging,N staging and TNM staging were important factors for the efficiency of esophageal cancer.The efficiency was poor in those of advanced stage.4.T staging,N staging,TNM staging and GTV could affect the prognosis of esophageal cancer patients underwent radiotherapy,and N staging and GTV were independent factors for the prognosis of patients.5.The sites of lymph node metastasis were closely related to the prognosis of esophageal cancer patients.6.The failure for IFI was mainly associated with the recurrence.The metastasis of lymph node outside the radiation field was not high,which indicated IFI was feasible in clinical practice...