The Study Of Postoperative Radiotherapy Of The Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma

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Failure Patterns of Stage p T3-4N0-3M0 Esophageal Squamous Cell Carcinoma Patients with or without Post-operative Radiotherapy after Radical SurgeryAim: This study was mainly to investigate the differences in the failure patterns of patients with stage p T3-4N0-3M0 esophageal squamous cell carcinoma(ESCC)after radical surgery with or without post-operative radiotherapy(PORT).Methods: Patients in this study were screened from a multi-institution prospective phase II trial and a retrospective cohort.The primary endpoint was to investigate the differences of failure patterns between patients who received surgery alone and patients who received PORT.The secondary endpoint was to estimate whether patients with stage p T3-4 could achieve disease-free survival(DFS)advantage after receiving adjuvant PORT.Statistical analyses were administrated by Kaplan-Meier method,Cox regression model and Chi-square test or Fisher's exact test.Results: In total,230 patients with stage p T3-4N0-3M0 were included in this study.Fifty-six patients who received PORT were screened from a prospective cohort(S+R arm).And 174 patients involving surgery alone were retrospectively selected from July 2006 to October 2014(S arm).There were no significant differences in the clinical and pathological characteristics of patients between the two arms,except for the tumor location(p=0.031).The failure patterns between two arms were significantly different(p<0.001).Patients in the S arm had a significantly higher proportion of locoregional recurrence and a lower proportion of distant metastasis than those in the S+R arm [92.0% vs.35.7%,(p<0.001)and 75.0% vs.19.0%,(p<0.001),respectively].The difference in the median DFS between two arms was statistically significant(12.7 vs.8 months,p=0.048).Univariate analysis and multivariate analysis both demonstrated that the number of lymph node metastases?3(HR=0.572,95%CI: 0.430-0.762,p<0.001)was an independent poor prognostic factor for DFS in patients with stage p T3-4N0-3M0.Conclusions: PORT could improve DFS and local control of patients with stage p T3-4N0-3M0 ESCC.However,further studies need to be conducted to control hematogenous metastasis after PORT.Part ? Randomized Phase II Trial Comparing Tumor Bed Alone with Tumor Bed and Elective Nodal Postoperative Radiotherapy in Patients with Locoregionally Advanced Thoracic Esophageal Squamous Cell CarcinomaAim: To compare the outcomes of different postoperative radiation fields for locoregionally advanced thoracic esophageal squamous cell carcinoma(ESCC)patients.Methods: This is a multi-institution randomized phase II trial and noninferior study.Patients with ESCC who had undergo esophagectomy(stage T3-4N0-3M0)were enrolled and randomized into the large-field irradiation arm(LFI;tumor bed and elective lymph node region)and small-field irradiation arm(SFI;tumor bed only).The primary endpoint was whether the disease-free survival(DFS)of SFI was not inferior to LFI.The secondary endpoint was to evaluate the rationality of the radiation target volume by analyzing failure patterns.Results: One hundred twenty-one patients(64 patients for LFI and 57 patients for SFI,respectively)were eligible in this mid-time analysis.The 1-and 3-year DFS were 79.9%,46.2% for LFI and 67.6%,44.3% for SFI,respectively(p=0.414).The locoregional recurrence-free survival(LRFS)of LFI was significantly better than that of SFI(p=0.003).however,there were no significant differences in the distant metastasis-free survival and overall survival between the two arms(p=0.332,p=0.405,respectively).The failure patterns of the two arms were significantly different(p=0.002).Conclusions: For p T3-4N0-3M0 ESCC patients,postoperative radiotherapy with SFI showed a similar survival outcome to LFI.However,the LRFS of patients with SFI was worse than that of patients with LFI.Part ?.Study on the Biological Factors Related to Distant Metastasis of Early Esophageal Squamous Cell CarcinomaAim: The purpose of this study is to explore the related biological factors of distant metastasis in early esophageal squamous cell carcinoma.Methods: 223 patients with or without distant metastasis were included.Six pairs of patients(group A,patients suffered from distant metastasis within 1 years;group B,patients lived with disease free over 2 years)were obtained after matched several clinical risk factors of patients by propensity-score matching analysis with SPSS v22.0.High-throughput sequencing analysis was performed on adjacent normal tissues and tumor tissues in FFPE samples by Illumina PE150 sequencing.Result: There are 6 samples in two groups,respectively.The high frequency mutation analysis by Mu Si C software showed that C>T is the predominant base substitution for both groups.There are more C>G transversion and C>A transversion in group B(p<0.001,Cochran-Mantel Haenszel test).The frequency of T>C transition mutation in group A was higher than that in group B(p<0.001,Cochran-Mantel Haenszel test).The highest mutation frequency gene for both groups is TP53.BAGE3,ZNF329,EDDM3 A,KRTAP9-2,VCAN and SERPINA1 only appeared in the patients of group A.However,PRSS35 and UBXN10 genes are only appeared in someone of group B.The difference of median TMB between the two groups is not significant.Conclusion: In the early stage of esophageal squamous cell carcinoma,C>T conversion is the main somatic base substitution.the inactivation of TP53 is a frequent event for patients in both group A and B.VCAN gene may be related to the distant metastasis of esophageal cancer,which needs further study.