Prognostic Model For Patients With Esophageal Cancer After Radical Esophagectomy And The Value Of Adjuvant Therapy

Part ⅠTitle:Nomogram to Predict Overall Survival in Thoracic Esophageal Squamous Cell Carcinoma Patients after Radical EsophagectomyPurpose:Effective tool lacks to evaluate prognosis for patients with esophageal cancer undergoing surgery.The present study aimed to develop a nomogram to predict overall survival(OS)and provide evidence for adjuvant therapy in patients with esophageal carcinoma after esophagectomy.Materials and methods:We retrospectively reviewed patients with pathological T1N+/T2-4aN0-3,MO thoracic esophageal squamous cell carcinoma after radical esophagectomy,with or without adjuvant therapy,in one institute as the training cohort(n=2281).A nomogram was established using Cox proportional hazard regression to identify prognostic factors for OS,which was validated in an independent validation cohort(n=1437).Area under curve(AUC)values of receiver operating characteristic(ROC)curves were calculated to evaluate prognostic efficacy.Results:In the training cohort,the median and 5-year OS were 50.46 months and 47.08%,respectively.Adjuvant therapy,sex,tumor location,grade,lymphovascular invasion,removed lymph nodes,T and N category were identified as predictive factors for OS.The nomogram showed favorable prognostic efficacy in the training and validation cohorts(5-year OS AUC:0.685 and 0.744),which was significantly higher than that of the AJCC staging systems.The nomogram distinguished OS rates among six risk groups,while AJCC could not separate the OS of ⅡA/ⅠB,ⅢC/ⅢB,or ⅢA/ⅡB.Patients with a nomogram score of 72-227 were predicted to achieve a 10%5-year OS increase with adjuvant therapy.Conclusion:The nomogram could effectively predict OS and aid decision-making on adjuvant therapy for patients with thoracic esophageal squamous cell carcinoma after esophagectomy.Part IITitle:Postoperative Radiotherapy in Pathological T2-3N0M0 Thoracic Esophageal Squamous Cell Carcinoma:Interim Report of a Prospective,Phase III,Randomized Controlled StudyPurpose:We aimed to evaluate the efficacy and safety of postoperative radiotherapy in patients with pathological T2-3N0M0 thoracic esophageal squamous cell carcinoma.Materials and methods:Patients aged 18-72 years with pathological stage T2-3N0M0 esophageal squamous cell carcinoma after radical surgery and without neoadjuvant therapy were eligible.Patients were randomly assigned to surgery alone or to receive postoperative radiotherapy of 50.4 Gy in supraclavicular field and 56 Gy in mediastinal field in 28 fractions over six weeks.The primary endpoint was disease-free survival.The secondary endpoints were local-regional recurrence rate,overall survival and radiation-related toxicities.Results:From October 2012 to February 2018,167 patients were enrolled in this study.We analyzed 157 patients whose follow-up time was more than one year or dead.The median follow-up time was 45.6 months.The 3-year disease-free survival rates were 75.1%(95%CI 65.9-85.5)in postoperative radiotherapy group and 58.7%(95%CI 48.2-71.5)in surgery group(HR 0.53,95%CI 0.30-0.94,p=0.030).Local-regional recurrence rate decreased significantly in radiotherapy group(10.0%vs.32.5%in surgery group,p=0.001).The overall survival and distant metastasis rates were not significantly different between two groups.Grade 3 toxicity rate related to radiotherapy was 12.5%.Conclusion:Postoperative radiotherapy significantly increased disease-free survival and decreased local regional recurrence rate in pathological T2-3N0M0 thoracic esophageal squamous cell carcinoma patients with acceptable toxicities in this interim analysis.Further enrollment and follow-up are warranted to validate these findings in this ongoing trial.Part IIITitle:Clinical Efficacy Analysis for Preoperative Radiotherapy with or without Concurrent Chemotherapy in Esophageal CarcinomaPurpose:To discuss the clinical efficacy of preoperative radiotherapy with or without concurrent chemotherapy for esophageal carcinoma.Materials and methods:We retrospectively analyze 103 esophageal carcinoma patients who received preoperative radiotherapy with or without concurrent chemotherapy from 2004 to 2014 in Cancer Hospital Chinese Academy of Medical Sciences.The median radiation dose was 40Gy,TP or PF regimens were used in concurrent chemotherapy.The survival rate was calculated by Kaplan-Meier method,and the difference was analyzed by Log-rank test.The Cox regression model was used for multivariate prognostic analysis.Results:Three-year OS and DFS were 61.1%and 54.9%,respectively.No significant difference between radiotherapy and concurrent chemoradiation(CRT)as to OS(p=0.876)and DFS(p=0.521).The pathologic complete,partial,and minimal response rate for primary tumor were 47.6%,39.8%and 11.7%.The differences for OS(p=0.039)and DFS(p=0.003)among three groups were significant.No significant difference between radiotherapy and CRT were detected in pathologic response rate for primary tumor(p=0.953).Pathological lymph node metastatic rate was 26.5%.As the pathologic response degree for primary tumor increased,the lymph node metastasis rate declined(14.3%,30.0%and 66.7%for minimal,partial and complete response groups,p=0.001).The OS(p=0.034)and DFS(p=0.020)were significant higher in patients without lymph node metastasis than that with metastasis.The surgery-related mortality was 7.8%.Patients in CRT group tended to experience higher rate of leukopenia(p=0.002),neutropenia(p=0.023),esophagitis(p=0.008)and nausea(p=0.023).Pathologic response rate for primary tumor and weight loss rate before treatment were independent prognostic factors for OS and DFS.Conclusion:Preoperative radiotherapy with or without chemotherapy can result in relative high complete pathologic response rate for primary tumor,hence improve survival rates.Further randomized clinical trials are warranted to validate whether preoperative CRT is better than radiotherapy in improving survival outcomes.Part IVTitle:The Relationship of Lymphocyte Recovery and Prognosis of Esophageal Cancer Patients with Severe Radiation-induced Lymphopenia after Chemoradiation TherapyPurpose:Radiation-induced lymphopenia(RIL)during therapy is associated with poor prognosis but is often temporary and resolves after treatment completion in esophageal cancer.How lymphocyte recovery contributes to prognosis is unknown.Materials and methods:We reviewed 755 patients with stage Ⅰ-Ⅲ esophageal carcinoma who received CRT with or without surgery in 2004-2015.Complete blood counts were obtained before,during,and at first follow-up after CRT.Lymphopenia was graded per the Common Terminology Criteria for Adverse Events(CTCAE)v4.03 during CRT(G)and as recovery after CRT(Gr).Clinical factors and lymphopenia grade were tested for association with survival in univariable and multivariable Cox proportional hazard regression analyses.Results:During CRT,294 patients(38.9%)had G4 lymphopenia;by the first follow-up,406 patients(53.8%)had recovered(Gr0-1).Relative to patients with GO-3 lymphopenia during CRT,G4 lymphopenia independently predicted worse OS in multivariable analyses.However,lymphocyte recovery was not associated with a better prognosis.Patients with G4 lymphopenia during CRT and recovery(Gr0-1)afterward still had poorer 5-year OS rate than patients with GO-3 during CRT without recovery(Gr2-4)afterward(36.6%vs.51.9%,HR=1.405 95%CI 1.04-1.89,P=0.027).Moreover,the lymphocyte recovery ability(post-CRT lymphocyte count divided by pre-CRT lymphocyte count)was not affected by lymphopenia grade during CRT(0.66 in G0-3 vs.0.65 in G4,p=0.473).Among patients with G4 lymphopenia during treatment,lymphocyte recovery was only associated with pre-CRT lymphocyte counts.Conclusion:Lymphocyte count recovery after CRT does not alter the poor long-term outcomes brought about by high-grade lymphopenia during CRT.