| BackgroundEsophageal cancer(EC)is a common digestive system malignant tumor in China,with over 90% were esophageal squamous cell carcinoma(ESCC).Radical surgery is the main method in the early and middle stages of EC,the prognosis of EC is poor after only surgery.The overall survival(OS)rate at 5 years after surgery is mostly below 40%.Previous studies have suggested that lymph node positivity is an important factor affecting patient OS.However,we had found that lymph node positivity EC also have a high risk of postoperative recurrence.It has been reported that about 30% of EC patients without lymph node metastasis experience tumor recurrence or metastasis after surgery.At present,research focused on patients with lymph node positivity,with less research related to postoperative pathological lymph node negativity of EC patients,therefore has further exploration value.Even patients with negative lymph nodes after EC surgery have a poor prognosis,the relapse rate is still very high.Therefore,the screening of high-risk factors,evaluation of prognosis,and exploration of recurrence patterns in these patients are of great value.Strengthen monitoring of patients with high-risk factors for recurrence and implement personalized diagnosis and treatment models,hoping to improve the prognosis of patients.Based on this,this study analyzed the high-risk factors that affect the prognosis and recurrence of p T2-3N0M0 ESCC patients,constructed OS prediction model,summarized the recurrence patterns,and further explored the feasibility of postoperative adjuvant radiotherapy combined with the recurrence patterns.Part I Construction and Validation of Prognostic Model to Predict p T2-3N0M0 Esophageal Squamous Cell Carcinoma after Radical SurgeryPurposeWe aimed to explore the risk factors affecting OS of ESCC patients in p T2-3N0M0,construct a nomogram model,through Surveillance,Epidemiology,and End Results Program(SEER)databases to validate the model,providing reference for clinician to formulate the prognosis and personalized treatment of patients.MethodsWe collected patients with p T2-3N0M0 ESCC undergoing radical surgery in our hospital were enrolled as a training cohort from January 2010 to August 2019,to analyze the factors affecting OS,and construct a column chart to predict OS.Evaluate the accuracy and feasibility of the predictive model by using the consistency index(C-index),the time dependent receiver operating characteristic(ROC),and area under the curve(AUC).Evaluate the accuracy and clinical value of the predictive model by using calibration curve and decision curve analysis(DCA).Finally,the data from SEER databases were used as a validation cohort for external validation to evaluate the accuracy of the nomogram.Result625 ESCC patients with p T2-3N0M0(505 patients in the training cohort,120 patients in the validation cohort)were ultimately included.The demographic and clinical pathological characteristics of the two groups were analyzed and summarized.Cox multivariate analysis showed that T stage,number of lymph node dissection,length and width diameter of tumor were independent risk factors affecting OS.These four factors to construct a Nomogram model,the C-index was 0.68,and AUC values for predicting patients’ 3-year,5-year,and 10-year OS were 0.72,0.74,and 0.73 respectively.Calibration curve showed a highly consistency between the predicted and actual survival rates of the model.DCA showed that it has certain clinical practical value.According to the scores of the column chart,patients were divided into low-risk,middle-risk,and high-risk groups.The survival analysis results indicated significant differences between different groups,and this predictive model can effectively distinguish OS under different risk groups.Finally,we used the SEER database to perform external validation.The AUC values of the 3-year,5-year,and 10-year OS in the validation cohort were 0.78,0.81,and 0.85 respectively.Calibration chart suggested good consistency between the predicted and actual values,and the DCA curve also showed great clinical net benefit rates.ConclusionWe constructed and validated a nomogram to predict OS of patients with p T2-3N0M0 ESCC,which has good risk stratification and clinical value.This nomogram can serve as a reference tool for clinicians to identify high-risk patients and instruct personalized treatment.Part II Postoperative Recurrence Risk Factors and Recurrence Patterns for p T2-3N0M0 Esophageal Squamous Cell CarcinomaPurposeWe analysis the demographic and pathological data of patients with p T2-3N0M0 ESCC after radical surgery in our hospital,to explore risk factors affecting postoperative recurrence and the patterns of postoperative recurrence.MethodsWe retrospectively analyzed p T2-3N0M0 ESCC patients from January 2010 to August 2019 in our hospital.We collected and analysis the databases based on inclusion and exclusion criteria,then closely followed up.Those were divided into three categories: anastomotic recurrence,lymph node recurrence,and hematogenous metastasis.We counted the sites of initial recurrence and metastasis;the indicators were analysis by univariate and multivariate Cox proportional hazard regression.It is expected to screen out the risk factors that affecting postoperative recurrence,and conduct statistical analysis of recurrence patterns in different situations.ResultUp to the last follow-up,485 patients with p T2-3N0M0 ESCC were ultimately included,176 patients(36.29%)experienced tumor recurrence or metastasis.Cox multivariate analysis results showed that postoperative T stage,surgical method,tumor location,and differentiation were independent risk factors affecting postoperative recurrence(P<0.05).The median recurrence time was 38 months,and the most common form of recurrence was lymph node recurrence in 126 patients(126/176,71.59%),followed by hematogenous metastasis in 73 patients(41.47%),and anastomotic recurrence in 21 patients(11.93%).According to the statistical results,119 patients(67.61%)experienced recurrence within 36 months,with a recurrence probability of 84.09% within 5 years.After 5 years,the recurrence trend remained relatively stable.The proportion of postoperative lymph node recurrence and hematogenous metastasis in ESCC patients with p T3N0M0 was significantly higher than that in p T2N0M0 stage patients(P<0.05).As the tumor site moved up,the proportion of lymph node recurrence increased(P<0.05).ConclusionPostoperative T stage,surgical approach,tumor location,and differentiation independent risk factors for postoperative recurrence with p T2-3N0M0 ESCC.The most common pattern of postoperative recurrence in those patients was regional lymph node recurrence,which usually occurs within 3 years.It is recommended to closely follow up ESCC patients with p T2-3N0M0 who have high-risk factors for postoperative recurrence,especially to strengthen monitoring of regional lymph nodes.Part III Exploring Lymph Node Recurrence Pattern and Target Volume for Postoperative Adjuvant Radiotherapy in p T2-3N0M0 Esophageal Squamous Cell CarcinomaPurposeWe collected the locations of all recurrent lymph nodes with p T2-3N0M0 ESCC in our hospital,draw CT reconstruction maps based on their distribution characteristics.We summarized the pattern of lymph node recurrence,to explore the feasibility and radiation range of postoperative radiotherapy.MethodsWe statistics p T2-3N0M0 patients who underwent radical surgery for esophageal cancer in our hospital from January 2010 to August 2019,and collected sites on patients who experienced lymph node recurrence after surgery.Based on the standards of the Japan Esophagus Society(JES)and the range of lymph node drainage area in the abdominal cavity of gastric cancer,we analyzed the specific locations of recurrent lymph nodes.Label the location of recurrent lymph nodes on CT mode for CT images reconstruction,to explore the range of clinical target volume(CTV)of postoperative tumors.Result96 patients with lymph node recurrence with p T2-3N0M0 ESCC were ultimately included,with a total of 193 recurrent lymph.the nodes classified as cervical lymph node recurrence,mediastinal lymph node recurrence,and abdominal lymph node recurrence.The highest proportion of recurrent lymph nodes were located in the mediastinum,with 95(49.22%),followed by 57(29.53%)in the neck and 41(21.24%)in the abdominal.The common recurrence sites in neck lymph node recurrence are 104 R station,104 L station,102 R station and 102 L station in sequence.Mediastinal lymph node recurrence is most likely to occur in 106 rec R station,followed by 105 station,106 rec L station,106 tb station,and 107 station.The proportion of lymph node recurrence in the abdominal cavity is relatively low,with the most common sites being 16a2 station,9 station,16a1 station,and 8 station.ConclusionWe performed CT image reconstruction based on the distribution of recurrent lymph nodes for p T2-3N0M0 ESCC patients.The results showed that postoperative lymph node recurrence was mainly distributed in the neck and upper mediastinal region(101R/L,102R/L,104R/L,105,106 rec R/L,106 tb,106pre,107,and 108 station).It is recommended to focus on postoperative CTV,with an anatomical range from the lower edge of the cricoid cartilage to the lower pulmonary vein.The probability of abdominal lymph node recurrence is low and it is not recommended to be within the CTV.Research significancePatients with negative lymph nodes after EC surgery have a poor prognosis and a high recurrence rate.Therefore,screening of high-risk factors,evaluation of prognosis,and exploration of recurrence patterns in these patients are of great value.Strengthen monitoring of patients with high-risk factors for recurrence and implement personalized diagnosis and treatment models,hoping to improve the prognosis of patients.For this reason,this study analyzed the high-risk factors that affect the prognosis and recurrence of p T2-3N0M0 ESCC patients,constructed nomogram model,summarized the recurrence patterns,and further explored the feasibility of postoperative adjuvant radiotherapy combined with the recurrence patterns. |
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