D. Fang

Nomogram and recursive partitioning analysis to predict overall survival in patients with stage IIB-III thoracic esophageal squamous cell carcinoma after esophagectomy

We have developed statistical models for predicting survival in patients with stage IIB–III thoracic esophageal squamous cell carcinoma (ESCC) and assessing the efficacy of adjuvant treatment. From a retrospective review of 3,636 patients, we created a database of 1,004 patients with stage IIB–III thoracic ESCC who underwent esophagectomy with or without postoperative radiation. Using a multivariate Cox regression model, we assessed the prognostic impact of clinical and histological factors on overall survival (OS). Logistic analysis was performed to identify factors to include in a recursive partitioning analysis (RPA) to predict 5-year OS. The nomogram was evaluated internally based on the concordance index (C-index) and a calibration plot. The median survival time in the training dataset was 30.9 months, and the 5-year survival rate was 33.9%. T stage, differentiated grade, adjuvant treatment, tumor location, lymph node metastatic ratio (LNMR), and the presence of vascular carcinomatous thrombi were statistically significant predictors of 5-year OS. The C-index of the nomogram was 0.70 (95% CI 0.67–0.73). RPA resulted in a three-class stratification: class 1, LNMR ≤ 0.15 with adjuvant treatment; class 2, LNMR ≤ 0.15 without adjuvant treatment and LNMR > 0.15 with adjuvant treatment; and class 3, LNMR > 0.15 without adjuvant treatment. The three classes were statistically significant for OS (P < 0.001). Thus, the nomogram and RPA models predicted the prognosis of stage IIB–III ESCC patients and could be used in decision-making and clinical trials.

A prognostic nomogram for overall survival after neoadjuvant radiotherapy or chemoradiotherapy in thoracic esophageal squamous cell carcinoma: a retrospective analysis

Background Currently, the AJCC staging system or pathological complete response (pCR) are considered not sufficiently accurate to evaluate the survival of patients with esophageal squamous cell carcinoma after neoadjuvant radiotherapy or chemoradiotherapy. This study aimed to establish a nomogram and a recursive partitioning analysis (RPA) model to estimate prognosis and to provide advice for subsequent treatments. Methods We analyzed retrospectively 407 patients that were diagnosed with thoracic esophageal squamous cell carcinoma (TESCC) and received neoadjuvant radiotherapy or chemoradiotherapy. Hazard ratios and 95% confidence intervals of categorical clinicopathological characteristics with overall survival (OS) were calculated using the Cox proportional hazard model. The nomogram and RPA model were then established and total scores according to each variable were calculated and stratified to predict OS. Results Patients were followed-up over a median 49.9 months. AJCC did not perform well in distinguishing OS among each stage except for IIB and IIIA. Patients were divided into 4 groups according to the total scores based on nomogram (low risk: ≤180; intermediate risk: 180-270; high risk: 270-340; very high risk: >340). The 5-year OS was 57.3%, 40.7%, 18.3%, 6.1% respectively (p<0.05). RPA model also divide the patients into 4 groups, though group2 and group3 were not statistically significant (p=0.574). Conclusion The nomogram is a good evaluation model for estimating the prognosis of patients with TESCC after neoadjuvant radiotherapy or chemoradiotherapy compared with the AJCC and RPA. The results of this study also suggested that the high-risk subgroups need further treatments.

Long-term survival of the middle and lower thoracic esophageal cancer patients after surgical treatment through left or right thoracic approach

Background Esophageal cancer is one of the most prevalent malignancies with a high incidence and mortality in China, the main treatment for esophageal cancer at present is still surgery-based multimodality treatment, and surgery is still the most effective measure. However, the modes of surgical treatment for esophageal cancer have been diverse. The surgical approaches can be mainly divided into the left thoracic approach and right thoracic approach in China. The long-term survival of the patients treated through right approach was reported better than that through left thoracic approach, but until now no statistically significant difference was found between two approaches, especially, for those with middle and lower thoracic esophageal cancer without suspected upper mediastinal lymph node metastasis in preoperative examinations, no definite conclusion have been made on selection of the approach, therefore, this studies try to compare the long-term survival between two approaches . Methods The data of 402 cases with complete resection and two-field lymph node dissection from January, 2011 to December, 2011 in the Cancer Hospital, Chinese Academy of Medical Sciences was retrospectively reviewed and analyzed. Propensity score matching (PSM) analysis and life-table in SPSS 22.0 and Stata 14.0 were used to analyze the survival. Results Totally, 402 cases were surgically treated either via left or right thoracic approach. The overall 5-year survival rate of this series was 38%, it was 37% in 281 cases surgically treated through left approach, and 39% in 121 cases through right approach (P=0.908). The 5-year survival of 256 patients without suspected lymph node metastasis in the upper mediastinum based on the preoperative examinations surgically treated through left approach was 38% versus 43% of 88 cases through right approach (P=0.404). After PSM, the 5-year survival of 110 cases surgically treated through left approach was 32% versus 40% of another matched 110 cases through right approach (P=0.146). for the patients without suspected lymph node metastasis in the upper mediastinum based on preoperative examinations, the 5-year survival of 88 surgically treated through left approach was 33% versus 44% of another matched 88 cases through right approach (P=0.239). Conclusions For the middle and lower thoracic esophageal cancer patients, whether or not who has suspected lymph node metastasis in the upper mediastinum based on preoperative CT and EUS, the surgical treatment through right thoracic approach can achieve better but not significantly better overall survival than that through left thoracic approach. Further prospective randomized clinical trials are still needed to verify this disputed issue on approach selection.

The Impact of Postoperative Conformal Radiotherapy after Radical Surgery on Survival and Recurrence in Pathologic T3N0M0 Esophageal Carcinoma: A Propensity Score-Matched Analysis

Introduction: The role of conformal radiotherapy (cRT) in thoracic esophageal squamous cell carcinoma (TESCC) has not been addressed in adjuvant settings. The aim of this study was to investigate whether postoperative radiotherapy using cRT after an R0 resection improves outcomes in pT3N0M0 TESCC compared with resection alone. Methods: This study included 678 patients with pT3N0M0 TESCC who were treated at the Cancer Hospital, Chinese Academy of Medical Sciences, from January 2004 to December 2011. The patients were divided into two groups: a surgery plus cRT group (S+cRT group) comprising patients who underwent cRT after an R0 resection and a surgery group (S group), comprising a control group of patients who underwent an R0 resection alone. Propensity score matching was used to create patient groups that were balanced across several covariates (n = 83 in each group). Outcome measures included overall survival (OS), disease‐free survival (DFS), and recurrence. Results: In the overall study cohort, 5‐year OS (75.2% versus 58.5%, p = 0.004) and DFS (71.8% versus 49.2%, p = 0.001) rates were significantly higher in the S+cRT group than in the S group. These data were confirmed in the matched samples (5‐year OS, 75.7% versus 58.8% [p = 0.017]; DFS, 71.7% versus 50.3% [p = 0.009]). The overall (p = 0.001) and locoregional (p = 0.004) recurrence rates in the S+cRT group were significantly lower than in the S group. Multivariate Cox analyses in the matched samples revealed that surgery and postoperative cRT were independently associated with longer OS (hazard ratio = 0.505, 95% confidence interval: 0.291–0.876, p = 0.015) and longer DFS (hazard ratio = 0.513, 95% confidence interval: 0.309–0.854, p = 0.010) than resection alone. Conclusions: Postoperative radiotherapy using cRT is strongly associated with improved OS and DFS in patients with pT3N0M0 TESCC. A multicenter, randomized phase III clinical trial is warranted to confirm these findings.

Experiences in the management of anastomotic leakages and analysis of the factors affecting leakage healing in patients with esophagogastric junction cancer

BACKGROUND It was reported in the literatures that the incidence of anastomotic leakage in patients with esophagogastric junction cancer decreased due to application of staplers and closure devices as well as gastric conduit technique in recent years, however, it increased slightly at our center since widely using the above devices and gastric conduit techniques from 2009. The objective of this study was to summarize our experiences in the management of anastomotic leakages and analyze the factors affecting leakage healing in the patients with esophagogastric junction cancer after surgical resection in recent 6 years. METHODS All patients who received surgical resections for esophagogastric junction cancer and diagnosed anastomotic leak at our center between January 2009 and December 2014 were retrospectively analyzed, we also enrolled the patients who had a longer hospital stay (>30 days) as they may develop anastomotic leak. The binary logistic regression in SPSS 16.0 was applied to analyze the factors that may affect leakage healing. RESULTS Of the 1,815 surgically treated esophagogastric junction cancer patients, 91 cases were diagnosed anastomotic leakage postoperatively. The patients were divided into two groups based on the median leakage healing time (40 days) in this series: fast healing group (37 cases) and slowly healing group (54 cases). All factors that may affect the leakage healing were put into analysis by using binary logistic regression. The results of the analysis showed that leakage size (OR =1.073, P=0.004), thoracic drainage (OR =12.937, P=0.037) and smoking index ≤400 (OR =1.001, P=0.04) significantly affected the healing time, while drinking history (P=0.177), duration of fever after anastomotic leak developed (P=0.084), and hypoproteinemia after leak (P=0.169) also apparently but not significantly affect the healing time. CONCLUSIONS Though many factors may affect leakage healing in the esophagogastric junction carcinoma patients, leakage size, thoracic drainage and smoking index (≤400) are the most important factors affecting the leakage healing. Placement of a chest tube beside the anastomosis area during operation for early identification and control of an anastomotic leak to minimize contamination of the mediastinum is the most important way to promote leakage healing. A chest tube placing into the purulent cavities after the patients experienced leaks is also important for the cure of leakage. More attention should be paid perioperatively to the patients who had a smoking index (≥400) and the patients who suffered fever or hypoproteinemia.