Thoracic Esophageal Squamous Cell Carcinoma Patients Research Articles

186. PROGNOSTIC ROLE OF NODAL SKIP METASTASIS IN THORACIC ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A LARGE-SCALE MULTICENTER STUDY

Abstract Background Nodal skip metastasis (NSM) is found in esophageal squamous cell carcinoma (ESCC), however, its prognostic role is controversial. We aimed to investigate the prognostic value of NSM in thoracic ESCC patients. Methods NSM was categorized according to the N-groupings of JES staging system, which is tumor location dependent. Using the Kaplan–Meier method and Cox-regression analysis, we retrospectively analyzed the overall survival (OS) in 2325 ESCC patients after radical esophagectomy in three high-volume esophageal cancer centers. Predictive models were also constructed. Results The overall NSM rate was 20.0% (229/1141); NSM rate was 37.4%, 12.9%, and 22.2% in upper, middle and lower thoracic ESCC, respectively. Patients with NSM always had better prognosis than those without NSM. Furthermore, NSM was an independent prognostic factor for thoracic ESCC patients (HR = 0.633; 95% confidence interval [CI]: 0.499, 0.803; P < 0.001). By integrating the prognostic value of NSM and N stage, we proposed the New N staging system. The categories defined by the New N staging system were more homogeneous in terms of OS than those defined by the current N system. Moreover, the New N system was shown as an independent prognostic factor for thoracic ESCC patients as well (HR = 1.607; 95%CI: 1.520, 1.700; P < 0.001). Overall, the New N system had a slightly better homogeneity, discriminatory ability, and monotonicity of gradient than the N system. Conclusions Our study emphasized the prognostic power of NSM and developed a modified Node staging system to improve the efficiency of the current UICC/AJCC N staging system.

187. PROGNOSTIC IMPACT OF LYMPH NODE HARVEST FOR PATIENTS WITH NODE-NEGATIVE ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A LARGE-SCALE MULTICENTER STUDY

Abstract Background We examined the association between the number of resected lymph nodes and survival to determine the optimal lymphadenectomy for thoracic Esophageal Squamous Cell Carcinoma (ESCC) patients with negative lymph node. Methods We included 1836 patients from Chinese three high-volumed hospitals with corresponding clinicopathological characters such as gender, age, tumor location, tumor grade and TNM stage of patients. The median follow-up of included patients was 45.7 months (range, 1.03–117.3). X-Tile plot was used to identify the lowest number of lymphadenectomy. The multivariate model’s construction was in use of parameters with clinical significance for survival and a nomogram based on clinical variable with P < 0.05 in Cox regression analysis. Both two models were validated using a cohort extracted from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database between 1975 and 2016 (n = 951). Results More lymphadenectomy numbers were significantly associated with better survival in patients both in training cohort (Hazard ratio [HR] = 0.980; 95% Confidence Interval [CI]: 0.971, 0.988; P < 0.001) and validation cohort (HR = 0.980; 95% CI: 0.968, 0.991; P = 0.001). Cut-off point analysis determined the lowest number of 9 for thoracic ESCC patients in N0 stage through training cohort (C-index: 0.623; Sensitivity: 80.7%; 1-Specificity: 72.5%) when compared with 10 in validation cohort (C-index: 0.643; Sensitivity: 78.2%; 1-Specificity: 63.0%). The cut-off points of 9 were examined in training cohort and validated in the divided cohort from validation cohort (all P < 0.05). Meanwhile, nomograms for both cohorts were constructed and the calibration curves for both cohorts agreed well with the actual observations in terms of predicting 3-year and 5-year survival, respectively. Conclusions Larger number for lymphadenectomy was associated with better survival in thoracic ESCC patients in N0 stage. 9 was we got as the lowest number for lymphadenectomy in pN0 ESCC patients through this study, and our result should be confirmed further.

Grading criteria for venous invasion in thoracic esophageal squamous cell carcinoma

BackgroundVenous invasion (VI) is an adverse prognostic indicator in esophageal squamous cell carcinoma. However, grading criteria for venous invasion in thoracic esophageal squamous cell carcinoma (ESCC) have not been established.MethodsWe enrolled 598 thoracic ESCC patients from 2005 to 2017. We detected the presence of venous invasion using the hematoxylin and eosin (H&E)-staining method and evaluated the VI grade on the basis of the number and maximal size of the involved veins. The degree of VI was classified as either 0, V1, V2, or V3, according to the combination of V-number and V-size.ResultsThe 1-year, 3-year and 5-year disease-free survival rates were 79.7%, 64.7% and 61.2%, respectively. Multivariate analysis demonstrated that lymphatic invasion (HR: 1.457, 95% CI: 1.058–2.006, p = 0.021), T category (HR: 1.457, 95% CI: 1.058–2.006, p = 0.022), N category (HR: 1.535, 95% CI: 1.276–2.846, p < 0.001), stage (HR: 1.563, 95% CI: 1.235–1.976, p < 0.001) and the degree of venous invasion (HR: 1.526, 95% CI: 1.279–2.822, p < 0.001) were significant indicators of recurrence. The disease-free survival curves were distinguished especially well by the degree of venous invasion in stage III and IV patients.ConclusionsThe present study explored an objective grading criterion for VI and proved the prognostic value of the degree of venous invasion in ESCC. The classification of venous invasion into 4 groups is useful for the differentiation of prognosis in ESCC patients. The prognostic significance of the degree of VI in advanced ESCC patients for recurrence may have to be considered.

Risk factors for early local lymph node recurrence of thoracic ESCC after McKeown esophagectomy.

Even underwent radical resection, some patients of thoracic esophageal squamous cell carcinoma (ESCC) are still exposed to local recurrence in a short time. To this end, the present study sought to differentiate patient subgroups by assessing risk factors for postoperative early (within one year) local lymph node recurrence (PELLNR). ESCC patients were selected from a prospective database, and divided into high- and low-risk groups according to the time of their local lymphatic recurrence (within one year or later). Survival analysis was conducted by the Cox regression model to evaluate the overall survival (OS) between the two groups. The hazard ratio (HR) and 95% confidence interval (CI) of different variables were also calculated. Logistic regression analysis was used to explore the high-risk factors for PELLNR with the odds ratio (OR) and 95% CI calculated. A total of 432 cases were included. The survival of patients in the high-risk group (n = 47) was significantly inferior to the low-risk group (n = 385) (HR = 11.331, 95% CI: 6.870-16.688, P < 0.001). The 1-year, 3-year, and 5-year OS rate of the patients in high/low-risk groups were 74.5% vs. 100%, 17% vs. 88.8%, and 11.3% vs. 79.2%, respectively (P < 0.001). Risk factors for local lymph noderecurrence within one year included upper thoracic location (OR = 4.071, 95% CI: 1.499-11.055, P = 0.006), advanced T staging (pT3-4, OR = 3.258, 95% CI: 1.547-6.861, P = 0.002), advanced N staging (pN2-3, OR = 5.195, 95% CI: 2.269-11.894, P < 0.001), and neoadjuvant treatment (OR = 3.609, 95% CI: 1.716-7.589, P = 0.001). In neoadjuvant therapy subgroup, high-risk group stillhad unfavorable survival (Log-rank P < 0.001). Multivariate analysis demonstrated that upper thoracic location (OR = 5.064, 95% CI: 1.485-17.261, P = 0.010) and advanced N staging (pN2-3) (OR = 5.999, 95% CI: 1.986-18.115, P = 0.001) were independent risk factors for early local lymphatic recurrence. However, the cT downstaging (OR = 0.862, 95% CI: 0.241-3.086, P = 0.819) and cN downstaging (OR = 0.937, 95% CI: 0.372-2.360, P = 0.890) for patients in the neoadjuvant subgroup failed to lower PELLNR. The predominant recurrence field type was single-field. Thoracic ESCC patients with lymph node recurrence within one year delivered poor outcomes, with advanced stages (pT3-4/pN2-3) and upper thoracic location considered risk factors for early recurrence.

The usefulness of the total metabolic tumor volume for predicting the postoperative recurrence of thoracic esophageal squamous cell carcinoma

BackgroundInduction or adjuvant therapies are not always beneficial for thoracic esophageal squamous cell carcinoma (ESCC) patients, and it is thus important to identify patients at high risk for postoperative ESCC recurrence. We investigated the usefulness of the total metabolic tumor volume (TMTV) for predicting the postoperative recurrence of thoracic ESCC.MethodsWe retrospectively analyzed the cases of 163 thoracic ESCC patients (135 men, 28 women; median age of 66 [range 34–82] years) treated at our hospital in 2007–2012. The TMTV was calculated from the fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the primary lesion and lymph node metastases. The optimal cut-off values for relapse and non-relapse were obtained by the time-dependent receiver operating curve analyses. Relapse-free survival (RFS) was evaluated by the Kaplan-Meier method, and between-subgroup differences in survival were analyzed by log-rank test. The prognostic significance of metabolic parameters and clinicopathological variables was assessed by a Cox proportional hazard regression analysis. The difference in the failure patterns after surgical resection was evaluated using the χ2-test.ResultsThe optimal cut-off value of TMTV for discriminating relapse from non-relapse was 3.82. The patients with a TMTV ≥3.82 showed significantly worse prognoses than those with low values (p < 0.001). The TMTV was significantly related to RFS (model 1 for preoperative risk factors: TMTV: hazard ratio [HR] =2.574, p = 0.004; model 2 for preoperative and postoperative risk factors: HR = 1.989, p = 0.044). The combination of the TMTV and cN0–1 or pN0–1 stage significantly stratified the patients into low-and high-risk recurrence groups (TMTV cN0–1, p < 0.001; TMTV pN0–1, p = 0.004). The rates of hematogenous and regional lymph node metastasis were significantly higher in the patients with TMTV ≥3.82 than those with low values (hematogenous metastasis, p < 0.001, regional lymph node metastasis, p = 0.011).ConclusionsThe TMTV was a more significantly independent prognostic factor for RFS than any other PET parameter in patients with resectable thoracic ESCC. The TMTV may be useful for the identifying thoracic ESCC patients at high risk for postoperative recurrence and for deciding the patient management.

Preliminary Evaluation of Postoperative Radiotherapy between Small T-Shaped Field and All Regional Lymph Nodes Field in Thoracic Esophageal Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> The optimal extent of clinical target volume (CTV) for postoperative radiotherapy in complete resection thoracic esophageal squamous cell carcinoma (ESCC) patients remains controversial. This study aimed to evaluate the preliminary results of postoperative radiotherapy with standard all regional lymph nodes field and adjusted small T-shaped field. <h3>Materials/Methods</h3> A total of 75 thoracic ESCC patients were enrolled from April 2017 to March 2021, retrospectively. Among them were 63 males and 12 females, with an average age of 64.28 (range, 49-82) years. All patients received intensity-modulated radiotherapy (IMRT) at a dose of 45-50.4Gy/25-28F after radical resection of esophageal carcinoma, of which 39 cases were small T-shaped field (including bilateral supraclavicular lymph nodes, upper and middle mediastinal lymph nodes, small T group),36 cases were all regional lymph nodes field (including tumor bed, bilateral supraclavicular lymph nodes, all mediastinal lymph nodes, left gastric lymph nodes and celiac lymph nodes, control group). 24 cases (32%) received concurrent chemotherapy and 57 cases (76%) received adjuvant chemotherapy. The median follow-up period was 31(range, 15-57) months. <h3>Results</h3> At the end of follow-up period, 7 (17.9%) cases had locoregional recurrence (LRR) and 8(20.5%) had distant metastasis (DM) in small T group, while 9 (25%) cases had LRR and 9 (25%) had DM in control group. There was no significant difference in LRR rate (p=0.456) and DM rate (p=0.643) between the two groups. There was also no significant difference in the total OS rate between the two groups (p=0.146). In terms of radiotherapy parameters, in small T group, the median values of V5, V20 and average dose of the lungs were 37.31%, 16.43% and 8.11Gy, respectively. The median value of the maximum dose of spinal cord was 29.95Gy. For the heart, the median value of the average dose and V30 were 5.13Gy and 2.64%. And the median value of V40 of the stomach was 34.32%. In control group, the median values of V5, V20 and average dose of the lungs were 53.49%, 22.08% and 11.41Gy. The median value of the maximum dose of spinal cord was 36Gy. For the heart, the median value of the average dose and V30 were 27.52Gy and 37.39%. And the median value of V40 of the stomach was 63%. All of the above parameters in small T group were significantly lower than those in control group (p<0.05). In addition, we observed grade 2 radiation pneumonitis and grade 2 radiation esophagitis in both groups:9 cases of radiation pneumonia with grade 2 or above in control group and only 1 case in small T group (p<0.001). There were 15 cases of radiation esophagitis with grade 2 or above in control group and 6 cases in small T group (p=0.024). <h3>Conclusion</h3> In conclusion, radiotherapy with small T-shaped field might be a feasible and efficacious postoperative approach for ESCC patients.

Patterns and timing of recurrence in esophageal squamous cell carcinoma patients treated with neoadjuvant chemoradiotherapy plus esophagectomy

BackgroundTumor regression grade (TRG) after neoadjuvant therapy is reportedly predictive of prognosis in esophageal cancer patients, as lack of a response to neoadjuvant therapy is associated with a poor prognosis. However, there is little information available on the timing and pattern of recurrence after esophagectomy for thoracic esophageal squamous cell carcinoma (TESCC) that takes into consideration TRG after neoadjuvant chemoradiotherapy (NACRT). Here, in an effort to gain insight into a treatment strategy that improves the prognosis of NACRT non-responders, we evaluated the patterns and timing of recurrence in TESCC patients, taking into consideration TRG after NACRT.MethodsA total of 127 TESCC patients treated with NACRT and esophagectomy between 2009 and 2017 were enrolled in this observational cohort study. TRGs were assigned based on the proportion of residual tumor cells in the area (TRG1, ≥1/3 viable cancer cells; 2, < 1/3 viable cancer cells; 3, no viable cancer cells). We retrospectively investigated the timing and patterns of recurrence and the prognoses in TESCC patients, taking into consideration TRG after NACRT.ResultsThe 127 participating TESCC patients were categorized as TRG1 (42 patients, 33%), TRG2 (56 patients, 44%) or TRG3 (29 patients, 23%). The locoregional recurrence rate was higher in TRG1 (36.4%) patients than combined TRG2–3 (7.4%) patients. Patients with TRG3 had better prognoses, though a few TRG3 patients experienced distant recurrence. There were no significant differences in median time to first recurrence or OS among patients with locoregional or distant recurrence. There was a trend toward better OS in TRG2–3 patients with recurrence than TRG1 patients with recurrence, but the difference was not significant.ConclusionsNACRT non-responders (TRG1 patients) experienced higher locoregional recurrence rates and earlier recurrence with distant or locoregional metastasis. TRG appears to be useful for establishing a strategy for perioperative treatments to improve TESCC patient survival, especially among TRG1 patients. (303 words).

Unresected small lymph node assessment predicts prognosis for patients with pT3N0M0 thoracic esophageal squamous cell carcinoma

BackgroundThe role of unresected small lymph nodes (LNs) which may contain metastases for thoracic esophageal squamous cell carcinoma (TESCC) has not been addressed. The aim of the study was to investigate the role of unresected small LNs assessment using computed tomography (CT) in prognostic estimates of pT3N0M0 TESCC patients.MethodsBetween January 2009 and December 2017, 294 patients who underwent esophagectomy with R0 resection at Sichuan Cancer Hospital were retrospectively examined, and the last follow-up time was July 2018. Patients were classified into CT-suspect and CT-negative groups according to the shortest diameter and the shape (axial ratio) of the unresected small LNs on preoperative CT. The Kaplan–Meier method was used to compare survival differences in prognostic factors. Univariate and multivariate analyses were performed to identify prognostic factors for survival and recurrence.ResultsEighty-four patients (28.6%) were classified as CT-suspect group according to the diagnostic criteria; survival analysis suggested that CT-suspect group of patients had a relatively poorer prognosis (P<0.05). Cox regression analysis indicated that unresected small LNs status, tumor grade, and postoperative adjuvant therapy were independent prognostic factors for patients with pT3N0M0 TESCC (P<0.05). Further analysis shown the rates of total recurrence (TR) and locoregional recurrence (LR) in the CT-suspect group were significantly higher than that in the CT-negative group (TR, P<0.001; LR, P<0.001). Among the LRs, the rate of supraclavicular lymph node recurrence in the CT-suspect group was significantly higher than that in the CT-negative group (P<0.001).ConclusionsUnresected small lymph node assessment is critically important and predict prognosis for pT3N0M0 TESCC patients.

Prognostic impact of lymph node harvest for patients with node-negative esophageal squamous cell carcinoma: a large-scale multicenter study.

We examined the association between the number of resected lymph nodes and survival to determine the optimal lymphadenectomy for thoracic esophageal squamous cell carcinoma (ESCC) patients with negative lymph node. We included 1,836 patients from Chinese three high-volumed hospitals with corresponding clinicopathological characters such as gender, age, tumor location, tumor grade and TNM stage of patients. The median follow-up of included patients was 45.7 months (range, 1.03-117.3 months). X-Tile plot was used to identify the lowest number of lymphadenectomy. The multivariate model's construction was in use of parameters with clinical significance for survival and a nomogram based on clinical variable with P<0.05 in Cox regression analysis. Both two models were validated using a cohort extracted from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database between 1975 and 2016 (n=951). More lymphadenectomy numbers were significantly associated with better survival in patients both in training cohort [hazard ratio (HR) =0.980; 95% confidence interval (CI): 0.971-0.988; P<0.001] and validation cohort (HR =0.980; 95% CI: 0.968-0.991; P=0.001). Cut-off point analysis determined the lowest number of 9 for thoracic ESCC patients in N0 stage through training cohort (C-index: 0.623; sensitivity: 80.7%; 1 - specificity: 72.5%) when compared with 10 in validation cohort (C-index: 0.643; sensitivity: 78.2%; 1 - specificity: 63.0%). The cut-off points of 9 were examined in training cohort and validated in the divided cohort from validation cohort (all P<0.05). Meanwhile, nomograms for both cohorts were constructed and the calibration curves for both cohorts agreed well with the actual observations in terms of predicting 3- and 5-year survival, respectively. Larger number for lymphadenectomy was associated with better survival in thoracic ESCC patients in N0 stage. Nine was what we got as the lowest number for lymphadenectomy in pN0 ESCC patients through this study, and our result should be confirmed further.

Preliminary evaluation of postoperative radiotherapy with small T-shaped field in thoracic esophageal squamous cell carcinoma.

The optimal extent of clinical target volume (CTV) for postoperative radiotherapy in complete resection thoracic esophageal squamous cell carcinoma (ESCC) patients remains controversial. This study aimed to evaluate the primary outcome of postoperative radiotherapy with small T-shaped field encompassing the tumor bed, positive lymph node areas, bilateral supraclavicular areas, and upper and middle mediastinal areas. A total of 96 thoracic ESCC patients were enrolled, with 49 and 47 cases in the small T-shaped field group and tumor bed field group, respectively. All of the patients received intensity-modulated radiotherapy (IMRT), and chemotherapy was administrated concurrently or sequentially. The median time of follow-up was 25 (range, 7-47) months. At the end of the follow-up period, in the small T-shaped field group, 8 (16.3%) patients had locoregional recurrence (LRR) and 12 (24.5%) had distant metastasis (DM), while in the tumor bed field group, 15 (31.9%) patients had LRR and 11 (23.4%) had DM. Although the rates of LRR and DM were not statistically different, LRR incidence in the mediastinal lymph nodes of the small T-shaped field group was strikingly lower than that of the tumor bed field group. The overall survival (OS) of the small T-shaped field group was higher than that of the tumor bed field group, but the difference was not statistically significance. In addition, we observed grade 2 radiation pneumonitis and grade 2 radiation esophagitis in both groups; all of these side effects were tolerable and controllable, and none of the patients experienced ≥ grade 3 pneumonitis, esophagitis, esophageal stricture, or life-threatening hemorrhage. In conclusion, radiotherapy with small T-shaped field might be a feasible and efficacious postoperative approach for ESCC patients.

The Role of Adjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma Patients with Pathological Positive Lymph Nodes After Neoadjuvant Chemotherapy Followed by Esophagectomy: a Single Institute Retrospective Analysis.

The need for adjuvant therapy after radical resection for patients with stage II–III thoracic esophageal squamous cell carcinoma (TESCC) who have undergone neoadjuvant chemotherapy (NAC) has not been determined. Since recurrence can occur after radical resection and since the prognosis is still poor, it is necessary to consider additional treatment strategies, including adjuvant chemotherapy. We retrospectively investigated the significance of adjuvant therapy after NAC followed by radical resection for TESCC. Between 2008 and 2018, 115 patients with clinical stage II–III underwent radical subtotal esophagectomy after neoadjuvant therapy. Among them, 62 were analyzed, excluding patients with T4 tumors and patients who had undergone R plus resection or who were receiving preoperative chemoradiotherapy. We compared patients who received adjuvant chemotherapy with those who only received observation; we examined overall survival (OS) and recurrence rates. Twenty-nine patients (46.7%) had lymph node metastasis, 12 of whom received adjuvant chemotherapy (41.3%). The recurrence rates for patients with and without lymph node metastasis were 55.1 % and 15.1%, respectively (p = 0.0022). Among patients with lymph node metastasis, there was no significant difference in the recurrence rate (p = 0.9270) or OS (p = 0.5416) based on the administration of adjuvant chemotherapy. However, in 15 patients with two or more positive lymph nodes, adjuvant chemotherapy increased OS (p = 0.0404). Adjuvant chemotherapy was associated with improved OS in clinical stage II–III TESCC patients with two or more pathological positive lymph nodes after NAC followed by radical surgery.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13193-021-01419-0.

PET-Uptake Reduction into Lymph Nodes After Neoadjuvant Therapy is Highly Predictive of Prognosis for Patients Who have Thoracic Esophageal Squamous Cell Carcinoma Treated with Chemoradiotherapy Plus Esophagectomy.

Patients with 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET)-positive lymph nodes before treatment have a poor prognosis after esophagectomy. This study investigated whether FDG uptake into lymph nodes on FDG-PET (PET-N) during the pre- or posttreatment stage is more predictive of survival for thoracic esophageal squamous cell carcinoma (TESCC) patients who received neoadjuvant chemoradiotherapy (NACRT) followed by esophagectomy. Of 129 TESCC patients with clinical lymphatic metastasis who underwent curative-intent esophagectomy after NACRT between 2010 and 2018, 97 who received PET before and after NACRT were enrolled in the study. The study defined lymph nodes with a maximum standardized uptake value (SUVmax) greater than 2.5 on FDG-PET before NACRT as cPET-N(+) and after NACRT as CRT-cPET-N(+). Both the cPET-N(+) and CRT-cPET-N(-) patients were defined as PET-N responders. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazard models. No significant difference in survival was detected between the cPET-N(+) and cPET-N(-) patients. However, the CRT-cPET-N(-) patients had significantly better 5-year overall survival (OS) and disease-specific survival (DSS) than the CRT-cPET-N (+) patients. The PET-N responders had significantly better 5-year OS and DSS than the PET-N non-responders, and PET-N response was an independent prognostic factor for 5-year DSS. The PET-N response is a highly predictive prognostic marker for TESCC patients who undergo NACRT followed by esophagectomy. The PET-N response may help clinicians to establish a strategy for perioperative treatments that improves survival for patients with lymph node metastasis in TESCC.

3D Deep Learning Model for the Pretreatment Evaluation of Treatment Response in Esophageal Carcinoma: A Prospective Study (ChiCTR2000039279)

To develop and validate a pretreatment computed tomography (CT)-based deep-learning (DL) model for predicting the treatment response to concurrent chemoradiation therapy (CCRT) among patients with locally advanced thoracic esophageal squamous cell carcinoma (TESCC). We conducted a prospective, multicenter study on the therapeutic efficacy of CCRT among TESCC patients across 9 hospitals in China (ChiCTR2000039279). A total of 306 patients with locally advanced TESCC diagnosed by histopathology from August 2015 to May 2020 were included in this study. A 3-dimensional DL radiomics model (3D-DLRM) was developed and validated based on pretreatment CT images to predict the response to CCRT. Furthermore, the prediction performance of the newly developed 3D-DLRM was analyzed according to 3 categories: radiation therapy plan, radiation field, and prescription dose used. The 3D-DLRM achieved good prediction performance, with areas under the receiver operating characteristic curve of 0.897 (95% confidence interval, 0.840-0.959) for the training cohort and 0.833 (95% confidence interval, 0.654-1.000) for the validation cohort. Specifically, the 3D-DLRM accurately predicted patients who would not respond to CCRT, with a positive predictive value (PPV) of 100% for the validation cohort. Moreover, the 3D-DLRM performed well in all 3 categories, each with areas under the receiver operating characteristic curve of >0.8 and positive predictive values of approximately 100%. The proposed pretreatment CT-based 3D-DLRM provides a potential tool for predicting the response to CCRT among patients with locally advanced TESCC. With the help of precise pretreatment prediction, we may guide the individualized treatment of patients and improve survival.

Prognostic Role of Nodal Skip Metastasis in Thoracic Esophageal Squamous Cell Carcinoma: A Large-Scale Multicenter Study.

Nodal-skip metastasis (NSM) is found in esophageal squamous cell carcinoma (ESCC), but its prognostic role is controversial. This study aimed to investigate the prognostic value of NSM for thoracic ESCC patients. Categorization of NSM was according to the N groupings of Japan Esophagus Society (JES) staging system, which is dependent on tumor location. Using the Kaplan-Meier method and Cox-regression analysis, this study retrospectively analyzed the overall survival (OS) for 2325 ESCC patients after radical esophagectomy at three high-volume esophageal cancer centers. Predictive models also were constructed. The overall NSM rate was 20% (229/1141): 37.4% in the in upper, 12.9% in the middle, and 22.2% in the lower thoracic ESCC. The patients with NSM always had a better prognosis than those without NSM. Furthermore, NSM was an independent prognostic factor for thoracic ESCC patients (hazard ratio [HR], 0.633; 95% confidence interval [CI], 0.499-0.803; P < 0.001). By integrating the prognostic values of NSM and N stage, the authors proposed the new N staging system. The categories defined by the new N staging system were more homogeneous in terms of OS than those defined by the current N system. Moreover, the new N system was shown to be an independent prognostic factor also for thoracic ESCC patients (HR, 1.607; 95% CI, 1.520-1.700; P < 0.001). Overall, the new N system had slightly better homogeneity, discriminatory ability, and monotonicity of gradient than the current N system. This study emphasized the prognostic power of NSM and developed a modified node-staging system to improve the efficiency of the current International Union for Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) N staging system.

Risk factors for tumor recurrence in patients with pT3N0M0 thoracic esophageal squamous cell carcinoma after esophagectomy

ObjectiveTo analyze the factors contributing to recurrence in patients with pT3N0M0 thoracic esophageal squamous cell carcinoma (ESCC).MethodsPatients with pT3N0M0 thoracic ESCC who underwent esophagectomy from January 2008 to December 2012 were included retrospectively. The last date of follow-up was 1 December 2016. Multivariate proportional hazard Cox models were used to identify factors associated with total (i.e., any) recurrence (TR), locoregional recurrence (LR), and distant metastasis (DM).ResultsA total of 692 patients were included. The median follow-up was 53 months (range: 3–107). The 3- and 5-year TR, LR, and DM rates were 35.8% and 41.0%, 28.7% and 32.1%, and 16.8% and 21.1%, respectively. The Cox analyses showed that the tumor location, number of dissected lymph nodes, and postoperative therapies were significantly associated with LR. The subgroup analysis showed that postoperative therapies could significantly decrease LR in the mediastinum but not in the neck and upper abdomen regions.ConclusionsThe recurrence rate of pT3N0M0 thoracic ESCC patients was high, especially for LR in the mediastinum. Postoperative therapies can significantly reduce the incidence of mediastinal recurrence.

Pattern of subcarinal lymph node metastasis and dissection strategy for thoracic esophageal cancer.

BackgroundThis study aimed to assess the role of subcarinal lymph nodes in lymph node metastasis in thoracic esophageal squamous cell carcinoma (ESCC) and to investigate the adequate range of lymph node dissection during esophagectomy.MethodsThis study included 782 thoracic ESCC patients who underwent esophagectomy between July 2008 and December 2010. The metastatic rate of subcarinal lymph nodes and their influencing factors were investigated. The outcome of subcarinal lymph node dissection was assessed using the efficacy index (the incidence of metastasis to a lymph node station (%) multiplied by the 5-year survival rate (%) of patients with metastasis to that lymph node station and divided by 100). Additionally, postoperative complications were compared between the subcarinal lymph node resection and reservation groups.ResultsThe metastatic rates of subcarinal lymph nodes in the upper, middle, and lower thoracic ESCC were 8.3% (4/48), 19.1% (79/414), and 16.2% (23/142), respectively (χ2=3.669, P>0.05) and in T1, T2, T3, and T4 tumors were 0% (0/71), 4% (4/100), 22.2% (85/383), and 34% (17/50), respectively (χ2=42.859, P<0.05). Tumor invasion and size were significantly correlated with metastasis. For upper thoracic ESCC with positive subcarinal lymph nodes, metastasis tendency was mainly to the lower mediastinum. In middle third esophageal cancer, after subcarinal lymph nodes were involved, metastasis to the lower mediastinal lymph nodes increased by nearly 50%, and bidirectional metastasis increased by nearly three times compared with that before involvement. For lower third cancer with positive subcarinal lymph nodes, metastasis tendency was mainly to the upper mediastinum. The postoperative complication rates in the resection and reservation groups were as follows: overall, 19% and 14.6%, respectively (P>0.05), and pulmonary, 10.3% and 7.3%, respectively (P>0.05). The efficacy indexes of lymph node dissection at the upper, middle, and lower third esophagus were 0%, 7.6%, and 27.5%, respectively.ConclusionsDissection of subcarinal lymph nodes, which does not increase postoperative complications, should be performed routinely in lower thoracic ESCC after submucosal invasion of tumor; meanwhile, tumors larger than 3cm should also result in subcarinal lymph node dissection in patients with a tumor located in the upper esophagus and T1-T2 ESCC.

Comparison between the effects of elective nodal irradiation and involved-field irradiation on long-term survival in thoracic esophageal squamous cell carcinoma patients: A prospective, multicenter, randomized, controlled study in China.

BackgroundThis study's initial results revealed significant decreases in treatment‐related esophagitis and pneumonitis cases in patients with thoracic esophageal squamous cell carcinoma (ESCC) treated with involved‐field irradiation (IFI), compared to elective nodal irradiation (ENI). This report outlines the long‐term trial results, specifically; overall survival (OS), progression‐free survival (PFS), metastasis‐free survival (MFS), and locoregional progression‐free survival (LRFS).Materials and MethodsStage II–III thoracic ESCC patients were assigned randomly, in a 1:1 ratio, into either the ENI or IFI arm. Radiation therapy was delivered once a day in 1.8‐2.0 Gy fractions to a total dose of 60.0‐66.0 Gy to the gross tumor volume and 50.0‐54.0 Gy to the clinical target volume. The primary endpoints were acute treatment‐related esophagitis and pneumonitis. The results for the primary endpoints were previously published in 2018. In this article, we analyzed the secondary endpoints including PFS, LRFS, MFS, and OS.ResultsBetween April 2012 and October 2016, 228 patients from nine participating centers in China were enrolled into this study and randomly assigned to two treatment groups. For ENI and IFI groups, respectively, the results showed similarity and were as follows: median PFS (20.3 months vs 21.4 months), OS (32.5 months vs 34.9 months), MFS (28.2 months vs 26.0 months), and LRFS (25.0 months vs 26.6 months). In particular, respective OS rates in the ENI and IFI groups were 84.6% and 82.5% after 1 year, 45.1% and 48.7% after 3 years, and 29.8% and 30.7% at 5 years. PFS rates after 1, 3, and 5 years were 58.9%, 34.2%, and 26.9%, respectively, in the ENI arm compared to 64.4%, 30.8%, and 27.7%, respectively, in the IFI arm. Multivariate analysis identified clinical stage and tumor responses as independent predictors of OS. Meanwhile, tumor location, cStage, and tumor response were identified as independent factors influencing PFS.ConclusionIFI was associated with similar survival as ENI in patients with thoracic ESCC, suggesting that IFI is an acceptable treatment method for thoracic ESCC.

Postoperative radiotherapy for the young-old patients with thoracic esophageal squamous cell carcinoma: A 2-center experience.

This study aimed to retrospectively analyze the efficacy and safety of esophagectomy and postoperative radiotherapy (PORT) for patients with thoracic esophageal squamous cell carcinoma (TESCC) in the young–old (aged between 65 and 75 years).The clinical data of 166 young–old patients with esophageal cancer who underwent esophagectomy and PORT from May 2004 to May 2018 in The First Affiliated Hospital of Nanjing Medical University and The PLA Cancer Center, Jinling Hospital were analyzed. The Kaplan–Meier method was used to calculate overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS). The log-rank method was used to test the differences. The Cox regression model was used for the multivariate prognostic analysis.The follow-up rate was 98.5%, and the median follow-up time was 41.2 months. The whole 1-, 3-, and 5-year OS rates were 92.0%, 69.3%, and 58.3%, respectively, and the median OS was 64.7 months (95% CI, 58.3–71.1). The median DFS was 57.9 months (95% CI, 47.4–68.4), and the 1-, 3-, and 5-year DFS rates were 84.8%, 61.5%, and 44.6%, respectively. The median LRFS was 60.8 months (95% CI, 50.5–71.0), and the 1-, 3-, and 5-year LRFS rates were 85.8%, 64.94%, and 53.9%, respectively. The median DMFS was 65.0 months (95% CI, 60.6–69.6), and the 1-, 3-, and 5-year DMFS rates were 91.9%, 77.0%, and 67.5%, respectively. Pathological T staging, lymph node metastasis, pathologic staging, and Karnofsk Performance Status (KPS) were the main factors affecting prognosis. In addition, T staging, lymph node metastasis are also independent prognostic factors. Little severe toxicity was observed.The result indicates that PORT for TESCC patients who can tolerate surgery is safe in the young–old. The efficacy is similar to that of previous patients including younger populations. Pathological T and N stage are major factors that affect prognosis. Concurrent chemotherapy may not improve the survival of the young–old patients undergoing postoperative radiotherapy.

High TLR4 expression predicts a poor prognosis after esophagectomy for advanced thoracic esophageal squamous cell carcinoma.

Poor oral health is an independent risk factor for upper aerodigestive tract cancers, including esophageal squamous cell carcinoma (ESCC). The pattern recognition receptor Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide in the cell walls of Gram-negative periodontal pathogens associated with the development and progression of ESCC. It is, therefore, plausible that TLR4 plays a crucial role in the pathogenesis of ESCC. We used an ESCC tissue microarray to confirm expression of TLR4 in patients with ESCC and to determine whether TLR4 expression status correlates with the clinicopathological features of these patients or their prognosis after esophagectomy. We also tested whether the combined expression statuses of TLR4 and TLR3 better correlate with prognosis in these patients than either parameter alone. Clinical ESCC samples from all 177 patients tested showed expression of TLR4. Moreover, high TLR4 expression (3 + and 2 +) correlated with poorer 5-year overall survival after esophagectomy than lower TLR4 expression (1 +) (p = 0.0491). Patients showing high TLR4 expression tended to have a poorer prognosis whether treated with surgery alone or with surgery and adjuvant chemotherapy. Univariate and multivariate analyses showed TLR4 expression status to be an independent prognostic factor affecting 5-year overall survival. Patients exhibiting high TLR4 expression with low TLR3 expression had a much poorer prognosis than other patients (p = < 0.0001). High TLR4 expression predicts a poor prognosis in advanced thoracic ESCC patients after esophagectomy.

The Number of Negative Lymph Nodes is Positively Associated with Survival in Esophageal Squamous Cell Carcinoma Patients in China.

BackgroundThere is a controversial relationship between the negative lymph nodes (NLNs) and survival in patients with esophageal squamous cell carcinoma (ESCC). This study investigates the implications of total number of NLNs on thoracic ESCC patient prognosis.Methods579 thoracic ESCC patients were categorized into four groups (0-9, 10-14, 15-19 and ≥20 NLNs). Univariate analysis was done by the log-rank tests while multivariate analysis was undertaken using Cox regression models. Survival analysis was determined employing the Kaplan-Meier method.ResultsWhen the numbers of NLNs were 9 or less, 10 to 14, 15 to 19 and 20 or more, patients of 3-year survival rates were 21.7%, 40.0%, 61.2% and 77.5%, respectively (P<0.001). In the node-negative and node-positive subgroups, 3-year survival rates were 34.9% and 14.3%, 50.9% and 19.3%, 65.6% and 51.8%, 81.4% and 68.9% respectively (P<0.001). Gender, tumor length, tumor differentiation, T and N stage as well as the total NLNs were found to be significantly linked to survival rates. Multivariate analysis showed tumor length, T stage, N stage and total NLNs were independent prognostic factors for ESCC patients.ConclusionNLNs numbers is a significant independent prognostic indicator for thoracic ESCC patients’ survival after curative esophagectomy.