Immune checkpoint inhibitors (ICIs) are effective in the treatment of advanced esophageal squamous cell carcinoma (ESCC); however, their efficacy in locally advanced resectable ESCC and the potential predictive biomarkers have limited data. In this study, locally advanced resectable ESCC patients were enrolled and received neoadjuvant toripalimab (240 mg, day 1) plus paclitaxel (135 mg/m², day 1) and carboplatin (area under the curve 5 mg/mL per min, day 1) in each 3-week cycle for 2 cycles, followed by esophagectomy planned 4-6 weeks after preoperative therapy. The primary endpoints were safety, feasibility, and the major pathological response (MPR) rate; the secondary endpoints were the pathological complete response (pCR) rate, disease-free survival (DFS), and overall survival (OS). Association between molecular signatures/tumor immune microenvironment and treatment response was also explored. Twenty resectable ESCC patients were enrolled. Treatment-related adverse events (AEs) occurred in all patients (100%), and 4 patients (22.2%) experienced grade 3 or higher treatment-related AEs. Sixteen patients underwent surgery without treatment-related surgical delay, and the R0 resection rate was 87.5% (14/16). Among the 16 patients, the MPR rate was 43.8% (7/16) and the pCR rate was 18.8% (3/16). The abundance of CD8⁺ T cells in surgical specimens increased (P = .0093), accompanied by a decreased proportion of M2-type tumor-associated macrophages (P = .036) in responders upon neoadjuvant therapy. Responders were associated with higher baseline gene expression levels of CXCL5 (P = .03) and lower baseline levels of CCL19 (P = .017) and UMODL1 (P = .03). The combination of toripalimab plus paclitaxel and carboplatin is safe, feasible, and effective in locally advanced resectable ESCC, indicating its potential as a neoadjuvant treatment for ESCC. NCT04177797

Background: The incidence and mortality of esophageal cancer are high. Therefore, we aimed to investigate how the number of dissected lymph nodes during esophagectomy for esophageal squamous cell carcinoma impacts overall survival, particularly that of patients with positive lymph nodes. Materials and methods: Data from 2010 to 2017 were obtained from the Sichuan Cancer Hospital and Institute Esophageal Cancer Case Management Database. Participants were divided into two groups: patients with negative lymph nodes (N0) and patients with positive lymph nodes (N+). The median number of resected lymph nodes during surgery was 24; therefore, patients with 15 to 23 and those with 24 or more resected lymph nodes were assigned to subgroups A and B, respectively. Results: After a median follow-up of 60.33 months, 1,624 patients who underwent esophagectomy were evaluated; 60.53% and 39.47% had a pathological diagnosis of N+ or N0, respectively. The median overall survival was 33.9 months for the N+ group; however, the N0 group did not achieve the median overall survival. The mean overall survival was 84.9 months. In the N+ group, the median overall survival times of subgroups A and B were 31.2 and 37.1 months, respectively. The overall survival rates at 1, 3, and 5 years were 82%, 43%, and 34%, respectively, for subgroup A of the N+ group; they were 86%, 51%, and 38%, respectively, for subgroup B of the N+ group. Subgroups A and B of the N0 group exhibited no statistically significant differences. Conclusion: Increasing the number of lymph nodes harvested during surgery to 24 or more could improve the overall survival of patients with positive lymph nodes but not that of patients with negative lymph nodes. Export

Background: Many studies have been carried out to test the hypothesis that the NQO1 C609T polymorphism might be associated with the risk of esophageal cancer. However, the results are poorly consistent, partly due to genetic or other sources of heterogeneity. To investigate the association between this polymorphism and the risk of esophageal cancer, a meta-analysis was performed. Methods: We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of association. The frequency of the putative risk allele in the controls was estimated by the inverse-variance method. Cochran’s Q statistic and the inconsistency index (I²) were used to check heterogeneity. Egger’s test and an inverted funnel plot were used to assess the publication bias. Results: Our study included eight published case-control studies about the NQO1 C609T polymorphism and esophageal cancer, including a total of 1,217 esophageal cancer patients and 1,560 controls. Overall, a significant association was found between the NQO1 C609T variant and esophageal cancer under a recessive model (OR = 1.647; 95% CI = 1.233-2.200). Regarding histological type, more significant evidence was found for esophageal squamous cell carcinoma (ESCC) (OR = 2.03; 95% CI = 1.29-3.19) than esophageal adenocarcinoma (EAC) (OR = 1.61; 95% CI = 1.01-2.56) under a recessive model. Conclusions: The meta-analysis suggests that the NQO1 C609T polymorphism considerably increases the risk of esophageal cancer.

Background: Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor with significant geographical variation and familial aggregation. However, the potentially different mechanisms underlying tumorigenesis in patients with ESCC with and without a family history of the disease remain unclear. In this study, the genes mutated in familial and nonfamilial ESCC were analyzed. Further, we aimed to explore the genes related to ESCC and attempt to identify potential patients in families with a history of ESCC. Methods: Next-generation sequencing technology was used to examine germline mutations and mutation profiles in 36 matched tumor-normal ESCC specimens. Additionally, tumor mutational burden (TMB) values were measured in two cohorts. Results: We identified four novel germline mutations in patients with familial ESCC, in BAX (c.121dupG: p.E41G), CDKN2A (c.374dupA: p.D125E), TP53 (c.856G>A: p.E286K), and CHEK1 (c.923+1G>A). Mutation profiles revealed that patients with and without a family history of ESCC had similar high-frequency gene mutation profiles, among which TP53 was the most commonly mutated gene. Additionally, tumor-specific mutated genes in patients with a positive family history of ESCC were APC, AKT3, DPYD, EP300, NFE2L2, PPP2R1A, RUNX1, and VEGFA, while those in patients without a family history of ESCC were CXCR4, PIK3R2, SMARCA4, and TTF1. Moreover, patients with positive family history had significantly higher TMB values (7.8 ± 4.1 vs 5.0 ± 2.4, for patients with and without a family history, respectively; P = 0.038). Conclusion: Our results identified mutation profiles in patients with familial and nonfamilial ESCC, and identified germline mutations in patients with positive history. TMB values may be informative for immunotherapy approaches in familial ESCC.

Background Oesophageal squamous cell carcinoma (OSCC) poses a considerable health burden, particularly in regions such as East Asia. This study aims to investigate the long-term outcomes of OSCC patients who are smokers and drinkers. Materials and methods In this retrospective analysis, data from Sichuan Cancer Hospital and Institute Esophageal Cancer Case Management Database between January 2010 and December 2017 were examined. Patients were categorised into different groups based on their smoking and alcohol consumption history: None, Smoker, Non-Smoker, Smoke-Only, Drinker, Non-Drinker, Drinker-Only, and Both. Survival outcomes were compared between the groups using Kaplan-Meier analysis and propensity score matching (PSM). The primary outcome was overall survival (OS), measured from surgery to death or last follow-up in April 2022. Results The OS median was 45.4 months for all patients after oesophagectomy. Smokers had a significantly lower median OS of 36.6 months compared with Non-Smokers with 66.2 months (p<0.001). Similarly, Drinkers had a lower median OS of 34.4 months compared with Non-Drinkers with 52.0 months (p<0.001). PSM analysis confirmed the significant differences in OS between Smokers and Non-Smokers (p=0.002) and between Drinkers and Non-Drinkers (p=0.002). Subgroup analyses showed no significant differences in OS between Group Another and Group Both, Group Smoker-Only and Group Drinker-Only, and Group Drinker-Only and Group Both. (figure 4) Conclusion Smoking and drinking were associated with significantly reduced OS in patients. However, no significant differences were found between the subgroups of patients who only smoked, only drank, or engaged in both habits.