Introduction 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. Methods 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. Results 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). Conclusions 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. Clinical Trial registration NCT04177797

No abstract

Background: Neoadjuvant chemoradiotherapy (NCRT) plus surgery is the standard treatment for esophageal squamous cell carcinoma (ESCC); however, further analysis is needed to detail the histopathological characteristics of ESCC and their clinical significance after NCRT. This study aimed to present the pathological characteristics of ESCC and their association with prognosis after NCRT.Methods: All patients with ESCC who underwent NCRT followed by surgical resection at Sichuan Cancer Hospital (China) from January 2018 to December 2019 were included. Resection specimens of both the primary disease and lymph nodes were re-evaluated by an experienced pathologist. After NCRT, the pathological characteristics of the residual tumor were evaluated based on the Japanese residual tumor pattern, Mandard tumor regression grade (Mandard-TRG), local inflammatory infiltration classification, and lymph node status.Results: Among the 103 patients with ESCC included in this study, the pathological complete response (pCR) rate was 34% (35/103). The pCR rate of patients with poorly differentiated tumors (31/72) was higher (43.1%) than that of patients with well or moderately differentiated tumors (P<0.05). The residual tumor rate was 66% (68/103). A positive correlation was noted between the Japanese residual tumor pattern and Mandard-TRG (Kendall's tau-b =0.857, P<0.001). Tumor infiltration depth, lymph node positivity, moderate differentiation, and tumor recurrence were associated with poor oncological outcomes (P<0.05).Conclusions: Patients with poorly differentiated tumors can obtain an excellent short-term response; however, they have extremely poor long-term survival. For patients with moderately differentiated tumors, both the short-and long-term outcomes are poor. Lymph node status after NCRT is a prognostic factor for ESCC treated with NCRT.

Squamous cell carcinoma is the main subtype of esophageal cancer in East Asia. The effect of the number of lymph nodes (LNs) removed to treat middle and lower thoracic esophageal squamous cell carcinoma (ESCC) in China remains controversial. Therefore, the present study aimed to investigate the impact of the number of LNs removed during lymphadenectomy on the survival of patients with middle and lower thoracic ESCC. Data were obtained from the Sichuan Cancer Hospital and Institute Esophageal Cancer Case Management Database from January 2010 to April 2020. Either three-field systematic lymphadenectomy (3F group) or two-field systematic lymphadenectomy (2F group) was performed for ESCC cases with or without suspicious tumor-positive cervical LNs, respectively. Subgroups were designed for further analysis based on the quartile number of resected LNs. After 50.7 months of median follow-up, 1,659 patients who underwent esophagectomy were enrolled. The median overall survival (OS) of the 2F and 3F groups was 50.0 months and 58.5 months, respectively. The OS rates at 1, 3 and 5 years were 86, 57 and 47%, respectively, in the 2F group, and 83, 52 and 47%, respectively, in the 3F group (P=0.732). The average OS of the 3F B and D groups was 57.7 months and 30.2 months, respectively (P=0.006). In the 2F group, the OS between subgroups was not significantly different. In conclusion, resection of >15 LNs during two-field dissection in patients with ESCC undergoing esophagectomy did not affect their survival outcomes. In three-field lymphadenectomy, the extent of LNs removed could lead to different survival outcomes.