Tumor immune microenvironment remodeling and prognosis of patients with esophageal squamous cell carcinoma after neoadjuvant chemotherapy with and without immunotherapy: a retrospective cohort study.

Background: Immunochemotherapy was an emerging neoadjuvant treatment mode that can potentially benefit patients with esophageal carcinoma, but its synergistic mechanism and impact on the tumor immune microenvironment were still unclear. The purpose of this study was to investigate the outcomes of neoadjuvant chemotherapy (nCT) and neoadjuvant immunochemotherapy (nICT) in tumor microenvironment (TME) remodeling among patients with esophageal squamous cell carcinoma (ESCC) and to evaluate the prognostic value of immune-related biomarkers and clinicopathological characteristics. Methods: Patients with locally advanced ESCC who underwent neoadjuvant therapy followed by esophagectomy at the Fourth Hospital of Hebei Medical University between December 2019 and March 2022 were enrolled in this retrospective study. We examined TME features and immune antigen-related biomarkers before and after neoadjuvant therapy. Logistic and Cox regression model were used to evaluate the correlation between these factors and other clinical features and outcomes. Results: A total of 50 eligible participants were analyzed, including 31 males (62%), 25 patients of ≥65 years old, 4/28/18 of upper/middle/lower thoracic cancer, 25/17/8 of poor/moderate/high tumor differentiation, 8/42 of cT1+2/T3+4 stages and 30/20 of cN0/N+ stages. In the entire cohort, the rates of pathological complete response (pCR) and major pathological response (MPR) were 18% and 30%, respectively. pCR rates were 7.1% and 22.2% (χ2=0.699; P=0.40) MPR rates were 7.1% and 38.9% (χ2=4.837; P=0.03) in the nCT and nICT groups, respectively. Compared with the non-pCR patients, the pCR patients had a higher baseline programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) positive expression rate (16.7% vs. 77.8%, χ2=13.089; P<0.001). Following neoadjuvant therapy, the expression rates of PD-L1, CD3+ T cells, and CD8+ T cells in the tumor tissue was higher in the nICT group compared to the nCT group (P<0.05). Deficient expression of mismatch repair (MMR) genes was only observed in one patient (2%). Among patient-related biomarkers, lymphocyte and neutrophil counts decreased after treatment, with no significant changes in the neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio (PLR). Cox regression analysis showed that pretreatment, well-differentiated tumors and positive PD-L1 status were positive predictors of MPR (P<0.05). MPR was an independent predictor of disease-free survival (DFS) (P=0.03). Conclusions: Compared to nCT, nICT could more significantly upregulates PD-L1 TPS, PD-L1 combined positive score (CPS), CD3+ T cells, and CD8+ T cells. Pretreatment tumor differentiation and PD-L1 TPS level could be predictive of MPR. Our findings suggested that the combination of chemotherapy and immunotherapy may be more beneficial for activating anti-tumor immunity in the TME.

Application of two-dimensional speckle-tracking echocardiography in radiotherapy-related cardiac systolic dysfunction and analysis of its risk factors: a prospective cohort study.

BACKGROUND: The cardiac toxicity of radiotherapy (RT) can affect cancer survival rates over the long term. This has been confirmed in patients with breast cancer and lymphoma. However, there are few studies utilizing the two-dimensional speckle-tracking echocardiography (2D-STE) to evaluate the risk factors affecting radiation induced heart disease (RIHD), and there is a lack of quantitative data. Therefore, we intend to explore the risk factors for RIHD and quantify them using 2D-STE technology. METHODS: We ultimately enrolled 40 patients who received RT for thoracic tumors. For each patient, 2D-STE was completed before, during, and after RT and in the follow up. We analyzed the sensitivity of 2D-STE in predicting RIHD and the relationship between RT parameters and cardiac systolic function decline. RESULTS: Left ventricle global longitudinal strain (LVGLS), LVGLS of the endocardium (LVGLS-Endo), LVGLS of the epicardium (LVGLS-Epi), and right ventricle free-wall longitudinal strain (RVFWLS) decreased mid- and post-treatment compared with pre-treatment, whereas traditional parameters such as left ventricular ejection fraction (LVEF), cardiac Tei index (Tei), and peak systolic velocity of the free wall of the tricuspid annulus (s') did not show any changes. The decreases in the LVGLS and LVGLS-Endo values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with mean heart dose (MHD) (all P values < 0.05). The decreases in the LVGLS-Epi values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with the percentage of heart volume exposed to 5 Gy or more (V5) (P values < 0.05). The decrease in RVFWLS and the ratio of the decrease to the baseline value were linearly related to MHD and patient age (all P values < 0.05). Endpoint events occurred more frequently in the right side of the heart than in the left side. Patients over 56.5 years of age had a greater probability of developing right-heart endpoint events. The same was true for patients with MHD over 20.2 Gy in both the left and right sides of the heart. CONCLUSIONS: 2D-STE could detect damages to the heart earlier and more sensitively than conventional echocardiography. MHD is an important prognostic parameter for LV systolic function, and V5 may also be an important prognostic parameter. MHD and age are important prognostic parameters for right ventricle systolic function.

Paclitaxel combined with platinum (PTX) versus fluorouracil combined with cisplatin (PF) in the treatment of unresectable esophageal cancer: a systematic review and meta-analysis of the efficacy and toxicity of two different regimens.

Background: Chemotherapy plays an important role in definitive chemoradiotherapy strategies. However, the most optimal concurrent chemotherapy scheme is still controversial. This study aimed to systematically evaluate the efficacy and toxicity of paclitaxel/docetaxel combined with platinum (PTX) and fluorouracil combined with cisplatin (PF) in the concurrent chemoradiotherapy (CCRT) of unresectable esophageal cancer. Methods: The PubMed, China National Knowledge Infrastructure (CNKI), Google Scholar and Embase databases were searched by combining subject words and free words through December 31, 2021. The inclusion criteria were pathologically confirmed esophageal cancer studies using CCRT, where the chemotherapy regimen only compared PTX and PF. Quality evaluation and data extraction of studies that met the inclusion criteria were carried out independently. Stata 11.1 software was used to perform the meta-analysis. The begger analysis and egger analysis were used to assess publication bias, and the robustness of the pooled results further assessed by the Trim and Fill analysis. Results: After screening, 13 randomized controlled trials (RCTs) were included. A total of 962 cases were enrolled, including 480 (49.9%) in the PTX group and 482 (50.1%) in the PF group. The gastrointestinal reaction to the PF regimen was the most serious [relative risk (RR) =0.54, 95% confidence interval (CI): 0.36-0.80, P=0.003]. The complete remission (CR) rate, objective response rate (ORR), and disease control rate (DCR) of the PTX group were higher than those of the PF group (RR =1.35, 95% CI: 1.03-1.76, P=0.030; RR =1.12, 95% CI: 1.03-1.22, P=0.006; RR =1.05, 95% CI: 1.01-1.09, P=0.022). In terms of the overall survival (OS) rate, the 2-year survival rates of the PTX group were higher than those of the PF group (P=0.005). There was no significant difference in the 1-, 3-, and 5-year survival rates between the two regimens (P=0.064, 0.144, and 0.341, respectively). There may be publication bias for ORR and DCR, and the results are reversed after applying the Trim and Fill method, so the combined results are not robust. Conclusions: PTX may be the preferred regimen for CCRT of esophageal squamous cell carcinoma, with better short-term therapeutic effect and 2-year OS rate and lower gastrointestinal toxicity.