Survival outcomes of neoadjuvant immunochemotherapy versus chemotherapy for locally advanced esophageal squamous cell carcinoma.

PURPOSE: Neoadjuvant chemotherapy (NCT) is the standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Some studies reported neoadjuvant immunochemotherapy (NICT) could improve pathological response with manageable safety. However, few studies have compared the efficacy and safety of NICT and NCT, especially survival outcomes. In this study, we compared the efficacy and safety of NICT and NCT after a median follow-up of 36.0 months. METHODS: This was a retrospective study with a 1:1 propensity score matching (PSM). Locally advanced ESCC patients treated with neoadjuvant sintilimab plus chemotherapy or chemotherapy followed by esophagectomy were reviewed. The primary outcome was recurrence-free survival (RFS). RESULTS: Forty-five patients were identified in each group by PSM. The pathological complete response (pCR) rate in NICT and NCT group were 28.9% and 8.9% (P = 0.02). The hazard ratio (HR) was 0.396 (95% CI 0.171-0.919, p = 0.025) for RFS and 0.377 (95% CI 0.145-0.981, p = 0.038) for overall survival (OS), 3-year RFS was 80.6% and 62.1%, 3-year OS was 86.2% and 68.1%. Patients with pCR, MPR or downstaging had better 3-year RFS and 3-year OS. The incidences of postoperative complications and treatment-related adverse events (TRAEs) were similar. CONCLUSION: This trial preliminarily shows that NICT improves pathological and survival outcomes over NCT for resectable locally advanced ESCC, with acceptable and manageable safety.

Efficacy and safety of envafolimab in the treatment of advanced dMMR/MSI­H solid tumors: A single­arm meta­analysis.

In November 2021, the National Medical Products Administration (China) approved the marketing of envafolimab injection for the treatment of advanced defective mismatch repair (dMMR)/high microsatellite instability (MSI-H) solid tumors. Envafolimab became the first domestic PD-L1 inhibitor approved in China and the first worldwide approved subcutaneously injectable PD-L1 inhibitor. To the best of our knowledge, there are no reports of systematic analyses regarding the use of envafolimab in the treatment of advanced dMMR/MSI-H solid tumors. The present study was a single-arm meta-analysis performed on data systematically searched and retrieved from literature published on PubMed, Web of Science, Cochrane Library, China National Knowledge Infra-structure and Wan Fang databases on 1 October 2022. Quality assessment using the 20 items developed by the Canadian Institute of Health Economics. Data heterogenicity was evaluated using the I2 statistics. For datasets with I2>50%, the cumulative incidence and 95% CI for the outcomes of interests were calculated using the random effects model, whereas for I2<50% the fixed effects model was used. The current meta-analysis included four studies enrolling 181 patients with advanced dMMR/MSI-H solid tumors. The pooled objective remission rate was 29.53% (95% CI, 8.61-50.45%). The pooled disease control rate was 60.58% (95% CI, 31.79-89.38%). The pooled median progression-free survival was 4.89 months (95% CI, 1.86-7.93 months). The pooled overall survival (OS) rate was 73.38% (95% CI, 65.76-80.99%). The pooled 6-month and 12-month OS rates were 75.80% (95% CI, 57.02-94.58%) and 69.32% (95% CI, 51.92-86.72%), respectively. The combined data on the incidence of treatment-emergent adverse events (TEAEs) of any grade from all the studies was 77.19% (95% CI, 63.15-91.23%). Most of the adverse reactions were mild and the rate of 3/4 grade TEAE was 10.37% (95% CI, 6.14-14.60%). Gevokizumab was effective and safe in the treatment of patients with advanced dMMR/MSI-H solid tumors and its convenience could significantly improve patient compliance; therefore, the clinical application of envafolimab is promising.

Comparisons of minimally invasive esophagectomy and open esophagectomy in lymph node metastasis/dissection for thoracic esophageal cancer.

BACKGROUND: The study aimed to clarify the characteristics of lymph node metastasis (LNM) and to compare the oncologic outcomes of minimally invasive esophagectomy (MIE) with open esophagectomy (OE) in terms of lymph node dissection (LND) in thoracic esophageal cancer patients. METHODS: The data from esophageal cancer patients who underwent MIE or OE from January 2016 to January 2019 were retrospectively reviewed. The characteristics of LNM in thoracic esophageal cancer were discussed, and the differences in numbers of LND, LND rate, and LNM rate/degree of upper mediastinum between MIE and OE were compared. RESULTS: For overall characteristics of LNM in 249 included patients, the highest rate of LNM was found in upper mediastinum, while LNM rate in middle and lower mediastinum, and abdomen increased with the tumor site moving down. The patients were divided into MIE ( n  = 204) and OE groups ( n  = 45). In terms of number of LND, there were significant differences in upper mediastinum between MIE and OE groups (8 [5, 11] vs. 5 [3, 8], P  < 0.001). The comparative analysis of regional lymph node showed there was no significant difference except the subgroup of upper mediastinal 2L and 4L group (3 [1, 5] vs. 0 [0, 2], P  < 0.001 and 0 [0, 2] vs. 0, P  = 0.012, respectively). Meanwhile, there was no significant difference in terms of LND rate except 2L (89.7% [183/204] vs. 71.1% [32/45], P  = 0.001) and 4L (41.2% [84/204] vs . 22.2% [10/45], P  = 0.018) groups. For LNM rate of T3 stage, there was no significant difference between MIE and OE groups, and the comparative analysis of regional lymph node showed that there was no significant difference except 2L group (11.1% [5/45] vs . 38.1% [8/21], P  = 0.025). The LNM degree of OE group was significantly higher than that of MIE group (27.2% [47/173] vs . 7.6% [32/419], P  < 0.001), and the comparative analysis of regional LNM degree showed that there was no significant difference except 2L (34.7% [17/49] vs . 7.7% [13/169], P  < 0.001) and 4L (23.8% [5/21] vs . 3.9% [2/51], P  = 0.031) subgroups. CONCLUSION: MIE may have an advantage in LND of upper mediastinum 2L and 4L groups, while it was similar to OE in other stations of LND.

Application of three-dimensional computed tomography bronchography and angiography in thoracoscopic anatomical segmentectomy of the right upper lobe: A cohort study.

Objective: Three-dimensional computed tomography bronchography and angiography (3D-CTBA) can provide detailed imaging information for pulmonary segmentectomy. This study aimed to investigate the safety and effectiveness of 3D-CTBA guidance of anatomical segmentectomy of the right upper lobe (RUL). Methods: This was a retrospective analysis of anatomical segmentectomy of the RUL at the Thoracic Surgery Department of the Fourth Hospital of Hebei Medical University from December 9, 2013, to June 2, 2021. Preoperatively, all patients underwent contrast-enhanced CT of the chest (to determine the size of the pulmonary nodule) and a lung function test. 3D-CTBA has been performed since 2018; patients with vs. without 3D-CTBA were compared. Segmentectomy was performed according to nodule location. Results: Of 139 patients (46 males and 93 females, aged 21-81 years), 93 (66.9%) completed single segmentectomy, 3 (2.2%) completed single subsegmentectomy, 29 had combined subsegmentectomy, 7 had segmentectomy combined with subsegmentectomy, and 6 had combined resection of two segments. Eighty-five (61.2%) patients underwent 3D-CTBA. 3D-CTBA cases had decreased intraoperative blood loss (67.4 ± 17.6 vs. 73.1 ± 11.0, P = 0.021) and shorter operation time (143.0 ± 10.8 vs. 133.4 ± 20.9, P = 0.001). 3D-CTBA (Beta = -7.594, 95% CI: -12.877 to -2.311, P = 0.005) and surgical procedure (Beta = 9.352, 95% CI: 3.551-15.153, P = 0.002) were independently associated with intraoperative blood loss. 3D-CTBA (Beta = -13.027, 95% CI: -18.632 to 17.422, P < 0.001) and surgical procedure (Beta = 7.072, 95% CI: 0.864-13.280, P = 0.026) were also independent factors affecting the operation time. Conclusion: Preoperative use of 3D-CTBA to evaluate the pulmonary vessels and bronchial branch patterns of the RUL decreased blood loss and procedure time and so would be expected to improve the safety and effectiveness of thoracoscopic segmentectomy.

Neoadjuvant Sintilimab Plus Chemotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma.

Background: Neoadjuvant chemotherapy (nCT) and chemoradiotherapy (nCRT) are the standard treatments in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). Adding PD-1 inhibitor to the chemotherapy has shown significant clinical benefits in first-line treatment of advanced ESCC. This study evaluated the efficacy and safety of neoadjuvant sintilimab plus chemotherapy in patients with resectable locally advanced ESCC. Methods: The clinical data of 96 patients with resectable locally advanced ESCC, treated with sintilimab plus chemotherapy followed by esophagectomy, were reviewed. The pathologic complete response (pCR) rate, major pathological response (MPR) rate, R0 resection rate, tumor downstaging, survival, and safety were retrospectively analyzed. Results: Patients were between the ages of 43 and 78 years (interquartile range [IQR], 60-69 years). Forty (41.7%) were diagnosed with stage II ESCC, 52 (54.2%) with stage III, and 4 (4.2%) with stage IVA. Sixty-seven (69.8%) were male, and 84 (87.5%) patients had an ECOG PS of ≤1. Forty-eight (50.0%) patients received 3-4 cycles of the neoadjuvant treatment. Twenty-nine (30.2%) patients obtained pCR, and MPR was achieved in 60 (62.5%) patients. The R0 resection rate was 99%. Eighty (83.3%) patients achieved clinical downstaging, and 71 (74.0%) achieved pathological downstaging. The median follow-up was 8.9 months, and 1-year DFS rate was 95.2% (95% CI, 88.8%-100%). Grade 3-4 TRAEs occurred in 12 (12.5%) patients, and the incidence of grade 3-4 surgical complications was 2.1%. No deaths were reported. Conclusion: These real-world data revealed that neoadjuvant sintilimab plus chemotherapy could provide encouraging pCR with good tolerability for resectable locally advanced ESCC, and this regimen warrants further exploration in prospective clinical studies.

The survival outcomes of neoadjuvant sintilimab combined with chemotherapy in patients with locally advanced esophageal squamous cell carcinoma.

Background: Neoadjuvant programmed death receptor-1 (PD-1) inhibitor combined with chemotherapy has been reported to improve the pathological response of locally advanced esophageal squamous cell carcinoma (ESCC), but the systematic report on survival follow-up is quite few. This study we will report the survival follow-up outcomes after a median follow-up of 21.1 months. Methods: This was a real-world retrospective study. Locally advanced ESCC patients treated with neoadjuvant sintilimab combined with albumin-bound paclitaxel and nedaplatin followed by surgery and completed at least 1-year follow-up were reviewed. The primary outcome was disease-free survival (DFS) at 24 months. The secondary outcome was overall survival (OS) at 24 months. Results: Ninety eligible patients were included in the analysis between July 2019 and October 2021. The median number of neoadjuvant cycles was 3 (range 2-4). All patients achieved R0 resection. With a median follow-up of 21.1 months (range 14.0-39.0), the median DFS and median OS had not reached, 2-year DFS rate was 78.3% (95%CI 68.8%-89.1%) and 2-years OS rate was 88.0% (95%CI 80.6%-96.0%). Postoperative pathological stage, pCR, MPR, tumor down-staging were significantly correlated with favorable survival outcome. Univariable and multivariable Cox regression analysis identified cycle number of neoadjuvant treatment as independent predictor of DFS. Conclusion: Our results preliminarily show a survival benefit of neoadjuvant sintilimab combined with chemotherapy in locally advanced ESCC.

Epigenetic Study of Esophageal Carcinoma Based on Methylation, Gene Integration and Weighted Correlation Network Analysis.

PURPOSE: Esophageal carcinoma is a common and highly metastatic malignant tumor of the digestive tract. The aim of the present study was to identify potential molecular markers of esophageal carcinoma that may help its diagnosis and treatment. MATERIALS AND METHODS: First, mRNA and DNA methylation data were downloaded from The Cancer Genome Atlas (TCGA) database for the identification of differentially expressed genes (DEGs) and DNA methylation analysis. Secondly, Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify important modules and hub genes. In addition, correlation analysis between DNA methylation genes and DEGs was performed. Thirdly, the GSE45670 dataset was used to validate the expression of the diagnostic and survival ability analysis of genes in TCGA data. Finally, reverse transcription-quantitative PCR and immunohistochemical analysis of genes were performed. RESULTS: A total of 2408 DEGs and 5134 differentially methylated sites were obtained. In the WGCNA analysis, the royal blue module was found to be the optimal module. In addition, hub genes in the module, including ESRRG, MFSD4, CCKBR, ATP4B, ESRRB, ATP4A, CCKAR and B3GAT1, were also differentially methylated genes and DEGs. It was found that CCKAR, MFSD4 and ESRRG may be diagnostic gene biomarkers for esophageal carcinoma. In addition, the high expression of MFSD4 was significantly correlated with patient survival. Immunohistochemistry analysis results showed that the gene expression levels of ATP4B, B3GAT1, CCKBR and ESRRG were decreased in esophageal carcinoma tissues, which was in line with the bioinformatics results. CONCLUSION: Therefore, these identified molecular markers may be helpful in the diagnosis and treatment of esophageal carcinoma.