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Background: The programmed death 1 inhibitor toripalimab plus the angio-immuno kinase inhibitor surufatinib showed a tolerable safety profile and preliminary efficacy in patients with advanced solid tumors in a phase I study. Methods: This open-label, multi-cohort study in China enrolled patients with advanced solid tumors who had failed or were intolerable to standard treatment into tumor-specific cohorts. Patients received surufatinib (250 mg orally, once daily) plus toripalimab (240 mg intravenously, once every three weeks). Results for three cohorts (gastric/gastroesophageal junction [GC/GEJ] adenocarcinoma, esophageal squamous cell carcinoma [ESCC], and biliary tract carcinoma [BTC]) are reported here. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation criteria in Solid Tumors version 1.1. Results: Between December 17, 2019, and January 29, 2021, 60 patients were enrolled (GC/GEJ, n = 20; ESCC, n = 20; BTC, n = 20). At data cutoff (February 28, 2023), ORRs were 31.6%, 30.0%, and 11.1%, respectively. Median progression-free survival was 4.1, 2.7, and 2.9 months, respectively. Median overall survival was 13.7, 10.4, and 7.0 months, respectively. Overall, grade ≥ 3 treatment-related adverse events occurred in 28 (46.7%) patients. Conclusions: Surufatinib plus toripalimab showed promising antitumor activity and a tolerable safety profile in immunotherapy-naïve patients with GC/GEJ adenocarcinoma, ESCC, or BTC. These findings warrant further study in larger randomized trials comparing surufatinib plus toripalimab with standard therapies in these tumors. ClinicalTrials.gov NCT04169672. [ABSTRACT FROM AUTHOR]

Background: Sintilimab plus chemotherapy has proven effective as a combination immunotherapy for patients with advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJC). A multi-center study conducted in China revealed a median progression-free survival (PFS) of 7.1 months. However, the prediction of response duration to this immunotherapy has not been thoroughly investigated. Additionally, the potential of baseline laboratory features in predicting PFS remains largely unexplored. Therefore, we developed an interpretable machine learning (ML) framework, iPFS-SC, aimed at predicting PFS using baseline (pre-treatment) laboratory features and providing interpretations of the predictions. Materials and methods: A cohort of 146 patients with advanced GC/GEJC, along with their baseline laboratory features, was included in the iPFS-SC framework. Through a forward feature selection process, predictive baseline features were identified, and four ML algorithms were developed to categorize PFS duration based on a threshold of 7.1 months. Furthermore, we employed explainable artificial intelligence (XAI) methodologies to elucidate the relationship between features and model predictions. Results: The findings demonstrated that LightGBM achieved an accuracy of 0.70 in predicting PFS for advanced GC/GEJC patients. Furthermore, an F1-score of 0.77 was attained for identifying patients with PFS durations shorter than 7.1 months. Through the feature selection process, we identified 11 predictive features. Additionally, our framework facilitated the discovery of relationships between laboratory features and PFS. Conclusion: A ML-based framework was developed to predict Sintilimab plus chemotherapy response duration with high accuracy. The suggested predictive features are easily accessible through routine laboratory tests. Furthermore, XAI techniques offer comprehensive explanations, both at the global and individual level, regarding PFS predictions. This framework enables patients to better understand their treatment plans, while clinicians can customize therapeutic approaches based on the explanations provided by the model. [ABSTRACT FROM AUTHOR]

This work was designed to assess the cost-effectiveness of front-line tislelizumab plus chemotherapy (TIS+Chemo) in advanced gastric cancer (GC) or gastroesophageal junction cancer (GEJC) with positive expression of programmed cell death ligand 1 (PD-L1) from the perspective of Chinese healthcare system. A 10-year partitioned survival model was undertaken utilizing clinical data from RATIONALE 305. Costs and utilities were both discounted at an annual rate of 5%. The primary outcome was incremental cost-effectiveness ratios (ICERs) and calculated as the cost per quality-adjusted life years (QALYs). The willingness-to-pay (WTP) threshold was set as $18,625/QALY. Only direct medical costs were considered. Sensitivity analyses and subgroup analyses were performed to evaluate the robustness of the model. In the base-case analysis, the incremental cost and effectiveness associated with TIS+Chemo vs Chemo was 7,361 and 0.38 QALYs, respectively, leading to an ICER of 19,371/QALY. At the WTP threshold of $18,625/QALY, the TIS+Chemo was not a cost-effective first-line treatment option. The model outcomes were robust. TIS+Chemo did not provide a cost-effective approach for PD-L1 positive advanced GC/GEJC in China setting. However, TIS+Chemo might be cost-effective in provinces with higher WTP threshold. RATIONALE 305, , identifier is NCT03777657. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does adding sintilimab, an IgG4 monoclonal antibody that binds to programmed cell death 1 (PD-1), to first-line chemotherapy improve survival for patients with previously untreated advanced gastric and gastroesophageal junction adenocarcinoma, both overall and in the subset of patients with the PD ligand 1 (PD-L1) combined positive score (CPS) of 5 or more? Findings: In this randomized clinical trial of 650 patients, from 62 centers in China, with previously untreated advanced gastric or gastroesophageal junction adenocarcinoma, the combination of sintilimab with chemotherapy compared with placebo with chemotherapy significantly improved overall survival in all randomized patients (median, 15.2 vs 12.3 months) and in patients with a CPS of 5 or more (median, 18.4 vs 12.9 months). Meaning: Among patients with previously untreated advanced gastric or gastroesophageal junction adenocarcinoma, adding sintilimab to chemotherapy significantly improved overall survival, compared with placebo with chemotherapy, among all randomized patients and in patients with a CPS of 5 or more. Importance: Gastric and gastroesophageal junction cancers are diagnosed in more than 1 million people worldwide annually, and few effective treatments are available. Sintilimab, a recombinant human IgG4 monoclonal antibody that binds to programmed cell death 1 (PD-1), in combination with chemotherapy, has demonstrated promising efficacy. Objective: To compare overall survival of patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancers who were treated with sintilimab with chemotherapy vs placebo with chemotherapy. Also compared were a subset of patients with a PD ligand 1 (PD-L1) combined positive score (CPS) of 5 or more (range, 1-100). Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 62 hospitals in China that enrolled 650 patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma between January 3, 2019, and August 5, 2020. Final follow-up occurred on June 20, 2021. Interventions: Patients were randomized 1:1 to either sintilimab (n = 327) or placebo (n = 323) combined with capecitabine and oxaliplatin (the XELOX regimen) every 3 weeks for a maximum of 6 cycles. Maintenance therapy with sintilimab or placebo plus capecitabine continued for up to 2 years. Main Outcomes and Measures: The primary end point was overall survival time from randomization. Results: Of the 650 patients (mean age, 59 years; 483 [74.3%] men), 327 were randomized to sintilimab plus chemotherapy and 323 to placebo plus chemotherapy. Among the randomized patients, 397 (61.1%) had tumors with a PD-L1 CPS of 5 or more; 563 (86.6%) discontinued study treatment and 388 (59.7%) died; 1 patient (<0.1%) was lost to follow-up. Among all randomized patients, sintilimab improved overall survival compared with placebo (median, 15.2 vs 12.3 months; stratified hazard ratio [HR], 0.77 [95% CI, 0.63-0.94]; P =.009). Among patients with a CPS of 5 or more, sintilimab improved overall survival compared with placebo (median, 18.4 vs 12.9 months; HR, 0.66 [95% CI, 0.50-0.86]; P =.002). The most common grade 3 or higher treatment-related adverse events were decreased platelet count (sintilimab, 24.7% vs placebo, 21.3%), decreased neutrophil count (sintilimab, 20.1% vs placebo, 18.8%), and anemia (sintilimab, 12.5% vs placebo, 8.8%). Conclusions and Relevance: Among patients with unresectable locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma treated with first-line chemotherapy, sintilimab significantly improved overall survival for all patients and for patients with a CPS of 5 or more compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03745170 This randomized clinical trial evaluates whether sintilimab plus chemotherapy vs placebo plus chemotherapy improved overall survival in patients in China with unresectable, locally advanced, recurrent, or metastatic gastric or gastroesophageal junction adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Immune-checkpoint inhibitors (ICIs) combined with chemotherapy have been successfully used in clinical trials to treat advanced gastric cancer. However, the efficacy and safety of first-line immunotherapy combined with chemotherapy in Chinese patients are unknown. Methods: This multicenter retrospective study included patients with human epidermal growth factor receptor-2 (HER-2) negative advanced gastric cancer treated with first-line chemotherapy or chemotherapy with an ICI between January 2019 and December 2022. Propensity score matching was used to compare progression-free survival (PFS), overall survival, objective response rates, and adverse reactions between cohorts. Results: After propensity score matching, 138 patients, who had balanced baseline characteristics, were included in the chemotherapy and combination treatment groups. The median follow-up duration was 16.90 months, and the median PFS was 8.53 months (95% confidence interval [CI] 7.77-9.28) in the combination treatment group and 5.97 months (95% CI 4.56-7.37) in the chemotherapy group. The median survival duration was 17.05 months (95% CI 14.18-19.92) in the combination treatment group and 16.46 months (95% CI 12.99-19.93) in the chemotherapy group. The PFS subgroup analysis revealed that age ≥65 years, women, Eastern Cooperative Oncology Group performance status of 1, non-signet ring cell carcinoma, esophagogastric junction, liver metastasis, peritoneal metastasis, no massive ascites, only one metastatic organ, and combined platinum-based chemotherapy correlated with treatment benefit. The incidences of adverse events above grade 3 were comparable between groups. Conclusions: Our study confirmed the ATTRACTION-4 trial results. Compared with chemotherapy, first-line ICIs combined with chemotherapy prolonged PFS but did not improve overall survival in patients with HER-2-negative advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that neoadjuvant chemoradiotherapy is superior to neoadjuvant chemotherapy for patients with locally advanced gastric cancer. However, a number of studies have come to the opposite conclusion. Therefore, our meta-analysis is to evaluate the efficacy and safety of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy in the treatment of locally advanced gastric cancer. Methods: We searched Wanfang Database, China National Knowledge Network database, VIP database, China Biomedical Literature Database, PubMed, Embase and Cochrane Library. The searched terms included'Stomach Neoplasms', 'Neoadjuvant Therapy' and 'Chemoradiotherapy'. The retrieval time was from the establishment of the corresponding database to September 2022, and our meta-analysis was performed using RevMan (version 5.3) and Stata (version 17) software. Results: A total of 17 literatures were included, which involved 7 randomized controlled trials and 10 retrospective studies, with a total of 6831 patients. The results of meta-analysis showed that compared with NACT group, the complete response rate(RR=1.95, 95%CI 1.39-2.73, p=0.0001), the partial response rate (RR=1.44, 95%CI 1.22-1.71, p=0.0001), the objective response rate(RR=1.37, 95% CI 1.27-1.54, p=0.00001), the pathologic complete response rate(RR=3.39, 95% CI 2.17-5.30, p=0.00001), the R0 resection rate(RR=1.18, 95%CI 1.09-1.29, p=0.0001) and 3-year overall survival rate(HR=0.89, 95%CI 0.82-0.96, p=0.002) of neoadjuvant chemoradiotherapy group were significantly improved. The results of subgroup analyses of gastric cancer subgroup and gastroesophageal junction cancer subgroup were consistent with the overall results. Meanwhile, the stable disease(RR=0.59, 95%CI:0.44-0.81, P=0.0010) of neoadjuvant chemoradiotherapy group was lower than that of neoadjuvant chemotherapy group, and there were no statistical significance in the progressive disease rate(RR=0.57, 95%CI:0.31-1.03, P=0.06), five-year overall survival rate(HR=1.03, 95%CI:0.99-1.07, P=0.839), postoperative complications and adverse reactions between the neoadjuvant chemoradiotherapy group and neoadjuvant chemotherapy group. Conclusion: Compared with neoadjuvant chemotherapy, neoadjuvant chemoradiotherapy might bring more survival benefits without significantly increasing adverse reactions. neoadjuvant chemoradiotherapy may be a recommended treatment for patients with locally advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Introduction: The immune checkpoint inhibitor (ICI) has been approved as the firstline therapy for metastatic gastric cancer in China. The treatment response of immune checkpoint inhibitor is highly dependent on the immune condition within the tumor microenvironment. Photodynamic therapy (PDT) has a long history in cancer treatment, and recent studies showed it had an immunomodulatory effect on the tumor. Here we will conduct a trial to assess whether or not a combination with Photodynamic therapy will improve the outcomes of immune checkpoint inhibitor-based treatment in patients with advanced or metastatic gastric cancer. Methods: This study is a single-center, open-label, randomized controlled, phase 2-3 trial. Patients (18-65 years old) with untreated gastric or gastroesophageal junction adenocarcinoma will be eligible for this trial. Sixty participants will be enrolled and randomly divided into the test group (n = 30) and control group (n = 30) to receive photodynamic therapy in combination with immune checkpoint inhibitor plus chemotherapy and immune checkpoint inhibitor plus chemotherapy, respectively. The primary is progression-free survival (PFS). The secondary outcomes include objective response rates (ORRs) and the occurrence of adverse events. In addition, we will also assess the changes in peripheral blood mononuclear cells (PBMCs) and tumor microenvironment after photodynamic therapy treatment in the test group. Evaluation of the tumor response will be performed every two cycles for a maximum of eight cycles. Discussion: Photodynamic therapy has an immunomodulatory effect on the tumor microenvironment; however, this has not been demonstrated for gastric cancer in a clinical trial. Based on our experience of photodynamic therapy treatment in digestive tract tumors, we plan to conduct a randomized controlled trial on this topic. This will be the first study to evaluate the synergistic effect of photodynamic therapy with immunochemotherapy for patients with advanced gastric cancer. Ethics and dissemination: It was approved by the Institutional Research Ethics Committee of Lanzhou University Second Hospital (No. 2022A-491). When this trial is completed, it will be shared at conferences and submitted for a potential publication in a peer-reviewed journal. [ABSTRACT FROM AUTHOR]

Purpose: Gastric cancer (GC) is one of the most frequently diagnosed cancers and one of the leading causes of cancer deaths worldwide, especially in eastern Asia and China. Anti-PD-1 immune checkpoint inhibitors, Pembrolizumab and Nivolumab, have been approved for the treatment of locally advanced or metastatic gastric or gastroesophageal junction cancer (GC/GEJC). Our study evaluated the effectiveness and safety of anti-PD-1-based treatment (monotherapy or combination therapy) in Chinese patients with advanced or metastatic GC/GEJCs in a real-world setting. Methods: A retrospective cohort study was conducted, and 54 patients from May 31, 2015, to May 31, 2021, were included in our analysis, including 19 patients treated with anti-PD-1 monotherapy and 35 patients treated with anti- PD-1 combination therapy. Demographic and clinical information were evaluated. Clinical response, survival outcomes, and safety profile were measured and analyzed. Results: Overall, the median overall survival (mOS) was 11.10 months (95% CI, 7.05-15.15), and the median progression-free survival (mPFS) was 3.93 months (95% CI, 2.47-5.39). Of the patients, 16.7% achieved a clinical response, and 72.2% achieved disease control. Prolonged overall survival (OS) and progression-free survival (PFS) and increased clinical response were observed in the combination group compared with the monotherapy group, although statistical significance was not reached. In subgroups with live metastases or elevated baseline neutrophil-to-lymphocyte ratio (NLR) levels, combination therapy outperformed anti-PD-1 alone in survival outcomes. Patients treated with anti-PD-1 monotherapy (n = 5, 26.3%) had fewer treatment-related adverse events (TRAEs) than those in the combination group (n = 22, 62.9%). There were also fewer patients with TRAEs of grades 3-5 with monotherapy (n = 2, 10.5%) than with combination therapy (n = 7, 20.0%). Pneumonitis in three patients was the only potential immune-related adverse event reported. Conclusions: Anti-PD-1-based monotherapy and combination therapy showed favorable survival outcomes and manageable safety profiles in advanced or metastatic GC/GEJCs. In clinical treatment, immunotherapy should be an indispensable choice in the treatment strategy for GC/GEJC. Patients with a heavy tumor burden and more metastatic sites might benefit more from combination therapy. Elderly patients and patients with more treatment lines or high Eastern Cooperative Oncology Group (ECOG) performance scores might be more suitable for immune monotherapy, and some clinical benefits have been observed. [ABSTRACT FROM AUTHOR]

Background: The safety and anti-tumor activity of penpulimab in patients with advanced upper gastrointestinal (UGI) cancers were evaluated in this study. Methods: Patients with advanced UGI cancers naive to immune checkpoint inhibitors were enrolled in two trials of penpulimab. In the Phase Ia/Ib trial in Australia, patients received penpulimab intravenous infusion of 1, 3 and 10 mg/kg every 2 weeks in dose-escalation phase and 200 mg every 2 weeks in dose-expansion phase. In the phase Ib/II trial conducted in China, patients received 200 mg penpulimab every 2 weeks. Primary endpoints were safety and tolerability for the phase Ia/Ib trial and the objective response rate for the phase Ib/II trial. The safety and efficacy of penpulimab in patients with UGI cancers in these two trials were evaluated. Results: A total of 67 patients with UGI cancers from Australia and China were enrolled in these two trials and had received penpulimab with a median of 6 (1–64) doses. 44.8% of patients experienced at least one treatment-related adverse event (TRAE), and 7.5% of patients experienced a grade ≥3 TRAE. Among 60 patients evaluable for response, the confirmed objective response rates ranged between 11.1 and 26.3% across cohorts for pancreatic cancer, cholangiocarcinoma, gastric or Gastroesophageal junction carcinoma (Gastric/GEJ), and hepatocellular carcinoma. 11/13 (85.0%) responders had ongoing responses at data cutoff date. Conclusions: Penpulimab monotherapy demonstrated an acceptable safety and encouraged anti-tumor activity in patients with advanced UGI cancers. Further exploration in a large cohort of patients is warranted. Trial registration: Phase Ia/Ib trial in Australia (NCT03352531) and phase Ib/II trial in China (NCT04172506). [ABSTRACT FROM AUTHOR]

Recently, the global incidence of gastric/gastroesophageal junction (G/GEJ) cancer has remained high. China is also a large country with a high gastric cancer (GC) incidence rate, where the cases of GC account for 40% of all cases worldwide. More than 90% of GEJ cancers are the adenocarcinoma pathological type. Patients with early-stage G/GEJ adenocarcinoma may have a better prognosis after surgery. In contrast, patients with advanced metastatic G/GEJ adenocarcinoma usually choose comprehensive treatment based on systemic pharmacotherapy, but the subsequent long-term survival is not optimistic. The discovery of various biomarkers, especially microsatellite instability (MSI), programmed cell death-ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), tumor mutational burden (TMB) and Epstein–Barr virus (EBV), has led to the identification of an increasing number of targeted populations and has greatly improved the clinical efficacy of treatments for G/GEJ adenocarcinoma. The ToGA trial added trastuzumab to standard chemotherapy, showed improved survival of patients with HER2-positive advanced G/GEJ adenocarcinoma and brought these patients into a new era of HER2-targeted therapy. Moreover, many HER2-targeted agents have been developed and studied in patients with advanced HER2-positive G/GEJ adenocarcinoma who have demonstrated excellent clinical outcomes. However, many patients experience disease progression with HER2-targeted therapy; hence, new anti-HER2 drugs keep being developed, significantly reducing HER2 resistance. This paper reviews HER2-targeted drugs for advanced metastatic G/GEJ adenocarcinoma, potential resistance mechanisms and future directions. [ABSTRACT FROM AUTHOR]

Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued "Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline". Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette–Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions. [ABSTRACT FROM AUTHOR]

Purpose: Concurrent chemoradiotherapy (cCRT) is the mainstay therapy of locally advanced gastric (G) and gastroesophageal junction (GEJ) cancers with a poor prognosis. Programmed cell death receptor-1 (PD-1) inhibitor has been approved and recommended to treat ≥ 3 line G/GEJ patients. A significant clinical benefit of PD-1 inhibitors in addition to cCRT has been observed in locally advanced lung cancer. Sintilimab, a humanized IgG4 monoclonal antibody with high affinity and specificity for PD-1, has shown promising efficacy with an overall response rate of 85% in combination with chemotherapy in gastric cancer in a phase Ib study (NCT02937116). Patients and Methods: SHARED is a prospective, multicentre, single-arm Phase II trial in China, exploring the efficacy of sintilimab in combination with cCRT in locally advanced G/GEJ adenocarcinoma. According to a Simon optimal two-stage clinical design, 34 patients will be enrolled. All the eligible patients will receive one cycle of induction chemotherapy (S-1 plus nab-PTX) combined with sintilimab, followed by cCRT (radiotherapy plus nab-PTX) combined with sintilimab. Prior to the surgery, patients will receive another cycle of chemotherapy (S-1 plus nab-PTX) combined with sintilimab. In the adjuvant setting, all participants will be treated with 3 cycles of chemotherapy (S-1 plus nab-PTX) combined with sintilimab. The primary endpoint is the rate of pathological complete response (pCR). The secondary endpoints include disease-free survival (DFS), major pathological response (MPR), R0 resection rate, surgical AEs, overall survival (OS), event-free survival (EFS), and safety profile. Moreover, the prognostic value of tumor biomarkers and immune biomarkers will be explored. Conclusion: SHARED is designed to primally evaluate the efficacy and safety of sintilimab in combination with cCRT in locally advanced G/GEJ cancers and to prospectively validate the prognostic value of tumor biomarkers and immune biomarkers. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the cost-effectiveness of nivolumab plus chemotherapy vs. chemotherapy as first-line therapy in patients with advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma from the perspective of the Chinese healthcare system. Methods: This economic evaluation used a state-transition Markov model to assess the cost and effectiveness of nivolumab plus chemotherapy vs. chemotherapy as first-line treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma. The characteristics of patients in the model came from a phase 3 open-label randomized clinical trial (CheckMate 649). Key clinical data were based on the CheckMate 649 trial conducted from March 2017 to April 2019, and costs and utilities were collected from the published literature. The total cost of treatment per patient, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated for the two treatment strategies. Deterministic sensitivity analysis and probabilistic sensitivity analysis were performed. Results: In the baseline analysis, the incremental effectiveness and cost of nivolumab plus chemotherapy vs. chemotherapy were 0.28 QALYs and $78,626.53, resulting in an ICER of $278,658.71/QALY, higher than the willingness-to-pay (WTP) threshold of China ($31,498.70/QALY). The model was sensitive to the duration of progression-free survival (PFS) for the nivolumab plus chemotherapy group, the cost of nivolumab per 100 mg, and the utility of PFS. Conclusion: Nivolumab plus chemotherapy was clearly not a cost-effective treatment strategy compared with chemotherapy as first-line therapy for patients with advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma in China. Reducing the price of nivolumab may improve its cost-effectiveness. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-related bacterial infection is a common side effect in patients receiving chemotherapy. The purpose of this study was to determine the risk factors and characteristics of bacterial infection in metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma patients treated with combined chemotherapy. Methods: Patients with metastatic gastric or GEJ adenocarcinoma were followed up from 2013 to 2016 at Peking University First Hospital in China. Patients were treated with multiple cycles of combined chemotherapy. The incidence rate of bacterial infection and patients' clinical data were manually reviewed. Results: A total of 154 patients were eligible and were enrolled in this study. A median of 6 chemotherapy cycles were administered (range, 1–14 cycles). Chemotherapy-related bacterial infections were observed in 36 of 154 patients (23.4%). Pulmonary is the most common site of infections. Ninety-four percent of patients with bacterial infection during chemotherapy received broad-spectrum antibiotics. The independent risk factors for chemotherapy-related bacterial infection identified by multivariable analysis were Nutritional Risk Screening 2002 (NRS2002) ≥ 3 (P = 0.008), ≥ grade 3 neutropenia (P = 0.028), and Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 2 (P = 0.042). Conclusions: Nearly a quarter of patients with metastatic gastric or GEJ adenocarcinoma who received combined chemotherapy had bacterial infection in this study. The proportion of broad-spectrum antibiotics used in patients with infection is very high. Improving nutritional status may help reduce the incidence of bacterial infection. [ABSTRACT FROM AUTHOR]

Gastric atrophy caused by Helicobacter pylori infection was suggested to influence the risk of adenocarcinoma of the esophagogastric junction (AEGJ), however, the evidence remains limited. We aimed to examine the associations of H. pylori infection and gastric atrophy (defined using serum pepsinogen [PG] I to PGII ratio) with AEGJ risk, based on a population‐based case‐control study in Taixing, China (2010‐2014), with 349 histopathologically confirmed AEGJ cases and 1859 controls. We explored the potential effect modification by H. pylori serostatus and sex on the association of serum PGs with AEGJ risk. We used unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). H. pylori seropositivity was associated with an elevated AEGJ risk (OR = 1.95, 95% CI: 1.47‐2.63). Neither CagA‐positive nor VacA‐positive strains dramatically changed this association. Gastric atrophy (PGI/PGII ratio ≤4) was positively associated with AEGJ risk (OR = 2.36, 95% CI: 1.72‐3.22). The fully adjusted ORs for AEGJ progressively increased with the increasing levels of PGII (P‐trend <.001). H. pylori showed nonsignificant effect modification (P‐interaction =.385) on the association of gastric atrophy with AEGJ. In conclusion, H. pylori and gastric atrophy were positively associated with AEGJ risk. These results may contribute evidence to the ongoing research on gastric atrophy‐related cancers and guide the prevention and control of AEGJ. What's new? Gastric atrophy caused by Helicobacter pylori may be linked to the development of adenocarcinoma of the oesophagogastric junction (AEGJ), which has unique anatomical and pathological features. However, few large‐scale studies have examined the association of gastric atrophy with AEGJ. In this population‐based case‐control study conducted in a high‐risk region of eastern China, H. pylori infection and gastric atrophy (defined using the serum pepsinogen (PG)I to PGII ratio) were positively associated with AEGJ risk. These results may contribute evidence to the ongoing research on gastric atrophy‐related cancers and guide the prevention and control of AEGJ. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether the dissection of pyloric lymph nodes (PLNs, No. 5 and No. 6 lymph nodes) is necessary for adenocarcinoma of the esophagogastric junction (AEG) with a tumor diameter >4 cm based on current guidelines. This study aimed at evaluating whether pyloric node lymphadenectomy is essential for patients with Siewert type II/III AEG according to different tumor diameters. Methods: This study included 300 patients on whom transabdominal total gastrectomy was performed for Siewert type II/III AEG at a high-volume center in China from January 2006 to December 2015. The index of estimated benefit from lymph node dissection (IEBLD) was used to analyze the priority of pyloric lymphadenectomy. Results: In Siewert type II AEG, the 5-year overall survival (OS) and the 5-year disease-free survival (DFS) were similar between patients with PLN-positive cancer and patients of stage III AEG without PLN metastasis (23.1% vs. 30.6%, p = 0.505; 23.1% vs. 27.1%, p = 0.678). However, in Siewert type III AEG, the OS and the DFS of patients with PLN-positive cancer were significantly lower than that of patients with stage III without PLN metastasis (7.9% vs. 27.8%, p = 0.021; 0 vs. 26.8%, p = 0.005). According to the IEBLD, the dissection of PLNs did not appear to be beneficial in either Siewert type II AEG or type III AEG, whereas a stratified analysis revealed that PLN dissection yielded a high therapeutic benefit for Siewert type II AEG with tumor diameters >4 cm. Conclusion: We recommended that the PLNs be dissected in Siewert type II AEG when a tumor diameter is >4 cm. Total gastrectomy should be optional for Siewert type II AEG with a tumor diameter >4 cm and Siewert type III AEG. [ABSTRACT FROM AUTHOR]

Background: The bispecific antibody (bsAbs) research around the world has undergone great changes. We analyzed the global trend of bsAbs research and compared the differences in clinical research of bsAbs between China and worldwide. Methods: BsAbs research clinical trials information was retrieved through the online open-resource clinical trial registration platform. Research information including organizations, identity numbers, locations, phases, participating centers, conditions, status, enrollment, targets, spectrums of mechanism of action (MOA), and start date was collected. Clinical trials were divided into two categories based on the attributes of pharmaceutical companies (international or China-initiated or involved). Results: From 1997 to 2020, 272 clinical trials regarding bsAbs research were retrieved. Twenty-nine percent of the studies were contributed by companies from Chinese institutions, which followed the USA and ranked second. The clinical trials of bsAbs are mainly concentrated on phase I (n = 161), phase I/II (n = 54), and phase II (n = 51), and the number of phase III trials is still rare (n = 4). Tumor species distribution analysis shows that there are significantly higher focuses on gastric cancer (n = 18), esophageal/gastroesophageal junction cancer (n = 16), bladder cancer (n = 10), biliary malignant tumor (n = 8), nasopharyngeal cancer (n = 6), and thymic cancer (n = 2) in China. BsAbs target and spectrums of MOA analysis showed that international companies mainly focus on bsAbs with CD3-based (n = 63) target with MOA of T-cell redirection, while researches in China pay more attention to PD-1 (n = 9)/PD-L1 (n = 7) axises with MOA of double immune checkpoint blocking. Conclusion: Global bsAbs research increased rapidly during the 1997 to 2020 period. The developed countries in America and Europe are leading the trend of bsAbs research. Anticancer bsAbs clinical research in China is booming and chasing after the world trend. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) has shown significant benefits for gastric cancer patients. However, it has not been well accepted in Asian countries. We conducted a prospective study on the safety and feasibility of the FLOT regimen in Chinese patients. Methods: Patients with adenocarcinoma of the stomach or esophagogastric junction received four cycles of neoadjuvant chemotherapy (NAC) and four cycles of adjuvant chemotherapy (AC) with the FLOT regimen. The completion status of chemotherapy, adverse events, postoperative morbidities, and pathological tumor regression were analyzed. The 2-year overall survival (OS) and relapse-free survival are presented. Results: Altogether, 10 patients were enrolled, and all patients completed four cycles of neoadjuvant chemotherapy. There were no severe hematological adverse events (grade 3 or above), except for a case of grade 3 anemia. All 10 patients underwent radical gastrectomy. Nine patients had R0 resection, and three patients had complete or subtotal pathological tumor regression. Nine patients completed four cycles of adjuvant chemotherapy, but only one patient completed the full dose of adjuvant chemotherapy. The dose of adjuvant chemotherapy was reduced by 25% or less in the other patients. The median follow-up time was 23.13 months, eight patients achieved the overall survival endpoint, and seven patients had relapse-free survival for this period. Two patients died of disease progression. Conclusions: Our study demonstrates that the neoadjuvant FLOT regimen is safe and effective for Chinese patients. Dose adjustment is necessary for adjuvant chemotherapy. The pathological regression and survival rates need reevaluation in a larger cohort. The trial is registered with ClinicalTrials.gov (number NCT03646591). [ABSTRACT FROM AUTHOR]

Background: Apatinib showed promising efficacy in the treatment of advanced or metastatic gastric cancer (mGC) in previous clinical studies. However, the real-world data are limited, and this study aimed to assess the effectiveness and safety of apatinib for the treatment of advanced or mGC in this setting. Methods: In this prospective observational study, progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR) and treatment-related adverse events (AEs) were recorded and evaluated. Univariate and multivariate analyses were conducted to explore potential biomarkers which might be related to the effectiveness. Results: A total of 321 mGC patients from 47 centers in China were enrolled between July 1, 2015, and March 1, 2018. Thirty-two patients achieved partial response, 155 patients achieved stable disease, and 115 patients had progressive disease, and no CR was achieved, illustrating an ORR of 10.60% and a DCR of 61.92%. The median PFS and OS were 4.0 and 8.2 months, respectively. Multivariate Cox analysis showed that the potential biomarkers associated with longer PFS were combination regimens plus taxel/docetaxel, and apatinib initial dosage ≥ 500mg, occurrence of AEs of leukopenia, and hand-foot syndrome. Main AEs were proteinuria (17.1%), hypertension (15.9%), and handfoot syndrome (8.7%). Conclusion: The present prospective observational study showed favorable effectiveness and safety of apatinib in real-world patients with advanced or metastatic GC in China. (A prospective, multi-center, non-intervention study of apatinib in the treatment of advanced gastric cancer-Trial Registry Number: ChiCTR-OPN-15006601). [ABSTRACT FROM AUTHOR]

Background and Aims: The techniques and indications for endoscopic submucosal dissection (ESD) and endoscopic submucosal tunnel dissection (ESTD) to remove superficial neoplasia at the esophagogastric junction (EGJ) have been developed and expanded. However, the resection of superficial neoplasia at the EGJ by ESD remains challenging, and the long-term clinical outcomes of curative and non-curative resections based on histological criteria remain unclear. We conducted a retrospective analysis on the safety and efficacy of the ESD and ESTD procedure with these patients.Methods: The records of 209 consecutive patients at the Chinese PLA General Hospital who received ESD and ESTD to treat EGJ superficial neoplasia from November 2006 to December 2016 were reviewed for this retrospective cohort study. We divided patients into two groups (curative and non-curative resection).Results: Of all 14 additional surgeries, 1 patient in the curative group and 13 in the non-curative group underwent surgical operation with residual tumor in 7 specimens. During a median follow-up period of 46.4 months (range 12.2-142.3 months), the 5-year survival rate was 98.6%. Two patients died 91 months and 66 months after surgery due to subarachnoid hemorrhage and lymphoma, respectively. One patient died of gastric cancer 1 year after the surgery. The 5-year disease-specific survival rate was 99.5%. Local tumor recurrence was detected in 9 of 209 cases.Conclusions: In conclusion, ESD was shown to be a safe and effective treatment strategy for early EGJ neoplasia. Mucosal adhesion may increase the difficulty of piecemeal curative resection, but the superficial depth of such an invasion favors better clinical outcomes. Additional surgical resection is a good choice for non-curative ESD, and re-ESD is also an alternative, in conjunction with intensive follow-up. [ABSTRACT FROM AUTHOR]

Purpose: We aim to investigate the current esophageal cancer staging according to the 7th edition TNM classification for esophageal carcinoma proposed by American Joint Committee on Cancer (AJCC) among oncology-related physicians in China. Methods: A specifically-designed 14-item questionnaire was distributed to 366 doctors who were working with esophageal cancer patients. We collected and analyzed the feedbacks and explored the possible associations within different departments, including thoracic surgery, the internal medicine of gastroenterology, oncology, and/ radiotherapy in eight different hospitals from central and southern China. Results: Among all the responses, 31.42% of them were from thoracic surgery department, 40.44% were from oncology and/or radiation therapy and 28.14% were from the internal medicine of gastroenterology, respectively. Surprisingly, in total 66.12% of all the physicians were unaware that the 7th edition of esophageal carcinoma TNM classification was released in 2009; only 21.86 and 16.67% of physicians recognized cervical nodes and celiac nodes as regional lymph nodes. Furthermore, 67.21% physicians didn't know that tumor location, histologic grade, and histopathology were accepted as new prognostic factors in the latest TNM system; and 51.37% physicians could not determine the correct TNM classification of esophagogastric junction cancers. Intriguingly, over 50% of them could still design appropriate perioperative strategies. Conclusions: The 7th edition of the TNM classification for esophageal carcinoma is poorly recognized and understood in central and southern China, which might contribute to the relatively low rates of appropriate perioperative procedures applied for esophageal cancer patients. [ABSTRACT FROM AUTHOR]

Background: Till present, there are still controversies over the epidemiology, pathological features, types of surgical treatment, and prognoses of primary small gastric GISTs (gGISTs).Methods: From January 1998 to January 2015, patients with primary small gGIST admitted from four high-volume medical centers of the Southern China were enrolled and their data were analyzed to evaluate their clinicopathological features, treatment and prognostic factors to provide evidence-based medical experience for clinical practice.Results: A total of 276 primary small gGIST cases over a period of 18 years were investigated and had a median age of 60 years (range 27-91 years old). Regarding the tumor sites, 24 (8.7%) cases were in the cardia of the stomach, 107 (38.8%) in the fundus, 117 (42.4%) in the gastric body, and 28 (10.1%) in the gastric antrum. Eleven patients (4.0%) underwent a preoperative biopsy. A total of 137 (49.6%), 75 (27.2%), and 64 (23.2%) patients underwent laparoscopic, open resection, and endoscopic resection, respectively. Sixty-four patients (23.2%) had local endoscopic resection, 172 (62.3%) had wedge resection, 7 (2.5%) had proximal gastrectomy, 19 (6.9%) had distal gastrectomy, and 14 (5.1%) had total gastrectomy. Mitotic counts were ≤ 5/50, (5-10)/50, and > 10/50 per HPF in 259 (93.8%), 7 (2.5%), and 10 (3.6%) cases, respectively. There were 259 cases (97.1%) of spindle cell type, 7 (2.5%) epithelial cell types and one case (0.4%) of mixed type. Immunohistochemistry showed 74.6% (206/276), 98.2% (271/276), and 97.4% (269/276) of the patients had co-expression of CD34+, CD117+, and DOG-1+, respectively. Thirty-nine patients underwent genetic testing (39/276, 14.1%). Three patients (1.1%) had positive resection margin. Five high-risk patients received follow-up treatment with imatinib with a median follow-up time of 38 months (range 3-156 months). The overall 1-, 3-, and 5-year overall survival rates were 100%, 99.6%, and 99.1%, respectively.Conclusion: Though the incidence of primary small gGISTs increased per annum, the overall survival prognoses were high. Surgery or endoscopic resection was the primary mode of treatment. Pathological features of primary small gGISTs were similar to large gGISTs, and to achieve a timely surgical intervention, the identification of intermediate- and high-risk cases should be a future focus of study. [ABSTRACT FROM AUTHOR]

Background: The new 8th TNM system attributes AEG Siewert type II to esophageal classification system. However, the gastric and esophageal classification system which was more suitable for type II remains in disputation. This study aimed to illuminate the 8th TNM-EC or TNM-GC system which was more rational for type II, especially for patients underwent transhiatal approaches. Methods: We collected the database of patients with AEG who underwent radical surgical resection from two high-volume institutions in China: West China Hospital (N = 773) and Xi Jing Hospital of Fourth Military University (N = 637). The cases were randomly matched into 705 training cohort and 705 validation cohort. All the cases were reclassified by the 8th edition of TNM-EC and TNM-GC. The distribution of patients in each stage, the hazard ratio of each stage, and the separation of the survival were compared. Multivariate analysis was performed using the Cox proportional hazard model. Comparisons between the different staging systems for the prognostic prediction were performed with the rcorrp.cens package in Hmisc in R (version 3.4.4. http://www.R-project.org/). The validity of these two systems was evaluated by Akaike information criterion (AIC) and concordance index (C-index). Results: By univariate analysis, the HRs from stage IA/IB to stage IV/IVB were monotonously increased according to TNM-GC scheme in both cohorts (training 2.63, 3.91, 5.02, 8.64, 15.51 and 29.64; validation 1.54, 3.55, 4.91, 7.14, 11.67, 18.71 and 48.32) whereas only a fluctuating increased tendency was found when staged by TNM-EC. After the multivariate analysis, TNM-GC (P < 0.001), TNM-EC (P = 0.001) in training cohort and TNM-GC (P < 0.001) TNM-EC (P < 0.001) in the validation cohort were both independent prognostic factors. The C-index value for the TNM-GC scheme was larger than that of TNM-EC system in both training (0.721 vs. 0.690, P < 0.001) and validation (0.721 vs. 0.696, P < 0.001) cohorts. After stratification analysis for Siewert type II, the C-index for TNM-GC scheme was still larger than that of TNM-EC in both training (0.724 vs. 0.694, P = 0.005) and validation (0.723 vs. 0.699, P < 0.001) cohorts. Conclusions: The 8th TNM-GC scheme is superior to TNM-EC in predicting the prognosis of AEG especially for type II among patients underwent transhiatal approaches. [ABSTRACT FROM AUTHOR]

Background: The clinical response to anti-programmed cell death 1 (PD-1) antibodies in patients with advanced gastric and gastroesophageal junction (GEJ) cancer in China has not been reported.Methods: This study evaluated the efficacy and safety of SHR-1210, an anti-PD-1 antibody, in patients with advanced gastric/GEJ cancer in a phase 1 trial. The associations between candidate biomarkers (programmed death ligand 1 [PD-L1] expression, mismatch repair status, tumor mutation load, and lactate dehydrogenase [LDH] levels) and the efficacy of SHR-1210 were also explored.Results: Thirty patients with recurrent or metastatic gastric/GEJ adenocarcinoma who were refractory or intolerant to previous chemotherapy were enrolled between June 2, 2016, and June 8, 2017. Seven patients (23.3%) demonstrated objective responses, including 1 complete response. The objective response rates for patients with PD-L1-positive and PD-L1-negative tumors were 23.1% (3 of 13) and 26.7% (4 of 15), respectively (P = 1.000). Two treatment-related grade 3 or higher adverse events were reported: one was grade 3 pruritus, and the other (3.3%) was grade 5 interstitial lung disease. All 20 patients tested for the mismatch repair status had mismatch repair-proficient tumors, and the response rate was 30.0% (95% confidence interval, 11.9%-54.3%). Patients with a higher mutation load (4 of 10) tended to have better responses than those with fewer mutations (2 of 10), but the difference was not significant (P = .628). Patients with a >10% relative increase from the baseline LDH level were more likely to experience disease progression (90% [9 of 10]) than patients with a ≤10% change (40% [8 of 20]; P = .017).Conclusions: Anti-PD-1 antibody SHR-1210 shows encouraging efficacy in patients with advanced gastric/GEJ cancer in China, including mismatch repair-proficient subgroups. [ABSTRACT FROM AUTHOR]

Background: The optimal extent of lymph node (LN) dissection remains controversial in adenocarcinoma of the esophagogastric junction (AEG), especially in Siewert types II and III. The aim of this study was to analyze clinicopathological characteristics of patients with Siewert type II and III AEGs to clarify whether pyloric (no. 5 and no.6) lymphadenectomy is essential in these patients.Methods: A retrospective analysis was performed in the Third Affiliated Hospital of Soochow University from September 2008 to December 2012, and clinicopathological characteristics on all patients with Siewert type II and III AEGs, who underwent curative total gastrectomy with lymphadenectomy were collected. The index of estimated benefit from lymph node dissection (IEBLD) was used to evaluate the efficacy of lymph node dissection of no. 5 and no. 6. Both clinicopathological characteristics and IEBLDs were set as the standards in the assessment of the value of pyloric lymph nodes dissection.Results: A total of 216 patients with AEG (Siewert type II: 141, Siewert type III: 75) were included into the study. Type III AEG had a larger tumor size and relatively advanced T stage compared to Type II AEG. The 5-year overall survival (OS) rates in type II and type III AEGs were almost similar (type II 50.4% vs. type III 46.7%, p = 0.782). There was a very low incidence of pyloric lymph nodes metastases in type II AEG (no. 5 is 1.4% and no. 6 is 0.7%). Hence, the IEBLDs of no. 5 and no. 6 lymph node were negligible regardless of the T stage and tumor differentiation. In type III AEG, metastasis rates of no. 5 and no. 6 lymph node were 9.3 and 5.3%, respectively. The IEBLDs of no. 5 and no. 6 lymph node were 2.7 and 1.3, respectively.Conclusions: Based on the IEBLDs of pyloric lymph nodes, dissection of no. 5 and no. 6 lymph nodes were worthwhile for Siewert type III AEG but not essential for Siewert type II AEG. [ABSTRACT FROM AUTHOR]

Objective: A retrospective analysis of 214 cases of esophagogastric junction cancers (EGJCs) in Kunming, Yunnan Province, was conducted to investigate the lymph node metastasis (LNM) pattern for EGJCs and its associated risk factors (RFs), as well as the predictive value of common clinical metabolic indicators for it., Methods: The clinical data of 214 patients diagnosed with EGJCs by electronic gastroscope and postoperative pathology between 2013 and 2021 at the First Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, and the Second Affiliated Hospital of Kunming Medical University were retrospectively examined. Preoperative gastroscopy, imaging, biochemical data, and postoperative pathological findings analysis in EGJCs were statistically analyzed to determine the RFs of LNM., Results: At presentation, 92.5% of EGJCs were progressive malignancies, including 68.2% LNMs, 79.5% abdominal lymph nodes (ALN), 20.1% mediastinal lymph nodes (MLN), and 27.1% distal metastases. The ratio of Siewert subtypes was approximately 2:11:7 (type I to type II to type III). In terms of age, disease duration at initial presentation, history, tumor length, pathological biopsy histology, degree of differentiation, depth of infiltration, LNM status, MLN metastasis, and surgical route, the differences between the three Siewert subgroups were statistically significant (p < 0.05). Multifactor analysis revealed that the proportion of patients aged <65 at the time of consultation was significantly more significant in Siewert II and Siewert III than in Siewert I. Significantly more patients than in Siewert I had <2 months of disease duration at the time of their first consultation. The proportion of patients with tumors <3 Cm in length was significantly higher than in Siewert I. For the RFs analysis of LNM, Siewert staging (type I and type II), depth of infiltration, and distant metastasis were the independent RFs for LNM. The depth of infiltration and family history of the tumor were the independent RFs for ALN metastasis, and the number of lymph nodes cleared in the abdominal and mediastinal regions was a protective factor for ALN metastasis. Siewert staging(type I and type II), infiltration depth, invasion of the esophagus by the tumor, tumor length, and distant metastasis were independent risk factors for MLN metastasis. Among the metabolic variables evaluated, BMI was an independent RF for LNM, fasting glucose was an independent RF for ALN metastasis, and triacylglycerol was a protective factor for MLN metastasis., Conclusions: EGJCs are frequently advanced at presentation, characterized by minimal differentiation and a high incidence of LNM. The Siewert subtype is concentrated near the stomach. Different Siewert subtypes exhibit distinct clinicopathological characteristics. LNM and MLN metastasis risk are considerably higher in type I tumors compared to types II and III. There is a strong correlation between LNM and MLN metastasis and distant metastasis in EGJCs, so Siewert I is more aggressive and associated with a worse prognosis. EGJCs have numerous RFs associated with LNM, and there are similarities and differences in the RFs affecting their LNM, ALN metastases, and MLN metastases, which are related to their unique anatomical features. There is a close relationship between metabolic factors and EGJCs with some predictive value., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background: Neoadjuvant chemotherapy has been increasingly practiced on gastric cancer (GC), and histological evaluation to predict outcome is urgent in clinical practice. There are five classic tumor regression grading (TRG) systems, including Mandard-TRG system, the Japanese Gastric Cancer Association (JGCA)-TRG system, College of American Pathologists (CAP)-TRG system, China-TRG system and Becker-TRG system.Methods: Totally, 192 patients of gastric adenocarcinoma (including adenocarcinoma of the esophagogastric junction) treated by neoadjuvant chemotherapy and surgery were evaluated using the above five TRG systems. The clinicopathological characteristics were also assessed. The correlation among TRG systems, clinicopathological characteristics and prognosis were analyzed.Results: All the five TRG systems were significantly correlated with differentiation, postsurgical T category, postsurgical N category, American Joint Committee on Cancer (AJCC) stage, lymph-vascular invasion, perineural invasion, as well as tumor size. All the five TRG systems were statistically significant in univariate Cox survival analysis. However, only postsurgical T category, postsurgical N category and R0 resection were independent in multivariate Cox survival analysis. The tight correlation between the TRG systems and other characteristics such as postsurgical stage might affect the independent prognostic role of the TRG systems. As compared with other TRG systems, the hazard ratio of no/slightly response in both Mandard TRG system and JGCA TRG system revealed higher hazard of death and disease progression than that of severe response when using univariate Cox survival analysis. The median survival time of complete response and nearly complete response were much longer than that of partial response, all classified by Mandard-TRG system. This could help clinicians predict prognosis more reasonably than JGCA-TRG which does not have the category of nearly complete response.Conclusion: We recommend Mandard-TRG system for GC after neoadjuvant chemotherapy due to its better prediction of prognosis. [ABSTRACT FROM AUTHOR]

Aim: To investigate the incidence and risk factors of microscopically positive proximal margins in Chinese patients with adenocarcinoma of the gastroesophageal junction. Methods: The medical records of 483 patients, who underwent surgical treatment with curative intent for adenocarcinoma of the gastroesophageal junction in a single high-volume tertiary medical center, were reviewed. Demographic, radiographic, endoscopic, pathologic, and treatment-related variables were evaluated. All proximal margins were re-evaluated by two experienced pathologists, and a positive proximal margin was defined as the microscopic presence of invasive tumor cells seen at the esophageal transaction margin submitted en face on final paraffin sections. Results: The incidence of positive proximal margins was 23.81% in this series. Siewert type, depth of tumor invasion, lymph node involvement, presence of vascular or lymphatic invasion, and presence of perineural invasion were significantly associated with positive proximal margins. On multivariate analysis, the presence of vascular or lymphatic invasion and advanced-stage disease were independent risk factors for positive proximal margins in patients with adenocarcinoma of the gastroesophageal junction. Conclusion: Residual cancer at proximal resection margins remains a major issue for the surgical treatment of adenocarcinoma of the gastroesophageal junction in China. [ABSTRACT FROM AUTHOR]

Background: The incidence of adenocarcinoma of the esophagogastric junction is increasing. This study aims to evaluate the clinicopathological features of Chinese patients with adenocarcinoma of the esophagogastric junction and to define prognostic factors. Methods: We retrospectively reviewed a database of 382 consecutive patients with adenocarcinoma of the esophagogastric junction at the First Affiliated Hospital of Xi'an Jiaotong University from January 2005 to March 2010. All patients were classified according to the Siewert's classification and staged according to the latest edition of the American Joint Committee on Cancer categories. Results: Six of the 382 patients had type I adenocarcinoma, 220 had type II, and 156 had type III. There was no significant difference in the overall survival of different Siewert subtypes. According to the multivariate analysis, pathological lymph node stage, age, and the existence of lymphovascular invasion were the independent factors of prognosis of adenocarcinoma of the esophagogastric junction following surgery. Conclusions: On the data, the distribution of the three types of tumor was found to be different from that reported in Western countries. Lymph node metastasis, lymphovascular invasion, and age were significant and independent factors for poor prognosis after R0 resection for adenocarcinoma of the esophagogastric junction. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinicopathological features of columnar-lined esophagus ( CLE) in Chinese patients. Methods Among 182 consecutive resections of proximal gastric cancer with residual esophageal tissue, 114 were eligible for the study. The maximal lengths of CLE and superficial esophageal glands ( SEG) and the presence or absence of chronic inflammation ( CI), lymphoid follicles ( LF), Helicobacter pylori ( H. pylori) infection, intestinal metaplasia ( IM), pancreatic metaplasia ( PM) and dysplasia were analyzed and compared with those in the adjacent proximal gastric mucosa. Results SEG were present in 110 cases with a mean length of 5.4 mm (range 1-16 mm, 90% equal to or under 10 mm and 10% between 11-16 mm). These glands were associated with CI (95%), LF (85%), H. pylori infection (42%), IM (25%), PM (36%) and dysplasia (10%). CLE was found in 65% of the cases and was associated with SEG (mean length of 4.0 mm, range 1-13 mm, 97% within 10 mm and 3% between 11-13 mm). The frequencies of CI (97%), LF (86%), H. pylori infection (65%) and PM (46%) in CLE were similar to those in the proximal stomach ( CI 90%, LF 54%, H. pylori infection 58%, PM 39%). In contrast, the frequencies of IM (37%) and dysplasia (15%) in CLE were significantly lower than those in the proximal stomach (66% and 31%, respectively; P < 0.01). Conclusions CLE in Chinese patients was within 10 mm in length in 97% of cases, and with SEG and H. pylori infection-related changes similar to those in the proximal stomach. [ABSTRACT FROM AUTHOR]

Background: The left thoracoabdominal (LTA) approach is the conventional way to treat adenocarcinoma of the esophagogastric junction (EGJ). The study was to review the outcome of the LTA approach with adenocarcinoma of the EGJ in a single institution in China. Methods: 135 consecutive adenocarcinomas of EGJ patients who underwent surgical treatment were retrospectively analyzed; data gathered included basic information on the tumor, surgical approach, postoperative complications and survival rate. Results: LTA esophagogastrectomy was performed in all patients. No patients received allogeneic blood transfusion during the operation. Among the resective procedures, proximal gastrectomy was performed in 122 cases. The mean operation time was 150 min (90-240). R0 resection was obtained in 120 patients (88.9%). Two patients developed respiratory failure 2 days after surgery. Contrast swallow revealed a leak at the anastomosis in 2 patients. One early anastomotic stricture was observed radiologically, and pneumonia was observed in 3 patients. The number of patients with spontaneous pneumothorax and wound infections were 3 and 5, respectively. The percentage was zero in-hospital deaths. The overall survival rates at 1 year and 2 years were 89.2 and 69%, respectively. The median survival was 27.1 months. Conclusion: LTA esophagogastrectomy has a major role in the management of adenocarcinoma of the EGJ, at least in the northern Henan Province of China. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Carcinomas involving the gastroesophageal junction are common in China. The histopathologic characteristics of these cancers have not been systematically investigated. Reported are 41 such resected cancers from Chinese patients (30 men, 11 women). Their mean age was 62 years. The mean tumor size was 4.4 cm (range, 2 to 9 cm), and 58% were poorly differentiated. An unusual spectrum of tumor differentiation was observed, including adenocarcinomas (83%), adenosquamous (32%), colloid (2%), signet-ring (10%), squamous (5%), oncocytic (7%), pancreatic acinar (12%), and neuroendocrine (5%) carcinomas. Cancers with multiple types of differentiation in the same tumor were identified in 37 cases (90%). The adjacent gastric cardiac mucosa showed hyperplasia, oncocytic, and pancreatic acinar metaplasia, and mild chronic inflammation. Dysplasia was uncommon (n = 6). Barrett esophagus was not identified. Carcinomas involving the gastroesophageal junction in the Chinese are morphologically distinct, heterogeneous, and may be of esophageal origin. [ABSTRACT FROM AUTHOR]

BACKGROUND Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism for AND AIMS: gastroesophageal reflux in the Western population. The major reflux mechanism in Chinese patients with GERD has not been studied before. METHODS: Fifty-four patients with GERD and 28 controls underwent stationary baseline manometry and the 24-h ambulatory esophageal pH monitoring. TLESRs were measured before and after an 850 kcal meal in the supine position. Primary peristalsis, secondary peristalsis, and esophageal acid clearance were measured by esophageal manometry. RESULTS: Total time esophageal pH ≤ 4 (7.3 vs 1.5, p = 0.001) was significantly higher in patients with GERD when compared to controls. Majority of acid reflux episodes was due to TLESR in both patients with GERD and controls. The frequency of TLESRs after meal was similar between patients with GERD and controls (1.0 vs 1.3/h, p = 0.34). There was no difference in the distribution of reflux mechanism between patients with GERD and controls. However, patients with GERD had a significantly lower successful primary peristalsis (59% vs 70%, p = 0.043) when compared to controls. CONCLUSION: The frequency of TLESR5 was similar between patients with GERD and controls during stationary manometry. Primary peristalsis was impaired in Chinese patients with GERD. Esophageal motor dysfunction may contribute to the pathophysiology of GERD in the Chinese population. [ABSTRACT FROM AUTHOR]

Background: SOX (oxaliplatin and S1, every 3 weeks) is one of the most common first-line chemotherapy for advanced or metastatic G/GEJ (gastric or gastroesophageal junction) cancer in Asia, but it has noticeable hematological and neurological toxicity. In China, the majority of gastric cancer patients are middle-aged and elderly with poor tolerance to 3-weekly chemotherapy. Therefore, we aimed to assess efficacy and safety of biweekly SOX for Chinese advanced G/GEJ cancer patients aged ≥ 60 years as the first-line treatment in a single arm phase 2 study., Methods: Oxaliplatin was administered intravenously on day 1 at 85 mg/m 2 . S-1 was given at 80, 100 or 120 mg/day, depending on the body surface area (< 1.25 m 2 , 1.25 to < 1.5 m 2 , or ≥ 1.5 m 2 ), twice daily, on day 1-10, every 2 weeks. The primary endpoint was objective response rate (ORR), and the secondary endpoints included progression free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR) and safety., Results: Between May 2016 and Sep 2018, 42 patients were enrolled. The median follow-up was 43.6 months. The ORR and DCR were 52.4% and 85.7%, respectively. The median PFS was 4.6 months (95%CI 2.486-6.714), and the median OS was 11.1 months (95%CI 8.001-14.199). The most common treatment-related adverse events (TRAEs) of any grade included thrombocytopenia (59.5%), neutropenia (57.1%), appetite loss (57.1%) and nausea (54.8%). Only two patients suffered from grade 3 TRAEs (4.8%), including neutropenia (1 patient, [2.4%]) and diarrhea (1 patient, [2.4%]). No ≥ grade 4 TRAEs occurred., Conclusions: Biweekly SOX seemed to have favorable tolerance without compromising the efficacy as the first-line therapy in Chinese elderly patients aged ≥ 60 years with advanced G/GEJ cancer., Trial Registration: ClinicalTrials.gov ID: NCT04694404 (5/1/2021). This study was approved by the Ethical Committee of National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, (17-048/1303)., (© 2022. The Author(s).)

Background: The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) has significantly increased over the past two decades. Surgery remains the only curative treatment. However, there are currently few studies on Chinese AEG patients. The purpose of this study was to retrospectively analyze the survival and prognostic factors of AEG patients in our center.Methods: Between January 2008 and September 2014, 249 AEG patients who underwent radical resection were enrolled in this retrospective study, including 196 males and 53 females, with a median age of 64 (range 31-82). Prognostic factors were assessed with the log-rank test and Cox univariate and multivariate analyses.Results: The 5-year survival rate of all patients was 49%. The median survival time of all enrolled patients was 70.1 months. Pathological type, intraoperative blood transfusion, tumor size, adjuvant chemotherapy, duration of hospital stay, serum CA199, CA125, CA242 and CEA, pTNM stage, lymphovascular or perineural invasion, and the ratio of positive to negative lymph nodes (PNLNR) were significantly associated with overall survival when analyzed in univariate analysis.Conclusions: Our study found that adjuvant chemotherapy, PNLNR, intraoperative blood transfusion, tumor size, perineural invasion, serum CEA, and duration of hospital stay after surgery had significance in multivariate analysis and were independent risk factors for survival. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the most common malignancy in China. Most of the patients of gastric cancer treated clinically are in advanced stage. In the past years, with the progress of anti-cancer drug therapy, after the comprehensive treatment based on drugs therapy of inoperative stage IV gastric cancer, some cases can reduce the tumor stage and get the opportunity of radical operation. Some of the patients who underwent surgical treatment can get the chance of long-term survival. The results of REGATTA trial confirmed that palliative surgery plus chemotherapy could not improve the long-term survival of patients with stage IV gastric cancer. Neoadjuvant intraperitoneal plus intravenous chemotherapy can reduce the tumor stage of some cases of stage IV gastric cancer with peritoneal metastasis and receive surgical treatment, so as to gain the chance of long-term survival. Regimen of intraperitoneal hyperthermia chemotherapy combined with PHOENIX trial is expected to improve the conversion operation rate of gastric cancer with peritoneal metastasis. Paclitaxel-based three-drug chemotherapy can reduce the tumor stage of some inoperable advanced gastric cancer and obtain the opportunity of radical operation, improving the disease-free survival rate and overall survival rate of patients, thus has become the cornerstone of conversion therapy for stage IV gastric cancer. Antiangiogenic targeted drug apatinib combined with paclitaxel is safe and reliable, and can be used as an alternative for the conversion therapy of stage IV gastric cancer, which provides a new idea for cytotoxic drugs combined with targeted drugs. In the era of immunotherapy, the combined application and first-line application of immunosuppressive drugs has become a clinical consensus. For advanced Her-2 positive esophagogastric junction adenocarcinoma cases, the successful exploration of the four-drug combination of chemotherapy+ anti-Her-2 targeted drugs+ anti-PD1 monoclonal antibody combined with the first-line therapy has opened up a new era of transformational therapy for stage IV gastric cancer. Gastric cancer is a malignant tumor with high heterogeneity, the classification of stage IV gastric cancer represented by Yoshida classification is based on imaging, and a more reasonable classification method should be developed in combination with gene detection in the future. Based on this, an individualized and accurate conversion therapy plan is formulated, so as to effectively improve the long-term survival of patients with stage IV gastric cancer.

Anti-PD-1 monoclonal antibody is approved as an option for third-line treatment of advanced gastric and gastroesophageal junction (G/GEJ) cancer in several countries, but no anti-PD-1 monoclonal antibody treatment is yet approved for first-line treatment of advanced G/GEJ cancer. We report a phase Ib trial of HX008, a highly selective, humanized anti-programmed death-1 monoclonal antibody, plus oxaliplatin and capecitabine as first-line treatment for advanced G/GEJ cancer. Patients with previously untreated, locally advanced or metastatic G/GEJ cancer were enrolled. All patients received HX008 3 mg/kg intravenously every 3 weeks, oxaliplatin 130 mg/m 2 intravenously on day 1 every 3 weeks (up to 6 cycles), and capecitabine 1000 mg/m 2 orally twice daily for 14 days continuous dosing followed by a 7-day break. The primary end point was the incidence of adverse events and serious adverse events. In total, 35 patients were enrolled. Median follow-up was 12.7 months. Most frequent (>10%) grade ≥3 treatment-related adverse events were anemia (27.5%), neutropenia (20%), thrombocytopenia (17.1%), leukopenia (17.1%) and fatigue (17.3%). Objective response rate was 60.0% (95% confidence interval [CI] 42.1-76.1%). Disease control rate was 77.1% (95% CI 59.9-89.6). Median time to response and duration of response were 1.4 months (range 1.3-2.9) and 12.3 months (range 1.4-17.9+), respectively. Median PFS was 9.2 months (95% CI 5.4-not reached). These results demonstrated that HX008 combined with oxaliplatin plus capecitabine was well tolerated and demonstrated encouraging efficacy as first-line treatment for advanced G/GEJ cancer. This study was registered in china, register number was CTR20181270., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Objective: We aimed to identify the differences in symptoms, high-resolution manometry (HRM) characteristics, and the efficacy of peroral endoscopic myotomy (POEM) regarding patients' sex in achalasia., Methods: All patients diagnosed with achalasia by HRM who underwent POEM and were followed up for more than 6 months were included. The individual characteristics, symptoms and signs, POEM findings, HRM results and potentially related complications in male and female patients were reviewed., Results: Prior to POEM, dysphagia was more severe in female than male patients (P = 0.044), while regurgitation was more severe (P = 0.013) and heartburn was more common in male patients (P = 0.003). Regarding HRM characteristics, the lower esophageal sphincter pressure (LESP) was higher (P = 0.01) and length of esophagus was shorter in female patients than in male patients. Eckardt scores, LESP and integrated relaxation pressure were significantly improved after the POEM procedure (P < 0.001). No significant difference was observed between the sexes regarding the efficacy of POEM, reflux symptoms, HRM data and complications after POEM., Conclusions: Before they seek treatment, female patients with achalasia may experience severe dysphagia and male patients are more likely to experience heartburn and more severe regurgitation. POEM is a safe and effective option for treating both male and female patients with achalasia., (© 2020 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background Clinical, pathological and molecular information combined with cancer stage in prognostication algorithms can offer more personalized estimates of survival, which may guide treatment choices. Our aim was to evaluate the quality of prognostication tools in esophageal cancer. Methods We systematically searched MEDLINE & Embase from 2005- 2017 for studies reporting development or validation of models predicting long-term survival in esophageal cancer. We evaluated tools using the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies guidelines and the American Joint Committee on Cancer acceptance criteria for risk models. Results We identified 16 prognostication tools for patients treated with curative intent and one for patients with metastatic disease. These tools frequently excluded adenocarcinoma, contained outdated data and were developed with a limited sample size. Nine tools were developed in China for squamous cell cancer, and 11 used data on patients diagnosed prior to 2010. The majority of tools excluded key prognostic factors such as age and sex. Tumor stage and grade were the most commonly, but not universally, included factors. Twelve tools were designed to predict overall survival; five predicted cancer-specific survival. Bootstrap internal validation was performed for most tools; c-statistics ranged from 0.63–0.77 and graphically evaluated calibration was 'good'. Five tools were externally validated; c-statistics ranged from 0.70–0.77. Conclusion Existing tools cannot be confidently used for esophageal cancer prognostication in current clinical practice. Better quality tools may help to more individually and accurately estimate disease course, select further treatments, and risk-stratify for future clinical trials. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the changes of esophagogastric junctional adenocarcinoma (EGJA) and gastroesophageal reflux disease (GERD) among surgical patients from 1988 to 2012 in a Chinese high-volume hospital., Background: The incidence of EGJA in Western countries has rapidly increased in recent decades. However, recent data from China remain sparse., Methods: A retrospective analysis was performed on the basis of 5053 patients who underwent surgery for gastric and distal esophageal adenocarcinoma. Total of 1723 patients with EGJA who underwent surgery were included. Changes of the prevalence of GERD and the clinicopathological features and surgical treatment of EGJA were longitudinally analyzed by a 5-year interval., Results: The proportion of EGJA was increased from 22.3% in period 1 (1988-1992) to 35.7% in period 5 (2008-2012) (P < 0.001). The proportion of Siewert type III (35.9% vs 47.0%) (P < 0.001) and type I (8.7% vs 15.8%) (P = 0.002) tumors of EGJA was also increased during the past 25 years. The prevalence of GERD had increased gradually from 6.5% in period 1 to 10.9% in period 5 for the 3 subgroups without significant difference (P = 0.459). There was an upward tendency with significant difference between the proportion of EGJA and the prevalence of GERD (r = 0.946, P = 0.000). Instead of type II and type III tumors, there was a positive correlation with change in GERD for type I tumors (r = 0.438, P = 0.029). Total gastrectomy was more preferred among patients with EGJA in period 5 than in period 1 (42.0% vs 19.6%) (P < 0.001)., Conclusions: An increasing trend of EGJA is observed during the past 25 years in West China Hospital. The prevalence of GERD among EGJA had showed a gradually increased trend. However, the causality between GERD and EGJA still needs to be researched further. Total gastrectomy is becoming more preferred procedure in patients with EGJA.

To compare the clinical outcomes and prognoses in patients with gastroesophageal junction adenocarcinoma (Siewert type II/III), by transthoracic and transabdominal hiatal approaches. Siewert II/III gastroesophageal junction adenocarcinomas patients (334 cases) underwent different surgical procedures at the Affiliated Hospital of Qingdao University from July 2007 to July 2012 and were analyzed retrospectively. In total, 140 patients underwent surgery by the transthoracic approach, and 194 patients underwent the transabdominal hiatal approach mainly with radical total and proximal gastrectomy (D2). All patients were followed up by telephone review or by outpatient reexamination until July 2013. The surgically related and clinical outcomes were compared using the χ2 test, t test, Fisher exact test, or nonparametric rank sum test according to different data. The survival curve was drawn by the Kaplan-Meier method and survival analysis used Cox regression analysis. The operative time, length of resected esophagus, number of lymph nodes harvested, postoperative pain scores, postoperative hospital stay, time of antibiotics use, postoperative morbidity, and costs for the transabdominal surgery group were better than that of the transthoracic group. The overall 5-year survival rate was 35.3% and 40.3%, respectively, in the transthoracic and transabdominal surgery groups, and differences were not statistically significant (x2 = 2.311, P > 0.05). The hazard ratio of death for the transthoracic compared with the transabdominal approach was 1.27 (0.93-1.72, P > 0.05). According to tumor node metastasis (TNM) staging, stratification analysis showed that stage III patient overall survival rates were 25.7% and 37.2%, respectively. The differences were statistically significant (x2 = 4.127, P < 0.05). In uni- and multivariate Cox regression analysis, the hazard ratio for the transabdominal versus the transthoracic approach was 0.66 (0 43 to 0.99, P < 0.05) and 1.47 (1.05-2.06, P < 0.05), respectively. There were no significant differences of 5-year overall survival in TNM stage I and II of the Siewert II/III adenocarcinoma patients, but improved survival of TNM stage III patients undergoing transabdominal hiatal compared with transthoracic total radical and proximal gastrectomy. The short-term clinical outcomes improved with the transabdominal hiatial surgery group., Competing Interests: The authors have no conflicts of interest to disclose.

Objective: Guided by the recently established histological criteria of the gastroesophageal junction (GEJ), we aimed to investigate and compare trends in the proportions of small (≤ 2 cm) proximal gastric carcinoma (PGC) vs non-PGC (NPGC) in Chinese patients over an 8-year period., Methods: The study was conducted with consecutive surgical resected specimens of small PGC that was located within 3 cm below the GEJ and NPGC (located at all other gastric regions) treated at a single medical center in China. Differences in proportions between the two groups were compared., Results: Among all 313 cases, 111 (35.5%) were classified as PGC and the remaining 202 (64.5%) as NPGC. Patients with PGC were significantly elder than those with NPGC, and none aged younger than 40 years. The proportions of PGC significantly and progressively increased from 16% in 2004 to 45% in 2011, in contrast to a steady decreasing trend for NPGC from 84% to 55% over the same period. The difference in trends between the two groups approached, but was not at a statistically significant level (P = 0.08). Proportions of small cancers in the gastric corpus and in female patients remained low and stable, in contrast to a significantly higher proportion in male patients (P < 0.05)., Conclusions: Our data showed a significantly upward-shifting trend in the proportions of small PGC, primarily in elderly male patients, in contrast to a downward shifting trend in NPGC over the most recent 8-year period in Chinese patients., (© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Background: The incidence of adenocarcinoma of the esophagogastric junction is increasing. This study aims to evaluate the clinicopathological features of Chinese patients with adenocarcinoma of the esophagogastric junction and to define prognostic factors., Methods: We retrospectively reviewed a database of 382 consecutive patients with adenocarcinoma of the esophagogastric junction at the First Affiliated Hospital of Xi'an Jiaotong University from January 2005 to March 2010. All patients were classified according to the Siewert's classification and staged according to the latest edition of the American Joint Committee on Cancer categories., Results: Six of the 382 patients had type I adenocarcinoma, 220 had type II, and 156 had type III. There was no significant difference in the overall survival of different Siewert subtypes. According to the multivariate analysis, pathological lymph node stage, age, and the existence of lymphovascular invasion were the independent factors of prognosis of adenocarcinoma of the esophagogastric junction following surgery., Conclusions: On the data, the distribution of the three types of tumor was found to be different from that reported in Western countries. Lymph node metastasis, lymphovascular invasion, and age were significant and independent factors for poor prognosis after R0 resection for adenocarcinoma of the esophagogastric junction.

Objective: To evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer., Methods: Fifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival., Results: Eighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively., Conclusions: Addition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.