Adenocarcinoma Of Esophagogastric Junction Research Articles

Anti–Helicobacter pylori Treatment in Patients With Gastric Cancer After Radical Gastrectomy

Whether anti-Helicobacter pylori treatment can provide survival benefits for patients with gastric cancer who are diagnosed with H pylori infection is an area with limited research. To explore the potential survival benefits of anti-H pylori treatment after radical gastrectomy in patients with gastric cancer and presurgical confirmation of H pylori infection. This retrospective cohort study was conducted using data from patients with gastric cancer treated between January 1, 2010, and December 31, 2018, and followed up for outcome ascertainment until May 19, 2021. Propensity score matching was performed in patients treated with or without anti-H pylori treatment. This study involved a single institute in a comprehensive cancer treatment and research center located in Guangzhou, Guangdong Province, China. The study included patients with gastric or esophagogastric junction adenocarcinoma who underwent curative gastrectomy with D2 lymphadenectomy and tested positive for H pylori infection. Data were analyzed from March to June 2023. Anti-H pylori treatment, which primarily includes triple therapy regimens consisting of amoxicillin, clarithromycin, and omeprazole for 14 days. Clinical outcomes, including overall survival (OS) and disease-free survival (DFS), were analyzed by Kaplan-Meier method, log-rank test, and Cox proportional hazards regression model. Subgroup analysis based on crucial clinical information was also conducted. All 1293 patients (median [IQR] age, 59 [50-65] years; 860 [66.5%] male) were divided into 2 groups, with 125 patients in the anti-H pylori treatment group and 1168 patients in the non-anti-H pylori treatment group based on whether they received anti-H pylori treatment during the perioperative period and the follow-up. Survival analysis showed that the 5-year OS rates were 94.1% (95% CI, 89.3%-99.2%) in the anti-H pylori group and 73.8% (95% CI, 70.7%-77.0%) in the non-anti-H pylori group, and the hazard ratio (HR) of these 2 groups was 0.33 (95% CI, 0.18-0.60; P < .001). The survival benefit remained after propensity score matching (HR, 0.50; 95% CI, 0.26-0.99; P = .048). Multivariable analysis for OS and DFS further showed the survival benefit of anti-H pylori treatment, with HRs of 0.38 (95% CI, 0.17-0.87; P = .02) and 0.48 (95% CI, 0.28-0.83; P = .008), respectively. Among patients with TNM stage II/III disease who received adjuvant chemotherapy, anti-H pylori treatment was associated with survival benefits (OS: HR, 0.49; 95% CI, 0.24-0.99; P = .046), whereas among those who did not receive adjuvant chemotherapy, anti-H pylori treatment was not associated with survival benefits (OS: HR, 0.29; 95% CI, 0.04-2.08; P = .22). This cohort study indicates that anti-H pylori treatment may be associated with improved survival in patients with gastric cancer who have H pylori infections. The study reinforces the importance of including H pylori screening and treatment in the surgical treatment of these patients.

High LINC00626 expression promotes esophagogastric junction adenocarcinoma metastasis: the mediating role of the JAK1/STAT3/KHSRP axis

To investigate the role of JAK1/STAT3/KHSRP axis in mediating the regulatory effect of LINC00626 on progression of esophagogastric junction adenocarcinoma. We collected surgical tumor and adjacent tissue specimens from 64 patients with esophagogastric junction adenocarcinoma and examined the expression levels of LINC00626 and KHSRP. qRT-PCR was used to detect the expressions of LINC00626 and KHSRP in 6 esophageal adenocarcinoma cell lines (OE-19, TE-7, Bic-1, Flo-1, SK-GT-4, and BE-3) and a normal esophageal epithelial cell line (HET-1A). OE-19 and TE-7 cell lines with stable LINC00626 knockdown and FLO-1 and SK-GT-4 cells stably overexpressing LINC00626 were constructed by lentiviral transfection, and the changes in proliferation, migration and invasion of the cells were evaluated using Cell Counting Kit-8 (CCK-8) assay and Transwell migration/invasion assay. The expressions of KHSRP and JAK/STAT pathway proteins in the transfected cells were detected with Western blotting. The effects of LINC006266 knockdown and overexpression on subcutaneous tumor formation and lung metastasis of OE-19 and FLO-1 cell xenografts were tested in nude mice. The expression levels of LINC00626 and KHSRP were significantly increased in esophagogastric junction adenocarcinoma tissues and in esophageal adenocarcinoma cells. LINC00626 knockdown obviously inhibited the proliferation, migration and invasion of esophageal adenocarcinoma cells in vitro and decreased their tumor formation and lung metastasis abilities in nude mice, while overexpression of LINC00626 produced the opposite effects. In esophageal adenocarcinoma cells, LINC0626 knockdown significantly decreased and LINC00626 overexpression strongly enhanced the phosphorylation of JAK1 and STAT3. High LINC00626 expression promotes esophageal-gastric junction adenocarcinoma metastasis by activating the JAK1/STAT3/KHSRP signal axis.

Preoperative ultrasound-guided dual localization with titanium clips and carbon nanoparticles for predicting the surgical approach and guiding the resection of Siewert type II esophagogastric junction adenocarcinoma

ObjectiveTo investigate the superiority of preoperative ultrasound-guided titanium clip and nanocarbon dual localization over traditional methods for determining the surgical approach and guiding resection of Siewert type II adenocarcinoma of the esophagogastric junction (AEG).MethodThis study included 66 patients with Siewert type II AEG who were treated at the PLA Joint Logistics Support Force 900th Hospital between September 1, 2021, and September 1, 2023. They were randomly divided into an experimental group (n = 33), in which resection was guided by the dual localization technique, and the routine group (n = 33), in which the localization technique was not used. Surgical approach predictions, proximal esophageal resection lengths, pathological features, and the occurrence of complications were compared between the groups.ResultThe use of the dual localization technique resulted in higher accuracy in predicting the surgical approach (96.8% vs. 75.9%, P = 0.02) and shorter proximal esophageal resection lengths (2.39 ± 0.28 cm vs. 2.86 ± 0.39 cm, P < 0.001) in the experimental group as compared to the routine group, while there was no significant difference in the incidence of postoperative complications (22.59% vs. 24.14%, P = 0.88).ConclusionPreoperative dual localization with titanium clips and carbon nanoparticles is significantly superior to traditional methods and can reliably delineate the actual infiltration boundaries of Siewert type II AEG, guide the surgical approach, and avoid excessive esophageal resection.

O220: The role of cardiopulmonary exercise testing in predicting sarcopenia after neoadjuvant chemotherapy and post-operative complications

Abstract Background Neoadjuvant chemotherapy (NAC) may contribute to sarcopenia development in patients with oesophageal and oesophagogastric junction (OGJ) adenocarcinoma. Preoperative cardiopulmonary fitness and sarcopenia are both variables which have been correlated with outcomes after major surgery. The aims of this study were to investigate if pre-operative cardiopulmonary exercise testing (CPET) variables were associated with radiological sarcopenia post NAC, and the effect of CPET variables on post-operative outcomes in sarcopenic patients. Methods Patients from a single high-volume tertiary centre diagnosed with oesophageal or OGJ adenocarcinoma between August 2015 and August 2022 were included. CPET variables and post-NAC CT scans to assess for radiological sarcopenia were evaluated. CPET variables included in statistical analyses were ventilatory equivalent for carbon dioxide (VE/VCO2), anaerobic threshold (AT) and peak oxygen consumption (VO2 peak). Results 208 patients were included. Median VE/VCO2 was 29 in patients with sarcopenia post-NAC and 28 in non-sarcopenic patients (p = 0.009). Other CPET variables were not associated with sarcopenia post NAC. Within the sarcopenic group, CPET variables were not associated with post-operative complications. Within the whole cohort, increased VE/VCO2 or decreased VO2 peak correlated with a longer hospital stay (p=0.043 and p=0.012 respectively), and an association was observed between VE/VCO2 and Clavien-Dindo grade of complications (p=0.019). Conclusions VE/VCO2 was associated with sarcopenia post NAC in patients with oesophageal and OGJ adenocarcinoma. Further analysis with a larger sample size might help establish this, which could be helpful in identifying and targeting patients at higher risk of sarcopenia and post-operative complications.

Endoscopic Surveillance of Intestinal Metaplasia of the Esophagogastric Junction: A Decision Modeling Analysis.

The incidence of esophagogastric junction adenocarcinoma (EGJAC) has been rising. Intestinal metaplasia of the esophagogastric junction (EGJIM) is a common finding in gastroesophageal reflux (irregular Z-line) and may represent an early step in the development of EGJAC in the West. Worldwide, EGJIM may represent progression along the Correa cascade triggered by Helicobacter pylori . We sought to evaluate the cost-effectiveness of endoscopic surveillance of EGJIM. We developed a decision analytic model to compare endoscopic surveillance strategies for 50-year-old patients after diagnosis of non-dysplastic EGJIM: (i) no surveillance (standard of care), (ii) endoscopy every 3 years, (iii) endoscopy every 5 years, or (iv) 1-time endoscopy at 3 years. We modeled 4 progression scenarios to reflect uncertainty: A (0.01% annual cancer incidence), B (0.05%), C (0.12%), and D (0.22%). Cost-effectiveness of endoscopic surveillance depended on the progression rate of EGJIM to cancer. At the lowest progression rate (scenario A, 0.01%), no surveillance strategies were cost-effective. In moderate progression scenarios, 1-time surveillance at 3 years was cost-effective, at $30,989 and $16,526 per quality-adjusted life year for scenarios B (0.05%) and C (0.12%), respectively. For scenario D (0.22%), surveillance every 5 years was cost-effective at $77,695 per quality-adjusted life year. Endoscopic surveillance is costly and can cause harm; however, low-intensity longitudinal surveillance (every 5 years) is cost-effective in populations with higher EGJAC incidence. No surveillance or 1-time endoscopic surveillance of patients with EGJIM was cost-effective in low-incidence populations. Future studies to better understand the natural history of EGJIM, identify risk factors of progression, and inform appropriate surveillance strategies are required.

Preoperative docetaxel, cisplatin, and 5-fluorouracil for resectable locally advanced esophageal and esophagogastric junctional adenocarcinoma.

Chemotherapy consisting of 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel is the standard perioperative treatment for resectable esophageal adenocarcinoma and esophagogastric junctional adenocarcinoma (EGJ-AC) in Western countries. Meanwhile, preoperative chemotherapy consisting of docetaxel, cisplatin, and 5-fluorouracil (DCF) has been developed for esophageal squamous cell carcinoma in Japan. However, there are few reports on the safety and efficacy of preoperative DCF for resectable EGJ-AC in the Japanese population. Patients with histologically confirmed resectable EGJ-AC who received preoperative DCF (docetaxel 70mg/m2 and cisplatin 70mg/m2 on day 1 and continuous infusion of 5-fluorouracil 750mg/m2/day on days 1-5 every 3weeks with a maximum of three cycles) between January 2015 and April 2020 were retrospectively evaluated. We assessed the rates of completion of ≥ 2 courses of DCF and R0 resection, histopathological response, progression-free survival (PFS), overall survival (OS), and adverse events. Thirty-two patients were included. Median follow-up was 28.7 (range, 5.2-70.8) months and median age was 63 (range, 42-80) years. Twenty-one patients (66%) had a performance status of 0. The proportions of clinical stage IIA/IIB/III/IVA/IVB disease were 3%/0%/44%/44%/9%, respectively. The treatment completion rate was 84%. A histopathological response of grade 1a/1b/2/3 was obtained in 58%/26%/13%/3% of cases. Median PFS was 40.7months (95% confidence interval 11.8-NA). Median OS was not reached (80.8% at 3years). Grade ≥ 3 adverse events were observed in 63% of cases (neutropenia, 44%; febrile neutropenia, 13%). No treatment-related deaths occurred. Preoperative DCF for resectable EGJ-AC was well tolerated and has promising efficacy.

Assessment of risk factors of lymph node metastasis and prognosis of Siewert II/III adenocarcinoma of esophagogastric junction: A retrospective study.

Adenocarcinoma of the esophagogastric junction (AEG) has a high incidence, and the extent of lymph node dissection (LND) and its impact on prognosis remain controversial. This study aimed to explore the risk factors for lymph node metastasis (LNM) and prognosis in Siewert II/III AEG patients. A retrospective review of 239 Siewert II/III AEG patients surgically treated at Beijing Friendship Hospital from July 2013 to December 2022 was conducted. Preoperative staging was conducted via endoscopy, ultrasound gastroscopy, CT, and biopsy. Depending on the stage, patients received radical gastrectomy with LND and chemotherapy. Clinicopathological data were collected, and survival was monitored semiannually until November 2023. Utilizing logistic regression for data analysis and Cox regression for survival studies, multivariate analysis identified infiltration depth (OR = 0.038, 95% CI: 0.011-0.139, P < .001), tumor deposit (OR = 0.101, 95% CI: 0.011-0.904, P = .040), and intravascular cancer embolus (OR = 0.234, 95% CI: 0.108-0.507, P < .001) as independent predictors of LNM. Lymph nodes No. 1, 2, 3, 4, 7, 10, and 11 were more prone to metastasis in the abdominal cavity. Notably, Siewert III AEG patients showed a higher metastatic rate in nodes No. 5 and No. 6 compared to Siewert II. Mediastinal LNM was predominantly found in nodes No. 110 and No. 111 for Siewert II AEG, with rates of 5.45% and 3.64%, respectively. A 3-year survival analysis underscored LNM as a significant prognostic factor (P = .001). Siewert II AEG patients should undergo removal of both celiac and mediastinal lymph nodes, specifically nodes No. 1, 2, 3, 4, 7, 10, 11, 110, and 111. Dissection of nodes No. 5 and No. 6 is not indicated for these patients. In contrast, Siewert III AEG patients do not require mediastinal LND, but pyloric lymphadenectomy for nodes No. 5 and No. 6 is essential. The presence of LNM is associated with poorer long-term prognosis. Perioperative chemotherapy may offer a survival advantage for AEG patients.

Chinese expert consensus on the surgical treatment for adenocarcinoma of esophagogastric junction (Edition 2024)

The publication of Chinese expert consensus on the surgical treatment for adenocarcinoma of esophagogastric junction (2018 edition) has widely accelerated the standardization and homogenization on the surgical treatment of adenocarcinoma of esophagogastric junction (AEG). In China, the surgical outcomes of AEG, the universality and practicability of this consensus has also been affirmed after the clinical practice during the past 5 years. Due to the persistent increasing incidence of AEG, the specificity on anatomic site, clinicopathological characteristics, molecular biological characteristics, AEG had been always the hotspot of many clinical trials and more clinical evidences had been published. However, its definition, classification, staging, surgical approach, resection pattern, extent of lymphadenectomy, and the digestive tract reconstruction etc. remain controversial. In light of the above, it is necessary to update the 2018 edition of consensus. The Chinese expert consensus on the surgical treatment for adenocarcinoma of esophagogastric junction (2024 edition) is generated based on the currently available and best clinical evidence, the latest global guidelines or consensuses, and the opinions from the Chinese expert panel. The present consensus focuses on the key points of surgical treatment and issues in dispute, and provides scientific recommendations. The goal of this expert consensus was to improve the homogeneity in understanding and practice between Chinese thoracic and gastrointestinal surgeons, and to further standardize surgical treatment of AEG. Those pending issues in this consensus need high-quality clinical research to further investigate.

Tumor stroma ratio, tumor stroma maturity, tumor-infiltrating immune cells in relation to prognosis, and neoadjuvant therapy response in esophagogastric junction adenocarcinoma.

Accurate predictions on prognosis and neoadjuvant therapy response are crucial for esophagogastric junction adenocarcinoma (EGJA) patients. Therefore, we aimed to investigate the predictive abilities of several indicators, including tumor stroma ratio (TSR), tumor stroma maturity (TSM), and the density and spatial distribution of tumor-infiltrating immune cells (TIICs), such as T cells, B cells, and tumor-associated macrophages (TAMs). Resection and biopsy specimens of a total of 695 patients were included, obtained from the National Cancer Center (NCC) and The Cancer Genome Atlas (TCGA) cohorts. TSR and TSM were evaluated based on histological assessment. TIICs were quantified by QuPath following immunohistochemical (IHC) staining in resection specimens, while the Klintrup-Mäkinen (KM) grade was employed for evaluating TIIC in biopsy specimens. Patients with high stromal levels or immature stroma had relatively worse prognoses. Furthermore, high CD8+T cell count in the tumor periphery, as well as low CD68+ TAM count either in the tumor center or in the tumor periphery, was an independent favorable prognostic factor. Significantly, the combination model incorporating TSM and CD163+TAMs emerged as an independent prognostic factor in both two independent cohorts (HR 3.644, 95% CI 1.341-9.900, p = 0.011 and HR 1.891, 95% CI 1.195-2.99, p = 0.006, respectively). Additionally, high stromal levels in preoperative biopsies correlated with poor neoadjuvant therapy response (p < 0.05). In conclusion, our findings suggest that TSR, TSM, CD8+T cell, CD68+TAMs, and CD163+TAMs predict the prognosis to some extent in patients with EGJA. Notably, the combined model incorporating TSM and CD163+TAM can contribute significantly to prognostic stratification. Additionally, high stromal levels evaluated in preoperative biopsy specimens correlated with poor neoadjuvant therapy response.

Prognostic nutritional index in predicting survival of patients with gastric or gastroesophageal junction adenocarcinoma: A systematic review.

Gastric cancer is the third most common cause of cancer related death worldwide. Surgery with or without chemotherapy is the most common approach with curative intent; however, the prognosis is poor as mortality rates remain high. Several indexes have been proposed in the past few years in order to estimate the survival of patients undergoing gastrectomy. The preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been developed. The aim of this systematic review was to assess the role of the prognostic nutritional index (PNI) in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative intent. To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction adenocarcinoma. A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival (OS) of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI value. The PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic review. The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO). Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic review. The patients were divided into high- and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual study. The 5-year OS of patients in the low-PNI groups ranged between 39% and 70.6%, while in the high-PNI groups, it ranged between 54.9% and 95.8%. In most of the included studies, patients with high preoperative PNI showed statistically significant better OS than the low PNI groups. In multivariate analyses, low PNI was repeatedly recognised as an independent prognostic factor for poor survival. According to the present study, low preoperative PNI seems to be an indicator of poor OS of patients undergoing gastrectomy for gastric or gastroesophageal cancer.

Comparison of postoperative survival between early-onset and late-onset adenocarcinoma of esophagogastric junction: a population-based study.

The prognosis of early-onset adenocarcinoma of esophagogastric junction (AEG) remains unclear. This research aimed at comparing the prognosis between early-onset and late-onset AEGs. We extracted eligible patients with surgically resected, pathologically confirmed, nonmetastatic AEG from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. The cutoff age of early-onset AEG was set at ≤50years old. Univariate and multivariate Cox analysis as well as competing risk model were adopted for comparing overall survival (OS) and cancer-specific survival (CSS) between early-onset and late-onset AEGs. In addition, multiple imputation and propensity score matching (PSM) were also carried out for sensitivity analysis. In total, 4610 eligible AEG patients were collected in this study, including 610 early-onset AEGs and 4000 late-onset AEGs. Kaplan-Meier curves revealed significantly better survival in early-onset AEGs than late-onset AEGs. After interpolating missing data by multiple imputation, multivariate Cox regression analysis similarly showed better OS and CSS in early-onset AEGs. By using PSM analysis at a ratio of 1:1, we matched 610 early-onset AEG patients with 610 late-onset AEG patients. After PSM, univariate Cox regression model still revealed favorable prognosis in early-onset AEGs. Similar results were confirmed by performing PSM analysis at a ratio of 1:2 and 1:3. In addition, competing risk model demonstrated significantly lower cancer-specific death in early-onset AEGs compared to late-onset AEGs before and after matching. By applying several effective sensitivity analyses, we reported significantly favorable OS and CSS in early-onset AEGs compared to late-onset AEGs.

Comparative study on the expression of Pax3, Rad51 and VEGF-C in esophageal gastric junction adenocarcinoma and distal gastric adenocarcinoma.

The purpose of this study was to explore the differential expression of Pax3, Rad51 and VEGF-C in esophageal gastric junction adenocarcinoma and distal gastric adenocarcinoma and their relationship with cancer occurrence and development. 57 patients with gastric cancer were included and divided into esophageal gastric junction adenocarcinoma group (n=28) and distal gastric adenocarcinoma group (n=29). The positive expressions of Pax3, Rad51 and VEGF-C in the control group were lower than those in the esophageal gastric junction adenocarcinoma group and distal gastric adenocarcinoma group respectively (P<0.05). In esophageal gastric junction adenocarcinoma with low differentiation, positive expressions of Pax3, Rad51, and VEGF-C surpassed those in high/medium differentiation (P<0.05). Serosa-infiltrated cases exhibited higher Pax3 and Rad51 expressions compared to non-infiltrated cases (P<0.05). Rad51 and VEGF-C positivity were notably elevated in cases with lymph node metastasis compared to those without (P<0.05). Distal gastric adenocarcinoma displayed higher VEGF expression than middle/low differentiated adenocarcinomas. Rad51 expression was significantly higher in women than in men (P<0.05). The positive rates of Pax3, Rad51, and VEGF-C were markedly increased in esophageal gastric junction adenocarcinoma and distal gastric adenocarcinoma compared to normal gastric tissue, and these were associated with the degree of differentiation, depth of invasion, and lymph node metastasis in patients. Particularly, Rad51 exhibited a positive correlation with cancer cell differentiation, invasion depth, and lymph node metastasis in cancer tissue.

Computed tomography-based nomogram of Siewert type II/III adenocarcinoma of esophagogastric junction to predict response to docetaxel, oxaliplatin and S-1.

Neoadjuvant chemotherapy (NAC) has become the standard care for advanced adenocarcinoma of esophagogastric junction (AEG), although a part of the patients cannot benefit from NAC. There are no models based on baseline computed tomography (CT) to predict response of Siewert type II or III AEG to NAC with docetaxel, oxaliplatin and S-1 (DOS). To develop a CT-based nomogram to predict response of Siewert type II/III AEG to NAC with DOS. One hundred and twenty-eight consecutive patients with confirmed Siewert type II/III AEG underwent CT before and after three cycles of NAC with DOS, and were randomly and consecutively assigned to the training cohort (TC) (n = 94) and the validation cohort (VC) (n = 34). Therapeutic effect was assessed by disease-control rate and progressive disease according to the Response Evaluation Criteria in Solid Tumors (version 1.1) criteria. Possible prognostic factors associated with responses after DOS treatment including Siewert classification, gross tumor volume (GTV), and cT and cN stages were evaluated using pretherapeutic CT data in addition to sex and age. Univariate and multivariate analyses of CT and clinical features in the TC were performed to determine independent factors associated with response to DOS. A nomogram was established based on independent factors to predict the response. The predictive performance of the nomogram was evaluated by Concordance index (C-index), calibration and receiver operating characteristics curve in the TC and VC. Univariate analysis showed that Siewert type (52/55 vs 29/39, P = 0.005), pretherapeutic cT stage (57/62 vs 24/32, P = 0.028), GTV (47.3 ± 27.4 vs 73.2 ± 54.3, P = 0.040) were significantly associated with response to DOS in the TC. Multivariate analysis of the TC also showed that the pretherapeutic cT stage, GTV and Siewert type were independent predictive factors related to response to DOS (odds ratio = 4.631, 1.027 and 7.639, respectively; all P < 0.05). The nomogram developed with these independent factors showed an excellent performance to predict response to DOS in the TC and VC (C-index: 0.838 and 0.824), with area under the receiver operating characteristic curve of 0.838 and 0.824, respectively. The calibration curves showed that the practical and predicted response to DOS effectively coincided. A novel nomogram developed with pretherapeutic cT stage, GTV and Siewert type predicted the response of Siewert type II/III AEG to NAC with DOS.

Real-world comparison of treatment outcomes between advanced esophagogastric junction adenocarcinoma and gastric adenocarcinoma.

267 Background: The characteristics of esophagogastric junction adenocarcinoma (EGJA) differ from those of gastric adenocarcinoma (GA). Although chemotherapy for advanced GA has been adapted for advanced EGJA, its efficacy remains unknown. This study aims to elucidate the effectiveness of chemotherapy for advanced EGJA in real-world practice. Methods: This retrospective study compared treatment outcomes between advanced GA and EGJA in patients with performance status (PS) 0 to 2 who received doublet or triplet chemotherapy, including platinum agents, as first-line treatment at our hospital between 2010 and 2020. Patients with non-curative resection factors limited to positive peritoneal cytology, or those who relapsed during adjuvant chemotherapy or within 6 months after its completion, were excluded. Results: Out of the total 825 patients, 765 had GA and 60 had EGJA. The baseline characteristics of the GA and EGJA groups were as follows, respectively: median age 65.0 and 59.5 years (p = 0.02); PS 0, 35.9% and 33.3%; PS 1, 57.5% and 65.0%; PS 2, 6.5% and 1.7% (p = 0.28); HER2 positive, 16.1% and 26.7% (p = 0.06); diffuse histology, 52.7% and 26.7% (p &lt; 0.01); lymph node metastasis, 74.0% and 93.3% (p &lt; 0.01); peritoneal metastasis, 66.4% and 25.0% (p &lt; 0.01); liver metastasis, 26.4% and 40.0% (p = 0.03); lung metastasis, 6.5% and 16.7% (p &lt; 0.01). The proportions of fluoropyrimidine, taxanes, and irinotecan in all treatment lines did not differ between the two groups (fluoropyrimidine, 99.7% vs. 100%; taxanes, 70.1% vs. 73.3%; irinotecan, 23.0% vs. 23.3%). However, the EGJA group used ramucirumab, trastuzumab, and immune checkpoint inhibitors (ICIs) significantly more frequently than the GA group (ramucirumab, 27.8% vs. 43.3%, p = 0.02; trastuzumab, 15.4% vs. 26.7%, p = 0.03; ICIs, 21.0% vs. 41.7%, p &lt; 0.01). Overall survival did not differ between the two groups (median, 14.8 months vs. 18.5 months, HR 0.80; 95% CI, 0.59-1.10, p = 0.17). Moreover, multivariate analysis revealed that EGJA and GA had a comparable prognosis (HR 1.23; 95% CI, 0.87-1.72, p = 0.24). HER2 positivity was a favorable prognostic factor in multivariate analysis, whereas diffuse histology, poor PS, lymph node metastasis, liver metastasis, and the presence of peritoneal metastasis were poor prognostic factors. There was no difference in time-to-treatment failure between the two groups for first-line (median, 6.1 vs. 4.9 months, HR 0.96; 95% CI, 0.73-1.28, p = 0.80), second-line (median, 2.9 vs. 3.5 months, HR 0.99; 95% CI, 0.73-1.34, p = 0.93), and third-line treatment (median, 1.9 vs. 2.7 months, HR 0.78; 95% CI, 0.53-1.13, p = 0.62). Conclusions: In real-world practice, the efficacy of chemotherapy for advanced EGJA was comparable to that for advanced GA.

Neoadjuvant toripalimab plus CapeOX in patients with localized dMMR/MSI-H gastric or esophagogastric junction adenocarcinoma (GC/EGJC): Results from the cohort C of phase II NICE trial.

349 Background: Surgery is the cornerstone of curative therapy for localized GC or EGJC and perioperative chemotherapy seems ineffective for those with dMMR/MSI-H tumors. Chemotherapy may booster antitumor immunity. There is a compelling need to investigate the efficacy of perioperative immunochemotherapy for those with dMMR/MSI-H tumors. Methods: NICE trial is a multicenter, multi-cohort phase II trial (NCT04744649) investigating the safety and efficacy of toripalimab combined with CapeOX regimen as perioperative treatment for localized GC or EGJC of PD-L1 CPS≥5 (IHC 22C3) (cohort A), EBV-positive (cohort B), and dMMR/MSI-H (cohort C). Among those cohorts, the cohort A was compared with the control group of perioperative CapeOX regimen in a randomized controlled trial manner, while the cohort B and C were single arm. In present study, we report the findings of Cohort C, and the patients (pts) received toripalimab 240 mg combined with standard dose CapeOX regimen q3 weeks for 4 cycles before and after surgery. The eligible tumor stages were cT3-4aNxM0 or cT2N+M0 diagnosed by chest and abdominal CT combined with staging laparoscopy as well as negative peritoneal cytology. The primary endpoint was major pathologic response (MPR, &lt;10% viable cells) rate. Multiplex fluorescence immunohistochemistry (mIHC) was utilized to explore changes of immune microenvironment. Results: Between March 2021 and April 2023, 15 pts with dMMR/MSI-H localized GC/GEJC were recruited in Cohort C. Tumor stages were cT3N0(n=2), cT3N1-3 (n=2), cT4aN0 (n=1) and cT4aN1-3 (n=10). 14 pts completed all 4 cycles therapy preoperatively and one patient completed 2 cycles therapy because of AEs. None had disease progression, while one achieved a complete clinical response at radiology and endoscopy and refused surgery and the other 14 pts underwent resection. The R0 resection rate was 100% (14/14). The MPR rate was 92.9% (13/14) and the residual tumor percentage was 33.8% in the other one patient (cT4aN2). pCR rate was 78.6% (11/14). Therapy-related grade 3/4 AEs occurred in 5 pts of safety population (n=15). One patient occurred grade 3 immune-related liver toxicity after 2 cycles treatment and recovered after steroids therapy. No pts died during the perioperative treatment, and one patient died of COVID-19 238 days after surgery without relapse. No disease relapse was observed in all pts. The mIHC revealed a significant reduction in CD20+ B cells, CD3+ T cells, NK dim cells, and M1 macrophages within tumor area after treatment for patients who reached pCR. Conclusions: Neoadjuvant toripalimab and CapeOX regimen for the localized dMMR/MSI-H GC/GEJC is safety with high MPR rate. These data indicate that neoadjuvant immunochemotherapy may potentially become one of the treatment options for these patients. Clinical trial information: NCT04744649 .

Ten-year overall survival of localized lower thoracic and esophagogastric junction carcinoma receiving trimodality therapy: A National Cancer Database analysis.

278 Background: Trimodality therapy, consisting of chemotherapy and radiation followed by esophagectomy, represents the prevailing standard of care for most patients with localized lower thoracic and esophagogastric junction (EGJ) carcinoma. However, robust data reporting the survival of this patient group treated in the real-world setting is lacking. The primary objective of the current study was to comprehensively analyze the long-term survival of this patient population receiving treatment in a real-world setting and the variables that significantly influence the survival. Methods: We identified adult patients in the National Cancer Database with localized (cT1N+M0 or cT2-T4N+/-M0) lower thoracic or EGJ adenocarcinoma (AC) or squamous cell carcinoma (SCC) receiving trimodality therapy between 2004 and 2020 with multi-agent chemotherapy and ≥ 4139 cGy of radiation followed by esophagectomy. The primary endpoint of the analysis was overall survival (OS), estimated using the Kaplan-Meier method. The impact of clinical and demographic features on OS was determined using the log-rank test. We performed a multivariable (MV) Cox analysis to evaluate the independent association of clinical and demographic variables on OS (data presented as hazard ratio [HR] and 95% Confidence Interval [CI]). Results: The analysis included 21,965 patients, characterized by a median age of 63 years, predominance of males (85.9%), non-Hispanic white patients (89.4%), and AC histology (93.6%). Most patients had T2/T3 tumors (87.3%) and regional lymph node (LN) involvement (62.1%). The 10-year OS for the entire cohort was 27.6% (95% CI, 26.8%-28.5%), with a median OS of 40.7 months (95% CI, 39.7-41.6). For patients aged ≤ 65, the 10-year OS was 31.2% (95% CI, 30.2%-32.3%), with a median OS of 44.1 months (95% CI, 42.8-45.5). On MV analysis, the following factors were associated with inferior OS with CI in the parenthesis: age ≥ 66 years (1.17, 1.11-1.22); male gender (1.13, 1.08-1.19); histology, AC vs. SCC (1.19, 1.10-1.28); T4 vs. T1-T3 tumor stage (1.20, 1.07-1.34); lymph node involvement (1.22, 1.18-1.27); Charlson-Deyo score ≥ 2 (1.23, 1.15-1.32); uninsured vs private insurance (1.20, 1.05-1.36); and low-volume facility (1.08, 1.01-1.16). Furthermore, patients treated after 2012 (2013-2019) had modestly improved OS (0.87, 0.84-0.90), perhaps reflecting the impact of the CROSS trial result published in 2012. Conclusions: This study illustrates the grim long-term survival of patients with localized lower thoracic and EGJ cancer undergoing standard trimodality therapy, underscoring the urgent necessity for innovative therapeutic approaches for this patient group. The improvement in OS following the publication of the CROSS trial was modest.

Organ preservation with durvalumab-based immunotherapy in combination with chemoradiation as definitive therapy for early stage, cT1, and cT2N0 esophageal adenocarcinoma with indication for radical surgery: A prospective, multicenter study of the FLOT-AIO Gastric Cancer Group (IKF-t057/PRESTO trial).

TPS431 Background: The outcome of patients (pts) with adenocarcinomas of stomach and esophagogastric junction (GEJ) remains unsatisfactory (5-year survival rates of 24-84%), whereby surgical resection is considered as cornerstone of the curative treatment for pts with early stage esophageal adenocarcinoma (EGA), however, it is associated with mortality, morbidity and an impact on the patient’s quality of life. Recent investigations showed that in locally advanced stage EGA surgery with neoadjuvant chemoradiotherapy (CROSS trial) is beneficial over surgery alone. Further benefit was achieved for locally advanced EGA by perioperative treatment with FLOT acc. to FLOT4- trial data. Immuno-oncology (IO) therapy by using checkpoint inhibitors is approved in the palliative and adjuvant EGA situation. In this trial we aim for the organ preservation treatment of EGA pts with a combination of the anti PD-L1 antibody durvalumab- FLOT - and chemoradio-therapy. Methods: This is a multicenter, single arm, open-label, phase II trial including a total of 32 pts with T1-T2N0 EGA (including GEJ) with indication for radical surgery. Enrolled pts will receive immunotherapy with durvalumab (1500 mg Q4W) in parallel to 2 cycles FLOT (50 mg/m2 docetaxel, 85 mg/m2 oxaliplatin, 200 mg/m2 calcium folinate and 2600 mg/m2 5FU, Q2W) induction followed by 3 cycles of mFOLFOX (85 mg/m2 oxaliplatin, 200 mg/m2 calcium folinate, 400 mg/m2 5FU bolus and 1600 mg/m2 5FU over 48h, Q2W) plus concomitant radiation (25 daily fractions with 2.0 Gy = Σ50Gy). 8 weeks after last treatment, pts will undergo tumor assessment by esophagogastroduodenoscopy with biopsies, endoscopic ultrasonography, and CT- or MRI-scans. Surgical resection would be offered only to pts in whom a locoregional persistence is confirmed. Pts with complete remission will enter the maintenance phase and will receive durvalumab monotherapy (1500 mg, Q4W) for a maximum of 12 cycles accompanied by regular tumor re-evaluation. Primary endpoint is the rate of cCR/pCR at time of re-evaluation. Secondary endpoints include rate of cCR/pCR at 1, 2 and 3 years, rate of salvage surgery, 90 day and 1 year mortality after start of treatment, safety and quality of life. In this exploratory trial a cCR/pCR rate of ≥75% would indicate that the study treatment should be further investigated, whereas a rate &lt; 55% indicates no further investigation. First patient was enrolled on 2023-08-28. Currently one patient is recruited. Clinical trial information: NCT05713838 .

A phase II trial of CapeOX plus nivolumab for early relapsed HER2-negative gastric cancer (JACCRO GC-11: FirSTAR trial).

TPS423 Background: Fluoropyrimidine-based post-operative chemotherapy is one of the standard adjuvant therapies for curatively resected gastric cancer (GC).1,2 The current standard first-line chemotherapy consists of fluoropyrimidine and oxaliplatin combined with nivolumab in advanced HER2-negative GC patients including cases with a recurrence &gt; 6 months after completion of post-operative chemotherapy, based on the CheckMate 649 and ATTRACTION-4 trials. However, in GC patients with early recurrence during or ≤ 6 months after completion of post-operative 5-FU based chemotherapy, optimal treatments remain to be established. A previous phase II study showed that capecitabine plus cisplatin is an active regimen for early relapsed GC after post-operative S-1 monotherapy.3 This trial aims to investigate the efficacy of capecitabine plus oxaliplatin (CapeOX) plus nivolumab for patients with early relapsed HER2-negative GC. Methods: This is a multicenter single-arm phase II trial. The main eligibility criteria include: histologically confirmed HER2-negative adenocarcinoma of stomach or esophagogastric junction; radiologically diagnosed recurrence during or ≤ 6 months after post-operative chemotherapy with S-1 or S-1 plus docetaxel conducted for stage II/III GC after curative resection; age ≥ 18 years; ECOG performance status 0-1; having measurable lesions according to RECIST ver. 1.1; and adequate oral intake and organ functions. Enrolled patients will receive 21-day cycles of nivolumab with CapeOX at the following dose until disease progression or unacceptable toxicities: capecitabine, 1000 mg/m2 twice per day on day 1-14; oxaliplatin, 130 mg/m2 on day 1; and nivolumab, 360 mg on day 1. The primary endpoint is objective response rate (ORR), and the secondary endpoints include overall survival, progression-free survival, disease control rate, duration of response, and safety. PD-L1 combined positive score will be tested for the association with efficacy. We assume null ORR of 20% and alternative ORR of 32%. With two-sided alpha level of 10% and 80% power, sample size would be calculated as 85. Thus, a total of 92 patients are planned for enrollment within a 2.5-year accrual period. Enrollment opened in March 2023. Clinical trial information: jRCTs031220572. 1. N Engl J Med. 2007;357:1810-20. 2. J Clin Oncol. 2019;37:1296-1304. 3. Gastric Cancer. 2018;21:811-8. Clinical trial information: jRCTs031220572 .

Prospective assessment of adenocarcinoma of esophagogastric junction (AEG) following radical resection: Real-world insights from the CLAEG study.

TPS415 Background: The CLAEG study (ChiCTR1900026131) is a prospective, real-world data evaluation of the clinical outcomes of patients with AEG following radical resection to investigate lymph node (LN) metastasis patterns and refine treatment strategies. Methods: Data from 44 hospitals in China were collected using a designed CRF, comprising baseline, surgical details, pathology results and recovery progress from January 1,2020. Data cut-off was August 31, 2023. The study is ongoing. Results: A total of 1322 patients were enrolled, and only 946 patients with complete data were included in the analysis. The median age was 65 years (range, 24-90). Among them, 28 patients were classified as Siewert type I, 601 as type II, and 317 as type III. Laparoscopic surgery was performed in 845 patients, while 101 underwent open surgery, with no significant difference in postoperative complication rate between them. However, the laparoscopic group demonstrated superior favorable outcomes in terms of postoperative recovery times, with shorter postoperative exhaust time (3.0 days vs 3.6 days, p&lt;0.001), feeding time (5.0 days vs 5.8 days, p=0.013), discharge time (11.6 days vs 14.6 days, p=0.002), as well as lower intraoperative blood loss (103.9 ml vs 163.4 ml, p=0.001). Among the patients, 891 underwent transhiatal approach, while 55 underwent thoracoabdominal approach, and no significant differences in postoperative complication rates, intraoperative blood loss and hospital stay were observed between these approaches. However, the transhiatal approach was associated with a shorter operative time (244.2 min vs 309.3 min, p&lt;0.001). LN dissection was performed in all patients within the abdominal region, with additional mediastinal LN dissection in 293 patients. The LN metastasis rates were 7.04%, 0% and 5.71% for No. 110, 111 and 112, respectively. Within the abdominal LNs, category-1 nodes included No. 1, 2, 3, 4, 5, 7, 8a, 9, 11, 19, while category-2 included No. 6, 12a, 20. Total gastrectomy was performed in 657 patients, while proximal gastrectomy was performed in 289 patients, and there were no significant differences in the rates of postoperative complications, postoperative recovery times and hospital stay between them. However, total gastrectomy took less operation time (243.7 min vs 258.0 min, p=0.019), and more LNs (36.6 vs 23.3, p&lt;0.001) were detected in abdomen. Conclusion: The CLAEG study confirms the safety and feasibility of laparoscopy in AEG surgery, although its long-term oncology effectiveness requires further investigation. Transhiatal surgery is advantageous due to its shorter operation time. Both proximal and total gastrectomy can be considered as viable surgical options. AEG patients have a higher rate of abdominal LN metastasis but a lower rate of mediastinal node involvement, emphasizing the importance of precise abdominal LN retrieval. Clinical trial information: ChiCTR1900026131 .

Comparative single-cell analysis reveals heterogeneous immune landscapes in adenocarcinoma of the esophagogastric junction and gastric adenocarcinoma

Adenocarcinoma of the esophagogastric junction (AEG) is a type of tumor that arises at the anatomical junction of the esophagus and stomach. Although AEG is commonly classified as a subtype of gastric adenocarcinoma (GAC), the tumor microenvironment (TME) of AEG remains poorly understood. To address this issue, we conducted single-cell RNA sequencing (scRNA-seq) on tumor and adjacent normal tissues from four AEG patients and performed integrated analysis with publicly available GAC single-cell datasets. Our study for the first time comprehensively deciphered the TME landscape of AEG, where heterogeneous AEG malignant cells were identified with diverse biological functions and intrinsic malignant nature. We also depicted transcriptional signatures and T cell receptor (TCR) repertoires for T cell subclusters, revealing enhanced exhaustion and reduced clone expansion along the developmental trajectory of tumor-infiltrating T cells within AEG. Notably, we observed prominent enrichment of tumorigenic cancer-associated fibroblasts (CAFs) in the AEG TME compared to GAC. These CAFs played a critical regulatory role in the intercellular communication network with other cell types in the AEG TME. Furthermore, we identified that the accumulation of CAFs in AEG might be induced by malignant cells through FGF-FGFR axes. Our findings provide a comprehensive depiction of the AEG TME, which underlies potential therapeutic targets for AEG patient treatment.