Gastroesophageal Junction Cancer Research Articles

Network Meta-analysis of Randomized Controlled Trials in Patients with Previously Treated Advanced Gastric or Gastroesophageal Junction Cancer: Comparisons Involving Ramucirumab.

With relatively few direct comparisons among treatment options for previously treated advanced gastric cancer or gastroesophageal junction (GEJ) cancer, network meta-analysis (NMA) may inform evidence-based decision-making. Ramucirumab plus paclitaxel (RAM + PTX) is a preferred regimen in guideline recommendations. NMA of key outcomes may further characterize the relative clinical value of RAM + PTX. A systematic literature review of randomized controlled trials of adult patients with previously treated advanced gastric/GEJ cancer informed a NMA which compared overall survival, progression-free survival, and discontinuations due to adverse events. Comparisons were reported relative to placebo/best supportive care (BSC) when possible, otherwise relative to RAM + PTX. The base-case NMA focused on second-line treatment only, from 19 of 28 studies identified. For overall survival, seven of 16 regimens were favorable relative to placebo/BSC, with RAM + PTX as the most favorable. For progression-free survival, five of 14 regimens were unfavorable relative to RAM + PTX. For discontinuations due to adverse events, two of 13 regimens were similar to placebo/BSC: ramucirumab monotherapy and fluorouracil; relative to RAM-PTX, all regimens were similar except ramucirumab monotherapy which was favorable and irinotecan + cisplatin which was unfavorable. This NMA of trials of previously treated gastric/GEJ cancer suggests that RAM + PTX has one of the more favorable clinical profiles.

Analysis of the treatment efficacy and prognostic factors of PD-1/PD-L1 inhibitors for advanced gastric or gastroesophageal junction cancer: a multicenter, retrospective clinical study

Analysis of the treatment efficacy and prognostic factors of PD-1/PD-L1 inhibitors for advanced gastric or gastroesophageal junction cancer: a multicenter, retrospective clinical study

Pembrolizumab (Keytruda)

Canada’s Drug Agency recommends that Keytruda should be reimbursed by public drug plans for the treatment of patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2) negative gastric or gastroesophageal junction (GEJ) adenocarcinoma if certain conditions are met. Keytruda should only be covered to treat patients who have not received previous treatment for HER2-negative advanced or metastatic gastric or GEJ cancer and who have good performance status. Keytruda should only be reimbursed if prescribed in combination with fluoropyrimidine- and platinum-containing chemotherapy by a clinician with expertise and experience in treating gastric and GEJ cancer, and the cost of Keytruda in combination with chemotherapy is reduced so that it does not exceed the drug program cost of treatment with nivolumab in combination with chemotherapy.

Survival and Treatment Patterns in Stage II to III Esophageal Cancer

Existing clinical trials favor neoadjuvant chemoradiation therapy (NCRT) followed by surgery alone for locally advanced esophageal cancer (EC) and perioperative chemotherapy as the preferred modality for esophageal adenocarcinoma (EAC). However, it is unclear whether these trial findings are reflected in the patterns of care and survival outcomes among patients in the clinical setting. To investigate survival outcomes in the clinical setting among patients with EC after various treatment modalities. This retrospective cohort study examined data from the National Cancer Database maintained by the American College of Surgeons and focused on patients with clinical stage II or III EC, excluding those with gastroesophageal junction cancer, who underwent trimodality therapy (NCRT followed by esophagectomy), definitive chemoradiation therapy (DCRT), radiotherapy (RT) alone, or perioperative chemotherapy from January 2006 to December 2020. Analyses were conducted from December 2023 to August 2024. Perioperative chemotherapy, trimodality therapy, DCRT, and single-modality RT. A Cox proportional hazards regression model was used to compare overall survival (OS) between treatment groups in the entire cohort, among patients with squamous cell carcinoma or adenocarcinoma, and among those older than 65 years. Landmark survival analysis at 6 months was performed to reduce survivorship bias. The study included 57 116 patients (median age, 64 [IQR, 57-72] years; 45 410 [79.5%] male); 21 619 patients (37.9%) received trimodality therapy, 32 493 (57.1%) received DCRT, 2692 (4.7%) received single-modality RT, and 312 (0.5%) received perioperative chemotherapy. In the overall study population, 37 698 patients (66.0%) had EAC, and of the 312 patients that received perioperative chemotherapy, 283 (90.7%) had EAC. In adjusted survival analysis, perioperative chemotherapy (adjusted hazard ratio [AHR], 0.33; 95% CI, 0.28-0.39; P <.001) and trimodality therapy (AHR, 0.45; 95% CI, 0.44-0.46; P < .001) were associated with improved OS compared with DCRT. In contrast, RT alone was associated with worse outcomes compared with DCRT (AHR, 1.37; 95% CI, 1.30-1.45; P < .001). The median OS for perioperative chemotherapy of 66.2 months (95% CI, 43.1-111.9 months; P < .001) was longer compared with that for DCRT alone (18.1 months; 95% CI, 17.8-18.4 months; P < .001). Trimodality therapy was associated with a median OS of 43.9 months (95% CI, 42.8-45.5 months; P < .001), which was shorter than that for perioperative chemotherapy but improved compared with DCRT and RT alone, which was associated with a median OS of 13.5 months (95% CI, 12.8-14.0 months; P < .001). In the subgroup of patients older than 65 years, those who received perioperative chemotherapy had longer median OS (56.7 months; 95% CI, 36.4-115.2 months; P < .001) compared with those receiving other treatment modalities (eg, trimodality therapy: 40.1 months; 95% CI, 38.1-42.0 months; P < .001). Patients who received RT alone had the worst median OS (13.6 months; 95% CI, 12.8-14.4 months; P < .001). In this cohort study of patients with stage II to III EC, trimodality therapy was associated with improved OS compared with DCRT or RT alone for locally advanced EC and perioperative chemotherapy was associated with improved OS for adenocarcinoma.

Real-world effectiveness and safety of trastuzumab-deruxtecan in Japanese patients with HER2-positive advanced gastric cancer (EN-DEAVOR study).

Trastuzumab-deruxtecan (T-DXd) was approved for the treatment of HER2-positive patients with advanced gastric cancer in Japan based on the results of the DESTINY-Gastric01 trial. This study aimed to collect real-world data and evaluate the effectiveness and safety of T-DXd. Patients aged ≥ 20years at the start of T-DXd administration with a histopathologically confirmed diagnosis of HER2-positive unresectable advanced or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma that had worsened after chemotherapy were enrolled in this retrospective cohort study. Key outcomes included T-DXd treatment status, overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response rate and frequency of grade ≥ 3 adverse events (AEs). Of the 312 patients included in the analysis, 75.3% were male, the median (range) age was 70.0 (27.0-89.0) years, 12.2% had an ECOG PS ≥ 2, 43.3% had ascites and the initial T-DXd dose was > 5.4- ≤ 6.4mg/kg in 78.2% of patients. The median (95% confidence interval) OS, rwPFS and TTF (months) was 8.9 (8.0-11.0), 4.6 (4.0-5.1) and 3.9 (3.4-4.2), respectively. The response rate was 42.9% in patients with a target lesion. In total, 48.4% of patients experienced a grade ≥ 3 AE, 2.6% experienced grade 5 AEs and 60.9% experienced AEs leading to T-DXd dose adjustments (reduction: 36.9%, interruption: 34.0% or discontinuation: 23.7%). No new safety signals were detected. T-DXd was effective and had a manageable safety profile as a third- or later-line treatment for patients with HER2-positive gastric or GEJ cancer in Japanese clinical practice. UMIN000049032.

Trastuzumab Deruxtecan in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Gastric Cancer in a Real-World Setting: A Nationwide Cohort Study.

Trastuzumab deruxtecan (T-DXd) has been approved for human epidermal growth factor receptor 2-positive locally advanced or metastatic gastric and gastroesophageal junction (HER2+ mG/GEJ) cancer since July 2022 in France, through an accelerated approval. The aim of this study was to evaluate its real-world use. We characterized T-DXd users treated for HER2+ mG/GEJ cancer using data from the French National Health Insurance database. The cohort included 196 patients, mostly men (78.1%), with a median age of 65 years. Median overall survival reached 7.7 months (95% CI: 6.2-9.0). Patients treated with T-DXd for HER2+ mG/GEJ cancer in the real world showed lower outcomes than those in pivotal clinical trials, consistent with previous reports on accelerated approvals.

Circulating tumor DNA predicts recurrence and survival in patients with resectable gastric and gastroesophageal junction cancer.

Gastric and gastroesophageal junction (GEJ) cancer represents a significant global health challenge, with high recurrence rates and poor survival outcomes. This study investigates circulating tumor DNA (ctDNA) as a biomarker for assessing recurrence risk in patients with resectable gastric and GEJ adenocarcinomas (AC). Patients with resectable gastric and GEJ AC, undergoing perioperative chemotherapy and surgery, were prospectively enrolled. Serial plasma samples were collected at baseline, after one cycle of chemotherapy, after preoperative chemotherapy, and after surgery. ctDNA was assessed by a ddPCR test (TriMeth), which targets the gastrointestinal cancer-specific methylation patterns of the genes C9orf50, KCNQ5, and CLIP4. ctDNA analysis was performed on 229 plasma samples from 86 patients. At baseline, ctDNA was detected in 56% of patients, which decreased to 37% following one cycle of chemotherapy, 25% after preoperative chemotherapy and 15% after surgical resection. The presence of ctDNA after one cycle of chemotherapy was associated with reduced recurrence-free survival (RFS) (HR = 2.54, 95% confidence interval (CI) 1.33-4.85, p = 0.005) and overall survival (OS) (HR = 2.23, 95% CI 1.07-4.62, p = 0.032). Similarly, ctDNA after surgery was associated with significantly shorter RFS (HR = 6.22, 95% CI 2.39-16.2, p < 0.001) and OS (HR = 6.37, 95% CI 2.10-19.3, p = 0.001). Multivariable regression analysis confirmed ctDNA after surgery as an independent prognostic factor (p < 0.001). ctDNA analysis has the potential to identify patients at elevated risk of recurrence, thus providing personalized treatment strategies for patients with resectable gastric and GEJ cancer. Further validation in larger cohorts and ctDNA-guided interventions are needed for future clinical use.

SY24-KL1 Perioperative chemotherapy for gastric and gastroesophageal junction cancer, European perspective

SY24-KL1 Perioperative chemotherapy for gastric and gastroesophageal junction cancer, European perspective

S2343 Efficacy and Safety of Sintilimab in Patients With Gastric or Gastroesophageal Junction Cancer: A Systematic Review and Meta-Analysis

S2343 Efficacy and Safety of Sintilimab in Patients With Gastric or Gastroesophageal Junction Cancer: A Systematic Review and Meta-Analysis

Cost-effectiveness analysis of first-line sintilimab plus chemotherapy vs. chemotherapy alone for unresectable advanced or metastatic gastric or gastroesophageal junction cancer in China.

The Chinese Society of Clinical Oncology (CSCO) has recommended sintilimab plus chemotherapy (SINT + Chemo) as a standard first-line therapy for advanced gastric cancer or gastroesophageal junction cancer (GC/GEJC), based on the proven effectiveness and safety in the ORINT-16 trail. Its cost-effectiveness, however, remains to be evaluated. We established a partitioned survival approach (PartSA) model with a 10-year time horizon to determine whether SINT + Chemo (vs. chemotherapy) was more cost-effective as a first-line treatment for unresectable advanced or metastatic GC/GEJC. Survival data was generated from the ORIENT-16 trail. Cost calculation was limited to direct medical costs. Database of Hunan Public Resources Trading Service Platform was used as the source for obtaining drug prices. Other cost and utility values were gathered from established literature. Incremental cost-effectiveness ratio (ICER) was the primary output. Additionally, we conducted sensitivity analysis, subgroup analysis, and scenario analysis. In the base-case analysis, group SINT + Chemo showed an increase in utility value by 0.32 quality-adjusted life-years (QALYs) at an extra cost of $7988.43, resulting in an ICER of $25239.29/QALY, below the Chinese cost-effective willingness-to-pay (WTP) threshold of $38223.34. Upon further subgroup analysis according to patients' programmed death 1 ligand (PD-L1) combined positive score (CPS), the ICERs were $26341.01/QALY for patients highly expressing PD-L1 (CPS ≥5) and $17658.26/QALY for patients lowly expressing PD-L1 (CPS <5). Based on the sensitivity analysis, we found the PFS utility was the parameter that had the most significant impact on the model's outcomes. Moreover, in scenario analysis, the results remained consistent despite variations in the model's time frame. In China, SINT + Chemo is a more cost-effective option (vs. chemotherapy) as a first-line therapy for unresectable advanced or metastatic GC/GEJC, irrespective of PD-L1 expression levels.

454. QUALITY OF LIFE AFTER ESOPHAGECTOMY WITH INTRATHORACIC VS CERVICAL ANASTOMOSIS: A NATIONWIDE COHORT STUDY

Abstract Background Transthoracic esophagectomy with either intrathoracic or cervical anastomosis is considered standard of care in patients with mid to distal esophageal or gastroesophageal junction (GEJ) cancer. Patients after esophagectomy will experience a deterioration in health-related quality of life (HR-QoL) after esophageal cancer surgery. Whilst some reports describe long-lasting deterioration, other reports show recovery of HR-QoL comparable with the general population after 2 years. The aim of this study was to investigate the difference in HR-QoL in patients after a transthoracic esophagectomy with either intrathoracic- or cervical anastomosis in a nationwide database. Methods A nationwide cohort study was performed combining data from two registries: Netherlands Cancer Registry (NCR) and Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients (POCOP). All patients after esophagectomy for mid/distal esophageal or GEJ cancer between 2015 and 2022 were included. HR-QoL was measured at baseline, 3, 6, 9, 12, 18, and 24 months postoperatively using EORTC QLQ-C30 and OG-25 questionnaires. Linear mixed models were used to assess the mean score difference between patients with intrathoracic and cervical anastomosis. A difference of 10 points or more was considered clinically relevant. Adjustments were made for potential confounders (age, gender, ASA classification). Results Of the 4269 registered patients in the NCR, in 1274 patients at least one questionnaire was available. Of these patients 346 underwent an esophagectomy with cervical - and 928 with intrathoracic anastomosis. Patients after esophagectomy with cervical anastomosis reported statistically significant more problems in the following categories: dysphagia, couching, trouble eating with others and swallowing saliva during the first 3 months, choked when swallowing and trouble talking during the first 12 months postoperatively. In all other categories no significant difference was found. Only trouble talking at the 3-month time point was considered as a clinically relevant difference. Conclusion Although the intrathoracic anastomosis is associated with significantly better HR-QoL in several categories, only trouble talking at 3 months postoperatively was considered clinically relevant. Overall HR-QoL was comparable for esophageal cancer patients after an esophagectomy with either a cervical or intrathoracic anastomosis.

New therapeutic target molecules for gastric and gastroesophageal junction cancer.

Molecularly targeted therapy for receptor tyrosine kinases (RTKs) has faced limitations in gastric and gastroesophageal junction (G/GEJ) cancer except for HER2-targeted agents, possibly due to inappropriate assay selection that has hindered identification of sensitive patients, in addition to coexisting genetic abnormalities as well as intratumoral heterogeneity. Immunohistochemistry of RTKs has, thus, proved largely unsuccessful for patient selection, and detection of RTK gene amplification as a true oncogenic driver is problematic given the small numbers of affected individuals. FGFR2 amplification is associated with poor prognosis in G/GEJ cancer, and immunohistochemistry of the FGFR2b protein isoform has proved effective for the detection of such FGFR2-dependent tumors. Phase III and Ib/III trials of the FGFR2-targeted antibody bemarituzumab for G/GEJ cancer overexpressing FGFR2b are ongoing based on the promising result in a phase II trial, especially in cases with an FGFR2b positivity of ≥ 10%. Challenges to EGFR- and MET-targeted therapies are being tackled with antibody-drug conjugates (ADCs) and bispecific antibodies. CLDN18.2 is expressed in some G/GEJ tumors but lacks oncogenic driver potential, and the CLDN18.2-targeted antibody zolbetuximab prolonged the survival of CLDN18.2-positive G/GEJ cancer patients in phase III trials. Antibody-drug conjugates and ADCs that target CLDN18.2 are also being pursued for treatment of such patients. Similarly, targeting of nondriver molecules such as DKK1, TROP2, and CEACAM5 is under investigation in early-stage clinical trials. This shift in focus from target molecules with driver potential to markers for precise drug delivery should increase the number of possible targets in G/GEJ cancer.

785. MANAGEMENT OF ESOPHAGEAL CANCER WITH CONCURRENT CERVICAL NODE METASTASIS: A NATIONWIDE POPULATION-BASED COHORT STUDY

Abstract Background In the Netherlands, the standard treatment of locally advanced, resectable esophageal cancer without metastasis is neoadjuvant chemoradiotherapy followed by esophagectomy. There is a small subset of patients that present with concurrent cervical lymph node metastasis (LNM). Historically this was seen as distant metastasis and surgical intervention has usually not been an option for these patients. The contemporary TNM classification now categorizes these lymph node stations as locoregional disease. Our current study aims to describe current treatment paradigms in the Netherlands for patients presenting with esophageal cancer and concurrent cervical LNM. Methods This population-based cohort study utilized data from the Netherlands Cancer Registry (NCR), encompassing patients with locally advanced thoracic esophageal or gastroesophageal junction cancer and concurrent cervical lymph node metastasis. Treatment modalities were categorized into five options: neoadjuvant therapy followed by surgery (Neo + S), definitive chemoradiotherapy (dCRT), chemotherapy with or without radiotherapy &amp;lt; 30 Gray (CT), radiotherapy (RT), and best supportive care (BSC). Overall survival (OS) was assessed using the Kaplan-Meier method and compared via the log-rank test. Hazard rates were computed using Cox proportional hazards regression, with adjustment for confounding achieved through inverse probability of treatment weighting (IPTW). Results Between 2015 and 2021, a cohort of 412 patients was identified from the NCR database. Median survival durations were observed as follows: 24.2 months for Neo + S, 18.0 months for dCRT, 14.5 months for CT, 7.0 months for RT, and 3.2 months for BSC (Figure). A comparison between the Neo + S group and dCRT demonstrated a significant improvement in survival (p=0.02). Further subdivision of the surgical group into neoadjuvant CRT or chemotherapy did not reveal a significant difference in survival (p=0.6). Utilizing IPTW to adjust for confounding factors, Neo + S maintained its survival advantage. Conclusion The retrospective cohort findings suggest that neoadjuvant therapy followed by surgery may represent the optimal approach for managing esophageal cancer patients with cervical LNMs Yet, it's vital to recognize the influence of confounding by indication, which statistical adjustments may not entirely rectify. Furthermore, immortal time bias notably skews results favorably toward surgery. Nevertheless, the results emphasize the importance of considering surgery as a viable option for these patients. These limitations underscore the critical need for a prospective study, prompting the launch of the NODE-II trial.

320. RISK FACTORS FOR BENIGN ANASTOMOTIC STENOSIS AFTER ESOPHAGEAL CANCER SURGERY

Abstract Background Benign strictures occur frequently following an esophagectomy, causing dysphagia, problems with eating, and a diminished overall quality of life. The aim of this study is to identify risk factors associated with anastomotic stenosis specified for anastomotic technique following esophagectomy for cancer. Methods This retrospective study included patients with esophageal and gastroesophageal junction cancer who underwent esophagectomy in a tertiary referral center between 2012 and 2022. Intrathoracic and cervical anastomoses were analyzed separately. Benign anastomotic stenosis was defined as the occurrence of postoperative dysphagia for which at least 1 endoscopic anastomotic dilation was needed. Possible predictive factors for anastomotic stenosis were analyzed with uni- and multivariate logistic regression. Results This study included 902 patients: 605 with an intrathoracic and 297 with a cervical anastomosis. Anastomotic stenosis was observed in 18.4% and 49.8% (p&amp;lt;0.001). Patients respectively requiring a median 4 and 7 dilations (p=0.001). Median of time to anastomotic stenosis was 99 and 78 days (p=0.001). In multivariate analysis of intrathoracic anastomosis, anastomotic leakage was a significant risk factor for stenosis (OR 2.034; 95% CI [1.116-3.708]). In patients without anastomotic leakage, stapler size 29mm was a negative predictor (OR 0.444; 95% CI [1.116-3.708]), immunosuppressants (OR 3.492; 95% CI [1.186-10.279]) and chronic pulmonary disease were significant risk factors (OR 2.717; 95% CI [1.293-5.707]). In multivariate analysis of cervical anastomosis, circular stapled anastomosis was a negative predictor (OR 0.350 95% [CI 0.188-0.652]) for stenosis. Conclusion This study identified the most important risk factors for anastomotic stricture after esophagectomy. Anastomotic leakage, the circular stapler diameter, and the circular stapled technique are factors that could be surgical modifiable, while patients taking immunosuppressants and with chronic pulmonary disease should be counseled for higher risk of stenosis.

1420P Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) protein overexpression and biomarker overlap in patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC)

1420P Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) protein overexpression and biomarker overlap in patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC)

367. IMPACT OF NEOADJUVANT IMMUNOTHERAPY ON POSTOPERATIVE COMPLICATIONS IN RESECTABLE ESOPHAGEAL ADENOCARCINOMA

Abstract Background Several studies are ongoing on the use of immunotherapy in the neoadjuvant setting for esophageal and gastroesophageal junction cancer but it is unclear the effect of an increased activation of the immune system on surgery and the postoperative course. Methods This multicenter retrospective cohort study included data from 3 high-volume centers for upper-GI surgery. Only patients with esophageal adenocarcinoma who underwent neoadjuvant therapy and radical surgery between 2015 and 2022 were included. Clinical characteristics and the postoperative outcomes were compared between patients who received standard neoadjuvant therapy or chemotherapy plus immunotherapy. A 1-to-1 matched comparison was also performed. The difference in overall survival (OS) and disease free survival (DFS) between the two groups was also evaluated. Results Overall, 563 patients were included and 21 received preoperative Pembrolizumab or Trastuzumab combined with at least a couple of chemotherapy drugs. The incidence of complications was 47% in the group with immunotherapy and 40.7% in the other group (p=0.53). The matched analysis confirmed no differences in rate of complications (p&amp;gt;0.99), gravity of complications (p=0.17) and pulmonary complications (p&amp;gt;0.99). Anastomotic leak rate was 4.7% in the immunotherapy group and 19% in the other one (p=0.34). Overall survival and disease free survival were comparable (respectively p=0.4 and p=0.9) also after the matched analysis (respectively p=0.15 and p=0.52). Conclusion Neoadjuvant immunotherapy-based regimen does not affect the postoperative course, in particular it does not appear to aggravate the major complications of esophagectomy.

784. NO SUPPORT FOR IMMEDIATE POSTOPERATIVE REMOVAL OF NASOGASTRIC TUBE AFTER ESOPHAGECTOMY, RESULTS FROM A NORDIC MULTICENTER RANDOMIZED CONTROLLED TRIAL

Abstract Background Esophagectomy is central in curative treatment of esophageal and gastroesophageal junctional cancer. Postoperative nasogastric (NG) tube for drainage of the gastric conduit is routine in most centers. The NG tube is typically associated with significant discomfort for the patients and may have risks of its own. Immediate postoperative removal of the NG tube has been suggested and deemed safe in several smaller trials. We hypothesized that immediate postoperative removal of the NG tube is non-inferior to keeping the NG-tube in place for 5 days postoperatively, with regard to anastomotic leak and other early outcomes. Methods Esophagectomy patients with a gastric conduit reconstruction were included in a multicenter, randomized controlled trial between February 2022 and March 2024. A 1:1 randomization stratified for center, age and anastomotic site (thorax/neck) was performed between immediate postoperative removal of NG tube (intervention) and 5 days of NG tube use (control). All patients underwent chest CT postoperative day 7. Anastomotic leak was the primary endpoint and a non-inferiority threshold of -9% difference in proportion of anastomotic leak, including 95% confidence interval, was set. Secondary endpoints included overall complications, pneumonia, length of stay as well as days in high dependency ward. Results Intention to treat analyses were performed on 444 patients whereof 215 were randomized to immediate NG-tube removal and 229 to control. Mean age was 67 years and neck anastomosis was performed in 78 patients (18%). 47 patients (22 %) had leak in the no NG tube group compared to 35 (15%) in the control group. Non-inferiority could not be established with a difference leak proportion to the advantage of NG tube use of 6.6% (95% CI: 13.8%-(-0.7%)). Overall complications (Clavien-Dindo &amp;gt;2) occurred in 94 patients (44%) in the experimental group and 91 patients (40%) in the control group. Overall 30d mortality was 1.1%. Conclusion In this randomized controlled multicenter trial, the by far largest to be performed so far, we could not establish non-inferiority for abstaining from postoperative NG tube use after esophagectomy with regards to anastomotic leak, and therefore support NG tube use. The somewhat high proportion of leak could be partly due to meticulous complication registration, including CT with peroral contrast on day seven in all patients. Use of postoperative decompression of the gastric conduit with an NG tube should be encouraged.

1451P Neoadjuvant and adjuvant pembrolizumab (pembro) + chemotherapy (chemo) for locally advanced gastric or gastroesophageal junction (G/GEJ) cancer: Patient-reported outcomes (PROs) from the phase III KEYNOTE-585 study

1451P Neoadjuvant and adjuvant pembrolizumab (pembro) + chemotherapy (chemo) for locally advanced gastric or gastroesophageal junction (G/GEJ) cancer: Patient-reported outcomes (PROs) from the phase III KEYNOTE-585 study

467. DISTRIBUTION OF LYMPH NODE INVOLVEMENT IN PATIENTS WITH GASTRO-ESOPHAGEAL JUNCTION ADENOCARCINOMA

Abstract Background Curative cancer surgery relies on understanding the lymphatic spread of the tumour to guide lymphadenectomy. The lymphatic involvement in patients with esophageal squamous cell carcinoma (SCC) has been evaluated extensively in large cohort studies from the East where SCC predominates, but the pattern of lymph node spread in gastro-esophageal junction (GEJ) adenocarcinoma is less clear. The primary aim of this study was to compare differences in the pattern of lymph node involvement according to the Siewert classification. Methods Consecutive patients who underwent curative resection for GEJ adenocarcinoma between February 2010 and April 2023 were analysed from a prospectively maintained database. Patient demographic data, neo-adjuvant treatment, operation type and histopathological report data were collected and analysed according to the pathological Siewert classification of GEJ cancer. Results 807 patients who underwent curative surgery for GEJ adenocarcinoma were analysed. The median lymph node yield was 26 (5-81). Comparing positive para-esophageal node yields, Type I and II tumours were similar but both significantly higher than Type III. For positive para-gastric nodes, Type 2 and 3 tumours were similar but both significantly higher than type 1. The significance of these comparisons is presented in table 1. There were no differences comparing other specific nodal groups. Evaluating the effect of node involvement on overall survival positive node status and positive hepatic artery nodes were found to be independent factors adversely affecting survival. Conclusion Siewert type I tumours have greater proximal lymph node involvement compared to type III tumours with higher proportions of positive para-esophageal nodes. Type III tumours on the other hand have higher proportions of para-gastric nodes. Type II tumours have similar para-esophageal node involvement to type 1 tumours and similar para-gastric involvement to type III tumours. Involvement of more specific nodal groups does not seem to vary between the sub types.

457. EVALUATING THE ACCURACY OF CLINICAL SIEWERT CLASSIFICATION, A RETROSPECTIVE REVIEW OF 807 PATIENTS

Abstract Background Adenocarcinoma of the gastro-esophageal junction (GEJ) is increasingly common in Western societies. GEJ tumours are typically categorized using the Siewert classification, which divides the tumours in to 3 types based on location relative to the GEJ. Studies have shown that there is improved survival with a proximal surgical resection such as esophagectomy for type 1 tumours while type 3 tumours have improved survival when managed as other gastric cancers with a total or extended total gastrectomy. This requires accurate clinical classification. This study aims to evaluate the accuracy of commonly used staging modalities in the clinical classification of GEJ tumours. Methods A review of 807 consecutive patients undergoing curative resection for GEJ cancer was performed. Patient data was obtained from a prospectively maintained database between February 2010 and April 2023. Siewert type was established clinically as part of the staging process. The standard staging modalities used for every patient included computerized tomography (CT) and endoscopy, with most patients also undergoing positron emission tomography (PET). Endoscopic ultra-sonography (EUS) and staging laparoscopy was also used selectively. Accuracy was determined by comparing clinical classification to pathological classification following surgery. Results 807 patients were included [319 type 1, 401 type 2, 87 type 3]. Clinical classification was the same as pathological classification in 59.5% of cases [69.6% for type 1, 48.6% for type 2, 71.3% for type 3 (p&amp;lt;0.001). The use of different staging modalities for each sub-type is presented in table 1. For patients that underwent EUS, Siewert type was accurate in 59.4% of cases overall. The failure rate for EUS was 2.9%. For patients undergoing staging laparoscopy Siewert type was accurate in 69.3% and for patients that underwent PET, EUS and staging lap the accuracy was 74.4%. Conclusion Accurately determining Siewert type clinically is challenging. This is particularly relevant for type 2 tumours which had the least accurate comparison of clinical to pathological type. The use of additional modalities including EUS, and staging laparoscopy improves accuracy but may not be feasible in all patients.