Gastroesophageal Junction Cancer Patients Research Articles

Risk, Predictive Factors, and Nomogram of Liver Metastatic Gastroesophageal Junction Cancer: A New Study Based on the Surveillance, Epidemiology, and End Results Database.

Liver metastasesare associated with a poor prognosisin gastroesophageal junction (GEJ) cancer patients. The high rate of liver involvement is attributed to the unique anatomical location of the GEJ, which is close to the liver. Patients with liver metastasis typically have advanced, unresectable disease and limited treatment options. Therefore, early detection and predictionare crucial to guide appropriate treatment planning and improve the outcomes for patients with GEJ cancer at risk of liver metastases. Using data from the Surveillance, Epidemiology, and End Results (SEER) database, the present study aimed to elucidate the incidenceand risk factorsof liver metastases in GEJ cancer patients diagnosed between 2010 and 2019. This research employed univariable and multivariable logistic regression models to identify risk factors for the development of liver metastases. A predictive nomogram for liver metastases was developed and assessed. Patients' overall survival (OS) with liver metastases was analyzed using the Kaplan-Meier method. The study included 1,322 eligible patients with GEJ cancer, 181 (13.6%) of whom were diagnosed with liver metastases. The median overall survival (mOS)for patients with liver metastasis was approximately eight months, compared to a shorter mOS for patients without liver metastasis (P < 0.001). Factors significantly associated with the occurrence of liver metastasis includedN3 stage (OR: 1.84; 95% CI: (1.13-2.96); P < 0.001),surgery (OR: 0.09; 95% CI: (0.06-0.14); P < 0.001), lung metastasis (OR: 2.88; 95% CI: (1.78-4.63); P < 0.001), chemotherapy (OR: 0.54; 95% CI: (0.32-0.87); P < 0.001), and radiation therapy (OR: 0.33; 95% CI: (0.25-0.45); P < 0.001). The nomogram demonstrated good performance in predicting liver metastases in GEJ cancer patients (c-index: 0.820). The study identified lymph node status, surgical, lung metastasis, chemotherapy, and radiation as important predictors of outcomes for patients with GEJ cancer. The developed nomogram might be a valuable tool for predicting the risk of liver metastases in GEJ cancer patients, potentially enhancing clinical decision-making processes.By predictingthe risk of liver metastasis occurrence, clinicians mightintervene in patients with GEJ cancersas early as possible.

A proactive financial navigation intervention in patients with newly diagnosed gastric and gastroesophageal junction adenocarcinoma

PurposeMany cancer patients and caregivers experience financial hardship, leading to poor outcomes. Gastric and gastroesophageal junction (GEJ) cancer patients are particularly at risk for financial hardship given the intensity of treatment. This pilot randomized study among gastric/GEJ cancer patients and caregivers tested a proactive financial navigation (FN) intervention to obtain a signal of efficacy to inform a larger, more rigorous randomized study.MethodsWe tested a 3-month proactive FN intervention among gastric/GEJ cancer patients and caregivers compared to usual care. Caregiver participation was optional. The primary endpoint was incidence of financial hardship, defined as follows: accrual of debt, income decline of ≥ 20%, or taking loans to pay for treatment. Data from participant surveys and documentation by partner organizations delivering the FN intervention was analyzed and outcomes were compared between study arms.ResultsNineteen patients and 12 caregivers consented. Primary FN resources provided included insurance navigation, budget planning, and help with out-of-pocket medical expenses. Usual care patients were more likely to experience financial hardship (50% vs 40%) and declines in quality of life (37.5% vs 0%) compared to intervention patients. Caregivers in both arms reported increased financial stress and poorer quality of life over the study period.ConclusionsProactive financial navigation has potentially positive impacts on financial hardship and quality of life for cancer patients and more large-scale randomized interventions should be conducted to rigorously explore the impact of similar interventions. Interventions that have the potential to lessen caregiver financial stress and burden need further exploration.Trial registrationTRN: NCT03986502, June 14, 2019.

Interleukin-6 as a Predictive Factor of Pathological Response to FLOT Regimen Systemic Treatment in Locally Advanced Gastroesophageal Junction or Gastric Cancer Patients.

Perioperative treatment is a gold standard in locally advanced gastric cancer or GEJ cancer in the Western population. Unfortunately, the response rate after neoadjuvant chemotherapy (NAC) remains limited. Moreover, there are currently no biomarkers enabling an individual prediction of therapeutic efficacy. The aim of this study was the identification of serum biomarkers of early response to NAC. We conducted this prospective study in the MSCNRIO in Warsaw, Poland. A total of 71 patients and 15 healthy volunteers gave informed consent. Complete blood count, carcinoembryonic antigen (CEA), carcinoma antigen 125 (CA125), carcinoma antigen 19.9 (CA19.9), and fibrinogen (F) were measured at baseline and before every cycle. Circulating tumour cells (CTCs) and interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) were measured in a pilot group of 40 patients at baseline and before cycle two (C2) and cycle three (C3). Of all the measured parameters, only the IL-6 serum level was statistically significant. The IL-6 level before C2 of chemotherapy was significantly decreased in the complete pathological response (pCR) vs. the non-pCR group (3.71 pg/mL vs. 7.63 pg/mL, p = 0.004). In all patients with an IL-6 level below 5.0 pg/mL in C2, tumour regression TRG1a/1b according to the Becker classification and ypN0 were detected in postoperative histopathological specimens. The IL-6 level before C1 of chemotherapy was significantly elevated in ypN+ vs. ypN0 (7.69 pg/mL vs. 2.89 pg/mL, p = 0.022). The trial showed that an elevated level of IL-6 prior to treatment and C2 might be a predictor of pathological response to NAC.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as biomarkers to prognosticate survival in advanced gastric cancer patients in the era of immunotherapy: a systematic review and meta-analysis.

Gastric cancer (GC) remains an important global health concern with limited treatment options for advanced cases. Immunotherapy has shown promising results, but identifying predictive biomarkers for treatment efficacy is challenging. Novel inflammatory markers, such as the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR), derived from complete blood count measurements, have gained attention as potential prognostic indicators. This systematic review and meta-analysis investigates the roles of the PLR and NLR as predictors of overall survival (OS) and progression-free survival (PFS) in advanced GC and gastroesophageal junction cancer (GEJC) patients treated with immunotherapy. A comprehensive search of the literature was conducted through PubMed, Embase, and Cochrane Library to identify relevant studies. A total of 16 studies involving NLR and 8 studies involving PLR were included. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the association between high biomarker values and poor OS and PFS. Subgroup analyses were performed to explore potential sources of heterogeneity. Poor OS, PFS were defined by each study as statistically significant shorter survival. A high NLR was significantly associated with worse OS (HR: 2.11; 95% CI: 1.70-2.62) and PFS (HR: 1.76; 95% CI: 1.43-2.17). High PLR was also significantly associated with poorer OS (HR: 1.77; 95% CI: 1.44-2.17) and PFS (HR: 1.61; 95% CI: 1.33-1.96). Subgroup analyses and sensitivity analyses supported the robustness of these findings. Publication bias was noted in NLR analysis for OS but not for PFS. PLR analysis showed low publication bias. Elevated NLR and PLR are associated with unfavorable OS and PFS outcomes in advanced GC/GEJC patients on immunotherapy. These findings imply the utility of these easily accessible biomarkers in prognostic assessment. However, standardized cutoff values and further research on interactions with the tumor microenvironment and comorbidities are needed. Additional prospective studies are warranted to validate these findings for both biomarkers.

1549P A prospective study of circulating tumor DNA (ctDNA) genomic profiling in gastric or gastroesophageal junction (GEJ) cancer patients with recurrence after adjuvant chemotherapy: Liquid-GEAR trial

1549P A prospective study of circulating tumor DNA (ctDNA) genomic profiling in gastric or gastroesophageal junction (GEJ) cancer patients with recurrence after adjuvant chemotherapy: Liquid-GEAR trial

Efficacy and safety of PD‑1/PD‑L1 inhibitors combined with chemotherapy in patients with advanced gastric or gastro‑esophageal junction cancer: A systematic review and meta‑analysis.

Although the efficacy and safety of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitor combined with chemotherapy vs. chemotherapy alone has been analyzed, there have been no in-depth studies on the outcomes of patients with PD-L1 positive advanced gastric or gastro-esophageal junction cancer patients (GC/GEJC). This systematic review and meta-analysis focused on comparing the efficacy and safety of PD-1/PD-L1 inhibitors vs. PD-1/PD-L1 inhibitors combined with chemotherapy vs. chemotherapy in PD-L1 positive advanced GC/GEJC patients, aiming to provide more precise guidance for the clinical treatment of GC/GEJC. In this meta-analysis, PubMed, Embase, and Cochrane Library were searched from the establishment of the database till June 2022. Randomized controlled trials (RCTs) in which control patients underwent chemotherapy and experimental group patients underwent PD-1/PD-L1 inhibitors or PD-1/PD-L1 inhibitors combined with chemotherapy were included in this investigation. Investigations without complete information, studies from which information could not be extracted, duplicate articles, animal studies, review articles, and systematic reviews were excluded. The pooled results suggested that chemotherapy combined with immunotherapy prolonged overall survival (OS) in patients with advanced GC/GEJC, while progression free-survival (PFS) with PD-1/PD-L1 inhibitors alone or in combination with chemotherapy were all improved compared with chemotherapy alone. However, PD-1/PD-L1 inhibitors did not significantly increase objective response rates (ORR) in PD-L1-positive patients compared with chemotherapy, but in combination with chemotherapy, they did improve ORR. The pooled results also showed that patients treated with PD-1/PD-L1 inhibitors had higher stable disease (SD) and progressive disease (PD) rates compared to chemotherapy in PD-L1-positive patients. Additionally, in PD-L1-positive patients, PD-1/PD-L1 inhibitors alone or combined with chemotherapy increased OS compared with chemotherapy alone. However, PD-1/PD-L1 inhibitors only prolonged PFS compared with chemotherapy alone in patients with a combined positive score (CPS; 100% of cells were required to be positively stained) for PD-L1, but when combined with chemotherapy, OS and PFS were prolonged in all PD-L1-positive patients compared with chemotherapy alone. Finally, the pooled results showed that the incidence of adverse events of PD-1/PD-L1 inhibitors in PD-L1-zpositive patients was significantly lower than that in patients treated with chemotherapy alone. In conclusion, single agent of PD-1/PD-L1 inhibitor alone or combined with chemotherapy significantly prolongs the survival of patients compared with chemotherapy alone, with fewer adverse effects. However, the degree of CPS may affect efficacy, thus further investigation is required.

254. THE IMPACT OF D2 VERSUS D1 LYMPHADENECTOMY IN SIEWERT II GASTROESOPHAGEAL JUNCTION (GEJ) CANCER

Abstract Background Though a myriad of multimodal treatment options exist for gastroesophageal junction (GEJ) cancer, surgical resection remains the mainstay for potential cure. Extended nodal dissection with a D2 lymphadenectomy (LAD) beyond the D1 peri-gastric dissection remains controversial for Siewert II GEJ cancer. Though D2 LAD may lead to increased lymph node harvest, its effect on overall survival remains elusive. We hypothesize that additional D2 dissection in Siewert II GEJ cancer does not lead to increased survival. Methods We reviewed Siewert II GEJ cancer patients who received either a D1 or D2 LAD after receiving neoadjuvant chemoradiation or perioperative chemotherapy from 2012 through 2022. Chi-square and Fisher exact tests were used to compare categorical variables and two-sample Wilcoxon rank sum tests for non-normally distributed continuous variables. The main outcomes measured were 1-year mortality from date of diagnosis, number of nodes sampled, and operative time. Results Among the 155 patients identified, 75% of Siewert II underwent a D1 and 25% underwent a D2 LAD. Patients with a D2 LAD more often had &amp;gt;15 lymph nodes harvested than D1 (83% vs 48%, p &amp;lt; 0.001) but had no significant difference in median number of positive nodes (Figure 1). Patients with a D2 LAD had a median operative time approximately 2 hours longer than D1, 362 min vs 244 min (p &amp;lt; 0.001). On multivariable logistic regression adjusting for patient and clinical characteristics, there was no significant difference in 1-year mortality from patients undergoing a D2 vs D1 LAD. Conclusion Despite the associated high mortality associated with gastroesophageal junction (GEJ) cancer, there remains little consensus guidelines regarding the optimal preoperative and operative management. Though D2 LAD may theoretically lead to more lymph node harvest, its role in staging may be unnecessarily excessive as there is no gain in number of positive nodes leading to increased operative morbidity with no significant change in survival.

Proximal gastrectomy and double-tract reconstruction vs total gastrectomy in gastric and gastro-esophageal junction cancer patients — a systematic review and meta-analysis protocol (PROSPERO registration number: CRD42021291500)

BackgroundIn Germany and Western Europe, gastroesophageal junction cancer (AEG) and proximal gastric cancer are currently treated with (transhiatal-extended) total gastrectomy (TG) according to the latest treatment guidelines. TG leads to a severe and long-lasting impairment of postoperative health-related quality of life (HRQoL) of the treated patients. Recent studies have suggested that HRQoL of these patients could be improved by proximal gastrectomy with double-tract reconstruction (PG-DTR) without compromising oncologic safety. Our aim is therefore to conduct a randomized controlled non-inferiority trial comparing PG-DTR with TG in AEG II/III and gastric cancer patients with overall survival as primary endpoint and HRQoL as key secondary endpoint.MethodsThis protocol is written with reference to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P 2015) statement. We will conduct searches in the electronic databases MEDLINE, Web of Science Core Collection, ScienceDirect, and Cochrane Library. We will also check references of relevant studies and perform a cited reference research. Titles and abstracts of the records identified by the searches will be screened, and full texts of all potentially relevant articles will be obtained. We will consider randomized trials and non-randomized studies. The selection of studies, data extraction, and assessment of risk of bias of the included studies will be conducted independently by two reviewers. Meta-analysis will be performed using RevMan 5.4 (Review Manager (RevMan) Version 5.4, The Cochrane Collaboration).DiscussionThis systematic review will identify the current study pool concerning the comparison of TG and PG-DTR and help to finally refine the research questions and to allow an evidence-based trial design of the planned multicenter randomized-controlled trial.Ethics and disseminationEthical approval is not required for this systematic review. Study findings will be shared by publication in a peer-reviewed journal.Systematic review registrationPROSPERO CRD42021291500.

Nomogram for predicting the overall survival of patients after D2/R0 resection and chemoradiotherapy for stage III gastric cancer or gastroesophageal junction cancer

ObjectiveTo explore the independent factors associated with the overall survival (OS) after D2/R0 resection and adjuvant chemoradiotherapy(CRT) for stage III gastric cancer (GC) and gastroesophageal junction (GEJ) cancer, and establish and validate a nomogram model to predict the OS in this patient population. MethodsA total of 569 stage III GC or GEJ cancer patients who underwent D2/R0 resection and adjuvant CRT at our center from January 2013 to May 2018 were retrospectively enrolled in this study. The patients were randomly divided into training and validation cohorts in a 3:1 ratio. In the training cohort, univariate and multivariate analysis were conducted to identify clinical factors associated with OS, and a nomogram model was established on the basis of the independent factors. The concordance index (C-index) and the calibration curve were used to validate the prediction power of the nomogram. ResultsOverall, 427 and 142 patients were enrolled in the training and validation cohorts, respectively. In the univariate and multivariate analyses, age, Lauren's classification, TNM stage, and administration of adjuvant CRT were independent factors for OS to construct the nomogram. The C-index values were 0.654 and 0.613 in the training and validation cohorts, respectively. The calibration curves were identical to the actual OS. Risk stratification based on the nomogram model showed good risk stratification for OS in both groups. ConclusionOur study included adjuvant CRT as a predictive factor and established a nomogram model for predicting the OS in patients with stage III GC or GEJ after D2/R0 resection and adjuvant therapy. This nomogram could facilitate more individualized prediction of OS in clinical practice.

Phase 2 study of bavituximab (bavi), a first-in-class antibody targeting phosphatidylserine (PS), plus pembrolizumab (P) in advanced gastric or gastroesophageal junction (GEJ) cancer.

e16023 Background: Bavi, a monoclonal antibody designed to inhibit the immunosuppressive effects of PS through interaction with TIM/TAM receptor family members in the tumor microenvironment (TME), was evaluated in combination with P in patients with advanced gastric and GEJ cancer. Methods: ONCG100 was a phase 2, multicenter, open-label, two-cohort global study designed to assess the safety, tolerability, and antitumor activity of bavi (3 mg/kg, QW) plus P (200 mg, Q3W) in advanced gastric or GEJ cancer patients who progressed on ≥1 prior standard therapy (NCT04099641). Patients were checkpoint inhibitor (CPI) naive (Grp 1) or CPI relapsed (Grp 2); known MSI-H patients were excluded. RNA expression was analyzed in pre-treatment tumor tissue using the Xerna TME Panel, an RNA-based diagnostic, to prospectively test hypothesis that tumors with high immune or immune-suppressed TME subtypes (B+) are more likely to respond to bavi plus P than high angiogenic/immune-desert TME subtypes (B-). Results: A total of 80 patients enrolled (Grp 1 n=61, Grp 2 = 19). The most frequently reported Grade ≥ 3 treatment emergent adverse events (occurring in ≥10% of patients overall) were anaemia and gastric cancer progression (n= 10/AE). Key efficacy parameters for Grp 1 patients (2L 57.4%) are summarized in Table 1. In Grp 2, the ORR was 5.3% (95% CI: 0.1, 26.0), whereby 0 patients achieved a complete response and only 1 (5.3%) patient achieved a partial response as the best overall response (BOR). In the remaining patients, BOR was stable disease in 9 (47.4%) patients, progressive disease in 8 (42.1%) patients, and not evaluable in 1 (5.3%) patient. Conclusions: The combination of Bavi and P was well tolerated; observed AEs were consistent with known profiles for each agent. Higher ORRs were observed in CPI-naïve patients with B+ status and baseline NLR&lt;4, and of note, in patients with PD-L1 CPS &lt;1. Future studies may be planned to confirm the activity of Bavi in combination with P with patient selection based on a particular genetic signature. Clinical trial information: NCT04099641 . [Table: see text]

Eligibility of patients with esophageal and gastroesophageal cancer for biology-guided radiotherapy in a retrospective cohort.

e16100 Background: Biology-guided radiotherapy (BgRT) is a novel radiotherapy modality that uses real-time positron emission tomography (PET) to guide radiotherapy beamlets. The FDA recently cleared BgRT for clinical use for tumors in lung and bone using 18F FDG radiotracer. We sought to identify esophageal cancer (EC) and gastroesophageal junction cancer (GEJC) patients who may be BgRT candidates based on diagnostic FDG PET/CT imaging. Methods: Through IRB-approved extraction of patient medical record data from an institutional repository of prospectively maintained data, we verified a database of EC and GEJC patients diagnosed at a US tertiary care center between 01/01/2006 and 12/31/2013. When insufficient diagnostic clinical information was present, patients were excluded. Patient and tumor qualities were quantified and subjected to parameters of tumor diameter (≥2cm, &lt;5cm) and maximum standardized uptake value (≥6) to observe potential characteristics of a patient population eligible for this novel BgRT mechanism. Results: Thirty patients met tumor size and FDG uptake criteria for BgRT therapy out of an overall patient cohort of 90 patients. A significantly greater proportion of patients within the BgRT-eligible cohort presented with esophageal tumors (83.3%) compared to non-eligible patients (58.3%, P=0.0177). Otherwise, there was no significant variation of patient sex, race, tumor histology, tumor stage, comorbidity score, and pre-treatment weight loss between patients eligible and not eligible for BgRT therapy. Conclusions: After applying current boundaries of tumor size and radiotracer uptake for effective BgRT intervention, we observed broad applicability of the novel treatment modality across EC/ GEJC patients of varying characteristics and tumor qualities. The high eligibility of patients with tumors located within the esophagus supports further investigation of BgRT in their management. [Table: see text]

Systematic review and meta-analysis comparing proximal gastrectomy with double-tract-reconstruction and total gastrectomy in gastric and gastroesophageal junction cancer patients: Still no sufficient evidence for clinical decision-making.

To compare proximal gastrectomy with double-tract reconstruction and total gastrectomy in patients with gastroesophageal junction (AEG II-III) and gastric cancer. We conducted systematic searches in Medline, Web of Science, and Cochrane Library until December 20, 2021 (PROSPERO registration number: CRD42021291500). Risk of bias was assessed using the revised Cochrane risk of bias tool and the ROBINS-I tool, as applicable. Evidence was rated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. One randomized controlled trial (RCT) and 13 non-RCTs with 1,317 patients (715 patients with total gastrectomy and 602 patients with proximal gastrectomy with double-tract reconstruction) were included. Patients treated by total gastrectomy had a significantly higher proportion of advanced cancer stages International Union Against Cancer IB-III (odds ratio: 0.68, 95% confidence interval: 0.51-0.91, P= .01). This heterogeneity biases the observed improved overall survival of patients after proximal gastrectomy with double-tract reconstruction (odds ratio: 0.67, 95% confidence interval: 0.44-1.01, P= .05). Both procedures were comparably efficient regarding perioperative parameters. Postoperative/preoperative bodyweight ratio (mean difference: 3.56, 95% confidence interval: 1.32-5.79, P= .002), postoperative/preoperative serum-hemoglobin ratio (mean difference 3.73, 95% confidence interval: 1.59-5.88, P < .001), and postoperative serum vitamin B12 levels (mean difference 42.46, 95% confidence interval: 6.37-78.55, P= .02) were superior after proximal gastrectomy with double-tract reconstruction, while postoperative/preoperative serum-albumin ratio (mean difference 1.24, 95% confidence interval: -4.76 to 7.24, P= .69) and postoperative/preoperative serum total protein ratio (mean difference 1.12, 95% confidence interval: -2.77 to 5.00, P= .57) were not different. Health-related quality of life data were reported in only 2 studies, which found no significant advantages for proximal gastrectomy with double-tract reconstruction. Proximal gastrectomy with double-tract reconstruction offers advantages in postoperative nutritional parameters compared to total gastrectomy (GRADE: moderate quality of evidence). Oncological effectiveness of proximal gastrectomy with double-tract reconstruction cannot be assessed (GRADE: very low quality of evidence). Further thoroughly planned randomized controlled trials in Western patient cohorts are necessary to improve treatment for gastric cancer patients.

Two decades of gastric and gastroesophageal junction cancer surgery.

Diagnosis and treatment of gastric and gastroesophageal junction cancer have undergone many critical changes during the last two decades. We addressed the question of how clinical reality outside of clinical trials has changed for gastric and gastroesophageal junction cancer patients in a European center for upper gastrointestinal surgery. In this retrospective cohort study, patients undergoing (sub)total gastrectomy for gastric or gastroesophageal junction adenocarcinoma between 1996 and 2017 in a tertiary upper gastrointestinal center were included. The time was divided into a) before (1996-2006) (pre-CTx) and b) after (2006-2017) (CTx) the MAGIC trial. Data were comprehensively analyzed for demographics, tumor stage, perioperative treatment, surgery, histopathology, and survival rates (SR). 737 patients (32% female) underwent gastrectomy, 255 patients in the pre-CTx era and 482 patients in the CTx era. The median age was 65years and the median follow-up was 27.5months for surviving patients. Around 16.9% of patients received neoadjuvant treatment in the pre-CTx era versus 46.3% in the CTx era. The 3-year survival rate (3-YSR) was 46.4% in the pre-CTx and 60.9% in the CTx era (p < 0.001). For pretreated patients, 3-YSR was 39.0% (pre-CTx) versus 55.3% (CTx) (p = 0.168). Survival rate (SR) for locally advanced tumor stages (cT3/cT4) was higher when neoadjuvant therapy was administered (3-YSR: 56.7% vs 40.6%; p = 0.022). There were no significant differences according to sex (p = 0.357), age (p = 0.379), pT category (p = 0.817), pN stage (p = 0.074), cM stage (p = 0.112), Laurén classification (p = 0.158), and SRs (3-YSR: 60.3% vs 59.4%; p = 0.898) between the MAGIC and FLOT regimens. Survival rates have dramatically improved for gastric cancer patients during the last two decades. MAGIC and FLOT regimens showed similar results in the postsurgical follow-up.

Association of inflammatory markers with survival in patients with advanced gastric cancer treated with immune checkpoint inhibitors combined with chemotherapy as first line treatment.

The emergence of immune checkpoint inhibitors has changed the landscape of first-line treatment of patients with advanced gastric cancer. Currently, the prognostic significance of inflammatory markers in first-line immunotherapy combined with chemotherapy for gastric cancer is currently unclear. This study aimed to identify inflammatory markers with potential to predict treatment outcome in advanced gastric cancer patients receiving immunotherapy combined with chemotherapy. This retrospective study enrolled untreated advanced or metastatic gastric or gastro-esophageal junction cancer patients from 5 clinical trials (the clinical trial cohort) and the real world (the real-word cohort). Inflammatory markers included in the analysis included neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and derived neutrophil-to-lymphocyte ratio (dNLR). Receiver operating characteristic (ROC) curves were constructed to identify optimal cut-off values. The prognostic potential of the markers was determined using Kaplan-Meier analysis, univariate and multivariate Cox-regression analyses in the clinical trial cohort and the findings were validated in the real-world cohort. In the clinical trial cohort (n=45), MLR, PLR and SII were associated with PFS but not OS (All P<0.05), while dNLR was not correlated with PFS or OS. Only NLR was associated with PFS and OS and identified as an independent prognostic predictor in the univariate and multivariate analyses. The prognostic value of NLR was validated in the real-world cohort (n=55). NLR was a strong predictor of PFS and OS in patients with advanced gastric cancer receiving immune checkpoint inhibitors combined with chemotherapy. Further prospective studies are required to validate our results.

Body composition dynamics and impact on clinical outcome in gastric and gastro-esophageal junction cancer patients undergoing perioperative chemotherapy with the FLOT protocol

PurposePerioperative chemotherapy with FLOT constitutes a standard of care approach for locally advanced, resectable gastric or gastro-esophageal junction (GEJ) cancer. We aimed at investigating anthropometric, CT-based and FDG-PET-based body composition parameters and dynamics during this multidisciplinary approach and the impact on clinical outcomes.MethodsThis retrospective, single-center study was based on medical records and (FDG-PET)-CT images among gastric/GEJ cancer patients undergoing perioperative FLOT chemotherapy.ResultsBetween 2016 and 2021, 46 gastric/GEJ cancer patients started perioperative FLOT at our tertiary cancer center (Salzburg, Austria). At a median follow-up of 32 months median PFS was 47.4 months and median OS was not reached. The skeletal muscle index (SMI, cm2/m2) turned out to be the only body composition parameter with a statistically significant decrease during pre-operative FLOT (51.3 versus 48.8 cm2/m2, p = 0.02). Neither pre-FLOT body mass index (BMI), nor SMI had an impact on the duration of pre-operative FLOT, the time interval from pre-operative FLOT initiation to surgery, the necessity of pre-operative or post-operative FLOT de-escalation or the likelihood of the start of postoperative chemotherapy. Pre-FLOT BMI (overweight versus normal, HR: 0.11, 95% CI: 0.02–0.65, p = 0.02) and pre-FLOT SMI (sarcopenia versus no sarcopenia, HR: 5.08, 95% CI: 1.27–20.31, p = 0.02) were statistically significantly associated with PFS in the multivariable analysis.ConclusionThe statistically significant SMI loss during pre-operative FLOT and the meaningful impact of baseline SMI and BMI on PFS argue for the implementation of a nutritional screening and support program prior to the initiation of pre-operative FLOT in clinical routine.

PD-L1 expression in gastric and gastroesophageal junction cancer patients treated with perioperative chemotherapy.

The incidence, predictive, and prognostic impact of programmed cell death(PD-L1) expression in gastric (GC)and gastroesophageal junction tumors(GEJC)treated with perioperative chemotherapy is poorly understood. We aimed to assess PD-L1 expression by immunohistochemistry (IHC) in both pre and posttreatment specimens evaluating its impact on pathological response and survival outcomes. Retrospective cohort of patients with GCand GEJ tumors treated in a single western cancer center between 2007 and 2017. PD-L1 expression was assessed by IHC before and after neoadjuvant chemotherapy, in surgical samples, and reported as combined positive score (CPS). CPS > 1% was tested for its association with pathological response and overall survival (OS). We were able to assess PD-L1 expression in at least one tissue sample from 155 subjects. PD-L1 positivity rate was 20%. In 74 paired samples, a 21% discordance between PD-L1 expression in biopsy sample and surgical specimen was observed. With a median follow-up period of 60.3 months, 5-years disease-free survivalwas 60.5% with a median OSnot reached. PD-L1 expression was neither associated with pathological response or survival outcomes. PD-L1 expression in the setting of locally advanced GCtumors was relatively low and can vary considering the tissue sample analyzed. This expression had no association with survival or pathological responsein this population.

P-256 Efficacy of FLOT regimen in the Polish population – real-world data from a prospective biomarker study

Gastric cancer is associated with poor prognosis. Currently in Europe the preferred management of locally advanced gastric cancer (GC) and gastroesophageal junction (GEJ) cancer is perioperative chemotherapy using FLOT regimen. According to previously published data, such treatment is associated with improved disease-free survival (DFS) as well as overall survival (OS) compared to ECF/ECX regimen. It was an academic, nonrandomized, prospective study, conducted in Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland. Between January 2018 and November 2019 we analysed a total of 61 patients aged 30-77 (median 63 years, 52.5% male and 47.5% female) with histologically confirmed GC or GEJ cancer. The patients were qualified by multidisciplinary team for perioperative treatment (FLOT regimen). All cases of reported adverse events were recorded and analysed. All patients received G-CSF prophylactically. After gastrectomy, assessment of pathological regression was performed according to the Becker classification. A total of 93.4% (57) patients completed four cycles of preoperative chemotherapy and 78.7% (48) received postoperative chemotherapy. All of them experienced grade 1/2 toxicities. The common AE G1/G2 in preoperative versus postoperative chemotherapy were: fatigue (75% vs. 60%), anaemia (64% vs 62%) nausea (60% vs 60%), peripheral neuropathy (60% vs 60%) and oral mucositis (59% vs 50%), respectively. Only 24.6% (15) had any G3/4 adverse events during preoperative chemotherapy and only 20.8% (10) during postoperative chemotherapy. The estimated disease-free survival (DFS) at 3 years was 53% (95% CI 40.5%-66.1%) and estimated overall survival (OS) at 3-years was 60.2% (95% CI 45.1%-72.3%). FLOT regimen significantly improved GC and GEJ cancer patients’ prognosis with acceptable side-effect profiles.

P-58 Body composition dynamics and impact on clinical outcome in gastric and gastro-esophageal junction cancer patients undergoing perioperative chemotherapy with the FLOT protocol

Perioperative chemotherapy with FLOT constitutes a standard of care approach for locally advanced, resectable gastric or gastro-esophageal junction (GEJ) cancer. We aimed at investigating anthropometric, CT-based and FDG-PET-based body composition parameters and dynamics during this multidisciplinary approach and the impact on clinical outcome.

Dynamic changes in systemic immune-inflammation index predict pathological tumor response and overall survival in patients with gastric or gastroesophageal junction cancer receiving neoadjuvant chemotherapy.

Systemic inflammation has been associated with chemoresistance and prognosis in solid tumors. Systemic immune-inflammation index (SII) is a novel marker derived from complete blood count. We investigated whether differences between SIIs measured before and after neoadjuvant chemotherapy (NACT) are associated with tumor regression grade (TRG) and survival in gastric and gastroesophageal junction (GEJ) cancer patients. Records of gastric and GEJ cancer patients treated with NACT in two centers were evaluated retrospectively. Patients were categorized according to difference between pre- and post-NACT SII values (ΔSII). Association between clinicopathological factors and TRG was analyzed using logistic regression method. Predictors of disease-free and overall survival (DFS and OS) were determined with Cox regression models. The study included 140 patients. Patients with ΔSII<0 were more likely to achieve TRG 0/1 (45.2% vs. 19.1%, p = 0.003) and ΔSII<0 was an independent predictor of TRG 0/1 (OR = 6.05, p<0.001). DFS and OS of patients with ΔSII<0 were also significantly longer (p = 0.031 and p = 0.006, respectively). After adjustment for other variables, ΔSII≥0 was an independent prognostic factor for OS (Hazard ratio (HR) = 2.13, p = 0.008). Changes in SII, which is a low-cost and easily accessible marker, may be used to estimate prognosis, individualize postoperative treatment and optimize surveillance in gastric and GEJ cancer patients treated with NACT.

Real life experience of patients with locally advanced gastric and gastroesophageal junction adenocarcinoma treated with neoadjuvant chemotherapy: a Turkish oncology group study

Neoadjuvant chemotherapy (NACT) in gastroesophageal junction (GEJ) and gastric cancer (GC) was shown to improve survival in recent studies. We aimed to share our real-life experience of patients who received NACT to compare the efficacy and toxicity profile of different chemotherapy regimens in our country. This retrospective multicentre study included locally advanced GC and GEJ cancer patients who received NACT between 2007 and 2021. Relation between CT regimens and pathological evaluation were analysed. A total of 794 patients from 45 oncology centers in Turkey were included. Median age at the time of diagnosis was 60 (range: 18–86). Most frequent NACT regimens used were FLOT (65.4%), DCF (17.4%) and ECF (8.1%), respectively. In the total study group, pathological complete remission (pCR) rate was 7.2%, R0 resection rate 86.4%, and D2 dissection rate was 66.8%. Rate of pCR and near-CR (24%), and R0 resection (84%) were numerically higher in FLOT arm (p > 0.05). Patients who received FLOT had also higher chemotherapy-related toxicity rate compared to patients who received other regimens (p > 0.05). Median follow-up time was 16 months (range: 1–154 months). Estimated median overall survival (OS) was 58.4months (95% CI: 35.2–85.7) and disease-free survival (DFS) was 50.7 months (95% CI: 25.4–75.9). The highest 3-year estimated OS rate was also shown in FLOT arm (68%). We still do not know which NACT regimen is the best choice for daily practice. Clinicians should tailor treatment regimens according to patients’ multifactorial status and comorbidities for to obtain best outcomes. Longer follow-up period needs to validate our results.