Prognosis Of Advanced Gastric Cancer Research Articles

A study predicting long-term survival capacity in postoperative advanced gastric cancer patients based on MAOA and subcutaneous muscle fat characteristics

BackgroundThe prognosis of advanced gastric cancer (AGC) is relatively poor, and long-term survival depends on timely intervention. Currently, predicting survival rates remains a hot topic. The application of radiomics and immunohistochemistry-related techniques in cancer research is increasingly widespread. However, their integration for predicting long-term survival in AGC patients has not been fully explored.MethodsWe Collected 150 patients diagnosed with AGC at the Affiliated Zhongshan Hospital of Dalian University who underwent radical surgery between 2015 and 2019. Following strict inclusion and exclusion criteria, 90 patients were included in the analysis. We Collected postoperative pathological specimens from enrolled patients, analyzed the expression levels of MAOA using immunohistochemical techniques, and quantified these levels as the MAOAHScore. Obtained plain abdominal CT images from patients, delineated the region of interest at the L3 vertebral body level, and extracted radiomics features. Lasso Cox regression was used to select significant features to establish a radionics risk score, convert it into a categorical variable named risk, and use Cox regression to identify independent predictive factors for constructing a clinical prediction model. ROC, DCA, and calibration curves validated the model’s performance.ResultsThe enrolled patients had an average age of 65.71 years, including 70 males and 20 females. Multivariate Cox regression analysis revealed that risk (P = 0.001, HR = 3.303), MAOAHScore (P = 0.043, HR = 2.055), and TNM stage (P = 0.047, HR = 2.273) emerged as independent prognostic risk factors for 3-year overall survival (OS) and The Similar results were found in the analysis of 3-year disease-specific survival (DSS). The nomogram developed could predict 3-year OS and DSS rates, with areas under the ROC curve (AUCs) of 0.81 and 0.797, respectively. Joint calibration and decision curve analyses (DCA) confirmed the nomogram’s good predictive performance and clinical utility.ConclusionIntegrating immunohistochemistry and muscle fat features provides a more accurate prediction of long-term survival in gastric cancer patients. This study offers new perspectives and methods for a deeper understanding of survival prediction in AGC.

Textbook oncological outcomes and prognosis after curative gastrectomy in advanced gastric cancer: A multicenter study

BackgroundThe impact of achieving textbook oncological outcome (TOO) as a multimodal therapy quality indicator on the prognosis of advanced gastric cancer (AGC) remains inadequately assessed. MethodsPatients with AGC who underwent curative gastrectomy between January 2010 and December 2017 at two East Asian medical centers were included. TOO was defined as achieving the textbook outcome (TO) and receiving neoadjuvant and/or adjuvant chemotherapy (NCT or ACT). Cox and logistic regression models were used to identify prognostic and non-TOO-associated risk factors. ResultsAmong 3626 patients, 57.6% achieved TOO (TOO group), exhibiting significantly better 5-year overall survival (OS) and disease-free survival (DFS) than the non-TOO group (both p < 0.05). Multivariate Cox regression identified TOO as an independent prognostic factor for 5-year OS (HR, 0.67; 95% CI, 0.61–0.74; p < 0.001) and DFS (HR, 0.73; 95% CI, 0.66–0.81; p < 0.001). Multivariate logistic regression showed that open gastrectomy, lack of health insurance, age ≥65 years, ASA score ≥ Ⅲ, and tumor size ≥50 mm are independent risk factors for non-achievement of TOO (all p < 0.05). On a sensitivity analysis of TOO's prognostic value using varying definitions of chemotherapy parameters, a stricter definition of chemotherapy resulted in a decrease in the TOO achievement rate from 57.6 to 22.3%. However, the associated reductions in the risk of death and recurrence fluctuated within the ranges of 33–39% and 28–37%, respectively. ConclusionsTOO is a reliable and stable metric for favorable prognosis in AGC. Optimizing the surgical approach and improving health insurance status may enhance TOO achievement.

Nomogram model including LATS2 expression was constructed to predict the prognosis of advanced gastric cancer after surgery.

Gastric cancer is a leading cause of cancer-related deaths worldwide. Prognostic assessments are typically based on the tumor-node-metastasis (TNM) staging system, which does not account for the molecular heterogeneity of this disease. LATS2, a tumor suppressor gene involved in the Hippo signaling pathway, has been identified as a potential prognostic biomarker in gastric cancer. To construct and validate a nomogram model that includes LATS2 expression to predict the survival prognosis of advanced gastric cancer patients following radical surgery, and compare its predictive performance with traditional TNM staging. A retrospective analysis of 245 advanced gastric cancer patients from the Fourth Hospital of Hebei Medical University was conducted. The patients were divided into a training group (171 patients) and a validation group (74 patients) to develop and test our prognostic model. The performance of the model was determined using C-indices, receiver operating characteristic curves, calibration plots, and decision curves. The model demonstrated a high predictive accuracy with C-indices of 0.829 in the training set and 0.862 in the validation set. Area under the curve values for three-year and five-year survival prediction were significantly robust, suggesting an excellent discrimination ability. Calibration plots confirmed the high concordance between the predictions and actual survival outcomes. We developed a nomogram model incorporating LATS2 expression, which significantly outperformed conventional TNM staging in predicting the prognosis of advanced gastric cancer patients postsurgery. This model may serve as a valuable tool for individualized patient management, allowing for more accurate stratification and improved clinical outcomes. Further validation in larger patient cohorts will be necessary to establish its generalizability and clinical utility.

Lipid Metabolism-Related Gene Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Advanced Gastric Cancer.

Abnormal lipid metabolism is known to influence the malignant behavior of gastric cancer. However, the underlying mechanism remains elusive. In this study, we comprehensively analyzed the biological significance of genes involved in lipid metabolism in advanced gastric cancer (AGC). We obtained gene expression profiles from The Cancer Genome Atlas (TCGA) database for early and advanced gastric cancer samples and performed differential expression analysis to identify specific lipid metabolism-related genes in AGC. We then used consensus cluster analysis to classify AGC patients into molecular subtypes based on lipid metabolism and constructed a diagnostic model using least absolute shrinkage and selection operator- (LASSO-) Cox regression analysis and Gene Set Enrichment Analysis (GSEA). We evaluated the discriminative ability and clinical significance of the model using the Kaplan-Meier (KM) curve, ROC curve, DCA curve, and nomogram. We also estimated immune levels based on immune microenvironment expression, immune checkpoints, and immune cell infiltration and obtained hub genes by weighted gene co-expression network analysis (WGCNA) of differential genes from the two molecular subtypes. We identified 6 lipid metabolism genes that were associated with the prognosis of AGC and used consistent clustering to classify AGC patients into two subgroups with significantly different overall survival and immune microenvironment. Our risk model successfully classified patients in the training and validation sets into high-risk and low-risk groups. The high-risk score predicted poor prognosis and indicated low degree of immune infiltration. Subgroup analysis showed that the risk model was an independent predictor of prognosis in AGC. Furthermore, our results indicated that most chemotherapeutic agents are more effective for AGC patients in the low-risk group than in the high-risk group, and risk scores for AGC are strongly correlated with drug sensitivity. Finally, we performed qRT-PCR experiments to verify the relevant results. Our findings suggest that lipid metabolism-related genes play an important role in predicting the prognosis of AGC and regulating immune invasion. These results have important implications for the development of targeted therapies for AGC patients.

Distribution and Clinicopathological Features of Mott Cells (Plasma Cells Containing Russell Bodies) in Gastric Cancer: Presence of Mott Cells Is Associated with Favorable Prognosis

Gastric cancer (GC) is still one of the leading causes of cancer-related mortality. We previously reported the relationship between histological heterogeneity of tumor cells and molecular features in GC. The tumor microenvironment also has a crucial role in GC progression and therapeutic resistance. In this study, we focused on the tumor microenvironment, especially inflammatory cells in GC. Using GC tissue slides, we investigated the distribution and clinicopathological significance of inflammatory cell counts including eosinophils, neutrophils, lymphocytes, and plasma cells. Additionally, we investigated the relationship between Mott cells (plasma cells containing Russell bodies) and clinicopathological features. In neoplastic gastric mucosa, a high number of plasma cells was associated with low T-grade, early stage, and good prognosis. We then focused on Mott cells and found that their presence in neoplastic gastric mucosa was associated with lower T and N grades, early stage, and Helicobacter pylori infection and was inversely associated with CD44 and EGFR expression. Additionally, the presence of Mott cells was associated with good prognosis in advanced GC and was an independent favorable prognostic predictor. The presence of Mott cells in GC might be one useful prognostic predictor, and Mott cells might have an important role in the carcinogenesis of H. pylori infection.

Abdominal Visceral-to-Subcutaneous Fat Volume Ratio Predicts Survival and Response to First-Line Palliative Chemotherapy in Patients with Advanced Gastric Cancer.

Prognosis in advanced gastric cancer (aGC) is predicted by clinical factors, such as stage, performance status, metastasis location, and the neutrophil-to-lymphocyte ratio. However, the role of body composition and sarcopenia in aGC survival remains debated. This study aimed to evaluate how abdominal visceral and subcutaneous fat volumes, psoas muscle volume, and the visceral-to-subcutaneous (VF/SF) volume ratio impact overall survival (OS) and progression-free survival (PFS) in aGC patients receiving first-line palliative chemotherapy. We retrospectively examined CT scans of 65 aGC patients, quantifying body composition parameters (BCPs) in 2D and 3D. Normalized 3D BCP volumes were determined, and the VF/SF ratio was computed. Survival outcomes were analyzed using the Cox Proportional Hazard model between the upper and lower halves of the distribution. Additionally, response to first-line chemotherapy was compared using the χ2 test. Patients with a higher VF/SF ratio (N = 33) exhibited significantly poorer OS (p = 0.02) and PFS (p < 0.005) and had a less favorable response to first-line chemotherapy (p = 0.033), with a lower Disease Control Rate (p = 0.016). Notably, absolute BCP measures and sarcopenia did not predict survival. In conclusion, radiologically assessed VF/SF volume ratio emerged as a robust and independent predictor of both survival and treatment response in aGC patients.

Challenge and Innovation of CAR-T Cell Therapy for Gastric Cancer: Target Antigens and Side Effects

Gastric cancer (GC) is one of the most common malignant tumors of digestive tract worldwide. The clinical symptoms of early GC are hidden and the prognosis of advanced GC is poor. Chimeric antigen receptor (CAR) T cell has got a great number of advantages such as strong lethality, high targeting, lasting curative effect and so on. The application of CAR-T cell therapy for hematological malignancies has made a major breakthrough. However, some problems still exist in the application of CAR-T cell for GC. The effect of CAR-T cell therapy for GC can be effectively enhanced by selecting effective antigen targets, reducing side effects and applying many innovative strategies. This article summarizes the development and characteristics as well as novel target antigens and severe side effects of CAR-T cell therapy in the treatment of GC to explore the possibility of benefit from CAR-T cell therapy in patients with advanced GC in the future.

Circulating neutrophils activated by cancer cells and M2 macrophages promote gastric cancer progression during PD-1 antibody-based immunotherapy.

Aims: To analyze the correlation between the neutrophil-to-lymphocyte ratio (NLR) and prognosis of advanced gastric cancer (AGC) patients treated by PD-1 antibody-based therapy and to delineate molecular characteristics of circulating neutrophils by single-cell RNA sequencing (scRNA-seq). Methods: The clinicopathological information of 45 AGC patients receiving PD-1 antibody-based regimens at the Department of Oncology, Ruijin Hospital, was reviewed. Treatment outcomes including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were recorded. The correlation between NLR and efficacy of PD-1 antibody-based treatment was analyzed. Single-cell RNA sequencing (scRNA-seq) analysis was performed based on multisite biopsy samples from two AGC patients to explore the molecular characteristics of circulating neutrophils and their pro-tumor mechanisms. Tissue samples from 88 gastric cancer patients who underwent radial gastrectomy were collected for immunochemistry staining. Results: A high posttreatment NLR was associated with poor outcomes of AGC patients receiving PD-1 antibody-based regimens. scRNA-seq analysis showed that an increased number of circulating neutrophils were found in peripheral blood samples after treatment in which neutrophil cluster 1 (NE-1) was the major subcluster. NE-1 was featured with a neutrophil activation phenotype with the high expression of MMP9, S100A8, S100A9, PORK2, and TGF-β1. NE-1 displayed an intermediate state in pseudotime trajectory analysis with gene function enrichment found in neutrophil activation, leukocyte chemotaxis, and negative regulation of MAP kinase activity. Cellular interaction analysis showed that the chemokine signaling pathway is the major interactional pathway of NE-1 between subclusters of malignant epithelial cells (EP-4) and M2 macrophages (M2-1 and M2-2). In turn, the MAPK signaling pathway and Jak-STAT signaling pathway of EP-4, including IL1B/IL1RAP, OSM/OSMR, and TGFB1/TGFBR2 axes, were identified as interacting pathways between EP-4 and NE-1. The high expression of OSMR in tumor cells was closely correlated with lymph node metastasis of gastric cancer. Conclusion: The posttreatment NLR could be a poor prognostic marker of AGC patients treated with immune checkpoint inhibitors (ICIs). Subclusters of circulating neutrophils activated by tumor cells and M2 macrophages could participate in gastric cancer progression through signaling interactions with tumor cells.

A nine-gene signature as prognostic biomarker in gastric cancer by bioinformatics analysis.

The prognosis of advanced gastric cancer (GC) remains poor. It is urgent and necessary to find suitable prognostic markers. miR-619-5p is highly expressed in GC. However, the value of miR-619-5p and its target genes as prognostic biomarkers of GC is unclear. RT-PCR was performed to verify the expression of miR-619-5p in GC cell lines and their exosomes. Western blotting and transmission electron microscope were used to identify exosomes. The target genes of miR-619-5p were predicted by RNA22 and TargetScan. The differentially expressed genes (DEGs) and prognosis-related genes (PRGs) were obtained using The Cancer Genome Atlas (TCGA) database. The DAVID database was used to analyse pathway enrichment and functional annotation of common target genes. The STRING database and Cytoscape software were used to screen key genes and visualize their functional modules. The survival analysis was conducted using TCGA and Kaplan-Meier Plotter (KMP) databases. Finally, a prognostic model was constructed on the foundation of the key genes to assess the reliability of the screening process. The expression of miR-619-5p in GC cells and their exosomes was proved to be significantly higher than that in normal cell lines. There are 129 common target genes involved in 3 pathways and 28 functional annotations. Finally, nine key target genes of GC (BRCA1, RAD51, KIF11, ERCC6L, BRIP1, TIMELESS, CDC25A, CLSPN and NCAPG2) were identified, and a prognostic model was successfully constructed with a good predictive ability. The model of 9-gene signature could effectively predict the prognosis of GC, and have great potential to be novel prognostic factors and therapeutic targets for patients with GC.

Abstract 2685: Synergistic antitumor effect of oncolytic virus and cytotoxic chemotherapy in gastric cancer

Abstract Introduction: The prognosis of advanced gastric cancer is extremely poor, and the development of novel effective treatment is necessary. Currently, platinum-based, fluoropyrimidine-based, and paclitaxel-based combinations are accepted worldwide as established first-line and second-line drug regimens. Pexa-Vec (pexastimogene devacirpvec; JX-594) engineered from the Wyeth vaccine strain has emerged as attractive oncolytic virotherapy in cancer treatment. Pexa-Vec demonstrated oncolytic, immunotherapeutic, and tumor vascular disrupting mechanisms of action. The aim of this study is to investigate the combination efficacy of JX-594 with paclitaxel in human gastric cancer cell lines and to identify potential biomarkers of oncolytic virotherapy. Method: The anti-proliferative activities of paclitaxel and JX-594 were performed using 49 human gastric cancer cell lines, and YCC-32 was selected for sensitive to JX-594 and resistance to paclitaxel. YCC-32 was treated with JX-594 and paclitaxel, alone and in combination. Cytotoxicity was evaluated by MTT assay. Compusyn and Combenefit software was used to evaluate synergistic efficacy. In addition, the synergism effect was evaluated in the xenograft mouse model in vivo. Tumors were implanted by subcutaneous injection of 5 x 106 YCC-32 cells into the right flank of nude mice. When tumors reached &amp;gt;100mm3, mice were treated with either PBS, 1 x 107 plaque-forming units (pfu) of JX-594 by intratumoral (IT), 5mg/kg paclitaxel by intraperitoneal (IP) injection, or combination every 7 days. Result: Cytopathic effect of Pexa-Vec and paclitaxel was observed in YCC-32 gastric cancer cell line. IC50 (half maximal inhibitory concentration) of JX-594 and paclitaxel were 0.0089 MOI and 7.021ng/ml in YCC-32 cell. JX-594 and paclitaxel in YCC-32 was used to assess the synergism of the two drugs in a dose-dependent manner. In YCC-32 cell line, in combination with JX-594 0.01 MOI and paclitaxel 7ng/ml had CI (combination index) value had 0.69, suggesting synergism. To assess the potential therapeutic benefit of combining JX-594 with paclitaxel in vivo, we employed YCC-32 xenograft models and observed the antitumor effects of JX-594, paclitaxel, and their combination. Paclitaxel, JX-594, and their combination reduced tumor growth compared to control at 64.1%, 59.2%, and 19.1% for YCC-32 xenografts. This result suggests that combined treatment with JX-594 and paclitaxel significantly enhanced tumor growth inhibition compared to monotherapy. Conclusion: Combination with JX-594 and paclitaxel showed enhanced antitumor effects in vitro and in vivo. This study shows combination synergism and provides a promising approach to combination therapy with an oncolytic virus on gastric cancer. For future research, additional studies on other gastric cancer cell lines and investigation of mechanisms are needed. Citation Format: Jee Hung Kim, YeLin Kim, Youkeun Shin, Dagyo Oh, Woo Sun Kwon, Tae Soo Kim, Namhee Lee, Keunhee Oh, Hyun Cheol Chung, Hei-Cheul Jeung, Sun Young Rha. Synergistic antitumor effect of oncolytic virus and cytotoxic chemotherapy in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2685.

Delta computed tomography radiomics features-based nomogram predicts long-term efficacy after neoadjuvant chemotherapy in advanced gastric cancer.

No effective preoperative tool is available for predicting the prognosis of advanced gastric cancer (AGC) treated by neoadjuvant chemotherapy (NAC). We aimed to explore the association between change values ("delta") in the radiomic signatures of computed tomography (CT) (delCT-RS) before and after NAC for AGC and overall survival(OS). A total of 132 AGC patients with AGC were studied as a training cohort in our center, and 45 patients from another center were used as an external validation set. A radiomic signatures-clinical-nomogram(RS-CN) was established using delCT-RS and preoperative clinical variables. The prediction performance of RS-CN was evaluated using the area under the receiver operating characteristic (ROC)curve (AUC values), time-dependent ROC, decision curve analysis(DCA) and C-index. Multivariable Cox regression analyses showed that delCT-RS, cT-stage, cN-stage, Lauren-type and the value of variation of carcinoma embryonic antigen (CEA) between NAC were independent risk factors for 3-year OS of AGC. In the training cohort, RS-CN had a good prediction performance for OS (C-Index 0.73) and AUC values were significantly better than those of delCT-RS, ypTNM-stage and tumor regression grade(TRG) (0.827 vs 0.704 vs 0.749 vs 0.571, p < 0.001). DCA and time-dependent ROC of RS-CN were better than those of ypTNM stage, TRG grade and delCT-RS. The prediction performance of the validation set was equivalent to that of the training set. The cut-off (177.2) of RS-CN score was obtained from X-Tile software, a score of > 177.2 was defined as high-risk group(HRG), and scores of ≤ 177.2 were defined as the low-risk group(LRG). The 3-year OS and disease free survival(DFS) of patients in the LRG were significantly better than those in the HRG. Adjuvant chemotherapy(AC) can only significantly improve the 3-year OS and DFS of the LRG. (p < 0.05). Our nomogram based on delCT-RS has good prediction of prognosis before surgery and helps identify patients that are most likely to benefit from AC. It works well in precise and individualised NAC in AGC.

The Influence of Group No.8p Lymph Node Dissection on the Prognosis of Advanced Gastric Cancer

BackgroundControversy over whether No.8p lymph nodes (LNs) involvement is distant or regional metastasis remains, and the possible inclusion of No.8p LNs in D2 lymphadenectomy is unclear. AimThis work aimed to investigate the effect of No.8p LN dissection on the prognosis of patients with different LN metastases in advanced gastric cancer (GC). MethodsA retrospective case–control study was used to collect 1149 cases of radical gastrectomy from July 2003 to April 2013. The patients were divided into the No.8a group (303 cases) and the No.8a + 8p group (846 cases) according to whether No.8p LN dissection was performed. The effect of No.8p LN dissection on the prognosis of patients with different total number of LN metastasis was analyzed. ResultsBoth No.8p positive and No.8p dissection were independent prognostic factors in patients with advanced GC. The 5-year overall survival rate (OS) of the positive No.8p group was 13.0%, and that of the negative No.8p group was 66.6%; the difference was significant (P < 0.05). In the group where the total number of LN metastasis was 3–15, the OS of patients with positive No.8p was significantly lower than that of the negative group (P < 0.05). The 5-year OS of the No.8a + 8p dissection group was 65.4%, and that of the No.8a dissection group was 55.5%; the difference was significant (P < 0.05). In the group where the total number of LN metastasis was 0–2, the No.8a + 8p dissection group had significantly higher OS than the No.8a dissection group (P < 0.05). ConclusionFor patients with advanced GC, No.8p LN metastasis indicates a poor prognosis. LN dissection in the No.8a + 8p group may further improve the prognosis of some patients, especially when the total number of LN metastasis is 0–2.

Exosomal hsa-let-7g-3p and hsa-miR-10395-3p derived from peritoneal lavage predict peritoneal metastasis and the efficacy of neoadjuvant intraperitoneal and systemic chemotherapy in patients with gastric cancer.

The prognosis of advanced gastric cancer (GC) invading the gastric serosa remains poor, mainly owing to high incidence of peritoneal recurrence. Patients with peritoneal metastases are often treated with neoadjuvant intraperitoneal and systemic chemotherapies (NIPS). Good responders to NIPS often undergo conversion gastrectomy. This study aims to explore biomarkers predicting the occurrence of peritoneal metastasis (PM) and evaluating the efficacy of NIPS in GC patients. We collected six peritoneal lavage (PL) samples from two patients with PM, two without PM, and two with diminished PM after NIPS via intraperitoneal access ports. We equally isolated microRNAs from exosomes derived from PL samples for deep sequencing. Two microRNAs (hsa-let-7g-3p and hsa-miR-10395-3p) were identified, and their expression levels were examined in PL samples of 99 GC patients using qRT-PCR. Moreover, we performed in vivo and in vitro functional assays to investigate effects of these microRNAs on metastasis and chemoresistance of GC cells. Exosomal microRNA expression profiling of six PL samples indicated that the microRNA signature in exosomes of PLs from patients with diminished PM was similar to that from patients without PM. Expression levels of hsa-let-7g-3p and hsa-miR-10395-3p were associated with PM. In vivo and in vitro functional assays confirmed that hsa-let-7g-3p and hsa-miR-10395-3p are involved in GC metastasis and chemoresistance. PL-derived exosomes in GC contain large amounts of microRNAs related to PM. Moreover, hsa-let-7g-3p and hsa-miR-10395-3p could be used as biomarkers predicting PM and NIPS efficacy and are involved in GC metastasis and chemoresistance.

Risk Stratification and Overall Survival Prediction in Advanced Gastric Cancer Patients Based on Whole-Volume MRI Radiomics.

The prognosis of advanced gastric cancer (AGC) patients has attracted much attention, but there is a lack of evaluation method. MRI-based radiomics has the potential to evaluate AGC patients' prognosis. To identify and validate the risk stratification and overall survival (OS) in AGC patients using MRI-based radiomics. Retrospective. A total of 233 patients (168 males, 63.6 ± 11.1 years; 65 females, 59.7 ± 11.8 years) confirmed AGC were collected. The data were randomly divided into a training (164) and validation set (69). A 3.0 T, axial T2-weighted, diffusion-weighted imaging, and contrast-enhanced T1-weighted (CE-T1WI). Radiologist 1 segmented 233 patients and radiologist 2 segmented randomly 50 patients on CE-T1WI. The risk score (RS) was summed by each sample based on the radiomics features and correlation coefficients. Patients were followed up for 7-67months (median 41; 138 dead and 95 alive). The intraclass correlation coefficient (ICC) and Kappa value were calculated. Differences in survival analysis were assessed by Kaplan-Meier curves and log-rank test. Cox-regression analysis was performed to identify the radiomics features and clinical indicators associated with OS. The calibration curves were built to assess the model. A two-tailed P value < 0.05 was considered statistically significant. Integrated with age, lymphovascular invasion (LVI) and RS, a survival combined model was built. The area under the curve (AUC) for predicting 3-year and 5-year OS was 0.765 and 0.788 in the training set, 0.757 and 0.729 in the validation set. There was no significant difference between the radiomics model and survival combined model for 3-year (0.690 vs. 0.757, P=0.425) and 5-year OS (0.687 vs. 729, P=0.412) in the validation set. The calibration curves showed a high degree of fit for the survival combined model. This study established a survival combined model that might help AGC patients in future clinical decision-making. 33 TECHNICAL EFFICACY: Stage 5.

Tumor budding as a predictor for prognosis and therapeutic response in gastric cancer: A mini review.

In recent years, the role of tumor budding in gastric cancer has received increased attention across a number of disciplines. Several studies have found associations between tumor budding and the prediction of lymph node metastasis in early gastric cancer, prognosis of advanced gastric cancer, predictors of therapeutic response to immune checkpoint inhibitors, such as microsatellite instability (MSI), and therapeutic targets of molecular targeted therapy, such as human epidermal growth factor receptor 2 (HER-2). Therefore, tumor budding is a major element in the formulation of risk stratification and precision medicine strategies for patients with gastric cancer.

Application of immune checkpoint inhibitors in immunotherapy for gastric cancer.

Gastric cancer is the fifth most common cancer worldwide. With the development of immunotherapy, especially the application of immune checkpoint inhibitors (ICIs), the prognosis of advanced gastric cancer has improved. At present, ICIs combined with other therapies or dual ICI strategies in the treatment of advanced gastric cancer have shown clinicaleffectivenessand controllable safety. In addition, predictive biomarkers facilitate the precise selection of patients. Therefore, it is crucial to explore rational combinations and reliable predictive biomarkers for ICI therapy. This article reviews the recent advances in ICIs and relevant predictive biomarkers in the treatment of gastric cancer.

Clinical Significance of Fibrinogen and Platelet to Pre-Albumin Ratio in Predicting the Prognosis of Advanced Gastric Cancer.

The aim of this study was to investigate the clinical significance of Fibrinogen and Platelet to Pre-albumin Ratio(FPAR) in predicting the prognosis of patients with advanced gastric cancer(AGC) and to construct a predictive model. We collected clinical data from 489 postoperative patients with AGC. FPAR was divided into high and low groups according to the receiver operating characteristic (ROC) curve. The value of FPAR in predicting the prognosis of progressive gastric cancer was analysed using univariate and multivariable Cox regression analysis and its relationship with clinicopathological features. Finally, the Overall Survival(OS) and recurrence-free survival(RFS) prediction models were constructed and validated using FPAR. Univariate and multifactorial cox regression analysis showed that grade (P<0.001), TNM-stage (P<0.001), chemotherapy (P<0.001), and FPAR (OR=3.054,95% CI:2.088-4.467, P<0.001) were independent risk factors for OS; grade (P=0.021), N-stage (P=0.024), TNM-stage (P=0.033), and FPAR (OR=2.215,95% CI:1.634-3.003, P<0.001) were independent risk factors for RFS. Subgroup analysis showed that the FPAR-low group had higher OS and RFS than the FPAR-high group, regardless of the patient's TNM stage (p<0.05). However, OS was instead higher in the the stage III-FPAR-low group than in the the stage II-FPAR-high group (p<0.05), while RFS was not significantly different. Predictive models incorporating FPAR had better predictive performance than those without FPAR, showing wide range of net benefit and AUC. After correction, the 2-year AUC, 3-year AUC and C-index of the OS model were 0.737, 0.756, and 0.746; the 2-year AUC, 3-year AUC, and C-index of the RFS model were 0.738, 0.758, and 0.711. FPAR levels were associated with prognosis in patients with AGC and could independently predict RFS and OS.

An abscopal effect in a gastric cancer patient treated with combined chemoimmunotherapy and palliative radiotherapy.

The prognosis of advanced gastric cancer remains poor. Palliative radiotherapy has been utilized to palliate bleeding in unresectable gastric cancer. Recent studies have described that a systemic immune response may be induced by local radiotherapy to the primary tumor lesion. Here we report a rare case of an abscopal effect in a patient with inoperable gastric cancer combined with tumor hemorrhage. A short course of radiotherapy was performed to palliate bleeding; additionally, the patient was treated with chemotherapy and immunotherapy. Complete response was achieved in the lung metastasis lesion. The observed abscopal effect suggests that there may be a synergistic effect between immunotherapy and radiotherapy. This case report supports the combination of immunotherapy and radiotherapy in patients with advanced gastric cancer.

Are anti-PD-1-associated immune related adverse events a harbinger of favorable clinical prognosis in patients with gastric cancer?

BackgroundImmune checkpoint inhibitors (ICIs) has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate immune related adverse events (irAEs) in patients. Some studies have shown that there is a close relationship between the occurrence of irAEs and prognosis. In present study, we have attempted to establish whether the occurrence of irAEs after the use of anti PD-1 antibodies is associated with treatment efficacy in people with advanced gastric cancer (AGC).MethodsThis study included patients treated with the anti-PD-1 antibodies for AGC patients at The Fourth Hospital of Hebei Medical University. IrAEs were identified clinically and graded as per the National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.03. Efficacy was evaluated with objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS). The analysis was performed to determine the association between irAEs and clinical outcomes.ResultOf the 74 AGC patients in our study, 24 developed irAEs. The DCR of the irAE displayed a trend better than that of non-irAE group but without statistical difference (41.70% VS 6.0%, p = 0.118). Median PFS in the irAE group was superior to that in the non-irAE group (176 days VS 94 days, p = 0.001). Median OS also showed this trend of difference at borderline statistical level (292 days VS 239 days, p = 0.057). Multivariate analysis also demonstrated irAE (HR = 0.269, 95%CI: 0.088 to 0.822, p = 0.021) were associated independently with the better prognosis for AGC patients.ConclusionIn advanced gastric cancer treated with anti PD-1 antibodies, the occourence of irAEs might contribute to the improved prognosis.

Pattern of disease progression during third-line or later chemotherapy with nivolumab associated with poor prognosis in advanced gastric cancer: a multicenter retrospective study in Japan

BackgroundAccelerated tumor growth during immunotherapy in pre-existing measurable lesions, hyperprogressive disease (HPD), has been reported. However, progression of non-measurable lesions and new lesions are frequently observed in patients with advanced gastric cancer (AGC).MethodsThis retrospective study involved AGC patients at 24 Japanese institutions who had measurable lesions and received nivolumab after ≥ 2 lines of chemotherapy. HPD was defined as a ≥ two-fold increase in the tumor growth rate of measurable lesions. The pattern of disease progression was classified according to new lesions in different organs and ascites appeared/increase of ascites.ResultsOf 245 patients, 147 (60.0%) showed progressive disease (PD) as the best response and 41 (16.7%) showed HPD during nivolumab monotherapy. There was no significant difference in overall survival (OS) between patients with HPD and those with PD other than HPD (median OS 5.0 vs 4.8 months; hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.6–1.5; p = 1.0). Fifty-three patients developed new lesions in different organs and 58 had appearance/increase of ascites; these patients showed shorter OS than those without each of these features (median OS 3.3 vs 7.1 months, HR 1.8, 95% CI 1.2–2.7, p = 0.0031 for new lesions, and 3.0 vs 7.8 months, HR 2.6, 95% CI 1.8–3.8, p < 0.0001 for ascites). Thirty-one patients who had both features showed the worst prognosis (median OS 2.6 months).ConclusionsNew lesions in different organs and appearance/increase of ascites, rather than the original definition of HPD, are the patterns of disease progression associated with poor prognosis in AGC patients receiving nivolumab whose best response was PD.