4009 Background: The addition of immune checkpoint inhibitors (ICIs) to chemotherapy (chemo) in the neoadjuvant/adjuvant setting for gastric cancer (GC) has yielded mixed efficacy. Target population and treatment regimen remain to be optimized. This study compared the efficacy of serplulimab (anti-PD-1 antibody) plus chemo versus placebo plus chemo as neoadjuvant therapy and serplulimab versus chemo as adjuvant therapy for resectable GC. Methods: Patients with PD-L1 positive (PD-L1 CPS ≥ 5), histologically confirmed, untreated, resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma were randomized 1:1 to receive 3 cycles of neoadjuvant intravenous (iv) serplulimab (4.5 mg/kg) or placebo, plus chemo (iv oxaliplatin, 130 mg/m 2 and oral S-1, 40-60 mg based on body surface area), followed by post-surgery adjuvant serplulimab monotherapy (up to 17 cycles) or adjuvant chemo (5 cycles), Q3W. The primary endpoint was investigator (INV)-assessed event-free survival (EFS). Efficacy superiority was first evaluated and established in patients with PD-L1 CPS ≥ 10 followed by that in the PD-L1 CPS ≥ 5 population. Results: Between November 26, 2019 and April 19, 2024, 588 patients were enrolled across 57 sites, with 292 randomized to the serplulimab group and 296 to the placebo group. As of the data cutoff date of August 19, 2025 with a median follow-up duration of 35.9 months, INV-assessed median EFS was significantly longer in the serplulimab group (n = 193) than in the placebo group (n = 217) in the PD-L1 CPS ≥ 10 population (not reached [NR], 95% CI 43.0–not estimable [NE] vs. 42.0 months, 95% CI 20.5–NE; HR 0.65, 95% CI 0.47–0.90; p = 0.0082), and in the PD-L1 CPS ≥ 5 population (NR, 95% CI 37.9–NE vs. 35.9 months, 95% CI 21.3–52.0; HR 0.73, 95% CI 0.56–0.94; p = 0.0152), meeting the protocol-specified superior criteria. Blinded independent central review-assessed median EFS was consistent with that of the investigator. Pathological complete response rate was higher in the serplulimab group than in the placebo group (21.6% vs 6.4%; odds ratio 3.95). Median OS was immature in both groups. Grade ≥ 3 treatment-related adverse events (TRAEs) were reported in 136 (46.6%) and 172 (58.5%) patients in the serplulimab and placebo groups, respectively. Discontinuation of any component of the study regimen due to TRAEs occurred in 19 (6.5%) and 31 (10.5%) patients in the respective groups. Conclusions: Neoadjuvant serplulimab plus chemo, followed by adjuvant serplulimab monotherapy, significantly prolonged EFS in patients with PD-L1-positive, resectable GC or GEJ adenocarcinoma. Improvements in other efficacy endpoints were also observed along with a favorable safety profile compared to neoadjuvant/adjuvant chemo. This world-first chemotherapy-free regimen (adjuvant) represents a promising treatment option for this indication. Clinical trial information: NCT04139135 .

Timely detection of gastric cancer is critical for improving prognosis and treatment outcomes, yet existing diagnostic methods often fail to identify early-stage cases. To address these challenges, this study introduces a hybrid diagnostic framework that combines a Gated Recurrent Unit (GRU) Network with the Adjusted Tyrannosaurus Optimization Algorithm (ATOA) for feature selection and classification. The ATOA, using advanced mechanisms such as Levy flights and chaotic sinusoidal maps, enhances the GRUs optimization process by overcoming premature convergence and improving global search efficiency. The model was applied to the GasHisSDB dataset, which consists of over 245,196 histopathological patches grouped into three sub-databases with various cropping sizes. After preprocessing and data augmentation, the ATOA/GRU model demonstrated superior performance compared to traditional algorithms, such as Logistic Regression (LR), Random Forest (RF), Gradient Boosting Decision Trees (GBDT), convolutional neural networks (CNN), and MBNet. Quantitatively, the ATOA/GRU achieved mean accuracy, precision, recall, and AUC values of 95.37%, 97.45%, 93.62%, and 0.946, respectively, on Sub-database A. On Sub-database B, it achieved an AUC of 0.930, significantly outperforming CNN, with the values of 84.61% and 0.888 for accuracy and AUC, respectively. These findings highlight the model's effectiveness in improving diagnostic accuracy and early detection of gastric cancer, emphasizing its potential in clinical applications.

Gastric cancer remains a significant global health challenge due to its high incidence and mortality, and limited treatment options in advanced stages. Notably, gastric cancer exhibits a complex tumor microenvironment (TME) with substantial cellular and spatial heterogeneity, which profoundly impacts disease pathogenesis and therapeutic resistance. Genetic mutations and chronic inflammation contribute to its development by promoting abnormal cell proliferation and creating an immunosuppressive TME. The TME comprises various cellular and acellular components—including tumor-infiltrating lymphocytes, myeloid lineage cells such as tumor-associated macrophages and myeloid-derived suppressor cells, cancer-associated fibroblasts, extracellular matrix, and peripheral nerves—that interact with cancer cells, influencing tumor initiation, progression, immune evasion, and resistance to therapy. These elements modulate immune responses, remodel the extracellular matrix, and facilitate tumor growth and metastasis, thereby adding to the complexity of the TME. Moreover, the TME plays a critical role in therapeutic resistance through mechanisms involving angiogenesis, fibrosis, and metabolic reprogramming. Understanding the dynamic interactions within the TME offers opportunities to develop novel therapeutic strategies. Emerging approaches targeting the TME—including modulation of immune components, inhibition of fibrosis, normalization of angiogenesis, and disruption of metabolic pathways—hold promise in overcoming therapeutic resistance. Advances in technologies such as single-cell sequencing and spatial transcriptomics further enhance our understanding of TME heterogeneity, paving the way for personalized medicine in gastric cancer treatment. This review summarized the current knowledge of the cellular and molecular composition of the TME of gastric cancer, its role in disease pathogenesis and therapy resistance, and explores potential therapeutic strategies targeting TME components.

Abstract Background Breast cancer (BC) is the most common malignancy among women worldwide. Women in Mongolia, China, with BC face distinct socioeconomic and cultural barriers that may affect their health-related quality of life (HRQoL), particularly during adjuvant endocrine therapy (AET). This study assessed the HRQoL of Mongolian-speaking BC patients undergoing AET. Methodology This descriptive, cross-sectional study included Mongolian-speaking BC patients from two hospitals in Inner Mongolia, China. Participants provided their sociodemographic and clinical information. They completed the Mongolian versions of the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES). Eastern Cooperative Oncology Group (ECOG) performance status was assessed by an oncologist during the clinical encounter and recorded for study purposes. Results Of 215 patients approached, 200 participated and completed the questionnaires. Mean(SD) age = 55.45 ± 9.63 years; 72.5% were Stages I-II, 76% had a mastectomy, and 12% had breast-conserving surgery. Fourteen symptoms were reported by over 20% of participants. The most frequently reported were joint pain (82%), hot flashes (72%), cold sweats (61%) and mood swings (60%). Emotional well-being scores were lower than those reported in healthy females and female cancer patients, while functional well-being scores were relatively higher. Univariate analysis revealed significant differences in various subscales and overall FACT-ES scores across different characteristics, including annual income, occupational status, previous surgical procedures, cancer stage at diagnosis, and ECOG performance status (all P <.05). In multivariate regression analysis, ECOG performance status was negatively associated with most subscales and the overall FACT-ES ( P <.001). Conclusions These findings highlight the complex relationships between AET and HRQoL, as well as the specific challenges for Mongolian-speaking BC patients receiving AET in Inner Mongolia, China, underscoring the need for multidimensional approaches to improving HRQoL.

BACKGROUND:Extrachromosomal DNA (ecDNA), as a dynamic genetic vector, enables tumor cells to exhibit enhanced adaptability under chemotherapeutic stress. However, its functional role in tumor malignancy and the development of drug resistance in gastric cancer (GC) remains unclear. OBJECTIVE:This study aimed to investigate the relationship between chemotherapy and ecDNA in GC, and to explore its potential as a novel therapeutic target. METHODS:We first analyzed our clinical data to reveal associations between ecDNA induction by chemotherapy and metastatic progression. Then we investigated the role of ecDNA in mediating chemoresistance and malignant phenotypes in cisplatin-resistant cell models using WGS, SEM, western blot, qPCR, flow cytometry, and immunofluorescence. RESULTS:We found that neoadjuvant chemotherapy (NAC) promoted ecDNA formation from linear amplicons, which was associated with increased tumor mutational burden, poorer survival, and higher distant metastasis risk. The generation of ecDNA in GC was more likely to originate from chromosomes 5, 7, 8, 9, and 12. In cisplatin-resistant models, ecDNA emergence promoted various malignant phenotypes, including DNA damage repair, G1 arrest, autophagy, proliferation, migration, and invasion, which were attenuated by ecDNA inhibition. EcDNA inhibitors delayed acquired resistance in wild-type cells and showed combinatorial activity with cisplatin in resistant GC, supporting clinical potential. CONCLUSION:Our study revealed that cisplatin could promote ecDNA generation, which enhanced malignant phenotypes, including cell proliferation, motility and drug resistance, and was associated with poorer patient prognosis. Targeting ecDNA with inhibitors could reverse these effects, supporting further preclinical evaluation.

With advances in pharmaceutical research,the treatment paradigm for gastric cancer in China has undergone profound changes. In the 1970s and 1980s,Japanese scholars introduced the concept of D2 lymphadenectomy in the Japanese Gastric Cancer Treatment Guidelines (1).Radical surgery centered on D2 lymphadenectomy has since become the cornerstone of gastric cancer surgery and has been widely adopted across China (2). The launch of the RESOLVE trial in 2012 marked the arrival of the neoadjuvant chemotherapy era for locally advanced gastric cancer (LAGC) in China,and its 2021 publication established the Chinese standard for perioperative chemotherapy for LAGC (3).

Neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (nCRT) are increasingly used to treat adenocarcinoma of the esophagogastric junction (AEG). However, there is insufficient clinical evidence to compare surgical safety among the three comprehensive treatment models, including the surgery‑first model, NAC model, and nCRT model. Therefore, this study was designed to compare surgical safety of the three comprehensive treatment models. This is a retrospective cohort study. From January 2012 to December 2018, 276 consecutive patients with Siewert II and III AEG (cT2-4NxM0) in the Gastrointestinal Cancer Center, Peking University Cancer Hospital Institute were enrolled in this study. All these patients underwent surgery and were categorized into three groups: surgery‑first group, NAC group and nCRT group. Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the three groups. The overall postoperative complication rate in nCRT groups was 59.6

Tumor-derived model biobanks comprise patient-derived xenografts, organoids, cell models or cultures, and selected paired derivatives linked to clinical, pathological, molecular, and functional data. In China, patient-derived organoid and xenograft resources have expanded through clinical and academic studies, enterprise-operated platforms, and conventional hospital biobank support for clinical sourcing and quality management. Published studies demonstrate disease-focused living resources in common tumors as well as selected premalignant and less common settings. Clinical and academic groups provide clinically annotated specimens and outcome context, whereas enterprise-operated platforms describe model-generation workflows, functional testing modules, database interfaces, and preclinical service capacity. Together, these activities suggest a transition from project-based model collections toward translational research infrastructure. However, public catalogues, model-level quality descriptors, case-model-data linkage, and access mechanisms remain uneven. This review summarizes representative Chinese resources and enterprise platform types, discusses international benchmark functions for model-biobank maturity, and emphasizes quality transparency for external verification and resource discovery. Future development should strengthen minimum information fields, quality reporting, and governance mechanisms that allow model resources to be discovered and used under appropriate access control.

Background:The medical expenses of cancer patients have been rising worldwide, and the current payment system based on diagnosis-related groups is limited in reflecting the actual burden at the patient level. We aimed to develop a prediction model for reasonably high cost of hospitalization, taking gastric cancer (GC) patients undergoing surgery as an example. Methods:In this real-world patient cohort study, we collected clinical data from 3981 GC surgery inpatients in a tertiary hospital in Beijing, China. Reasonably high cost was defined as exceeding the 75th percentile of the hospitalization costs. The final model for reasonably high cost was derived based on univariate and multivariate unconditional logistic regression, with predictors selected according to the Akaike information criterion. Model performance was evaluated in terms of discrimination and calibration. Results:The final model consisted of 13 predictors, with the area under the receiver operating characteristics curve of 0.718 (95% confidence interval: 0.700-0.736). Leave-one-out cross-validation generated an area under the receiver operating characteristics curve of 0.708 (95% confidence interval: 0.690-0.727). No significant differences in model discrimination were detected among the subgroups stratified by gender, age, N stage, surgical method, and admission year. The calibration plot showed good agreement between predicted probability and observed frequency of reasonably high cost. Conclusions:Our prediction tool for reasonably high cost of GC surgery patients has demonstrated good performance. The combined use of diagnosis-related groups payment and reasonably high cost assessment is expected to promote individualization and precision in medical cost control and ensure rational, efficient, and equitable provision of medical services.

BACKGROUND:Perioperative chemo-immunotherapy shows variable outcomes in resectable gastric or gastro-oesophageal junction adenocarcinoma. We evaluated the efficacy and safety of neoadjuvant serplulimab with S-1 plus oxaliplatin (SOX) chemotherapy followed by adjuvant serplulimab versus neoadjuvant placebo plus SOX followed by adjuvant SOX in patients with PD-L1-positive, locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma. METHODS:In this randomised, double-blind, multicentre phase 3 ASTRUM-006 study, patients were screened at 75 hospitals in China and Thailand. Eligible patients aged 18-70 years with PD-L1 combined positive score (CPS) ≥5, resectable gastric or gastro-oesophageal junction adenocarcinoma were randomly assigned 1:1 to neoadjuvant serplulimab or placebo (intravenous; 4·5 mg/kg) plus SOX chemotherapy (intravenous oxaliplatin 130 mg/m2 on day 1, and oral S1 40-60 mg twice daily on days 1-14) for three cycles (cycle length 21 days), followed by adjuvant serplulimab (up to 17 cycles; serplulimab group) or SOX (five cycles; placebo group). The primary endpoint was investigator-assessed event-free survival (defined as the time from randomisation to the occurrence of progressive disease or local or distant recurrence, other new malignancies, or death), with efficacy first evaluated in PD-L1 CPS ≥10, then in the intention-to-treat (CPS ≥5) population. This study is registered with ClinicalTrials.gov, NCT04139135, and is ongoing. FINDINGS:Between Nov 26, 2019, and April 19, 2024, 1646 patients were screened, of whom 588 patients (median age 61·0 years [IQR 55-66]; 124 [21%] female and 464 [79%] male) at 57 hospitals in China were randomly assigned to the serplulimab group (n=292) or placebo group (n=296). With a median follow-up duration of 42·7 months (IQR 24·3-53·6), median event-free survival was significantly longer with serplulimab than with placebo in the PD-L1 CPS ≥10 population (not reached [NR] vs 42·0 months; hazard ratio 0·65 [95% CI 0·47-0·90]; p=0·0082). With a median follow-up of 35·9 months (IQR 23·5-49·4), median event-free survival was also significantly longer with serplulimab than with placebo in the intention-to-treat population (NR vs 35·9 months; 0·73 [95% CI 0·56-0·94]; p=0·015). Grade 3 or worse treatment-related adverse events occurred in 136 (47%) patients in the serplulimab group and 172 (59%) patients in the placebo group; 19 (7%) and 31 (11%) patients in the respective groups discontinued treatment due to treatment-related adverse events. INTERPRETATION:Neoadjuvant serplulimab plus SOX followed by adjuvant serplulimab significantly improved event-free survival and demonstrated a better safety profile compared with neoadjuvant and adjuvant SOX in PD-L1-positive, resectable gastric or gastro-oesophageal junction adenocarcinoma. Extended follow-up for the overall survival data is warranted to confirm a survival advantage of this perioperative strategy with a chemotherapy-sparing adjuvant component for this indication. FUNDING:Shanghai Henlius Biotech.

Gastric cancer is one of the most prevalent and deadly malignancies worldwide. In recent years, with the development of immune checkpoint inhibitors (such as PD-1/PD-L1 and CTLA-4 inhibitors), immunotherapy has emerged as a new strategy in gastric cancer treatment. However, the incidence of immune-related adverse events (irAEs) has also increased. Here, we report eleven cases of gastric cancer patients who developed pituitary or adrenal cortisol insufficiency in the first postoperative week following neoadjuvant immunotherapy. We present a retrospective analysis of patients who underwent surgical resection for gastric cancer at our center starting from December 2023. We evaluated their perioperative cortisol function and identified those who developed perioperative cortisol insufficiency, and identified eleven gastric cancer patients with normal cortisol functions who had received neoadjuvant immunotherapy, and subsequently experienced postoperative changes within a short period following surgery. Among them, six patients showed decreased ACTH and cortisol levels, four patients had reduced cortisol levels, and one patient with no ACTH testing also showed reduced cortisol levels. Six patients received hormone replacement therapy, with one developing anastomotic leakage after surgery. Notably, cortisol function was normal in all eleven patients preoperatively. All patients exhibited decreased cortisol function postoperatively, and 27

Gastrointestinal (GI) cancers represent a leading cause of cancer-related mortality globally, characterized by a complex tumor microenvironment where bidirectional neuro-cancer-immune interactions critically influence disease progression. The CNS integrates ascending gut-derived signals and transmits descending regulatory responses through distinct autonomic neural pathways, while peripheral sensory, sympathetic, parasympathetic, and enteric neurons modulate innate and adaptive immune cell functions through specialized neurotransmitter circuits. This coordinated neural-immune crosstalk operates within the neuro-endocrine-immune axis, forming an integrated regulatory network that governs tissue homeostasis and tumor surveillance. Emerging evidence demonstrates that neural dysregulation promotes GI tumorigenesis through immunosuppressive mechanisms, while therapeutic neural interventions show promising efficacy in preclinical cancer models. The gut-brain axis represents a paradigmatic framework for understanding how neuroimmune signaling influences cancer progression and metastasis, revealing previously unrecognized diagnostic, prognostic, and therapeutic opportunities. Here, we review the molecular mechanisms underlying neuroimmune interactions in GI cancer pathogenesis and evaluate the therapeutic potential of neurally targeted interventions for cancer management.

The tumour microenvironment is a focal point in cancer immunotherapy: its cellular composition and spatial organisation can affect the clinical outcomes of cancer patients. By integrating single-cell and spatial transcriptomics, we identify four spatial regions and survey how cellular spatial distribution varies across them in gastric cancer. One region, the Lymphocyte Aggregated Region, consists of lymphocyte aggregates and tertiary lymphoid structures. Within it, we observe associations between naive T cell abundance and T cell activation-associated pathways, and correlations exist between distribution patterns of different lymphocytes and two transcriptomically distinct groups — more activated lymphocytes reside in the adjacent cancerous regions of Group A, while more resting lymphocytes settle in those of Group B. Within Group A, PD1+CD27+ CD8 T cells cluster in closer proximity to CD70+LAMP3+ dendritic cells. Our study unveils the gastric cancer tumour microenvironment at a spatial resolution and provides insights into the exploration of immunotherapy biomarkers. The spatial organisation of the tumour microenvironment (TME) can affect immune responses that control tumour growth. Here, the authors use single-cell transcriptomics and spatial transcriptomics to identify a lymphocyte aggregated region (LAR) in gastric cancer and compare its cellular and molecular composition with the neighbouring TME.

Gastric cancer constitutes a significant global health burden,and its clinical management is undergoing a critical transition from a traditional experience-driven paradigm toward the deep integration of precision medicine and artificial intelligence(AI).At present,the main bottleneck has shifted from a lack of therapeutic options to insufficient capacity for precise clinical decision-making.In recent years,diagnostic approaches have seen marked advances through the application of AI-augmented endoscopy,radiomics,molecular subtyping,and liquid biopsy,reflecting progress in both precision and intelligence.Therapeutically,notable strides have been made in function-preserving strategies for early-stage disease,multimodal perioperative management for locally advanced cancer,and biomarker-guided stratified thera-py for advanced gastric cancer.However,challenges persist,including low early-detection rates,inaccu-rate staging,difficulties in treatment personalization,and delayed assessment of therapeutic response.The future of gastric cancer care lies in the synergistic combination of precision medicine and AI technolo-gies:leveraging multi-omics and other precision tools to delineate tumor biology,while deploying intelli-gent systems across the entire continuum from screening and diagnosis to treatment selection and follow-up.This integrated approach is key to establishing a more efficient clinical framework and ultimately im-proving patient survival outcomes.

Background: Circulating tumor DNA (ctDNA)-defined molecular residual disease (MRD) is increasingly used after curative-intent treatment to identify recurrence risk. The central evidentiary problem is that prognostic clinical validity is often treated as if it were predictive utility or clinical utility. Methods: We conducted a systematic evidence synthesis with an embedded aggregate-data random-effects meta-analysis of human solid-tumor studies evaluating ctDNA/MRD positivity, persistence, or molecular relapse after curative-intent treatment or at a recurrence-relevant post-treatment landmark. HR-compatible estimates were extracted from eligible full-text reports. PubMed/MEDLINE and ClinicalTrials.gov were searched, and contextual literature was retained for assay, disease-domain, and clinical-utility interpretation. Results: The primary quantitative analysis included 53 HR-compatible estimates and showed worse outcomes among ctDNA/MRD-positive, persistent, or molecular-relapse patients (HR 4.669, 95% CI 3.167–6.884; I2 89.8%; tau2 1.6321; prediction interval 0.349–62.413). Broader (k=58; HR 4.264, 95% CI 2.864–6.349), conservative (k=51; HR 4.737, 95% CI 3.163–7.095), and colorectal subgroup analyses (k=30; HR 4.565, 95% CI 2.656–7.846) were directionally consistent. Heterogeneity was high and prediction intervals were wide, indicating that effect magnitude should not be treated as uniform across tumor domains, assays, landmarks, or endpoints. Conclusions: ctDNA-defined MRD was consistently associated with worse recurrence-compatible or survival outcomes across solid tumors. The finding supports prognostic clinical validity, not a universal treatment mandate. Clinical utility requires disease-specific strategy trials linking biomarker-guided escalation, de-escalation, surveillance, or trial enrichment to patient-relevant outcomes.