Non-small cell lung cancer (NSCLC) remains the most prevalent malignancy worldwide and is a leading cause of cancer-related mortality, particularly among older adults. The global demographic shift towards an aging population underscores the critical role of immunosenescence as a pivotal factor influencing NSCLC pathogenesis, progression, and response to immunotherapy. Immunosenescence, defined by the progressive decline in immune system function with advancing age, is characterized by quantitative and qualitative changes in immune cells. These changes include thymic involution, T-cell exhaustion, epigenetic modifications, reduced immune responsiveness, and a chronic low-grade inflammatory state. This review aims to integrate the current understanding of the biomarkers, molecular mechanisms, and genetic factors underlying immunosenescence. Additionally, it critically examines how immunosenescence affects tumor immune surveillance and the tumor microenvironment (TME). By synthesizing these insights, we aim to inform the development of targeted therapeutic strategies for advanced NSCLC in elderly patients, ultimately enhancing treatment efficacy and patient outcomes.

In most advanced cancers, standard medical treatments are generally employed. With the emergence of Antibody-Drug Conjugates (ADCs), more optimal therapeutic methods have become available for treating tumors. ADC is composed of a monoclonal antibody that targets a specific antigen and a cytotoxic payload, which conjugates via the synthetic linkers. Therefore, ADC combines the accurate targeting of monoclonal antibodies with the potent efficacy of cytotoxic chemotherapy drugs while circumventing systemic toxicity. Besides, the epidermal growth factor receptor (EGFR) family, expressing differently between tumors and normal tissues, is one of the most frequently targeted antigens for ADC therapy, which mainly encompasses EGFR1/ErbB1, human epidermal growth factor receptor 2/ epidermal growth factor receptor 2 (HER2/ErbB2), HER3/ErbB3, and HER4/ErbB4. In contrast to other targets, HER3 stands out as a promising one, closely associated with the pathogenesis of treatment resistance in several cancers. Moreover, solid tumors, which are more prevalent than hematological malignancies, present a vast field of opportunities for the development of HER3-targeting ADCs. However, research on HER3-targeting ADCs treating solid tumors remains insufficient. Therefore, it is imperative for researchers to gather more clinical trial data and continue to elucidate the efficacy and safety of HER3-ADCs in solid tumors. This review summarizes recent advances and future potentials, aiming to provide insights into targeted therapy. We hope that this review will provide useful information to physicians in the field.

Introduction: Malnutrition, sarcopenia, and frailty are highly prevalent (with rates ranging from 56% to 74%) among hospitalized elderly patients with comorbidities, and they are key geriatric syndromes that contribute to disability, reduced quality of life, and poor clinical outcomes. However, existing Western medicine guidelines mainly focus on isolated nutritional support and exercise interventions, lack holistic thinking and often treat the three conditions separately, which leads to suboptimal comprehensive clinical effectiveness. To address this, the present study adopts a cross-sectional design and employs data mining techniques to explore the intrinsic associations between these three geriatric conditions and traditional Chinese medicine (TCM) syndrome types in hospitalized elderly patients with comorbidities, aiming to provide empirical evidence for developing targeted integrated Chinese-Western dietary intervention strategies. Methods: This cross-sectional study enrolled hospitalized elderly patients to collect nutritional status indicators and TCM disease and syndrome diagnosis data. The Apriori algorithm was adopted to excavate association rules with screening criteria of support >0.01, confidence >0.5, lift >1, and p < 0.05. Association heatmaps were used to visualize correlation intensity. Results: A total of 1,049 patients were included. Among those with co-existing nutritional risk, malnutrition, sarcopenia, and frailty, the main TCM diseases were consumptive disease (“Xū Láo”), cough and fever, and the dominant TCM syndromes included turbid phlegm obstructing the lung, dual deficiency of qi and blood, qi deficiency combined with blood stasis. Statistically significant associations were found: dyspnea was related to nutritional risk; fever and cough were closely associated with frailty and nutritional risk; consumptive disease correlated with nutritional risk, malnutrition and frailty. Among TCM syndromes, dampness-heat pouring downward corresponded to nutritional risk; qi deficiency with blood stasis and turbid phlegm obstructing the lung were linked to frailty and nutritional risk, while qi-blood dual deficiency was associated with all three adverse nutritional conditions. Conclusion: Typical TCM diseases and common syndromes are closely associated with adverse nutritional status in elderly inpatients. Clinically, active targeted screening for malnutrition, sarcopenia, and frailty should be conducted in patients presenting the above TCM syndromes, with differentiated dietary interventions implemented simultaneously.

[Objective] To investigate the effects of Xiaoyan Decoction ( XYT) on autophagy and glucose metabolism reprogramming in Non-small Cell Lung Cancer(NSCLC) cells and to explore its mechanism of action. [Methods] ① Screen the half maximal inhibitory concentration (IC50) of XYT-containing serum using Cell Counting Kit 8 (CCK8); ② After pretreatment with the autophagy inhibitor 3-methyladenine (3-MA) and the activator Rapamycin (RAPA) and intervention with XYT, transmission electron microscopy was used to observe the overall autophagy status of A549 cells, and Western Blot was used to detect changes in Sequestosome1(P62) and Microtubule-associated protein 1 light chain 3(LC3); ③ The kit was used to detect glucose uptake and lactate production, Seahorse was used to assess cellular energy metabolism, and Western Blot was used to assess the expression of Hypoxia inducible factor-1α(HIF-1α) protein in A549 cells after XYT drug-containing serum intervention alone and in combination with RAPA intervention. [Results] ①XYT-containing serum can slow down cell proliferation in a concentration-dependent manner, with a 30% concentration of XYT-containing serum for 24 hours being the optimal concentration and duration of intervention. ②Following XYT intervention, the number of autophagosomes—a characteristic double-membrane structure of autophagy—significantly increased in A549 cells. Western blot analysis revealed a significant downregulation of P62 expression and a significant upregulation of LC3-II/LC3-I protein expression. ③After XYT intervention, glucose uptake and lactate production in A549 cells were significantly reduced, glycolytic rate was significantly slowed, and maximum glycolytic capacity was also significantly reduced. Western blot analysis showed a significant downregulation of HIF-1α expression. Additionally, Oxygen consumption rate(OCR) assay results indicated that O₂ consumption significantly increased after XYT intervention, with parameters such as basal respiration and maximal respiration significantly up-regulated. These effects were further enhanced by co-treatment with autophagy modulators 3-MA/RAPA. [Conclusion] XYT can inhibit A549 cell proliferation, upregulate cellular autophagy levels, regulate HIF-1α expression, shift the metabolic phenotype from glycolysis to aerobic oxidation, reprogram glucose metabolism, and thereby exert an inhibitory effect on cell proliferation.

Abstract Tumor deposits (TDs) are discontinuous tumor spread in the mesocolon/mesorectum which is found in approximately 20–25% of colorectal cancer (CRC). Current research has observed that tumor deposits (TDs) have a negative impact on the prognosis and distant metastasis of CRC. However, there is still controversy regarding the definition and understanding of TDs, and the prognostic information of TDs based on the current TNM staging system has not been fully utilized. Researchers have made respective attempts to improve the current staging system; however, there is currently no consensus on the matter. This review integrates current literature on the association between TDs and prognosis of CRC. It explores the impact of TDs on the prognosis and metastasis of CRC, as well as feasible approaches to modify the current TNM staging system based on TDs. The aim of this review is to provide a reference for further understanding the prognostic significance of TDs in CRC and determining the optimal modification of the TNM staging system.

Pulmonary sarcomatoid carcinoma (PSC) is a rare pathological type of non-small cell lung cancer that combines the characteristics of epithelial and mesenchymal tumors and is an extremely malignant and highly heterogeneous malignant tumor. PSC is difficult to diagnose and has a poor sensitivity to radiotherapy. In recent years, with the efficacy breakthroughs of molecularly targeted drugs and immune checkpoint inhibitors in tumor therapy, the treatment of PSC is gradually exploring precise targeted therapy and immunotherapy. In this article, we will provide a comprehensive review of the clinical features, diagnostic points, and progress in the clinical therapeutic research of PSC. We hope to provide guidance and help with clinical treatment and scientific research.

Immunotherapy has become a promising therapeutic strategy for various solid tumors because it harnesses the immune system to target malignant cells. However, prostate cancer (PCa) remains largely resistant to immune-mediated therapies and is often described as a “cold” tumor, characterized by limited immune cell infiltration and pronounced immunosuppressive signaling in its tumor microenvironment. These biological characteristics substantially limit the clinical efficacy of immunotherapeutic approaches in PCa. This review provides a comprehensive summary of current advances and persisting challenges in the field of PCa immunotherapy. It provides an updated overview of therapeutic vaccines targeting tumor-associated antigens, the clinical application and limitations of immune checkpoint inhibitors, and emerging cellular therapies such as chimeric antigen receptor T cell (CAR-T) therapy and bispecific antibodies. The review also discusses emerging combination strategies that integrate immunotherapy with androgen receptor-targeted therapies and novel immune modulators. Furthermore, it highlights the critical role of the tumor microenvironment and molecular biomarkers in predicting therapeutic response and optimizing patient selection. Although the immunosuppressive nature of PCa presents substantial therapeutic challenges, recent advances in immunotherapy and combinatorial strategies has demonstrated promising signs of efficacy. Continued translational research aimed at overcoming immune resistance, refining patient selection, and developing rational immunotherapy-based combinations may ultimately transform the therapeutic landscape of PCa.

BACKGROUND:There are increasing concerns of cardiovascular safety related to endocrine therapy use in women with breast cancer (BC). We examined risk of cardiovascular disease (CVD) events and mortality associated with endocrine therapy use in postmenopausal women with early-stage BC. METHODS:Postmenopausal women diagnosed with stage I-III hormone receptor-positive BC from 2005 to 2013 were included (n = 8495). Women were classified as aromatase inhibitor (AI) users, tamoxifen users, and non-users of endocrine therapy in the 12 months after BC diagnosis. Likelihood ratio tests examined whether the association of endocrine therapy use with CVD and mortality outcomes varied by body mass index (BMI) and history of CVD before BC diagnosis. RESULTS:Over a median follow-up of 7.5 years, women who used AIs were less likely to develop major adverse cardiovascular events (MACE) (HR = 0.84, 95% CI = 0.73 to 0.97) and heart failure (HR = 0.81, 95% CI = 0.66 to 0.99) compared with non-users of endocrine therapy. No associations between tamoxifen use and CVD outcomes were observed. AI use was associated with lower risk all-cause, CVD-related, and non-CVD-related mortality, compared with non-use of endocrine therapy. Tamoxifen use was associated with lower risk of all-cause mortality and non-CVD-related mortality, compared with non-use of endocrine therapy, and the association was modified by BMI (P for interaction < .05). CONCLUSION:Our findings suggest endocrine therapy use reduces all-cause mortality risk and may not increase CVD risk in postmenopausal women with early-stage hormone receptor-positive BC.

Ethnopharmacological relevance: Traditional Chinese Medicines (TCMs) have emerged as a promising complementary therapy in the management of prostate cancer (PCa), particularly in addressing resistance to Docetaxel (DTX) chemotherapy. Aim of the review: This review aims to elucidate the mechanisms underlying the development of resistance to DTX in PCa and explore the innovative approach of integrating TCMs in PCa treatment to overcome this resistance. Key areas of investigation include alterations in microtubule proteins, androgen receptor and androgen receptor splice variant 7, ERG rearrangement, drug efflux mechanisms, cancer stem cells, centrosome clustering, upregulation of the PI3K/AKT signaling pathway, enhanced DNA damage repair capability, and the involvement of neurotrophin receptor 1/protein kinase C. Materials and methods: With "Prostate cancer", "Docetaxel", "Docetaxel resistance", "Natural compounds", "Traditional Chinese medicine", "Traditional Chinese medicine compound", "Medicinal plants" as the main keywords, PubMed, Web of Science and other online search engines were used for literature retrieval. Results: Our findings underscore the intricate interplay of molecular alterations that collectively contribute to the resistance of PCa cells to DTX. Moreover, we highlight the potential of TCMs as a promising complementary therapy, showcasing their ability to counteract DTX resistance and enhance therapeutic efficacy. Conclusion: The integration of TCMs in PCa treatment emerges as an innovative approach with significant potential to overcome DTX resistance. This review not only provides insights into the mechanisms of resistance but also presents new prospects for improving the clinical outcomes of patients with PCa undergoing DTX therapy. The comprehensive understanding of these mechanisms lays the foundation for future research and the development of more effective therapeutic interventions.

Background and Objective: Enhancing therapy choices for varying stages of esophageal cancer and improving patient survival depend on timely and precise diagnosis. Blood metabolites may play a role in either causing or preventing esophageal cancer, but further research is needed to determine whether blood metabolites constitute a genetic risk factor for the disease. In order to tackle these problems, we evaluated the causal association between esophageal cancer and 486 blood metabolites that functioned as genetic proxies using a two-sample Mendelian randomization (MR) study. Methods: We utilized two-sample MR analyses to evaluate the causal links between blood metabolites and esophageal cancer. For the exposure, we used a genome-wide association study (GWAS) of 486 metabolites, and a GWAS study on esophageal cancer from Sakaue et al. was used for preliminary analyses. Causal analyses employed randomized inverse variance weighted (IVW) as the main method, supplemented by MR-Egger and weighted median (WM) analyses. Sensitivity analyses included the MR-Egger intercept test, Cochran Q test, MR-PRESSO, and leave-one-out analysis. Additionally, independent esophageal cancer GWAS data were utilized for replication and meta-analysis. FDR correction was applied to discern features with causal relationships. For conclusive metabolite identification, we conducted Steiger tests, linkage disequilibrium score regression, and colocalization analyses. Moreover, we utilized the program MetaboAnalyst 5.0 to analyze metabolic pathways. Results: This study found an important association between esophageal cancer and three metabolites: 1-linoleoylglycerophosphoethanolamine* [odds ratio (OR) = 3.21, 95% confidence interval (CI): 1.42-7.26, p < 0.01], pyroglutamine* (OR = 1.92, 95% CI: 1.17-3.17, p < 0.01), and laurate (12:0) (OR = 3.06, 95% CI: 1.38-6.78, p < 0.01). Conclusion: This study establishes a causal link between three defined blood metabolites and esophageal cancer, offering fresh insights into its pathogenesis.

Colorectal cancer (CRC) is one of the three most common malignancies globally while the mortality ranks second. Currently immunotherapy, like therapeutic monoclonal antibodies targeting immune checkpoints, have been found to have obvious benefit for patients who are DNA mismatch repair deficiency (dMMR)/high microsatellite instability (MSI-H) CRC, however the majority of patients are the DNA mismatch repair proficient (pMMR)/microsatellite stable (MSS) or low microsatellite instability (MSI-L), which are considered as the “cold tumors”. The absent of tumor T cell infiltration, which is an essential feature of socalled “cold tumors,” and thus contributes to the resistance to immune checkpoint inhibitors. In this article, we want to review the progress of immune combination therapy in MSS CRC (for example, anti-VEGF drugs, anti-EGFR drugs, MAPK signaling pathway target drugs, TGF-β antibodies, radiotherapy, bispecific antibodies, neoantigens vaccines and oncolytic viruses), and we hope to provide new sparks for the treatment of this group of patients.

Objective: To observe the clinical efficacy and differences of the Zhuyu Juanbi formula delivered through ultrasound at Zusanli on patients with chemotherapy-induced peripheral neuropathy (CIPN) due to paclitaxel injection. Methods: A total of 72 breast cancer patients with CIPN were randomly divided into two groups. The treatment group (36 cases) was treated with oral methylcobalamin plus ultrasonic medicine permeating Zhuyu Juanbi formulae, while the control group (36 cases) was treated with oral methylcobalamin alone. Following two 2 cycles of continuous treatment, the efficacy of peripheral neurotoxicity, TCM syndrome score, FACT/GOG-Ntx score, total neuropathy score, and safety indicators of gynecological cancer patients were observed in the two groups. Result: In the treatment of CIPN, the addition of ultrasonic medicine permeating Zhuyu Juanbi formulae was more effective than oral methylcobalamin alone in reducing peripheral neurotoxicity and improving the quality of life of patients. The difference between the two groups was statistically significant (P < 0.05), and ultrasound drug penetration Zhuyu Juanbi formulae significantly reduced the FACT/GOG-Ntx score and TNS score in the treatment group. In terms of drug safety, it rarely caused adverse reactions such as grade 3 and 4 leukopenia, and the safety profile was therefore good. Conclusion: The combination of ultrasonic medicine permeating Zhuyu Juanbi formulae and methylcobalamin has been demonstrated to be an effective treatment for peripheral neurotoxicity in patients with PIPN. It has been shown to significantly improve the clinical symptoms of PIPN patients, improve the quality of life of patients, and have a good safety profile.

Objective:This study aimed to analyze the impact of PRR11 protein expression levels on the prognosis of patients with diabetes mellitus and pancreatic cancer. Methods:Immunohistochemical staining was performed to detect the expression levels of PRR11 protein in cancerous tissues of 70 pancreatic cancer patients, including 45 patients with diabetes mellitus (Group A) and 25 patients without diabetes mellitus (Group B). Patients' blood glucose, lipid profiles, and glycemic control status were compared between the groups. Survival curves were plotted to explore the impact of PRR11 protein expression levels on the prognosis of patients with diabetes mellitus and pancreatic cancer. Results:The positive rate of PRR11 protein expression in Group A patients (86.67%) was significantly higher than in Group B patients (52.00%), P < .05. Group A patients exhibited significantly higher levels of fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), and glycated hemoglobin (HbAlc) compared to Group B patients (P < .05). Interestingly, the expression levels of PRR11 in cancerous tissues were positively correlated with FBG, TC, TG, and HbAlc levels (P < .05). The positive rate of PRR11 protein expression in patients with poor glycemic control (93.75%) was significantly higher than in patients with good glycemic control (53.85%), P < .05. Notably, the survival rate of PRR11 protein-positive patients was significantly lower than that of negative patients (P < .05). Conclusion:The finding highlights that the positive expression of PRR11 protein in patients with diabetes mellitus and pancreatic cancer is associated with a poor prognosis. It suggests that PRR11 may play a role in the occurrence and development of pancreatic cancer and could serve as a potential predictive marker and therapeutic target. However, further research is warranted to explore the functional mechanisms and pathways of PRR11 to better understand its role in pancreatic cancer, and develop personalized therapies.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis. The number of cases increased by 2.26 million in 2020, making it the most commonly diagnosed cancer type in the world. TNBCs lack hormone receptor (HR) and human epidermal growth factor 2 (HER2), which limits treatment options. Currently, paclitaxel-based drugs combined with other chemotherapeutics remain the main treatment for TNBC. There is currently no consensus on the best therapeutic regimen for TNBC. However, there have been successful clinical trials exploring large-molecule monoclonal antibodies, small-molecule targeted drugs, and novel antibody-drug conjugate (ADC). Although monoclonal antibodies have produced clinical success, their large molecular weight can limit therapeutic benefits. It is worth noting that in the past 30 years, the FDA has approved small molecule drugs for HER2-positive breast cancers. The lack of effective targets and the occurrence of drug resistance pose significant challenges in the treatment of TNBC. To improve the prognosis of TNBC, it is crucial to search for effective targets and to overcome drug resistance. This review examines the clinical efficacy, adverse effects, resistance mechanisms, and potential solutions of targeted small molecule drugs in both monotherapies and combination therapies. New therapeutic targets, including nuclear export protein 1 (XPO1) and hedgehog (Hh), are emerging as potential options for researchers and become integrated into clinical trials for TNBC. Additionally, there is growing interest in the potential of targeted protein degradation chimeras (PROTACs), degraders of rogue proteins, as a future therapy direction. This review provides potentially valuable insights with clinical implications.

Introduction: Maintenance therapy aimed to strengthen the first-line chemotherapy and improve quality of life is needed for gastric cancer (GC). Currently, many clinical studies have confirmed the important role of fluoropyrimidine in the maintenance stage. Our team has created patented prescriptions “Fuzheng jiedu Quyu Method” recipe (FJQR), which was considered as an adjuvant therapeutic scheme (reduce toxicity and increase the efficacy of chemotherapy). This study aimed to evaluate the efficacy and safety of FJQR combined with fluoropyrimidine as a maintenance treatment in HER-2 negative GC patients. Methods: We performed the analysis of 129 patients with HER-2 negative GC who entered the maintenance stage in our hospital and Tianjin Cancer Hospital between January 2018 and December 2020. Out of the 129 eligible patients, 64 were categorized into the maintenance treatment group with FJQR+fluoropyrimidine, and 65 patients were assigned to the control group if they received fluoropyrimidine alone. Capecitabine was orally 1000mg/m2, Qd, half an hour after meals, and FGQR was 15g Bid after capecitabine. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), overall remission rate (ORR), quality of Life (QOL), TCM syndrome and safety. Results: The mPFS in the treatment group was significantly prolonged compared with the control group (6.3 vs. 5.0 months, p = 0.03), while the mOS was not substantially improved (11.4 vs. 10.5 months, p = 0.38). Gastrointestinal symptoms and pain became better in the treatment group. The number of distant metastatic organs, first-line chemotherapy cycles, and lymph node metastasis were independent risk predictors for PFS. Blood stasis syndrome may be the protective factor. In terms of safety, treatment-related adverse events (AEs) in the treatment group were relatively lighter, and the incidence of grade III-IV AEs could be significantly reduced. Conclusion: FJQR and fluoropyrimidine have synergistic effects as maintenance treatment in HER-2 negative GC, with good efficacy and safety.

Nonsmall cell lung cancer (NSCLC) predominantly affects the elderly since its incidence and mortality rates skyrocket beyond the age of 65. The landscape of NSCLC treatment has been revolutionized by immune checkpoint inhibitors (ICIs), which have emerged after a long and mostly inactive period of conventional treatment protocols. However, there is limited data on the exact effects of these chemicals on older patients, whose care can be complicated by a variety of conditions. This highlights the need to understand the efficacy of emerging cancer medicines in older patients. In this study, we will review the data of ICIs from clinical trials that were relevant to older people with NSCLC and poor performance status. We will also discuss the role of immunosenescence in immunotherapy and biomarkers in predicting the efficacy of ICIs in patients with advanced NSCLC.

Objective: The aim of the study was to investigate the gene expression profile features in distant metastatic breast cancer (BC) patients, identify the metastasis-associated genes correlated with prognosis, and construct a survival rate nomogram. Methods: Transcriptome data of BC patients were downloaded from The Cancer Genome Atlas (TCGA) database, and divided into metastatic and non-metastatic groups. Differentially expressed genes (DEGs) were analyzed between the two groups, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to explore the potential functions of DEGs. Univariate COX, LASSO regression, and multivariate Cox regression models were applied to screen prognostic-related genes, and a prediction model was established. Results: A total of 215 DEGs were identified. FAM9C, CRISP2, TFPI2, TUBA3E, IL12Rβ2, BP1 and CSN3 were independent influencing factors for overall survival (OS) rate. Area under the curve (AUC) values outweighed 0.6, and calibration curves did not deviate from the reference line. Conclusion: The metastasis-related genes prognostic nomogram for BC patients established in this study had favourablepredictive power that could provide a theoretical reference for subsequent studies.

BackgroundImmunotherapy offers new hope for improved survival in patients with advanced gastric cancer. Although large randomized controlled trials (RCTs) have been conducted to explore the efficacy and safety of first-line immunotherapy plus chemotherapy versus chemotherapy alone for advanced gastric cancer, the results are not completely consistent. And the strict inclusion criteria of RCTs lead to limited extrapolation. Therefore, it is of great significance to continue to conduct real-world studies comparing the clinical efficacy and safety of immunotherapy combined with chemotherapy versus chemotherapy alone in advanced gastric cancer.MethodsThis retrospective study included patients with HER-2 negative, unresectable advanced or recurrent gastric/gastroesophageal junction cancer (GC/GEJC) who received first-line immune checkpoint inhibitors (ICIs) in combination with chemotherapy or chemotherapy alone between January 1, 2018 to May 31, 2023. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR) and adverse events (AEs) were compared between two groups.ResultsA total of 210 patients were enrolled in the combination treatment group (n=100) and chemotherapy alone group (n=110). After 12 months of follow-up, median PFS (mPFS) was 270 days (95%CI 177.510-362.490) in the chemotherapy alone group and 357 days (95%CI 250.103-463.897) in the combination treatment group (P<0.05). The median OS (mOS) was 14.9 months (95%CI 9.831-17.769) in the chemotherapy alone group and 15 months (95%CI 12.386-17.614) in the combination treatment group (P>0.05). There was no statistically significant difference in ORR between two groups (P=0.050). The DCR was 14.5% in the chemotherapy alone group and 38% in the combination treatment group (P<0.05). Subgroup analyses showed that primary tumor location of GEJC, ECOG PS of 1, without liver metastasis, and chemotherapy plus ICIs were associated with PFS benefit. Cox multivariate analysis showed that only surgery or not was correlated with patients’ prognosis (P<0.05). Most of AEs were grade 1-2 and manageable.ConclusionsCompared with chemotherapy alone, first-line ICIs combined with chemotherapy in patients with advanced GC/GEJC could greatly prolong PFS, but OS was not significantly improved, and the AEs were manageable.