The efficacy and safety of anti-HER2 therapy and immune checkpoint inhibitors combined with chemotherapy to treat HER2-positive advanced breast cancer that has failed standard HER2-directed therapies is unknown. This study evaluated the efficacy and safety of a novel, fully China-developed combination therapy—comprising inetetamab (an anti-HER2 monoclonal antibody), camrelizumab (an anti-PD-1 antibody), and utidelone (a microtubule inhibitor)—in this treatment-refractory population. The ICU study (NCT04681287) was a single-arm, multicentre, phase 2 trial conducted at five centres in China. Patients with HER2-positive MBC who had experienced progression on prior trastuzumab and TKIs were enrolled. The primary endpoint was the 3-month progression-free survival (PFS) rate in the per-protocol population. A total of 48 patients with a median of three previous systemic therapies for advanced disease (range, 1–4) were enrolled (median follow-up duration 43.0 months). The 3-month PFS rate in 46 patients was 71.67

Purpose Prognosis for patients with EGFR- mutant non-small-cell lung cancer and leptomeningeal metastasis is highly uncertain, complicating treatment decisions. We aimed to develop and validate a multimodal risk score for predicting overall survival to enable risk-stratified management. Methods In this retrospective, multicenter study, a derivation cohort (n = 350) and an independent external validation cohort (n = 302) were used. Independent prognostic factors were identified via Cox regression and integrated into an integer-based risk score. Model performance was evaluated by the C-index, calibration, and decision curve analysis. Results Multivariate analysis identified five independent predictors of poorer OS: ECOG PS ≥ 3, brain metastasis, meningeal enhancement on MRI, positive Cerebrospinal Fluid cytology (CSFC) and intracranial pressure > 220 mmH2O. The resulting risk score stratified patients into low-risk and high-risk groups, with median OS of 22.6 months versus 9.9 months, respectively (p < 0.001). The model demonstrated good discrimination, with a bias-corrected C-index of 0.73. In the external validation cohort, all factors remained significant, and the model maintained consistent performance (C-index = 0.71). The model showed good calibration and positive net benefit. Conclusion We developed and validated a robust, clinically accessible risk score that accurately stratifies OS in patients with EGFR- mutant NSCLC and LM. This practical tool facilitates risk‑stratified patient counseling and may aid in the design of future clinical trials.

e22500 Background: To assess the global distribution of lung cancer staging at diagnosis and explore the impact of economic disparities and screening practices on staging outcomes. Methods: The MEDLINE and Embase databases were systematically searched, supplemented by a review of gray literature and published cancer reports. Population- or hospital-based cancer registry reports on lung cancer staging at diagnosis were also included. The percentage of lung cancer stages in different countries was extracted and the distribution of stages, changes in stage incidence over time, and the impact of screening programs were examined Correlations between the Human Development Index (HDI), Social Development Index (SDI), and proportion of distant metastatic lung cancer were assessed. Subgroup analyses were conducted based on sex, age, tumor histology. Results: Among the 35 countries in the main analysis, the proportion of distant metastatic lung cancer ranged from 30.4% in Hungary to 81.2% in Brunei Darussalam, with a median of 50.8% (interquartile range: 44.8–59.2%). Higher HDI and SDI were not significantly associated with lower proportions of distant metastatic lung cancer (HDI: ρ = −0.19, 95% confidence level (CI): −0.50 to 0.15; SDI: ρ = −0.22, 95% CI: −0.51 to 0.13). In countries with lung cancer screening programs, the proportion of metastatic cases decreased in the United States (from 56.5% in 2004 to 48.5% in 2021) and England (from 54.7% in 2013 to 48.7% in 2021). Additionally, the United States and the Republic of Korea experienced an increase in early-stage incidence, while the United States saw a significant decline in late-stage incidence. Higher metastasis rates were observed in males, younger patients, and patients with small cell lung cancer. Conclusions: Significant global variations in lung cancer staging at diagnosis highlight the need for targeted strategies to enhance early detection and improve treatment outcomes, particularly in regions with a high incidence of metastatic disease.

Introduction: China bears the highest global burden of esophageal cancer (EC), with smoking, high alcohol use, a diet low in vegetables, and tobacco chewing as established risk factors. However, the specific impact on EC-related mortality and disability-adjusted life years (DALYs) in China remains unclear. This study aimed to use the Global Burden of Disease Study (GBD) 2023 to analyze trends in the attributable burden of EC from 1990 to 2023 and to project the burden of disease through 2040 to inform targeted prevention strategies. Methods: In this study, the effects of four risk factors (smoking, high alcohol use, diet low in vegetables, and chewing tobacco) on mortality and DALYs of EC in China were calculated based on the GBD 2023 data, stratified by sex and age. A Joinpoint regression model was used to assess trend changes from 1990 to 2023, and a Bayesian Age-Period-Cohort model was used to predict trend changes up to 2040. Results: Between 1990 and 2023, the age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life years for the four major risk factors showed an overall decreasing trend, with diets low in vegetables showing the largest decrease. In 2023, smoking was the leading cause of EC deaths in China (65.21%), followed by high alcohol use (29.11%). The burden of EC was significantly higher in males than in females. The age distribution shows that men aged 50–70 years have the highest attributable burden, whereas the peak for females is relatively delayed. Projections indicate that by 2040, the ASMR for the four major modifiable risk factors of EC shows a declining trend. Conclusions: Although the burden of EC in China is decreasing, smoking and high alcohol use remain major risk factors, particularly among male individuals and those in the middle-aged and elderly demographic. To further reduce the disease burden, it is necessary to enhance tobacco and alcohol control, optimize endoscopic screening for high-risk populations, and integrate early detection programs into healthcare policies, while promoting dietary modifications.

Background: Postoperative pneumonia (POP) is a critical complication after minimally invasive esophagectomy (MIE) for esophageal squamous cell carcinoma (ESCC). However, the comparative odds of POP among different neoadjuvant treatment strategies remain controversial. This study aimed to compare the associations between different treatment strategies and POP in this population. Methods: A retrospective cohort of ESCC patients undergoing MIE between March 2021 and July 2025 was analyzed. Patients were divided into four groups: the surgery alone (S-alone) group (n = 282), the neoadjuvant chemotherapy (NCT) group (n = 127), the neoadjuvant chemoradiotherapy (NCRT) group (n = 60), and the neoadjuvant chemoimmunotherapy (NCIT) group (n = 71). To address baseline confounding, generalized overlap weighting (GOW) was used for the four-group comparison, and overlap weighting (OW) was used for the pairwise comparisons of NCRT versus NCT and NCIT versus NCT. Logistic regression models were used to evaluate the associations between treatment strategies and the odds of POP. Sensitivity analyses of the pairwise comparisons were performed using stabilized inverse probability of treatment weighting (S-IPTW). Results: In the four-group comparison, neither NCT nor NCRT was associated with significantly higher odds of POP than S-alone, whereas NCIT was associated with higher odds (weighted odds ratio [OR], 1.95; 95% confidence interval [CI], 1.02-3.70). In pairwise analyses, the weighted ORs were 0.45 (95% CI, 0.20-1.01) for NCRT versus NCT and 2.32 (95% CI, 1.14-4.71) for NCIT versus NCT. Sensitivity analyses were directionally consistent. Conclusions: In this single-center observational cohort, NCRT was not associated with higher odds of POP than S-alone or NCT, whereas NCIT was associated with higher odds of POP. These findings support careful perioperative respiratory management in patients receiving neoadjuvant immunotherapy.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with stage at diagnosis significantly influencing survival outcomes. This systematic review evaluates global variations in lung cancer stage distribution at diagnosis and examines the associations of socioeconomic factors and screening programs with these disparities. We conducted a systematic review following PRISMA guidelines, searching PubMed, Embase, and grey literature up to August 14, 2024, to identify population- or hospital-based cancer registry data on lung cancer staging. Data from 36 countries were analyzed, focusing on the proportion of distant metastatic cases. We assessed associations with Human Development Index (HDI) and Socio-Demographic Index (SDI) using case-number-weighted linear regression model and evaluated time trends in countries with and without screening programs. Subgroup analyses explored variations by sex, age, and tumor type. Among the 35 countries analyzed in the main study, the median proportion of lung cancer cases diagnosed with distant metastasis was 50.8

Background Breast cancer is the most common malignancy worldwide. Survival outcomes from phase III RCTs guide approvals, guidelines, and treatment strategies, making statistical stability important. HRs, CIs, and P values show statistical significance but do not directly quantify robustness to outcome changes in a few patients. Methods We conducted a systematic review-based meta-epidemiologic study of phase III breast cancer drug RCTs ( Jan 1, 2015-Dec 31, 2025) from PubMed, Embase, and Cochrane Library. Eligible endpoints were prespecified primary survival and key secondary time-to-event outcomes with reconstructable Kaplan–Meier curves and number-at-risk data. Primary outcome: SIFI; secondary: SFQ and WCLFU ≥ |SIFI|, with subgroup analyses. Results We included 157 endpoint outcomes: 83 (52.9%) positive and 74 (47.1%) negative. Median SIFI was 14 (IQR, 5 to 34.5) for positive and − 17 (− 45 to − 5.2) for negative. Median SFQ was 0.0157 (IQR 0.0093–0.0353) and − 0.0157 (− 0.0219 to − 0.0058), respectively. Among 117 with WCLFU data, 69 (59.0%) had WCLFU ≥ |SIFI|; blinding was independently associated with higher odds. Associated factors for SIFI/SFQ differed by positivity, including sample size, disease setting, therapeutic line, endpoint, and HR category. Conclusions Survival conclusions showed substantial statistical instability; in over half of evaluable outcomes, WCLFU met or exceeded the fragility boundary. Statistical significance alone may overstate stability. Reporting SIFI, SFQ, and follow-up completeness alongside HRs, 95% CIs, and P values may support more transparent interpretation for treatment decisions and regulatory evaluation.

Target trial emulation (TTE) has demonstrated popularity because of its ability to improve the reliability of causal inference from observational data. Nevertheless, knowledge about the current use, potential challenges, and insights of target trials in oncology is scarce. A total of 90 TTE studies in cancer areas were identified through systematic reviews in PubMed and Embase. Among the 54 applications in cancer treatment, registry databases (44.4%) and overall survival (OS, 63.0%) were predominantly used as data sources and primary endpoints, respectively. Approximately 30 (55.6%) of the included TTE cases were associated with immortal time bias, and 21 (38.9%) were associated with prevalent user bias. Among the 21 trials from 13 studies that aimed to calibrate the results from preexisting randomized controlled trials (RCTs), only 42.9% met both statistical agreement and estimate agreement. The availability of fit-for-purpose data sources and uncertainty about result concordance were the main hurdles limiting the quantity and quality of TTE in oncology areas. Promoting regulatory acceptance by initiating special projects could be crucial for the expanded application of real-world data (RWD) using TTE. Potential solutions, such as the integration of electronic medical records at the regional or country level, linkage with insurance claims databases, the modernization of eligibility criteria, the use of OS as the primary endpoint, and other best practices, were recommended for improving the feasibility and quality of oncology TTE.

Background Fertility decline and delayed childbearing may influence women’s long-term cancer risk. Objectives To quantify associations of parous status, parity and age at first birth with incident female cancers and assess dose-response/non-linearity. Search strategy PubMed and Embase were searched from inception to 18 Nov 2024. Selection criteria Cohort and case–control studies in adult women reporting parous status, parity or age at first birth in relation to incident cancer. Data collection and analysis Cancers were harmonized using WHO Global Health Estimates 2021. Random-effects meta-analysis and prespecified linear/quadratic/spline dose–response models were used with AIC-guided selection. Main results We included 123 studies (~18.75 million women) across 17 cancer sites and seven tumors’ subtypes. Ever-parous versus nulliparous women had lower breast cancer risk (ES 0.79, 95% CI 0.67–0.91). Each additional birth was associated with lower risks of breast (7% per birth), ovarian (14%), endometrial (29%) and lung cancers (21%). Each one-year increase in age at first birth was associated with higher risks of breast cancer (3% per year) and melanoma/skin cancer (2.5% per year). U-shaped associations were observed for endometrial and thyroid cancers. Subtype analyses suggested reduced epithelial ovarian cancer risk and increased triple-negative breast cancer risk among parous women. Conclusions Reproductive history shows heterogeneous, site- and subtype-specific associations with cancer risk; parity appears protective for several cancers, whereas delayed childbearing may increase breast and skin cancer risk.

Background Lung cancer is among the most burdensome malignancies worldwide, with marked disparities between China and the United States in terms of its epidemiological characteristics, risk factors, and prevention outcomes. In this study, the long-term trends in lung cancer burden and risk factors in China and the United States from 1990 to 2023 were systematically analyzed using Global Burden of Disease (GBD) Study data, and disease burden was projected through 2050, aiming to provide evidence for optimizing lung cancer prevention and control strategies in both countries. Methods Data, including incident cases, deaths, prevalence cases, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), age-standardized prevalence rates (ASPRs), and age-standardized DALY rates (ASDRs) for lung cancer in China and the United States, along with data on smoking, air pollution, occupational exposure, and metabolic and dietary risk factors, were extracted from the GBD 2023 database. Joinpoint regression was used to calculate annual percentage changes (APCs) and average annual percentage changes (AAPCs). The threefactor DasGupta decomposition analysis was used to quantify independent contributions of population size, population aging, and epidemiological change to variations in the absolute case burden of lung cancer in China and the United States, and Bayesian age–period–cohort models were used to project disease burden trends from 2024 to 2050. Results From 1990 to 2023, the numbers of lung cancer incident cases, deaths, and DALYs in China increased substantially and were far greater than those in the United States by 2023; the ASIR remained relatively stable (36.91 vs. 37.28 per 100,000), while ASMR decreased from 36.95 to 32.86 per 100,000, the ASPR increased from 40.04 to 53.03 per 100,000, and ASDR decreased from 935.08 to 742.26 per 100,000. In the United States, the ASIR, ASMR, and ASDR declined continuously and substantially, with a significant reduction in disease burden. With respect to risk factors, China experienced a continuous increase in the burden attributable to smoking (DALYs increased by 109.97%), ambient particulate matter pollution (DALYs increased by 414.84%), secondhand smoke (DALYs increased by 79.99%), high fasting plasma glucose (DALYs increased by 102.05%), and occupational exposure (including asbestos, diesel engine exhaust, and silica, with DALY increased by 219.97%, 164.39% and 110.59%), with only household air pollution from solid fuels declining (DALYs decreased by 85.58%). In the United States, all the major risk factors significantly decreased. Sex-specific analyses revealed that disease burden was consistently greater in males than in females in both countries; the sex disparity remained stable in China but narrowed substantially in the United States. Projections through 2050 indicate that the absolute case burden of lung cancer in China will continue to increase, whereas that in the United States will continue to decrease, further widening the disparity between the two countries. Conclusions From 1990 to 2023, China and the United States exhibited diametrically opposite lung cancer burden trajectories. China remains in a phase of increasing risk factors and the absolute case burden, whereas the United States has entered a phase of comprehensive risk factor control and sustained burden reduction. China should implement long-term stringent tobacco control, strengthen ambient PM2.5 management, target middle-aged and elderly populations for focused interventions, and promote universal low-dose computed tomography (LDCT) screening. The United States should consolidate tobacco control achievements and enhance screening among high-risk persons. The experiences of both countries provide stratified references for countries at different stages of development.

Pathogenic/likely pathogenic variants (P/LPVs) in DNA damage response (DDR) genes are known ovarian cancer (OC) risk factors, but gene-specific risk estimates in Han Chinese remain unclear. To accurately assess the risk associated with DDR genes in the Han Chinese population to facilitate personalized risk management and enhance clinical decision-making. We performed next-generation sequencing of 45 DDR genes in 666 OC patients from Henan, China. Associations between P/LPVs and clinical features were assessed using chi-squared tests. Variant frequencies were compared with population controls (gnomAD and ChinaMAP databases) to estimate gene-specific odds ratios (ORs) using Fisher’s test. In Henan Ovarian Cancer patients, the median disease onset age was 53 years (range: 24–81), with 7.7

ObjectiveTo assess the global and Chinese disease burden of early-onset lung cancer(diagnosed in patients aged 15-49 years) and its major risk factors.MethodsBased on the GLOBOCAN 2022 and Global Burden of Disease(GBD) 2021 datasets, we evaluated the disease burden and associated risk factors of early-onset lung cancer globally and in China, stratified by age, sex, geographic location, and human development index(HDI). Key indicators included age-standardized incidence rate(ASIR), age-standardized mortality rate(ASMR), and disability adjusted life years(DALYs) attributable to risk factors.ResultsIn 2022, there were 137 705 new cases and 72 646 deaths from early-onset lung cancer globally, with ASIR and ASMR of 3.43 per 100 000 and 1.82 per 100 000 population, respectively. The disease burden was higher in males than in females(ASIR: 3.72 per 100 000 vs. 3.14 per 100 000; ASMR: 2.31 per 100 000 vs. 1.33 per 100 000). High-HDI regions exhibited the highest ASIR(5.51 per 100 000) and ASMR(2.57 per 100 000), with health inequality analysis revealing a concentration of disease burden in higher-HDI areas. China bore the heaviest burden, accounting for 48.69% of global new cases and 35.77% of deaths. China's ASIR(8.21 per 100 000) and ASMR(3.17 per 100 000) exceeded global averages, with incidence higher in females(8.78 per 100 000 vs. 7.67 per 100 000) but mortality higher in males(4.01 per 100 000 vs. 2.29 per 100 000). Smoking and ambient particulate matter pollution were the leading risk factors globally(DALYs contribution: 42.01% and 15.62%) and in China(DALYs contribution: 46.78% and 20.84%). Globally, household air pollution ranked third, whereas in China, secondhand smoke replaced it as the third leading risk factor, with household air pollution dropping to fifth. Risk factor profiles varied significantly across age groups, with modifiable risks contributing less to disease burden in the 15-24 age group.ConclusionsThe burden of early-onset lung cancer varies markedly by sex, region, and HDI, with China facing a disproportionately high burden. Policymakers should prioritize equitable resource allocation and targeted interventions, particularly in tobacco control and air pollution mitigation, to enhance cancer prevention and control efforts.

BACKGROUND:Although guidelines stress the importance of early screening for individuals at high risk of lung cancer in China, there is a lack of data on risk-adapted starting ages for screening. This study aims to determine the appropriate starting age for lung cancer screening in China, considering various risk factors associated with the disease. METHODS:The data used were from the Cancer Screening Program in Urban China. A total of 413,725 eligible participants aged 40-74 years from eight cities in China were enrolled between 2013 and 2021. The outcomes of the study included lung cancer diagnosis and age at diagnosis. The risk-adapted starting age for screening was defined as the age at which individuals with varying levels of lung cancer risk reached a 10-year cumulative risk level similar to that of those aged 50 years in the general population. RESULTS:Among the 413,725 individuals who participated in the study, 1607 were diagnosed with lung cancer with a median follow-up of 4.90 (3.01, 6.84) years. The participants were categorized into different risk groups based on their lung cancer risk scores, which were determined by various risk factors, such as gender, education level, body mass index, vegetable intake, smoking pack-years, and tea consumption. In the study, the optimal starting age for lung cancer screening was determined on the basis of an individual's risk level. Using the 10-year cumulative risk of lung cancer at age 50 years in the general population as a benchmark (0.59% [95% confidence interval, 0.52-0.63%]), the study revealed that individuals with high, medium, or low risk of lung cancer should start screening at ages 46, 48, or 54 years and older, respectively. CONCLUSIONS:This study establishes the age at which lung cancer screening should begin on the basis of the principle of equal management and risk management. These findings have the potential to contribute to updates in the current screening guidelines.

Deep learning (DL) demonstrates high sensitivity but low specificity in lung cancer (LC) detection during CT screening, and the seven Tumor-associated antigens autoantibodies (7-TAAbs), known for its high specificity in LC, was employed to improve the DL’s specificity for the efficiency of LC screening in China. To develop and evaluate a risk model combining 7-TAAbs test and DL scores for diagnosing LC with pulmonary lesions < 70 mm. Four hundreds and six patients with 406 lesions were enrolled and assigned into training set (n = 313) and test set (n = 93) randomly. The malignant lesions were defined as those lesions with high malignant risks by DL or those with positive expression of 7-TAAbs panel. Model performance was assessed using the area under the receiver operating characteristic curves (AUC). In the training set, the AUCs for DL, 7-TAAbs, combined model (DL and 7-TAAbs) and combined model (DL or 7-TAAbs) were 0.771, 0.638, 0.606, 0.809 seperately. In the test set, the combined model (DL or 7-TAAbs) achieved achieved the highest sensitivity (82.6

OBJECTIVE:The standard treatment for locally advanced oral squamous cell carcinoma (OSCC) involves radical surgery followed by adjuvant therapy, often resulting in significant functional impairment. Neoadjuvant immunochemotherapy (NICT) has emerged as a promising strategy to facilitate surgical de-escalation while preserving oncologic outcomes. This study evaluates the feasibility of response-adapted surgery (RAS) following NICT in OSCC. METHODS:In this retrospective analysis, 152 patients with previously untreated OSCC received NICT followed by either RAS (n = 66) or traditional surgery (TS, n = 86). RAS was tailored to post-NICT tumor regression, while TS adhered to pretreatment tumor extent. Primary endpoints were 3-year event-free survival (EFS) and overall survival (OS). Secondary endpoints included quality of life (QoL, assessed via EORTC QLQ-HN35) and perioperative complications. RESULTS:The RAS and TS cohorts exhibited comparable 3-year EFS (78.8 % vs. 79.1 %, p = 0.944) and OS (90.9 % vs. 91.9 %, p = 0.826). RAS significantly reduced the need for mandibulectomy (16.7 % vs. 41.9 %, p = 0.009) and free flap reconstruction (15.2 % vs. 48.8 %, p = 0.018), with fewer major complications (4.5 % vs. 11.6 %, p = 0.048). QoL metrics favored RAS, particularly in swallowing (15 ± 3.8 vs. 28 ± 5.5, p < 0.001) and speech (14 ± 3.9 vs. 25 ± 5.2, p < 0.001) at 12 months. Major pathologic response and PD-L1 CPS > 20 were associated with improved survival. CONCLUSIONS:RAS after NICT achieves oncologic outcomes equivalent to TS while significantly reducing treatment-related morbidity and improving functional recovery. These findings support RAS as a viable de-escalation strategy for OSCC, aligning with the goals of precision oncology. Prospective trials are needed to validate long-term efficacy and refine patient selection criteria.

Supplementary Data from Risk of Liver Cirrhosis in HBV/HCV-Infected Individuals with First-Degree Relatives Who Have Liver Cancer: Development and Validation of a Simple Model

Background Large language models (LLMs) have shown remarkable progress in text-based tasks, but their ability to interpret and respond to image-based clinical scenarios remains underexplored. This study evaluated and compared the performance of ChatGPT-5 and Claude in answering subjective image-based medical case questions. Methods A cross-sectional comparative study was conducted using 71 dermatological case scenarios subjective questions designed by the research team. Each AI system generated responses to identical visual and textual inputs without external assistance. Two experienced dermatologists, blinded to model identity, independently scored the responses against standard answers. Inter-rater reliability was assessed using intraclass correlation coefficients (ICC), and comparative analyses employed Mann–Whitney U tests, Bland–Altman plots, and correlation metrics. Results Both evaluators demonstrated excellent inter-rater reliability (ICC > 0.86). Claude achieved higher mean scores (27.39 ± 11.44) than ChatGPT-5 (25.53 ± 11.45; p < 0.001). Claude also showed stronger correlation with reference standards (ρ = 0.88 vs. 0.83), lower mean absolute error (14.76% vs. 19.98%), and reduced root mean square error (7.24 vs. 9.24). Bland–Altman analysis revealed minimal systematic bias between evaluators, indicating consistent scoring reliability. Conclusions Both multimodal LLMs demonstrated strong competence in interpreting image-based medical scenarios. Claude exhibited a modest but consistent advantage in diagnostic reasoning and clinical alignment. These findings support the potential of LLMs as supplementary educational tools in visual disciplines such as dermatology, emphasizing the importance of model selection, supervised use, and continued evaluation as AI integration in medical education expands.

OBJECTIVE:China faces a significant burden of gastrointestinal tumors driven by socioeconomic, environmental, and lifestyle factors. Using GBD2021 data, this study analyses epidemiological trends and disease burden for six major gastrointestinal tumor cancers (esophagus, gastric, colorectum, liver, pancreas, gallbladder and biliary tract) in China (1990-2021). METHODS:The GBD 2021 was used to extract the incidence, mortality, and disability-adjusted life years (DALYs) data of gastrointestinal tumors in China. Age-standardized rates (ASRs) and 95% uncertainty intervals (UIs) were calculated. Temporal trends were assessed by joinpoint regression analysis, and average annual percent change (AAPC) and annual percentage change (APC) were calculated and analyzed stratified by gender and age group. RESULTS:In 2021, China recorded 1.96 million new gastrointestinal cancer cases, with 1.35 million deaths and 33.07 million DALYs. Gastric cancer led in mortality, and colorectal cancer demonstrated the most rapid incidence growth (AAPC = 1.68). Significant reductions were observed in gastric cancer age-standardized mortality rates (ASMR) (AAPC = -2.44) and esophageal cancer age-standardized disability-adjusted life year rates (ASDR) (AAPC = -2.31). Gender disparities were particularly pronounced in esophageal cancer, with the male-to-female mortality ratio (M/F) escalating from 2.50 (1990) to 4.12 (2021). The age group with the highest mortality burden was 70-74, while the age group with the most significant loss of DALYs was 65-69. CONCLUSION:China has significantly reduced gastrointestinal cancer burden, but gender and age disparities persist, necessitating targeted interventions. Future efforts should focus on tertiary prevention for high-risk groups, especially males and the elderly, while enhancing molecular subtyping and regional data stratification for precision cancer control.