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Background: This multi-center cohort study aimed to investigate whether sex and prediagnosis lifestyle affect the prognosis of gastric cancer. Methods: Patients with gastric cancer were from four gastric cancer cohorts of the National Cancer Center of China, The First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Provincial Cancer Hospital. Prediagnosis lifestyle factors in our study included body mass index (BMI) at diagnosis, usual BMI, weight loss, the history of Helicobacter pylori (Hp) infection, and the status of smoking and drinking. Results: Four gastric cancer cohorts with 29,779 gastric cancer patients were included. In total patients, female patients had a better prognosis than male patients (HR = 0.938, 95%CI: 0.881–0.999, P = 0.046). For prediagnosis lifestyle factors, BMI at diagnosis, usual BMI and the amount of smoking were statistically associated with the prognosis of gastric cancer patients. Female patients with smoking history had a poorer survival than non-smoking females (HR = 0.782, 95%CI: 0.616–0.993, P = 0.044). Tobacco consumption > 40 cigarettes per day (HR = 1.182, 95%CI: 1.035–1.350, P = 0.013) was independent adverse prognostic factors in male patients. Obesity paradox was observed only in male patients (BMI < 18.5, HR = 1.145, 95%CI: 1.019–1.286, P = 0.023; BMI: 23–27.4, HR = 0.875, 95%CI: 0.824–0.930, P < 0.001; BMI ≥ 27.5, HR = 0.807, 95%CI: 0.735–0.886, P < 0.001). Conclusions: Sex and some prediagnosis lifestyle factors, including BMI at diagnosis, usual BMI and the amount of smoking, were associated with the prognosis of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is a major health problem worldwide, with a high incidence among older adults. Given the aging overall population, it was crucial to understand the current burden and prospective trend of older gastric cancer. This study aimed to analyze the temporal trends of the incidence, mortality, and survival of older gastric cancer in the highest gastric cancer risk area in China from 2010 to 2019, and to predict the future burden of older gastric cancer up to 2024. Methods: The study was conducted in Gansu province, an area characterized by the highest gastric cancer incidence and mortality in China. The registration data of gastric cancer incidence and mortality from 2010 to 2019 were pooled from registries in the Gansu Cancer Registration System, while survival data were collected from the First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Cancer Hospital. Chinese standard population in 2000 and the Segi's world standard population were applied to calculate the age-standardized rate. Joinpoint regression was used to analyze the average annual percentage change (AAPC) in cancer incidence and mortality. Autoregressive Integrated Moving Average (ARIMA) models were employed to generate forecasts for incidence and mortality from 2020 to 2024. Results: Based on registry data from 2010 to 2019, the incidence and mortality rates of gastric cancer among older adults remained stable. The incidence rates declined from 439.65 per 100,000 in 2010 to 330.40 per 100,000 in 2019, with an AAPC of -2.59% (95% confidence interval[CI], -5.14 to 0.04, P = 0.06). Similarly, the mortality rate changed from 366.98 per 100,000 in 2010 to 262.03 per 100,000 in 2019, with an AAPC of -2.55% (95% CI, -8.77–4.08%, P = 0.44). In the hospital-based cohort, the decline in survival rates was reported among older patients with gastric cancer in the highest gastric cancer risk area in China, with the 3-year overall survival (OS) decreasing from 58.5% (95% CI, 53.5–63.2%) in 2010 to 34.4% (95%CI, 32.1–36.7%) in 2019, and the 3-year progression-free survival (PFS) decreasing from 51.3% (95%CI, 47.5–55.1%) in 2010 to 34.2% (95%CI, 32.0–36.3%) in 2019, respectively. Moreover, forecasts generated by ARIMA models revealed a significant decline in the incidence and mortality of older gastric cancer in China from 2020 to 2024. Specifically, the incidence rate of older gastric cancer was expected to decrease from 317.94 per 100,000 population in 2020 to 205.59 per 100,000 population in 2024, while the anticipated mortality rate was estimated to decrease from 222.52 per 100,000 population in 2020 to 186.22 per 100,000 population in 2024. Conclusion: From 2010 to 2019, the incidence and mortality of older gastric cancer remained stable in the highest gastric cancer risk area in China, while the survival rates showed a decline. Based on the ARIMA models, it was anticipated that there might be a continued decline in older gastric cancer incidence and mortality in the highest-risk area in China over the next five years. [ABSTRACT FROM AUTHOR]

Background: Response of locally advanced gastric cancer (LAGC) to neoadjuvant therapy (NAT) may be associated with prognosis, but which of the clinical or pathological evaluation can accurately predict a favorable prognosis is still controversial. This study aims to compare the effect of clinical and pathological response on the prognosis of patients with gastric cancer. Methods: This study retrospectively analyzed LAGC patients who underwent NAT followed by surgery in the China National Cancer Center from January 2004 to January 2021. Clinical and pathological responses after NAT were evaluated using RECIST 1.1 and Mandard tumor regression grade system (TRG) respectively. Complete response (CR) and partial response (PR) assessed by computed tomography were regarded as clinical response. For histopathology regression assessment, response was defined as Mandard 1, 2, 3 and non-response as Mandard 4, 5. Furthermore, we combined clinical and pathological evaluation results into a variable termed "comprehensive assessment" and divided it into four groups based on the presence or absence of response (concurrent response, only clinical response, only pathological response, both non-response). The association between the prognosis and clinicopathological factors was assessed in univariate and multivariate Cox regression analysis. Results: In total, 238 of 1073 patients were included in the study after screening. The postoperative pathological response rate and clinical response rate were 50.84% (121/238) and 39.92% (95/238), respectively. 154 patients got consistent results in clinical and pathological evaluation (66 were concurrent response and 88 were both non-response), while the other 84 patients did not. The kappa value was 0.297(p < 0.001), which showed poor consistency. Multivariate Cox regression analysis revealed that comprehensive assessment (P = 0.03), clinical N stage(P < 0.001), vascular or lymphatic invasion (VOLI) (HR 2.745, P < 0.001), and pre-CA724(HR 1.577, P = 0.047) were independent factors for overall survival in patients with gastric cancer. Among four groups in the comprehensive assessment, concurrent response had significantly better survival (median OS: 103.5 months) than the other groups (P = 0.008). Conclusion: Concurrent clinical and pathological response might predict a favorable prognosis of patients with gastric cancer after neoadjuvant therapy, further validation is needed in prospective clinical trials with larger samples. [ABSTRACT FROM AUTHOR]

Introduction: The current National Comprehensive Cancer Network (NCCN) guidelines recommend that at least 16 lymph nodes should be examined for gastric cancer patients to reduce staging migration. However, there is still debate regarding the optimal management of examined lymph nodes (ELNs) for gastric cancer patients. In this study, we aimed to develop and test the minimum number of ELNs that should be retrieved during gastrectomy for optimal survival in patients with gastric cancer. Methods: We used the restricted cubic spline (RCS) to identify the optimal threshold of ELNs that should be retrieved during gastrectomy based on the China National Cancer Center Gastric Cancer (NCCGC) database. Northwest cohort, which sourced from the highest gastric cancer incidence areas in China, was used to verify the optimal cutoff value. Survival analysis was performed via Kaplan-Meier estimates and Cox proportional hazards models. Results: In this study, 12,670 gastrectomy patients were included in the NCCGC cohort and 4941 patients in the Northwest cohort. During 1999–2019, the average number of ELNs increased from 17.88 to 34.45 nodes in the NCCGC cohort, while the number of positive lymph nodes remained stable (5–6 nodes). The RCS model showed a U-curved association between ELNs and the risk of all-cause mortality, and the optimal threshold of ELNs was 24 [Hazard ratio (HR) = 1.00]. The ELN ≥ 24 group had a better overall survival (OS) than the ELN < 24 group clearly (P = 0.003), however, with respect to the threshold of 16 ELNs, there was no significantly difference between the two groups (P = 0.101). In the multivariate analysis, ELN ≥ 24 group was associated with improved survival outcomes in total gastrectomy patients [HR = 0.787, 95% confidence interval (CI): 0.711–0.870, P < 0.001], as well as the subgroup analysis of T2 patients (HR = 0.621, 95%CI: 0.399–0.966, P = 0.035), T3 patients (HR = 0.787, 95%CI: 0.659–0.940, P = 0.008) and T4 patients (HR = 0.775, 95%CI: 0.675–0.888, P < 0.001). Conclusion: In conclusion, the minimum number of ELNs for optimal survival of gastric cancer with pathological T2-4 was 24. [ABSTRACT FROM AUTHOR]

Background: Little is known on the tumor microenvironment (TME) response after neoadjuvant chemotherapy (NACT) in gastric cancer on the molecular level. Methods: Here, we profiled 33,589 cell transcriptomes in 14 samples from 11 gastric cancer patients (4 pre-treatment samples, 4 post-treatment samples and 3 pre-post pairs) using single-cell RNA sequencing (scRNA-seq) to generate the cell atlas. The ligand-receptor-based intercellular communication networks of the single cells were also characterized before and after NACT. Results: Compered to pre-treatment samples, CD4+ T cells (P = 0.018) and CD8+ T cells (P = 0.010) of post-treatment samples were significantly decreased, while endothelial cells and fibroblasts were increased (P = 0.034 and P = 0.005, respectively). No significant difference observed with respect to CD4+ Tregs cells, cycling T cells, B cells, plasma cells, macrophages, monocytes, dendritic cells, and mast cells (P > 0.05). In the unsupervised nonnegative matrix factorization (NMF) analysis, we revealed that there were three transcriptional programs (NMF1, NMF2 and NMF3) shared among these samples. Compared to pre-treatment samples, signature score of NMF1 was significantly downregulated after treatment (P = 0.009), while the NMF2 signature was significantly upregulated after treatment (P = 0.013). The downregulated NMF1 and upregulated NMF2 signatures were both associated with improved overall survival outcomes based on The Cancer Genome Atlas (TCGA) database. Additionally, proangiogenic pathways were activated in tumor and endothelial cells after treatment, indicating that NACT triggers vascular remodeling by cancer cells together with stromal cells. Conclusions: In conclusion, our study provided transcriptional profiles of TME between pre-treatment and post-treatment for in-depth understanding on the mechanisms of NACT in gastric cancer and empowering the development of potential optimized therapy procedures and novel drugs. [ABSTRACT FROM AUTHOR]

Background: The survival outcomes of younger patients with gastric cancer (GC) have remained controversial. This study explores the clinicopathological characteristics, survival outcomes, and genetic alterations of younger and older patients with GC. Methods: Patients with GC were identified from the China National Cancer Center Gastric Cancer Database (NCCGCDB) during 1998–2018. Survival analysis was conducted using Kaplan–Meier estimates and Cox proportional hazards models. Sequencing datasets were enrolled from The Cancer Genome Atlas (TCGA) and Memorial Sloan–Kettering Cancer Center (MSKCC) databases. Results: A total of 1146 younger (<40 years of age) and 16,988 older (≥40 years of age) cases were included in the study. Younger patients had more poorly differentiated lesions than older patients (53.7% vs. 33.8%, respectively; p < 0.0001), and were more often pTNM stage IV (19.5% vs. 11.8%, respectively; p < 0.001). The 5‐year overall survival (OS) of patients from the NCCGCDB increased from 1998 to 2018. Younger patients with pTNM stage III had a lower survival rate than older patients (p = 0.014), while no differences by age were observed at other stages. The mutation frequency of the LRP1B, GNAS, APC, and KMT2D genes was higher for older than younger patients (p < 0.05 for all genes). While not significantly different, younger patients from the TCGA and MSKCC databases were more likely to have CDH1, RHOA, and CTNNB1 gene mutations. Conclusions: A stable proportion and improved survival of younger patients were reported using NCCGCDB data. Younger patients with pTNM stage III had lower rates of survival than older patients. Distinct molecular characteristics were identified in younger GC patients which may partly explain the histopathology and prognosis specific to this subpopulation. [ABSTRACT FROM AUTHOR]

It was generally believed that the prognosis of gastric neuroendocrine carcinoma (GNEC) was worse than gastric adenocarcinoma (GAC). However, almost all previous studies compared the prognosis of GNEC and GAC based on East Asians. In this study, we evaluated the clinicopathological features and prognosis of GNEC and GAC in Whites. Patients with GNEC and GAC were identified from 2000 to 2018 in the Surveillance, Epidemiology, and End Results (SEER) database. We used propensity score matching (PSM) analysis to match the age, sex, TNM stage, and treatments received between GNEC and GAC, then compared the overall survival (OS) and cancer-specific survival (CSS) in the two types. A total of 392 cases of GNEC and 12,835 cases of GAC in Whites were recognized. After PSM, the 5-year OS rates of GNEC and GAC were 50.3% and 43.0%, respectively (p = 0.010). The 5-year CSS rates of GNEC and GAC were 57.4% and 50.1%, respectively (p = 0.012). Besides, multivariable cox regression analyses showed that GNEC was an independent predictor of improved OS (HR 0.719; 95% CI 0.607–0.853) and CSS (HR 0.691; 95% CI 0.571–0.835) in the matched data. The prognosis of GNEC was better than GAC in Whites, showing significant ethnic differences. Appropriate treatments and follow-up strategies for GNEC in Whites are probably different from East Asians. The potential genetic and molecular mechanisms need to be further explored. [ABSTRACT FROM AUTHOR]

Background: Margin positivity after gastric cancer resection is associated with poorer outcomes. However, the prognostic factors and the choice of postoperative adjuvant treatment of patients with positive margin (PM) after gastrectomy are still being debated. Methods: A single-center, retrospective analysis was conducted for patients with PM after gastrectomy from the China National Cancer Center Gastric Cancer Database (NCCGCDB) from 1998 to 2018. Univariate and multivariate Cox regression analyses were performed to identify prognostic factors of overall survival (OS) and recurrence-free survival (RFS). Results: A total of 449 patients were included in the study, including 192 (42.8%) in the proximal PM group (PPM), 205 (45.7%) in the distal PM group (DPM), and 52 (11.6%) in the bilateral PM group (BPM). The 3- and 5-year OS rates for the PM patients investigated were 47.5% and 39.3%, respectively, and the 3- and 5-year RFS rates were 60.0% and 53.6%, respectively. Multivariate Cox regression analysis proved total gastrectomy (hazard ratio (HR): 1.783, 95%CI: 1.133–2.805, p = 0.012), pT4 (HR: 5.264, 95%CI: 1.493–18.565, p = 0.01), pN2 (HR: 2.263, 95%CI: 1.164–4.397, p = 0.016), pN3 (HR: 2.327, 95%CI: 1.233–4.393, p = 0.009), and combined resection (HR: 1.952, 95%CI: 1.256–3.034, p = 0.003) to be independent risk factors of OS, and pT3 (HR: 9.257, 95%CI: 1.152–74.386, p = 0.036) and pT4 (HR: 11.361, 95%CI: 1.469–87.847, p = 0.020) to be independent risk factors for RFS. Adjuvant chemotherapy prolonged OS in the PPM group (p = 0.032) and prolonged RFS in the PPM group (p < 0.001) and the DPM group (p = 0.035) compared with surgery alone. Conclusions: Advanced pathologic stage was associated with poor prognosis, and postoperative adjuvant chemotherapy might be recommended in PM patients after gastrectomy. Still, further prospective trials are warranted to verify and support our conclusions. [ABSTRACT FROM AUTHOR]

Background: Given the growing incidence and aggressive biological behavior of proximal gastric cancer (PGC) as reported, it is important to understand which regional or racial populations are at poor prognosis so that interventions can be treated appropriately. We sought to explore regional treatment differences as well as racial genes influence survival outcomes in China and the US patients with PGC. Methods: PGC patients defined as tumors with the epicenter located in cardia (C16.0) or fundus (C16.1) from 1996 to 2016 were identified from the Surveillance Epidemiology and End Results (SEER) in the United States as well as data from a high‐volume National Cancer Center Database in China. Overall survival (OS) curves were plotted for different regional or racial groups, respectively, using the Kaplan‐Meier method and compared statistically using the log‐rank test. Differentially expressed genes (DEGs) analysis was performed using TCGA database. Results: Finally, the cohort consistent of 40973 PGC patients who enrolled in SEER database (n = 36305) or China National Cancer Center (n = 4668), and divided into 4 racial groups: Chinese (n = 5179), Black (n = 2429), White (n = 31185), and Others (n = 2096). After controlling for confounding variables, racial factors were independently associated with poor survival included Black ethnicity (HR = 1.376, 95% CI: 1.066–1.7760, p = 0.014) and White ethnicity (HR = 1.262, 95% CI: 1.005–1.583, p = 0.045) when compared to Chinese ethnicity in total PGC patients. Even in the same region for only US group, Chinese PGC patients also showed better prognosis. Conclusions: In conclusion, we demonstrated the different survival outcomes of PGC patients in different regions or races from two high‐volume database SEER and China National Cancer Center database. These survival differences are likely influenced by a number of factors (e.g., access to screening, quality of gastrectomy, neo/adjuvant therapy, and biological genes itself). More importantly, a better understanding of these disparities could lead to interventions that may help to abolish these disparities. [ABSTRACT FROM AUTHOR]