Search

Abstract Background Circulating tumor DNA (ctDNA) is a promising biomarker for predicting relapse in multiple solid cancers. However, the predictive value of ctDNA for disease recurrence remains indefinite in locoregional gastric cancer (GC). Here, we aimed to evaluate the predictive value of ctDNA in this context. Methods From 2016 to 2019, 100 patients with stage II/III resectable GC were recruited in this prospective cohort study (NCT02887612). Primary tumors were collected during surgical resection, and plasma samples were collected perioperatively and within 3 months after adjuvant chemotherapy (ACT). Somatic variants were captured via a targeted sequencing panel of 425 cancer‐related genes. The plasma was defined as ctDNA‐positive only if one or more variants detected in the plasma were presented in at least 2% of the primary tumors. Results Compared with ctDNA‐negative patients, patients with positive postoperative ctDNA had moderately higher risk of recurrence [hazard ratio (HR) = 2.74, 95% confidence interval (CI) = 1.37–5.48; P = 0.003], while patients with positive post‐ACT ctDNA showed remarkably higher risk (HR = 14.99, 95% CI = 3.08‐72.96; P < 0.001). Multivariate analyses indicated that both postoperative and post‐ACT ctDNA positivity were independent predictors of recurrence‐free survival (RFS). Moreover, post‐ACT ctDNA achieved better predictive performance (sensitivity, 77.8%; specificity, 90.6%) than both postoperative ctDNA and serial cancer antigen. A comprehensive model incorporating ctDNA for recurrence risk prediction showed a higher C‐index (0.78; 95% CI = 0.71–0.84) than the model without ctDNA (0.71; 95% CI = 0.64–0.79; P = 0.009). Conclusions Residual ctDNA after ACT effectively predicts high recurrence risk in stage II/III GC, and the combination of tissue‐based and circulating tumor features could achieve better risk prediction.

Abstract Objective The benefit of adjuvant chemotherapy is still controversial for stage II gastric cancer patients. This study aims to identify prognostic factors to guide individualized treatment for stage II gastric cancer patients. Methods We retrospectively reviewed 1121 stage II gastric cancer patients who underwent D2 radical gastrectomy from 2007 to 2017 in the Sixth Affiliated Hospital of Sun Yat-sen University, FuJian Medical School Affiliated Union Hospital and Sun Yat-sen University Cancer Center. Propensity score matching was used to ensure that the baseline data were balanced between the adjuvant chemotherapy group and surgery-only group. Kaplan–Meier survival and multivariate Cox regression analyses were carried out to identify independent prognostic factors. Results In univariate analysis, after propensity score matching, age, tumor location, tumor size, CEA, T stage and N stage were associated with overall survival (OS). Multivariate analysis illustrated that age ≥ 60 years old, linitis plastica and T4 were independent risk factors for OS, but lower location and adjuvant chemotherapy were protective factors. Conclusion Stage II gastric cancer patients with adverse prognostic factors (age ≥ 60, linitis plastica and T4) have poor prognosis. Adjuvant chemotherapy may be more beneficial for these patients.

Crosstalk between pyroptosis and tumor immune microenvironment (TIME) in cancer has yet to be elucidated. Herein, we aimed to explore the role of pyroptosis and its association with TIME in gastric cancer. Unsupervised clustering was performed to identify the pyroptosis-related clusters. Pyroptosis risk score was constructed using LASSO Cox regression. Clinicopathological and genetic data of pyroptosis clusters and pyroptosis risk scores were explored. Reproducibility of pyroptosis risk score in predicting response to immunotherapy and screening potential antitumor drugs was also investigated. Three pyroptosis clusters with distinct prognosis, immune cell fractions and signatures, were constructed. A low-pyroptosis risk score was characterized by increased activated T-cell subtype and M1 macrophage, decreased M2 macrophage, higher MSI status, and TMB. Meanwhile, low-score significantly correlated with PD-L1 expression, antigen presentation markers, and IFN-γ signature. The 5-year AUCs of PRS were 0.67, 0.62, 0.65, 0.67, and 0.67 in the TCGA, three external public and one real-world validation (SYSUCC) cohorts. Multivariable analyses further validated the prognostic performance of the pyroptosis risk scoring system, with HRs of 2.43, 1.83, 1.78, 2.35, and 2.67 (all p < 0.05) in the five cohorts. GSEA indicated significant enrichment of DNA damage repair pathways in the low-score group. Finally, the pyroptosis risk scoring system was demonstrated to be useful in predicting response to immunotherapy, and in screening potential antitumor drugs. Our study highlights the crucial role of interaction between pyroptosis and TIME in gastric cancer. The pyroptosis risk scoring system can be used independently to predict the survival of individuals and their response to immunotherapy.

Abstract Background We aimed to assess whether disease-free survival (DFS) could serve as a reliable surrogate endpoint for overall survival (OS) in adjuvant trials of pancreatic cancer. Methods We systematically reviewed adjuvant randomized trials for non-metastatic pancreatic cancer after curative resection that reported a hazard ratio (HR) for DFS and OS. We assessed the correlation between treatment effect (HR) on DFS and OS, weighted by sample size or precision of hazard ratio estimate, assuming fixed and random effects, and calculated the surrogate threshold effect (STE). We also performed sensitivity analyses and a leave-one-out cross validation approach to evaluate the robustness of our findings. Results After screening 450 relevant articles, we identified a total of 20 qualifying trails comprising 5170 patients for quantitative analysis. We noted a strong correlation between the treatment effects for DFS and OS, with coefficient of determination of 0.82 in the random effect model, 0.82 in the fixed effect model, and 0.80 in the sample size weighting; the robustness of this finding was further verified by the leave-one-out cross-validation approach. Sensitivity analyses with restriction to phase 3 trials, large trials, trials with mature follow-up periods, and trials with adjuvant therapy versus adjuvant therapy strengthened the correlation (0.75 to 0.88) between DFS and OS. The STE was 0.96 for DFS. Conclusions Therefore, DFS could be regarded as a surrogate endpoint for OS in adjuvant trials of pancreatic cancer. In future similar adjuvant trials, a hazard ratio for DFS of 0.96 or less would predict a treatment impact on OS.

Background: Dysregulation of lipid metabolism plays important roles in the tumorigenesis and progression of gastric cancer (GC). The present study aimed to establish a prognostic model based on the lipid metabolism–related genes in GC patients.Materials and Methods: Two GC datasets from the Gene Expression Atlas, GSE62254 (n = 300) and GSE26942 (n = 217), were used as training and validation cohorts to establish a risk predictive scoring model. The efficacy of this model was assessed by ROC analysis. The association of the risk predictive scores with patient characteristics and immune cell subtypes was evaluated. A nomogram was constructed based on the risk predictive score model and other prognostic factors.Results: A risk predictive score model was established based on the expression of 19 lipid metabolism–related genes (LPL, IPMK, PLCB3, CDIPT, PIK3CA, DPM2, PIGZ, GPD2, GPX3, LTC4S, CYP1A2, GALC, SGMS1, SMPD2, SMPD3, FUT6, ST3GAL1, B4GALNT1, and ACADS). The time-dependent ROC analysis revealed that the risk predictive score model was stable and robust. Patients with high risk scores had significantly unfavorable overall survival compared with those with low risk scores in both the training and validation cohorts. A higher risk score was associated with more aggressive features, including a higher tumor grade, a more advanced TNM stage, and diffuse type of Lauren classification of GC. Moreover, distinct immune cell subtypes and signaling pathways were found between the high–risk and low–risk score groups. A nomogram containing patients’ age, tumor stage, adjuvant chemotherapy, and the risk predictive score could accurately predict the survival probability of patients at 1, 3, and 5 years.Conclusion: A novel 19-gene risk predictive score model was developed based on the lipid metabolism–related genes, which could be a potential prognostic indicator and therapeutic target of GC.

BackgroundAccording to the 8th edition AJCC staging manual, a least of 16 lymph nodes retrieval (LNRs) is the minimal requirement for lymph nodes (LNs) dissection of gastric cancer surgery. Previous studies have shown that increasing the number of LNRs (≥30) prolongs survival for selected patients. However, the necessity of retrieving 30 or more LN for stage II gastric cancer patients is still under debate.AimThis study aims to explore the impact of retrieving 30 or more lymph nodes on the survival of stage II cancer patients.MethodsA total of 1,177 patients diagnosed with stage II gastric cancer were enrolled in this study. The clinicopathological parameters and the impact of different LNRs (60 years/male/underwent total gastrectomy/stage IIB. For N+ patients, higher NR was significantly correlated with poor survival.ConclusionThe survival benefit of retrieving 30 LNs varies in different subgroups. An LNRs of 30 is mandatory for selected stage II gastric cancer patients.

Abstract Background The present meta-analysis was to explore the surgical and oncological outcomes of bursectomy for advanced gastric cancer (AGC). Methods Relevant studies that evaluated the role of bursectomy for AGC were comprehensively examined to perform a meta-analysis. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes were the number of harvested lymph nodes (LNs), operation time, operative bleeding, hospital stay, postoperative complication and mortality. Results A total of seven studies comprising 2633 cases (1176 cases in the bursectomy group and 1457 cases in the non-bursectomy group) were finally included. There was no significant difference in OS (HR 0.95, P = 0.647) and DFS (HR 0.99, P = 0.936) between the two groups. Even for patients with serosa-penetrating tumours, OS was comparable between the two groups (HR 0.87, P = 0.356). The operation time of the bursectomy group was longer (weighted mean difference, WMD 32.76 min, P = 0.002). No significant difference was found between the two groups in terms of the number of dissected LNs (WMD 5.86, P = 0.157), operative bleeding (WMD 66.99 ml, P = 0.192) and hospital stay (WMD − 0.15 days, P = 0.766). The overall postoperative complication (relative risk, RR 1.08, P = 0.421) and mortality (RR 0.44, P = 0.195) were similar between two groups. Conclusions This meta-analysis indicated that bursectomy is time-consuming without increasing the number of harvested LNs. Although bursectomy can be safely performed without increasing complications and mortality, it does not prolong the OS and DFS of AGC patients, including patients with serosa-penetrating tumours. Therefore, bursectomy should not be recommended as a standard procedure for AGC.

Abstract Background The current study sought to perform a meta-analysis to compare the preoperative staging of endoscopic ultrasonography (EUS) and multidetector computed tomography (MDCT) in gastric carcinoma. Methods Articles published between January 1, 2000, and April 1, 2016, that compared EUS with MDCT were included, and data were presented as 2 × 2 tables. The sensitivities, specificities and summary receiver operating characteristic (ROC) curves for T and N staging were calculated using a bivariate mixed effects model. Data were weighted by generic variance and then pooled by random-effects modeling. Results Eight studies comprising 1736 patients were included in this meta-analysis. For T1 staging, the sensitivity value for EUS (82%) was significantly higher than that for MDCT (41%) (relative risk (RR): 2.06, 95% confidence interval (CI) 1.07–3.94; P = 0.030). For lymph node involvement, the sensitivity value for EUS (91%) was also significantly higher than that for MDCT (77%) (RR 1.14, 95% CI 1.05–1.23; P = 0.001). However, the specificity values of both EUS and MDCT were quite low, at 49 and 63%, respectively. No significant differences in T2–4 staging between EUS and MDCT were noted. Conclusion This meta-analysis indicates that EUS may be superior to MDCT in preoperative T1 and N staging. Additionally, the low specificity values of EUS and MDCT for N staging merits attention.

Aim. To investigate whether tumor size is a reasonable indication for adjuvant chemotherapy for T3-4aN0M0 gastric cancer patients after D2 gastrectomy. Method. We performed a retrospective study of 269 patients with a histological diagnosis of T3-4aN0M0 stage gastric cancer who underwent D2 radical surgery at the Sun Yat-sen University Cancer Center or the Sixth Affiliated Hospital of Sun Yat-sen University between January 2006 and December 2010. The follow-up lasted until June of 2015. Chi-square tests and Kaplan-Meier methods were employed to compare the clinicopathological variables and prognoses. Result. For this group of patients, univariate analyses revealed that tumor size (p

To assess the clinical significance and risk factors of solitary lymph node metastasis (SLM) in gastric carcinoma and establish a more accurate method to evaluate the possibility of lymph node metastasis (LM).A total of 385 patients with gastric carcinoma who underwent D2 lymphadenectomy at the Cancer Center of Sun Yat-Sen University were included in this research. Then we used a group of data from Sun Yat-sen University Gastrointestinal Hospital (SYSUGIH) to validate the accuracy of our developed method. The χ2 test, Kaplan-Meier analysis, log-rank test, COX model, and discriminate analysis were used to analyze the data with SPSS13.0.We found that the LM number and pathological T staging were independent prognostic risk factors. CEA grading, LN status by CT, and T staging by CT were independent risk factors for LM in gastric carcinoma. In addition, we developed the equation Y = -5.0 + X1 + 1.8X3 + 0.7X4 (X1 = CEA grading, X3 = LN status by CT, X4 = T staging by CT) to evaluate the situation of LM. The data from SYSUGIH shows this equation has a better accuracy compared with CT.SLM is an independent risk factor in gastric cancer. And there was no survival difference between the skip metastasis group and the other SLM group (P = 0.659). It is inappropriate for the patient with SLM doing a standard D2 lymphadenectomy, due to the fact that LM rarely occurs in the splenic artery, splenic hilum. The risk factors for LM include CEA grading, LN status by CT, and T staging by CT. And we can use Y = -5.0 + X1 + 1.8X3 + 0.7X4 (X1, CEA grading, X3 = LN status by CT, X4 = T staging by CT, the critical value is 0.3) to estimate the possibility of LM, which has a better accuracy compared with CT.

It has been confirmed that B and T lymphocyte attenuator (BTLA; also known as CD272) is a novel co-inhibitory molecule that exhibits a critical role in restraining cell-mediated antitumor immunity. The present study aimed to investigate the expression and prognostic significance of BTLA in gastric adenocarcinoma. Immunohistochemical (IHC) staining was performed to investigate BTLA expression in gastric cancer tissues and normal mucosal tissues. In total, 123 pathologically confirmed specimens were obtained from stage IIIa gastric cancers. A correlation test, Kaplan-Meier curves, and a Cox proportional hazards regression model were used to analyze the data. No BTLA staining in the normal tissues was found, while BTLA-stained gastric carcinoma cells were detected in 75.6% (93/123) of the gastric cancer specimens. High expression levels of BTLA were detected in 31.7% (39/123) of the specimens, while low expression levels were detected in 68.3% (84/123) of the specimens. High BTLA expression levels were associated with shorter survival time, as confirmed by univariate and multivariate analyses. These findings provide a basis for the concept that high BTLA expression levels in gastric cancer, identified by IHC, are an independent biomarker for the poor prognosis of patients with gastric cancer. [ABSTRACT FROM AUTHOR]