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Abstract Background Independent and valid prognostic predictors for locally advanced gastric cancer (LAGC) patients with non-elevated serum tumor markers (Triple-negative: CA199

Abstract Background Systemic inflammatory factors can predict the survival prognosis of gastric cancer (GC) patients after neoadjuvant chemotherapy (NACT). However, whether longitudinal changes in systemic inflammatory factors are associated with short - and long-term outcomes has not been reported. Methods This study is a retrospective analysis of 216 patients with advanced gastric cancer who received NACT between January 2011 and June 2019, comparing receiver operating characteristic (ROC) curves for screening suitable inflammatory markers. Group-based trajectory modeling (GBTM) was used to analyze longitudinal changes in inflammatory markers during NACT to identify different potential subgroups and to compare postoperative complications, recurrence-free survival (RFS), and overall survival (OS) among subgroups. Results Ultimately, neutrophil-lymphocyte ratio (NLR) had the highest area under the curve (AUC) value in predicting prognosis was included in the GBTM analysis. Three trajectories of NLR were obtained: Stable group (SG) (n = 89), Ascent-descend group (ADG) (n = 80) and Continuous descend group (CDG) (n = 47). Compared with SG, ADG and CDG are associated with an increased risk of postoperative recurrence and death. The median time of RFS and OS of SG was longer than that of ADG and CDG (median RFS 81 vs. 44 and 22 months; median OS 69 vs. 41 and 30 months). In addition, CDG had significantly higher postoperative serious complications than SG and ADG (17 (36.2%) vs. 17 (19.1%) and 12 (15.0%); p = 0.005). Conclusion There were different trajectories of NLR during NACT, and these potential trajectories were significantly associated with severe postoperative complications, recurrence, and mortality in patients with GC.

Abstract Background The long-term dynamic recurrence hazard of locally advanced gastric cancer (LAGC) in the clinical setting of adjuvant chemotherapy (ACT) remains unclear. Purpose This study aimed to investigate the dynamic recurrence risk of LAGC in patients who received ACT or not. Methods The study assessed data from patients with LAGC who underwent radical gastrectomy between January, 2010 and October, 2015. Inverse probability of treatment weighting (IPTW) was performed to reduce selection bias between the ACT and observational (OBS) groups. Conditional recurrence-free survival (cRFS) and restricted mean survival time (RMST) were used to assess the survival differences. Results In total, 1,661 LAGC patients were included (ACT group, n = 1,236 and OBS group, n = 425). The recurrence hazard gradually declined; in contrast, cRFS increased with RFS already accrued. Following IPTW adjustment, the cRFS rates were higher in the ACT group than those in the OBS group for patients at baseline or with accrued RFS of 1 and 2 years (p˂0.05). However, the cRFS rates of the ACT group were comparable with those of the OBS group for patients with accrued RFS of 3 or more years (p > 0.05). Likewise, the 5-year △RMST between the ACT and OBS groups demonstrated a similar trend. Moreover, the hematological metastasis rate of the ACT group was significantly lower than that of the OBS group for patients at baseline or with accrued RFS of 1 and 2 years, respectively (p˂0.05). Conclusions Although ACT could provide substantial benefits for patients with LAGC, the differences in recurrence hazard between the ACT and OBS groups may attenuate over time, which could help guide surveillance and alleviate patients’ anxiety. Further prospective large-scale studies are warranted.

Abstract Background The relationship between sarcopenia and the prognoses of patients with gastric neuroendocrine neoplasms (g-NENs) is unclear. This study was designed to explore the effects of sarcopenia on short-term and long-term outcomes of patients with g-NENs after radical gastrectomy. Methods This study retrospectively collected data from 138 patients with g-NENs after radical gastrectomy. The skeletal muscle index (SMI) diagnostic threshold for sarcopenia was determined using X-tile software. Cox regression analyses were performed to determine the independent risk factors for 3-year overall survival (OS) and 3-year recurrence-free survival (RFS). Results In this study, 59 patients (42.8%) were diagnosed with sarcopenia. Among patients in the sarcopenia group and nonsarcopenia group, the incidences of total postoperative complications were 33.9 and 30.4%, incidences of serious postoperative complications were 0 and 3.7%, incidences of postoperative surgical complications were 13.6 and 15.2%, and incidences of postoperative systemic complications were 20.3 and 15.2%, respectively (all p > 0.05). The 3-year OS and RFS rates were significantly worse in the sarcopenia group than in the nonsarcopenia group (OS: 42.37% vs 65.82%, p = 0.004; RFS: 52.54% vs 68.35%, p = 0.036). The multivariate analysis revealed a relation between sarcopenia and the long-term prognoses of patients with g-NENs. A stratified analysis based on the pathological type revealed that the Kaplan-Meier curve was only significantly different in patients with gastric mixed adenoneuroendocrine carcinoma (gMANEC) (OS: 40.00% vs 71.79%, p = 0.007; RFS: 51.43% vs 74.36%, p = 0.026); furthermore, the multivariate analysis identified sarcopenia as an independent risk factor for patients with gMANEC (p

Abstract Background Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. Methods We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. Results A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers. For colorectal cancer, a benefit that was associated with postdiagnosis aspirin use was observed for overall survival and cancer-specific survival [HR = 0.83, 95%CI(0.75, 0.9.);HR = 0.78, 95%CI(0.66, 0.92), respectively. However, a prediagnosis of aspirin use did not provide a benefit for overall or cancer-specific survival in colorectal cancer. HR values for overall and cancer-specific survival benefits for colorectal cancer associated with both prediagnosis and postdiagnosis aspirin were as follows: HR = 0.75, 95%CI(0.61, 0.92) and HR = 0.78, 95%CI(0.73, 0.85), respectively. In addition, the survival benefit of postdiagnosis aspirin use appeared to be confined to patients with mutated PIK3CA tumors [HR = 0.78, 95%CI(0.50, 0.99)] and was positive for PTGS2 (COX-2) expression [HR = 0.75, 95%CI(0.43, 1.30)]. Conclusions These findings provide further indications that postdiagnosis aspirin use improves overall survival and cancer-specific survival in colorectal cancer, especially for patients who are positive for PTGS2 (COX-2) expression and PIK3CA-mutated tumors. However, aspirin therapy does not improve overall survival in esophageal and gastric cancers, although the meta-analysis was mainly limited to retrospective studies.

Abstract Background We sought to investigate the prognostic value of complete blood count (CBC)-based biomarkers for patients with resectable gastric cancer (GC). Methods Patients with GC who underwent primary surgical resection between December 2008 and December 2013 were included. The estimated area under the curve (AUC) and multivariate Cox regression models were used to identify the best CBC-based biomarker. Time-dependent receiver operating characteristic (t-ROC) curve analysis was used to predict overall survival and compare the prognostic impact. Results In the 1810 patients analyzed, the median follow-up period was 51.0 months (range 1–101 months). Based on multivariate analysis, the lymphocyte-monocyte ratio (LMR) and hemoglobin (Hb) level were independent prognostic factors (both P

Abstract Background The platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and neutrophil to lymphocyte ratio (NLR) reflect the systematic inflammatory response, with some evidence revealing that they are associated with poorer survival in patients with gastric cancer. However, the effect of the white blood cell to hemoglobin ratio (WHR) on the long-term prognosis of patients with gastric cancer has not been reported. Therefore, we sought to characterize the effect of WHR on long-term survival after radical gastrectomy and compare its value with that of other preoperative inflammation-based prognostic scores (PIPS). Methods Data from 924 patients with a diagnosis of nonmetastatic gastric adenocarcinoma who underwent surgical resection between December 2009 and May 2013 were included in this study. Results The optimal cutoff values for the WHR, PLR, LMR, and NLR were 2.855, 133.03, 3.405, and 2.61, respectively. Patients with an increased WHR (53% vs. 88.1%, p

Abstract Background Most lymph node metastasis (LNM) models for early gastric cancer (EGC) include lymphovascular invasion (LVI) as a predictor. However, LVI must be confirmed by postoperative pathology. In this study, we aimed to develop a model for predicting the risk of LNM/LVI in EGC using preoperative factors. Methods EGC patients who underwent radical gastrectomy at Fujian Medical University Union Hospital and Sun Yat-sen University Cancer Center (n = 1460) were selected as the training set. The risk factors of LNM/LVI were investigated. Data from the International study group on Minimally Invasive surgery for GASTRIc Cancer trial (n = 172) were selected as the validation set. Results In the training set, the incidence of LNM/LVI was 21.6%. The 5-year cancer-specific survival rates of patients with and without LNM/LVI were 92.4 and 95.0%, respectively, with significant difference (P = 0.030). Multivariable logistic regression analysis showed that the four independent risk factors for LNM/LVI were female, tumor larger than 20 mm, submucosal invasion and undifferentiated tumor histological type (all P

Abstract Background This study investigated a large number of patients to develop a predictive nomogram for survival and a web-based survival rate calculator that can dynamically predict the long-term survival of patients with primary gastric diffuse large B-cell lymphoma. Methods A total of 2647 patients diagnosed with primary gastric diffuse large B-cell lymphoma from 1998 to 2014 were extracted from the SEER database. We used the Lasso Cox regression model to identify independent risk factors for long-term survival and to develop a predictive nomogram for survival and a web-based survival rate calculator. Results The median (mean) follow-up time was 30 months (52.8 months). Cancer-specific survival rates decreased with time, while the 5-year conditional survival increased with time. Cancer-specific deaths were not constant. Cancer-specific deaths of patients within the first 2 years were high, while the risk remained relatively constant after 2 years. The independent risk factors included surgery, chemotherapy, tumor stage and age, according to the Lasso Cox regression analysis. We developed a predictive nomogram and a web-based survival rate calculator (https://linjuli1991.shinyapps.io/dynnomapp/). The calibration plot suggested that the actual value exhibited good agreement with the predicted value. Conclusions We found that patients with primary gastric diffuse large B-cell lymphoma had a high risk of death during the first 2 years. Additional active follow-up strategies should be provided during this period. This is the first study to develop a predictive nomogram and a web-based survival rate calculator that can provide evidence for individual treatment and follow-up.

Abstract Background Tumor-infiltrating immune cells are present in various malignant tumors, but their clinical significance in gastric cancer (GC) remains unclear. This study aimed to investigate the prognostic significance of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). Methods Using a prospective database containing 401 cases of GC, we evaluated TIL (cluster of differentiation 8 (CD8) expression) and TAM (cluster of differentiation 68 (CD68) expression) statuses via immunohistochemical staining. Results Compared with CD8+ TIL-negative cases (n = 196, 48.6%), CD8+ TIL-positive cases (n = 205, 51.1%) showed significantly better recurrence-free survival (RFS) [log-rank p

Abstract Background This study sought to explore whether lymphovascular invasion can affect the prognosis of patients with stage N0 gastric cancer and to evaluate the survival benefit of adjuvant chemotherapy for such patients. Method From January 2006 to December 2011, a total of 2102 gastric cancer patients undergoing radical gastric resection were enrolled in this study. Homogeneity, discriminatory ability, and monotonicity of gradients in the combination of lymphovascular invasion and the 8th edition of the AJCC staging system and the 8th edition of the AJCC staging system alone were compared using linear trend χ2, likelihood ratio χ2 statistics, and Akaike information criterion (AIC) calculations. The Kaplan-Meier method and the log-rank test were used to analyze between-group differences in survival rate. Result The median follow-up time of the whole group was 58 months, and the average age of the whole group was 63.9 years (range 21–89 years). The 3-year and 5-year overall survival rates in N0 patients with lymphovascular invasion were lower than those in N0 patients without lymphovascular invasion (3-year OS: 78.3% vs 92.5%, 5-year OS: 70.0% vs 88.3%, p

Abstract Background The eighth TNM classification for gastric cancer categorizes N3 as N3a and N3b in the final pathologic stage. The cutoff for N3a/N3b is defined as 15 metastatic lymph nodes, but the rationale for this cutoff remains unclear. This study aimed to determine the optimal N3a/N3b cutoff and evaluate its prognostic significance. Methods An international database was constructed by combining data from patients with N3 gastric cancer and complete five-year follow-up data from the Surveillance, Epidemiology, and End Results program database (n = 1833) and the Fujian Medical University Union Hospital database (n = 920) (total n = 2753). A log-rank test was performed to determine the optimal N3a/N3b cutoff, and its prognostic significance was confirmed in a two-step multivariate analysis and compared to that of the eighth TNM. Results A cut-point analysis performed at each metastatic lymph node number identified the greatest survival difference between N3a and N3b at 13 metastatic lymph nodes (χ2 = 157.671, P = 3.65 × 10− 36). In patients with 14–15 metastatic lymph nodes, prognoses were significantly worse than those in patients with 7–13 metastatic lymph nodes (P 15 metastatic lymph nodes (P = 0.078). Therefore, patients with 14–15 metastatic lymph nodes were incorporated into a modified N3b classification. In the two-step multivariate analysis, the eighth N3 classification fell out of the model, while the modified N3 classification remained intact (HR 1.51, P

Abstract Background The types of patients with gastric adenocarcinoma (GA) for whom postoperative radiotherapy can improve the disease-specific survival rate (DSS) remain controversial. This study aims to explore the ideal indications. Methods Patients in the Surveillance, Epidemiology, and End Results (SEER) database with T3–4Nx or TxN+ GA from January 1988 to December 2012 were included and divided into a postoperative chemoradiotherapy group (Group R) and a postoperative chemotherapy group (Group C). We established a nomogram to predict DSS and then divided entire patient cohort into low-risk and high-risk groups based on the DSS predicted by the nomogram. Results The Cox multiple regression analysis demonstrated that various risk factors affected DSS for Group R. Based on these risk factors, a nomogram for predicting DSS was established. The decision curve indicated that the best clinical effect could be obtained when the threshold probability was 0–58%. The patients were then divided into low-risk (

Abstract Background To assess the prognostic factors and investigate the optimal treatment of gastric mixed adenoneuroendocrine tumors. Methods We retrospectively analyzed clinical data from 80 patients with gastric mixed adenoneuroendocrine carcinoma that received radical resection in our department from January 2007 to December 2016. Risk factors for relapse and survival were analyzed using a multivariate Cox proportional hazards regression model. Gastric mixed adenoneuroendocrine carcinoma was divided into neuroendocrine carcinoma and adenocarcinoma based on the predominant type in the tumor. Results The 3-year overall survival was 40% in the neuroendocrine carcinoma group and 75% in the adenocarcinoma group (P = 0.006). The neuroendocrine carcinoma (NEC)-dominant tumors and a Ki-67-positive index ≥60% were independent risk factors for worse overall survival. The 3-year recurrence-free survival was 33% in the neuroendocrine carcinoma group and 68% in the adenocarcinoma group. NEC-dominant tumors and a Ki-67-positive index ≥60% were independent risk factors for gastric mixed adenoneuroendocrine carcinoma recurrence. Patients in the adenocarcinoma group that received adjuvant chemotherapy exhibited significantly better overall survival than patients that did not receive chemotherapy (median survival time 43 months vs. 13 months, P = 0.026). Conclusion The NEC-dominant tumors and a Ki-67-positive index ≥60% were significantly associated with worse survival and a higher recurrence rate for gastric mixed adenoneuroendocrine carcinoma patients. Patients in the adenocarcinoma group may benefit from gastric adenocarcinoma treatments.