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Background: The aim of this study was to evaluate the effect of neoadjuvant therapies (NAT) on patients with locally advanced gastric cancer (LAGC). Methods: This study retrospectively analyzed LAGC patients treated at the China National Cancer Center between October 2006 and December 2018. All patients included were divided into two groups, NAT followed by surgery (NAT-Surgery) and adjuvant chemotherapy following surgery (Surgery-ACT). Subgroup analysis compared between patients underwent either neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiation (nCRT) was conducted. Propensity score matching (PSM) was implemented to reduce selection bias. Results: In total, 2779 patients were included in this study (494 of NAT-Surgery group and 2285 of Surgery-ACT group). After PSM, the patients in NAT-Surgery group had a significantly longer overall survival (OS) than patients in Surgery-ACT group (P

Background: Neoadjuvant chemotherapy (NAC) has been shown to improve the prognosis for patients with locally advanced gastric cancer (LAGC). Neutropenia, a predominant chemotherapy-related adverse event, affects the therapeutic course for NAC. Methods: Data for 233 patients with LAGC treated with NAC and curative gastrectomy at our center were retrospectively analysed in terms of the relationship between neutropenia and clinicopathological features or outcomes. Results: NAC-induced neutropenia, NAC-induced severe (grade 3/4) neutropenia (NISN), and a favorable histopathological response (HPR) were observed in 102 (43.8%), 35 (15.0%), and 103 (44.2%) patients, respectively. Together with tumor differentiation, clinical response, and lymphovascular invasion (LVI), and NISN independently predicted a favorable HPR [odds ratio (OR) =4.158, 95% confidence interval (CI): 1.762–9.812, P=0.001). Among patients treated with postoperative chemotherapy, NISN independently predicted poor compliance with postoperative chemotherapy (OR 0.364, 95% CI: 0.148–0.894, P=0.028) and thus poor overall survival (OS) and disease-free survival (DFS). Among patients treated with preoperative chemotherapy alone, NISN was associated with a tendency towards a better DFS (P=0.116) and independently predicted superior OS (hazard ratio =0.253, 95% CI: 0.077–0.830, P=0.023). Conclusions: In conclusion, our study revealed a link between NISN, HPR, treatment compliance, and survival. NISN is useful for guiding treatment strategies and predicting prognosis for LAGC patients.

Background Adenocarcinoma in Esophagogastric Junction (AEG) is a severe gastrointestinal malignancy with a unique clinicopathological feature. Hence, we aimed to develop a competing risk nomogram for predicting survival for AEG patients and compared it with new 8th traditional tumor-node-metastasis (TNM) staging system. Methods Based on data from the Surveillance, Epidemiology, and End Results (SEER) database of AEG patients between 2004 and 2010, we used univariate and multivariate analysis to filter clinical factors and then built a competing risk nomogram to predict AEG cause-specific survival. We then measured the clinical accuracy by comparing them to the 8th TNM stage with a Receiver Operating Characteristic (ROC) curve, Brier score, and Decision Curve Analysis (DCA). External validation was performed in 273 patients from China National Cancer Center. Results A total of 1755 patients were included in this study. The nomogram was based on five variables: Number of examined lymph nodes, grade, invasion, metastatic LNs, and age. The results of the nomogram was greater than traditional TNM staging with ROC curve (1-year AUC: 0.747 vs. 0.641, 3-year AUC: 0.761 vs. 0.679, 5-year AUC: 0.759 vs. 0.682, 7-year AUC: 0.749 vs. 0.673, P P = 0.012; 5-year: 0.198 vs. 0.216, P = 0.008; 7-year: 0.199 vs. 0.215, P = 0.014) and DCA. In external validation, the nomogram also showed better diagnostic value than traditional TNM staging and great prediction accuracy. Conclusion We developed and validated a novel nomogram and risk stratification system integrating clinicopathological characteristics for AEG patients. The model showed superior prediction ability for AEG patients than traditional TNM classification.

Background: Adenocarcinoma in Esophagogastric Junction (AEG) is a severe gastrointestinal malignancy with a unique clinicopathological feature. To develop a competing risk nomogram for AEG patients and compared it with new 8th traditional tumor-node-metastasis (TNM) staging system.Methods: Based on AEG patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2010, we used the univariate and multivariate analysis to filter clinical factors and then built the competing risk nomogram to predicting the AEG cause-specific survival. We measured the clinical accuracy by comparing to the 8th TNM stage with receiver operating characteristic (ROC) curve, Brier score, and decision curve analysis (DCA).Results: Total of 1755 patients were included into this study. This nomogram was based on five variables: Number of examined lymph nodes, grade, invasion, metastatic LNs and age. The nomogram model was greater than traditional TNM staging with ROC curve (1-year AUC:0.747 vs. 0.641, 3-year AUC: 0.761 vs. 0.679, 5-year AUC: 0.759 vs. 0.682, 7-year AUC: 0.749 vs. 0.673, P

Background: Lifestyle factors such as body mass index (BMI), alcohol drinking, and cigarette smoking, are likely to profoundly impact the prognosis of gastric cancer, but evidence has been inconsistent. Methods: Patients with gastric cancer were identified from the China National Cancer Center Gastric Cancer Database (NCCGCDB) 1998-2018. Survival analysis performed via Kaplan-Meier estimates and Cox proportional hazards models. Results: In this study, we reviewed 18 441 cases of gastric cancer patients. Individuals who were overweight or obese was associated with positive smoking and drinking history (P=0.002 and P10% groups), but not BMI values at diagnosis, was related to survival results. For other factors, smoking history of more than 30 years conferred a worse prognosis for only gastrectomy patients. Extensive efforts are needed to elucidate mechanisms targeting the complex effects of lifestyles factors.

e16084 Background: There are 10-20% of gastric cancer (GC) with overexpressed Her2. Her2 status remains an essential biomarker for guiding the trastuzumab (Herceptin) therapy, a monoclonal antibody approved for the first-line treatment of late-stage Her2-positive GC. Although IHC, together with FISH, is comprehensively applied to verify Her2 status on tissue samples, an accurate blood test is highly desirable due to the inaccessibility of tissue samples, especially in very late stage GC patients as well as tumor heterogeneity of tissue biopsy. Detecting copy number aberration of Her2 gene in cell-free DNA (cfDNA) gains a lot of interest for its non-invasive approach. However, the limited signal-to-noise ratio poses a great challenge for the accuracy and robustness of the tests (either targeted sequencing or ddPCR). Here, we report a non-invasive test for Her2 status verification based on novel surrogate DNA methylation markers. Methods: Genome-wide DNA methylation sequencing was performed in 30 Her2-negative (IHC 0/1+) and 44 Her2-positive (IHC 3+) tissue samples to identify Her2-overexpression-specific methylation markers. Then we analyzed the performance of these candidate markers using methylation-specific quantitative PCR (qMSP) in plasma samples collected from 102 GC patients before surgical treatment. A Her2-status diagnostic model was built and further validated in a multi-center, prospective cohort (n = 150). The concordance of Her2 status between GC plasma and matching tissue samples (IHC/FISH) was determined. Results: We first discovered 102 statistically significant methylation markers of Her2 status in tissue. Out of these candidate markers, a 3-marker diagnostic model was built and validated on plasma samples, which could discriminate Her2-positive from Her2-negative GC patients with high sensitivity (86.7%) and specificity (96.8%). The overall plasma-tissue concordance of this liquid biopsy test was 95.3%. Furthermore, the Her2-status test was able to classify Her2 2+ status (IHC) into either Her2-negative or Her2-positive status, which was confirmed by conventional FISH test. Conclusions: Overall, the cfDNA-based test is a novel, accurate and noninvasive approach for determining Her2 status in GC patients. The high concordance with IHC/FISH results of this blood test holds great promise as an auxiliary method for guiding Her2-targeted therapy in GC patients. A clinical trial is undergoing to validate this test in the phase-2 clinical trial of a Her2-targeted drug (for GC) in China.

Background Primary tumor resection (PTR) and lymph node dissection (LND) may be performed occasionally in patients with de novo metastatic pancreatic ductal adenocarcinoma (mPDAC). However, the role of PTR and LND in such cases remains unclear. Thus, we aimed to test the effect of PTR and LND on overall survival (OS) and cancer-specific survival (CSS) in mPDAC patients. Methods Patients with de novo mPDAC were identified from the Surveillance Epidemiology and End Results (SEER) database (2010–2015). The inverse probability of treatment weighting (IPTW) method was used to minimize the selection bias. IPTW-adjusted Kaplan-Meier curves and Cox proportional hazards models were used to compare OS and CSS in different treatment groups. Results A total of 10,036 patients met the inclusion criteria. Of these patients, 275 (2.7%) underwent PTR, while 217 (2.2%) also underwent LND with a median of 16 nodes removed. In the IPTW-adjusted Kaplan-Meier analysis, the median OS was 13 versus 6 months (P

Background: Gastrectomy is usually recommended within 5 to 6 weeks after the completion of neoadjuvant chemotherapy (NCT). However, the optimal timing of surgery is not clearly defined. Methods: This study retrospectively reviewed the clinical records of 229 patients with locally advanced gastric cancer (GC) who underwent curative gastrectomy after NCT between 2006 and 2016. The effect of the time to surgery (TTS), defined as ≤4, 5–6, and >6 weeks, on patient outcomes was examined. Descriptive statistics and Cox proportional hazards models were used. Results: Seventy of 229 patients (30.6%) had surgery within 4 weeks after their last dose of NCT, 103 (45.0%) within 5–6 weeks, and 56 (24.5%) after 6 weeks. The median age was 56.0 [interquartile range (IQR), 47.0–63.0] years, and the median TTS was 34.0 (IQR, 26.0–42.0) days. The three groups did not significantly differ regarding most surgical and histopathological characteristics except for the NCT regimen (P=0.010), number of cycles of NCT (P=0.017) and pathological stage (P=0.015). The NCT regimen was the only independent factor associated with TTS >6 weeks (P=0.015). The 3-year progression-free survival (PFS) estimates were 41.9%, 42.8% and 61.7% in patients who underwent surgery in ≤4, 5–6, and >6 weeks after NCT, respectively (P=0.044). The 3-year overall survival (OS) estimates were 57.7%, 58.0% and 68.2% in the three groups, respectively (P=0.202). According to multivariable analysis, compared with the interval of ≤4 weeks, patients who underwent surgery at 5–6 or >6 weeks had equivalent PFS and OS. Conclusions: The NCT-surgery interval time has no impact on patient outcomes.

Background/Aims: Evidence regarding gastric cancer (GC) patients

Neutropenia, the major adverse event in chemotherapy, is associated with favourable clinical outcome in several solid tumours. We aimed to investigate the predictive value of neo-adjuvant chemotherapy (NAC)–induced neutropenia for the pathological response and prognosis in colorectal liver metastases (CRLM) patients. A retrospective review was performed in 141 CRLM patients receiving NAC followed by liver resection. A logistic regression was applied to analyse potential predictors. A Cox proportional hazards analysis was used to analyse survival. Neutropenia due to NAC was observed in 42.6% (60/141) of all patients, and grade 3/4 neutropenia was noted in 31.7% (19/60). A pathological response (tumour regression grade (TRG) 1–3) was reported in 46.1% (65/141) of patients. Multivariate analysis showed that neutropenia significantly predicted the favourable pathological response (OR = 3.718, 95% CI 1.716–8.329, P = 0.001), as well as targeted therapy, good differentiation and preoperative CEA

Whether neoadjuvant chemotherapy (NAC) increased the risk of postoperative morbidities for patients with locally advanced gastric cancer (GC) is unknown. Whether neoadjuvant chemotherapy toxicity (NCT) and postoperative complications (POCs) correlate with short-term and long-term outcomes also remains unclear. We aimed to evaluate the role of NAC on the development of POCs, as well as the impact of NCT and POCs on postoperative and oncologic outcomes in curatively resected GC treated with NAC. This study retrospectively reviewed 230 patients who underwent curative gastrectomy for locally advanced GC (clinically T3/4 or N+) after NAC between 2006 and 2016. Five hundred patients undergoing upfront and curative surgery were selected as a control group. After matching, the incidence of POCs was compared between two groups. In the NAC group, clinicopathological characteristics of patients who experienced POCs were compared to those who did not. Logistic and Cox multivariate regression analyses were used to examine factors associated with POCs, disease-free survival (DFS), and overall survival (OS). Following matching, 230 and 230 patients treated with surgery plus NAC and upfront surgery remained, respectively. The incidence of POCs was 28.7% and 24.3%, respectively (p = 0.290). In the NAC group, NCT (OR [odds ratio] 22.968, 95% CI [confidence interval] 2.948–> 99, p = 0.003) and operation time (OR 1.006, 95% CI 1.001–1.011, p = 0.021) were independent predictive factors of POCs. NCT did not affect oncologic outcomes. The Cox regression model demonstrated that POCs were independently associated with worse DFS (HR [hazard ratio] 2.128, 95% CI 1.240–3.653, p = 0.006) but not OS for patients treated with NAC. The administration of NAC is not associated with an elevated risk of POCs. For patients treated with NAC, NCT is an independent predictor of POCs, but does not affect oncologic outcomes. POCs is independently associated with worse DFS but not OS. NAC should be considered a safe approach in patients who have locally advanced GC. Strategies to minimize chemotherapy toxicity and postoperative morbidities associated with NAC are warranted.

To review the osteoclasts (OC) function beyond bone resorption.The related literature on OC function beyond bone resorption was reviewed, analyzed, and summarized.OC control the bone formation through releasing of matrix-derived growth factors, bidirectional cell-to-cell signals, and secreting OC-coupling factors, and play an important role in the niche formation, hematopoietic stem cells mobilization, and maintenance of its quantity and function; besides, OCs also regulate angiogenesis.These discoveries greatly enrich the current knowledge of OC function and open up an all-new research domain. However, the exact regulatory mechanism of OC affecting the hematopoiesis is still lack in-depth understood. Additionally, it remains to be elucidated how OC-coupling factors act on osteoblast lineage differentiation and how OC-induced angiogenesis participates in physiological and pathological processes. Unclosing the underlying mechanisms will facilitate providing scientific therapeutic strategies for treatment of many OC-related diseases.