Resectable Gastric Cancer Research Articles

Theory and practice on mesentery margin in vessel-oriented complete mesentery resection of gastric cancer

The concept of mesenteric anatomy has been evolving in cognition. With the continuous development of endoscopic techniques, the submicroscopic structures of many mesenteries have been gradually understood, ultimately confirming the ubiquitous presence of mesenteries in the digestive organs. Based on various domestic and foreign mesenteric anatomical theories and combined with years of clinical practice, we have summarized and proposed a new concept and theory-vascular-guided complete mesenteric resection for gastric cancer. The theoretical basis is that, from the perspective of the embryonic development of the digestive tract, the rotation of the digestive tract and its associated mesentery is always centered on blood vessels. Therefore, the supply vessels and digestive tracts and their associated mesentery are naturally connected. The mesentery is a complex structure that encompasses blood vessels, nerves, and lymphatic tissues. The blood vessels serve as the boundary of the mesentery, ensuring that the lymphatic network that drains the tumor is maximally resected. This article focuses on the complete mesenteric resection margins in gastric cancer surgery, that is, the lateral boundary of the mesentery as the vascular-supplied guided resection boundary and its mesentery, and the base boundary as the mesenteric bed. Using precise vascular guidance to define the extent of mesenteric resection will help accurately define the mesenteric margin during radical resection for different stages of gastric cancer.

Optimal Surveillance of Metachronous Gastric Lesion after Endoscopic Resection of Early Gastric Cancer.

Endoscopic resection (ER)-a minimal invasive procedure, compared to surgical gastrectomy, with the advantage of preserving the entire stomach and maintaining the patient's quality of life-is a widely used curative treatment for early gastric cancers (EGCs). Despite its advantages, such as the preservation of the whole stomach, a large area of the gastric mucosa with histologic changes such as atrophy and intestinal metaplasia remains after ER, and so does the risk of metachronous gastric cancers (MGCs). Therefore, regular surveillance endoscopy after curative ER of EGCs is important so that MGCs are detected early and so minimally invasive ER remains a treatment option. To date, the optimal interval for surveillance endoscopy after curative ER of EGCs has not been established. Therefore, this review summarizes the results of the published studies on this topic with the aim of establishing the optimal surveillance interval for early identification of MGCs. Based on my review, the median timing of MGC occurrence is within 3 years, and reports suggest biannual endoscopy during the first 3 years; however, the evidence suggests that individual patient characteristics may influence the risk of MGCs. Therefore, stratified endoscopic strategies for surveillance based on patient characteristics, such as age, family history of gastric cancer, synchronous gastric lesions, and corpus intestinal metaplasia, should be applied.

Preoperative Chemoradiotherapy for Resectable Gastric Cancer

BackgroundIn Western countries, the current standard of care for resectable gastric cancer is perioperative chemotherapy. Preoperative chemoradiotherapy has been considered, but data are limited regarding this treatment as compared with perioperative chemotherapy alone.MethodsWe conducted an international, phase 3 trial in which patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to receive preoperative chemoradiotherapy plus perioperative chemotherapy or perioperative chemotherapy alone (control). In both groups, patients received either epirubicin, cisplatin, and fluorouracil or fluorouracil, leucovorin, oxaliplatin, and docetaxel both before and after surgery; the preoperative-chemoradiotherapy group also received chemoradiotherapy (45 Gy in 25 fractions of radiation, plus fluorouracil infusion). The primary end point was overall survival, and secondary end points included progression-free survival, pathological complete response, toxic effects, and quality of life.ResultsA total of 574 patients underwent randomization at 70 sites in Australasia, Canada, and Europe: 286 to the preoperative-chemoradiotherapy group and 288 to the perioperative-chemotherapy group. A higher percentage of patients in the preoperative-chemoradiotherapy group than in the perioperative-chemotherapy group had a pathological complete response (17% vs. 8%) and greater tumor downstaging after resection. At a median follow-up of 67 months, no significant between-group differences in overall survival or progression-free survival were noted. The median overall survival was 46 months with preoperative chemoradiotherapy and 49 months with perioperative chemotherapy (hazard ratio for death, 1.05; 95% confidence interval, 0.83 to 1.31), and the median progression-free survival was 31 months and 32 months, respectively. Treatment-related toxic effects were similar in the two groups.ConclusionsThe addition of preoperative chemoradiotherapy to perioperative chemotherapy did not improve overall survival as compared with perioperative chemotherapy alone among patients with resectable gastric and gastroesophageal junction adenocarcinoma. (Funded by the National Health and Medical Research Council and others; TOPGEAR ClinicalTrials.gov number, NCT01924819.)

Perioperative blood transfusions associated with reduced survival in gastroesophageal cancers – A Swedish population-based study

BackgroundBlood transfusion has been associated with decreased long-term survival in cancer patients, possibly due to various immunological factors. We aimed to evaluate if perioperative transfusions decrease survival in patients who undergo resection for esophageal or gastric cancer and to identify factors associated with such events. MethodsA population-based cohort study was conducted based on the Swedish National Registry for Esophageal and Gastric Cancer, which prospectively collects clinical data of patients with these tumors. Almost all patients (96 %) resected for esophageal or gastric cancer in Sweden between 2017 and 2022 were included. Survival data were acquired from the Swedish Cause of Death Registry. Multivariable Cox regression was used to calculate hazard ratios (HR) with 95 % confidence intervals (CI), adjusted for age, fitness, neoadjuvant therapy, surgical access, and pathological TNM stage. ResultsOf all 1365 patients, 227 (17 %) received perioperative transfusions. Transfusion was associated with an increased risk of all-cause mortality within 3 years of surgery (adjusted HR 1.50, 95 % CI 1.17–1.91). To exclude the influence of surgery-related postoperative complications, a sensitivity analysis was performed excluding patients who died within 30 days of resection and the negative impact of transfusions on 3-year mortality remained (adjusted HR 1.30, 95 % CI 1.01–1.68). Increasing age, open surgery, esophagectomy, perioperative bleeding, and nodal tumor involvement were all associated with an increased likelihood of receiving transfusions. ConclusionPerioperative blood transfusions might have a negative impact on 3-year survival in patients who undergo surgery for esophageal or gastric cancer.

Advanced diffusion-weighted MRI models for preoperative prediction of lymph node metastasis in resectable gastric cancer.

To investigate the potential of six advanced diffusion-weighted imaging (DWI) models for preoperative prediction of lymph node metastasis (LNM) in resectable gastric cancer (GC). Between Nov 2022 and Nov 2023, standard MRI scans were prospectively performed in consecutive patients with endoscopic pathology-confirmed gastric adenocarcinoma who were referred for direct radical gastrectomy. Six DWI models, including fractional order calculus (FROC), continuous-time random walk (CTRW), diffusion kurtosis imaging (DKI), intravoxel incoherent motion (IVIM), the mono-exponential model (MEM) and the stretched exponential model (SEM) were computed. Surgical pathologic diagnosis of LNM was the reference standard, and patients were classified into LNM-positive or LNM-negative groups accordingly. The morphological features and quantitative parameters of the DWI models in different LNM categories were analyzed and compared. Multivariable logistic regression was used to screen significant predictors. Receiver-operating characteristic curves and the area under the curve (AUC) were plotted to evaluate the performances, the Delong test was performed to compare the AUCs. In the LNM-positive group, tumor thickness and kurtosis (DKI_K) were significantly higher, while anomalous diffusion coefficient (CTRW_D), diffusivity (DKI_D), diffusion coefficient (FROC_D), pseudodiffusion coefficient (IVIM_D*), perfusion fraction (IVIM_f), and ADC were lower compared to the LNM-negative group. Clinical tumor staging (cT) and CTRW_D were independent predictors. Their combination demonstrated a superior AUC of 0.930, significantly higher than that of individual parameters. Tumor thickness, DKI_K, CTRW_D, DKI_D, FROC_D, IVIM_D*, IVIM_f and ADC were associated with LNM status. The combination of independent predictors of cT and CTRW_D further enhanced the performance.

Effect of prehabilitation for patients undergoing gastric cancer surgery: a protocol of a systematic review and meta-analysis

IntroductionGastric cancer is a high-risk cancer with surgical treatments often leading to significant postoperative complications and mortality. Prehabilitation, involving exercise, nutrition and psychological support before surgery, aims to boost patients’...

Omentum preservation versus complete omentectomy in gastrectomy for gastric cancer (OMEGA trial): study protocol for a randomized controlled trial

BackgroundPotentially curative therapy for locally advanced gastric cancer consists of gastrectomy, usually in combination with perioperative chemotherapy. An oncological resection includes a radical (R0) gastrectomy and modified D2 lymphadenectomy; generally, a total omentectomy is also performed, to ensure the removal of possible microscopic disease. However, the omentum functions as a regulator of regional immune responses to prevent infections and prevents adhesions which could lead to bowel obstructions. Evidence supporting a survival benefit of routine complete omentectomy during gastrectomy is lacking.MethodsOMEGA is a randomized controlled, open, parallel, non-inferiority, multicenter trial. Eligible patients are operable (ASA < 4) and have resectable (≦ cT4aN3bM0) primary gastric cancer. Patients will be 1:1 randomized between (sub)total gastrectomy with omentum preservation distal of the gastroepiploic vessels versus complete omentectomy. For a power of 80%, the target sample size is 654 patients. The primary objective is to investigate whether omentum preservation in gastrectomy for cancer is non-inferior to complete omentectomy in terms of 3-year overall survival. Secondary endpoints include intra- and postoperative outcomes, such as blood loss, operative time, hospital stay, readmission rate, quality of life, disease-free survival, and cost-effectiveness.DiscussionThe OMEGA trial investigates if omentum preservation during gastrectomy for gastric cancer is non-inferior to complete omentectomy in terms of 3-year overall survival, with non-inferiority being determined based on results from both the intention-to-treat and the per-protocol analyses. The OMEGA trial will elucidate whether routine complete omentectomy could be omitted, potentially reducing overtreatment.Trial registrationClinicalTrials.gov NCT05180864. Registered on 6th January 2022.

Quantification of Gremlin 1 throughout the tumor stroma using whole slide imaging and its clinicopathological significance in gastric cancer.

Gremlin 1 (GREM1) is an antagonist of bone morphogenetic protein (BMP). GREM1 is expressed in the stromal cells of various carcinomas and promotes tumor progression by suppressing BMP signaling. We designed this study to establish an evaluation strategy for GREM1 expression, focusing on the tumor stroma, and to examine its clinicopathological significance in gastric cancer (GC) progression. We employed RNA in situ hybridization (ISH) to evaluate the prognostic value of GREM1 expression in a cohort of 104 surgically resected GC cases and assessed ISH scores according to previous reports. GREM1 expression was observed in tumor stromal cells, including fibroblasts. We defined GREM1-positive cells as those expressing ISH score ≥ 3 and quantified the number of GREM1-positive cells using image analysis software. We examined the relationship between the number of GREM1-positive cells in the tumor stroma and clinicopathological features. The number of GREM1-positive cells per tumor stroma ranged from 0 to 714.7 cells/mm2 (median, 1.65 cells/mm2). We divided the 104 GC cases into GREM1-High and GREM1-Low expression groups based on the abovementioned median value. GREM1-High expression group was significantly associated with a more advanced pT grade, pN grade, lymphatic invasion, and venous invasion. Kaplan-Meier analysis showed significantly poorer survival in the GREM1-High expression group than in the GREM1-Low expression group. These results indicated that GREM1 expression in GC is localized in tumor stromal cells, and that high GREM1 expression in the tumor stroma could be a poor prognostic factor.

Helicobacter pylori eradication following endoscopic resection might prevent metachronous gastric cancer: a systematic review and meta-analysis of studies from Japan and Korea.

A systematic review and meta-analysis was performed to evaluate the preventive effectiveness of Helicobacter pylori eradication against metachronous gastric cancer (MGC) or dysplasia following endoscopic resection (ER) for early gastric cancer (EGC) or dysplasia. PubMed, Cochrane Library, MEDLINE, and EMBASE were searched until 31 October 2023, and randomized controlled trials or cohort studies were peer-reviewed. The incidence of metachronous gastric lesions (MGLs) including MGC or dysplasia was compared between Helicobacter pylori persistent and negative groups, eradicated and negative groups, and eradicated and persistent groups. Totally, 21 eligible studies including 82,256 observations were analyzed. Compared to those never infected, Helicobacter pylori persistent group (RR = 1.58, 95% CI = 0.98-2.53) trended to have a higher risk of MGLs and significantly in partial subgroups, while the post-ER eradicated group (RR = 0.79, 95% CI = 0.43-1.45) did not increase the risk of MGLs. Moreover, successful post-ER eradication could significantly decrease the risk of MGLs (RR = 0.54, 95% CI = 0.44-0.65) compared to those persistently infected. Sensitivity analysis obtained generally consistent results, and no significant publication bias was found. The persistent Helicobacter pylori infection trends to increase the post-ER incidence of MGC or dysplasia, but post-ER eradication can decrease the risk correspondingly. Post-ER screening and eradication of Helicobacter pylori have preventive effectiveness on MGC, and the protocol should be recommended to all the post-ER patients.Systematic review registration: The PROSPERO registration identification was CRD42024512101.

1418P Tumor microenvironment B-cell abundance and survival in resectable gastric cancer: A translational analysis from the CLASSIC trial

1418P Tumor microenvironment B-cell abundance and survival in resectable gastric cancer: A translational analysis from the CLASSIC trial

Impact of D2 Total Gastrectomy Including Splenectomy for Scirrhous Gastric Cancer in the Era of Effective Adjuvant Chemotherapy.

Total gastrectomy with D2 dissection including splenectomy (TGS) is usually selected for locally resectable scirrhous gastric cancer (SGC), which was established in the era of surgery alone. However, it remains unclear whether TGS for SGC is justified in the era of effective adjuvant chemotherapy. This study included 112 SGC patients, consisting of 60 cases treated between January 2000 and December 2006 (Former group), and 52 cases treated between January 2007 and December 2016 (Latter group). We collected clinicopathological data and then examined the survival and the therapeutic value indexes. The background characteristics were well-balanced, except for sex and physical status. The Latter group might be characterized by frequent female (P = 0.037) and poorer physical status (P = 0.048). Adjuvant chemotherapy was administered to 86.5% of the Latter group and was 11.7% of the Former group (P < 0.001). The 5-year-overall survival rate of the Latter group was 58.7% (95% confidence interval: 43.5-71.1), seems better than that of the Former group (44.5%; 95% confidence interval 31.7-56.6) (hazard ratio = 0.758, P = 0.291). Improvement of the index from the Former group was observed in the Latter group at almost all stations. The ratio of the index between two groups was 1.42 at the D1 station and 1.67 at the D2 station. Index of splenic hilar node ranked similarly high in both groups. The therapeutic value index was improved in almost all nodal stations by S-1 adjuvant chemotherapy, especially in D2 nodes. TGS would be more important for locally resectable SGC in the era of effective adjuvant chemotherapy.

LBA58 A randomized phase III trial of perioperative chemotherapy (periop CT) with or without preoperative chemoradiotherapy (preop CRT) for resectable gastric cancer (AGITG TOPGEAR): Final results from an intergroup trial of AGITG, TROG, EORTC and CCTG

LBA58 A randomized phase III trial of perioperative chemotherapy (periop CT) with or without preoperative chemoradiotherapy (preop CRT) for resectable gastric cancer (AGITG TOPGEAR): Final results from an intergroup trial of AGITG, TROG, EORTC and CCTG

Targeting NUF2 suppresses gastric cancer progression through G2/M phase arrest and apoptosis induction.

Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2 , a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression. Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2 -associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC. NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro . NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models. Collectively, NUF2 -mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.

Comparison of treatment strategies based on clinical and pathological nodal status in resectable gastric adenocarcinoma.

To determine the optimal multimodal treatment strategy between perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) in resected gastric cancer (GC) patients based on nodal status. In this retrospective analysis, the National Cancer Database was used to identify resected non-metastatic GC (2006-2016). Patients were stratified by clinical nodal status-negative (cLN-) and positive (cLN+). In patients with cLN- disease who underwent upfront resection and were upstaged to pathological LN+, overall survival (OS) was compared between POC and POCR. In patients with cLN- and cLN+ disease, OS was compared between PEC, POCR, and POC. Kaplan-Meier survival estimate, log-rank test, and multivariable Cox proportional hazards analysis were performed. We identified 7827 patients (cLN- 4828; cLN+ 2999). On multivariable analysis in patients with cLN- disease who underwent upfront resection (n = 4314) and were upstaged to pLN+ disease (70%), POCR (n = 2300, aHR 0.78, 95% CI 0.70-0.87, p < 0.001) was associated with improved OS compared to POC (n = 907). No significant difference was noted between POCR (n = 766, aHR 1.11, 95% CI 0.88-1.40, p = 0.39) and POC (n = 341) in patients with pLN- disease. On multivariable analysis in all patients with cLN- disease, POCR (n = 3066) was significantly associated with improved OS (aHR 0.84, 95% CI 0.75-0.92, p < 0.01) compared to POC (n = 1248). No significant difference was noted between POCR (aHR 1.0, 95% CI 0.70-1.01, p = 0.958) and PEC (n = 514). These results remained consistent in patients with cLN+ disease (POCR = 1602, POC = 720, PEC = 677). Postoperative chemoradiation is associated with improved survival in GC patients upstaged from clinically node-negative disease to pathologically node-positive disease. Negative clinical nodal disease status is not a reliable indicator of pathological nodal disease.

Oncological similarities between large type 3 and type 4 tumors in patients with resectable gastric cancer: a propensity score-matched analysis of a multi-institutional dataset

BackgroundLarge type 3 (diameter ≥ 8 cm) and type 4 gastric cancers have been arbitrarily combined in Japan as a single entity. However, whether these two types are oncologically similar remain unclear. This study aimed to clarify this issue.MethodsIn this retrospective study, we analyzed a database of 3,575 patients from nine institutions who underwent gastrectomy between 2010 and 2014. Using propensity scores to balance significant variables, we compared prognoses and tumor recurrences.ResultsOf patients with clinical T3/T4 who underwent R0 resection, 75 and 73 had large type 3 and 4 tumors, respectively. Patients with type 4 tumors had significantly lower overall survival rates than those of patients with large type 3 tumors (hazard ratio [HR] 1.77; 95% confidence interval [CI] 1.14–2.74). However, among the large type 3 tumors, a remarkable difference in prognosis was observed between the differentiated and undifferentiated histological types. A comparison was made between large type 3 with undifferentiated phenotype and type 4, each with 39 patients after propensity score matching. Outcomes in both groups were similar in terms of overall survival (HR 1.28; 95% CI 0.73–2.25) and relapse-free survival (HR 1.34; 95% CI 0.80–2.27). No statistically significant differences were observed in the incidence of peritoneal recurrence (35.9% vs. 46.1%, P = 0.36) and lymph node recurrence (25.6% vs. 12.8%, P = 0.15).ConclusionsLarge type 3 tumors with undifferentiated phenotype and type 4 tumors were oncologically similar. This subgroup could be considered as a new entity for future clinical trials.

Impact and effect of preoperative short-term preoperative pulmonary-related training on patients with gastric cancer: a randomized controlled single center trial

PurposeThis study aimed is to evaluate the impact of pre- and postoperative pulmonary-related training, including respiratory and aerobic training, on postoperative pulmonary complications (PPCs) after radical resection of gastric cancer (GC). MethodsWe conducted a randomized controlled trial of 121 participants who received a systematic, comprehensive, high-intensity pulmonary exercise regimen for 5 days preoperatively and at least 5 days postoperatively. The control group received standard preoperative care. We analyzed the occurrence of PPCs in both groups as the primary outcome ResultsA total of 43 of 121 participants (35.5%) were diagnosed as having PPCs, and the incidence of PPCs was markedly lower in the training group than in the control group (26.2% [16 of 61] vs 45.0% [27 of 60]; P = .031). Moreover, the duration of the postoperative hospital stay was shorter in the training group (8.69 ± 1.92 days) than the control group (9.57 ± 2.16 days; P = .020) and reduced hospitalization costs, amounting to €9605.1 ± €2556.26 in the training group and €10,594.6 ± €2560.7 in the control group (P = .035). ConclusionOur study established that a perioperative pulmonary-related training notably diminishes the incidence of PPCs, curtails the duration of hospitalization, and mitigates hospitalization expenses for patients undergoing GC surgery.

Chromosomal copy number based stratification of gastric cancer has added prognostic value to Lauren’s histological classification

BackgroundThe Cancer Genome Atlas (TCGA) recognizes four molecular subgroups of gastric cancer: Epstein-Barr virus (EBV) positive, microsatellite instable (MSI), genomically stable (GS), and chromosomal instable (CIN). Since a GS/CIN classifier is lacking, alternative markers such as Lauren’s histopathology or CDH1/p53 immunohistochemistry are commonly applied. Here we compared survival of gastric cancer subgroups determined by four methods.Methods309 EBV negative and microsatellite stable tumors were included from the Dutch D1/D2 trial and assigned to subgroups by: (i) TCGA’s specific chromosomal copy number aberrations, (ii) genome instability index (GII), (iii) Lauren’s classification, and (iv) CDH1/p53 immunohistochemistry. Subgroups were associated with cancer-related survival (CRS).ResultsFive-year CRS was 42.0% for diffuse and 49.5% for patients with intestinal type tumors, and 57.8% for GS and 41.6% for patients with CIN tumors. Classification by GII or CDH1/p53 IHC did not correlate with CRS. The combination of TCGA and Lauren classifications resulted in four distinct subgroups. Five-year CRS for GS-intestinal (n = 24), GS-diffuse (n = 57), CIN-intestinal (n = 142) and CIN-diffuse (n = 86) was 61.4%, 56.5%, 47.6%, and 31.5%, respectively.ConclusionsTCGA’s GS and CIN subgroups have additional prognostic value to Lauren’s classification in resectable gastric cancer. GS-intestinal, GS-diffuse, CIN-intestinal and CIN-diffuse are suggested stratification variables for future studies.

Novel nomogram and risk stratification for peritoneal recurrence after curative resection in gastric cancer

Peritoneal recurrence (PR) in gastric cancer after curative resection has poor prognosis. Therefore, we aimed to construct a nomogram to predict PR, and establish PR score for risk stratification to guide adjuvant chemotherapy. A total of 315 patients with gastric cancer after radical surgery were included, and randomly stratified into training group (n = 221) and validation group (n = 94). Univariate and multivariate analyses were used to determine predictive factors of PR. The nomogram was constructed to predict the risk of PR. We utilized the time-dependent area under the receiver operating characteristic (ROC) curves (AUCs), calibration curves, and decision curve analysis (DCA) to evaluate the performance of the nomogram. Multivariate analysis showed that tumor site, N stage, preoperative CEA, and postoperative CA199 were independent predictors of PR. A nomogram was constructed to predict PR based on these factors. The AUC value was 0.755 in the training group and 0.715 in the validation group. The calibration curves showed good agreement between prediction and observation in the training and validation groups. The decision curve analysis displayed a good net benefit of the nomogram. The novel PR score was developed and patients were stratified into the low-, medium-, and high -risk groups. For the high-risk group, postoperative adjuvant chemotherapy significantly improved patients' overall survival (OS) and disease-free survival (DFS). The establishment of nomogram facilitates the prediction of PR after radical gastrectomy, and a novel PR score may help guide adjuvant chemotherapy for gastric cancer.

Prognostic significance of microsatellite instability in patients with resectable gastric cancer

BackgroundMicrosatellite instability (MSI) gastric cancer (GC) generally has a better prognosis than microsatellite-stable (MSS) GC and has been associated with nonsurvival benefit with the addition of chemotherapy (CMT) compared with surgery alone. However, patients with MSI have distinct clinicopathological characteristics. This study aimed to compare the survival outcomes between patients with MSI GC and those with MSS GC. In addition, this study analyzed the survival outcomes of patients with MSI GC who received CMT. MethodsThis study reviewed all patients with GC who underwent curative gastrectomy. Patients were divided into MSI group and the MSS group. Propensity score matching (PSM) was used to match clinicopathological factors. ResultsAmong the 378 patients enrolled, 78 (20.6%) had MSI. Older age (P < .001), subtotal gastrectomy (P = .008), pN0 (P = .020), and earlier pTNM stage (P = .012) were associated with MSI GC. Survival analysis showed better disease-free survival (DFS) and overall survival (OS) of patients in the MSI group (P = .012 and P = .019, respectively). After PSM, 78 patients were matched to each group. All variables assigned to the scores were well matched, and both groups became equivalent. After the matching, the differences in DFS and OS according to MSI/MSS status were estimated to be larger than before (DFS: 63.3% vs 41.4%; P = .002; OS: 65.8% vs 42.5%; P = .002). Regarding patients referred for CMT, there was no difference in DFS and OS between patients with MSI GC who underwent CMT and those who underwent surgery alone (P = .255 and P = .178, respectively). ConclusionEven after controlling for clinicopathological characteristics, MSI was identified as a prognostic factor for patient survival. MSI GC showed no significant survival benefit with the addition of CMT.

Perioperative FLOT + immunotherapy for resectable gastric and gastroesophageal junction cancer: A systematic review and meta-analysis.

66 Background: The current standard of care for resectable gastric and GEJ cancers is perioperative chemotherapy with FLOT.Although its benefits in improving rates of pathologic complete response, increasing prospects of R0 resection, and improving survival have been proven, efforts to find novel strategies which can improve on its gains continue.The addition of an immune checkpoint inhibitor to FLOT has been a focal point of research in this field. This meta-analysis evaluated high-quality data from clinical trials to determine the efficacy of this chemoimmunotherapy combination. Methods: A systematic search of English-language articles on PubMed, Cochrane and Google scholar was done to identify randomized trials investigating the use of perioperative FLOT and immune checkpoint inhibitors in the treatment of resectable gastric and GEJ cancer. Quality of studies was assessed using the Revised Cochrane risk-of-bias tool for randomized trials. Inverse variance was the statistical method used with random effects as the analysis model in the production of the Forest plot and calculation of odds ratio at 95% CI. Results: Three RCTs (N = 1446), each with two arms, were included in the meta-analysis. The Phase II Dante Trial (N= 295)compared perioperative FLOT alone with perioperative atezolizumab + FLOT. The Phase III Keynote 585 trial(N=203) and the phase III Matterhorn trial (N=948) compared perioperative placebo + FLOT with perioperative pembrolizumab + FLOT, and perioperative Durvalumab + FLOT, respectively. Risk of bias and heterogeneity were low. Pooled results showed that in patients given perioperative FLOT + immunotherapy, there is statistically significant improvement in the rate of pathologic complete response (OR 2.60 95% CI 1.88-3.61, p &lt;0.0001). In terms of rate of R0 resection, there was no statistically significant difference between the two groups (OR 1.02 95% CI 0.75-1.38,p= 0.92). Conclusions: This analysis shows that adding immunotherapy to FLOT improves the rate of pathologic complete response, and maintains the high rate of R0 resection, in resectable gastric and GEJ cancers. Favorable results of pending survival outcomes from these trials may help re-shape the current standard of care in this field.