There is a clinical need to identify early predictors for response to neoadjuvant chemotherapy (NAC) in patients with gastric and gastroesophageal junction cancer (GC and GEJC). Radiomics involves extracting quantitative features from medical images. This study aimed to apply radiomics to build prediction models for the response to NAC.

All consecutive patients with non-metastatic GC and GEJC undergoing NAC and surgical resection in an Italian high-volume referral center between 2005 and 2021 were considered eligible. In patients selected, the CT scans performed upon staging were reviewed to segment the tumor and extract radiomic features using MODDICOM. The primary endpoint was to develop and validate radiomic-based predictive models to identify major responders (MR: tumor regression grade TRG 1-2) and non-responders (NR: TRG 4-5) to NAC. Following an initial feature selection, radiomic and combined radiomic-clinicopathologic prediction models were built for the MR or NR status based on logistic regressions. Internal validation was performed for each model. Radiomic models (in the entire case series and according to NAC regimens) were evaluated using the receiver operating characteristic area under the curve (AUC), sensitivity, and negative predictive value (NPV).

The study included 77 patients undergoing NAC and subsequent tumor resection. The MR prediction model after all types of NAC (AUC of 0.876, CI 95% 0.786 - 0.966, sensitivity 83%, and NPV 96%) was based on a statistical feature. The models predicting NR among patients undergoing epirubicin with cisplatin and fluorouracil (ECF), epirubicin with oxaliplatin and capecitabin (EOX), or fluorouracil with oxaliplatin and docetaxel (FLOT) (AUC 0.760, CI 95% 0.639-0.882), oxaliplatin-based chemotherapy (AUC 0.810, CI 95% 0.692-0.928), and FLOT (AUC 0.907, CI 95% 0.818 - 0.995) were based on statistical, morphological and textural features.

The developed radiomic models resulted promising in predicting the response to different neoadjuvant chemotherapy strategies. Once further implemented on larger datasets, they could be valuable and cost-effective instruments to target multimodal treatment in patients with GC.

This study evaluates the impact of perioperative S-1 and oxaliplatin (SOX) versus postoperative SOX or capecitabine and oxaliplatin (XELOX) on patient prognosis to identify suitable candidates for each therapy.

A retrospective real-world cohort study was conducted using data from Zhejiang Cancer Hospital on gastric cancer patients treated between 2010 and 2019. Patients were divided into perioperative SOX and postoperative SOX or XELOX groups. Propensity score matching (PSM) was used to control for selection bias. Overall survival (OS) was the primary outcome, analyzed using the Kaplan-Meier method and Cox regression.

A total of 816 patients were included: 293 in the perioperative SOX group and 523 in the postoperative chemotherapy group (408 SOX and 115 XELOX). In the perioperative SOX group, the tumor regression grade (TRG) 2-3 subgroup demonstrated a significantly worse overall survival (OS) compared to the postoperative XELOX group (95% CI = 1.064-3.444, P = 0.027). Subgroup analysis revealed that older patients (95% CI = 0.210-0.950, P = 0.036), and those at the cT3 (95% CI = 0.05-1.19, P = 0.008) stage experienced greater benefits from postoperative chemotherapy. When comparing the benefited populations, it was found that patients with CA125 positivity had an advantage trend with adjuvant chemotherapy compared to perioperative SOX chemotherapy.

Real-world data suggest that perioperative SOX chemotherapy does not benefit all patients with advanced gastric cancer. Patients with TRG 2-3, older age, or cT3 stage may achieve better outcomes with postoperative chemotherapy. Additionally, an exploratory analysis indicated that CA125 positivity may be associated with improved survival following adjuvant treatment.

Perioperative chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel has improved survival in patients with locally advanced resectable gastric or gastroesophageal junction adenocarcinomas in Europe.

We report two cases of laparoscopic curative resection with perioperative docetaxel-based chemotherapy for advanced gastroesophageal junction or gastric adenocarcinoma and investigated variations in Claudin18.2 expressions associated with chemotherapy.

Preoperative four-cycle docetaxel-based chemotherapy enabled laparoscopic total gastrectomy with distal esophagectomy via trans-hiatal approach or laparoscopic distal gastrectomy with extensive lymph node dissection. Postoperative left inferior pulmonary arterial thrombosis and chylous ascites recovered with pharmacotherapy and lipiodol lymphatic embolization. Despite discontinuing postoperative one-cycle chemotherapy, no recurrence was observed for over 1.5 and 1 year. Immunohistochemical staining showed increased Claudin18.2 expression in undifferentiated adenocarcinomas in the resected specimens than in pre-chemotherapeutic biopsies.

Perioperative docetaxel-based chemotherapy was effective for Japanese patients with gastroesophageal junction and gastric adenocarcinoma, suggesting a combination treatment with anti-Claudin18.2 antibody as neoadjuvant or first-line chemotherapy.

Disease recurrence is the primary cause of death in patients with gastric cancer who have undergone complete surgical resection. No prognostic factors for recurrence, other than the Tumor, Node, and Metastasis stage, have been established. However, recurrence rates differ even within the same Tumor, Node, and Metastasis stage. Therefore, we aimed to develop a new prognostic confidence measure for gastric cancer recurrence and demonstrate its practical utility.

This was a retrospective study based on the medical records of the Chungnam National University Hospital, Republic of Korea. We enrolled patients diagnosed with stage II/III gastric cancer who underwent complete surgical resection and adjuvant chemotherapy over the past 12 years. The association between seven variables, including the systemic inflammation response index (SIRI) and gastric cancer recurrence, was analyzed.

A total of 296 patients were enrolled in this study. Although other factors did not exhibit significant correlations, SIRI showed a significant positive correlation with gastric cancer recurrence risk, confirmed through Cox regression testing (hazard ratio, 1.231; 95% confidence interval, 1.04-1.45). Linear regression analysis revealed a significant association between higher SIRI values and shorter recurrence time (p = 0.044; β = -0.225).

In this study, other than SIRI, effective prognostic factors related to gastric cancer recurrence were not verified, thus indicating SIRI as a potential independent prognostic factor.

The safety and feasibility of laparoscopic surgery for T4b gastric cancer with transverse colon or mesocolon invasion remain insufficiently characterized. This study aimed to compare the surgical outcomes of laparoscopic and open gastrectomy in individuals with T4b gastric cancer involving these anatomical structures.

A retrospective cohort study was conducted across two centers, including 53 individuals with T4b gastric cancer involving the transverse colon or mesocolon who underwent curative-intent surgery between January 2011 and December 2019. Participants were divided into two groups based on the surgical approach: laparoscopic surgery (n = 32) and open surgery (n = 21). Perioperative outcomes, postoperative complications, and survival outcomes were evaluated and compared.

Baseline characteristics were comparable between the groups. The laparoscopic approach demonstrated significantly reduced intraoperative blood loss compared to open surgery (92.5 ± 101.9 mL vs. 147.6 ± 76.6 mL, p = 0.039). No significant differences were observed in operating time (187.8 ± 52.7 vs. 185.9 ± 52.3 min, p = 0.896), R0 resection rates (93.8% vs. 90.5%, p = 0.659), lymph node yield, or length of postoperative hospital stay. The incidence of postoperative complications was similar between the groups (10.3% vs. 10.5%, p = 0.986). Additionally, mean overall survival (31.4 vs. 27.2 months, p = 0.506) and progression-free survival (26.1 vs. 23.5 months, p = 0.573) did not differ significantly.

Laparoscopic gastrectomy with combined resection appears to be a feasible and safe alternative to open surgery for selected individuals with T4b gastric cancer involving the transverse colon or mesocolon. This approach achieves similar perioperative and long-term clinical outcomes compared to open surgery.

As a global health concern, gastric cancer management has been systematized by individual countries and regions into regimented guidelines. To explore international differences, we examined the guidelines of Korea, Japan, Europe, and the United States. Guidelines are created by experts in the field, focusing on evidence-based recommendations to standardize and improve patient care, but the methodology for guideline creation, incorporation of new innovations, and review differs significantly. National and regional differences within the guidelines are apparent, stemming from various factors including local incidence, stage, presentation, patient preferences, and governmental influences. Differences include the use of neoadjuvant chemotherapy, criteria for endoscopic resection, and extent of lymphadenectomy. Nonetheless, fundamental treatment principles remain universal, and the goals of national guidelines are uniform: standardizing patient care, providing the highest quality treatments, incorporating cutting-edge clinical trial results, and consensus in guidelines to help formulate governmental policies. This review highlights how the guidelines are constructed, the unique elements of each guideline, how they differ, and why they differ.

Neoadjuvant chemotherapy is widely recognized as the established treatment for advanced gastric cancer. However, predicting its efficacy before surgery remains challenging.

The present study aimed to evaluate the effectiveness of 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) as a predictor of treatment response to the S-1+Oxaliplatin regimen (SOX).

Thirty patients who underwent gastrectomy following neoadjuvant SOX between January 2021 and July 2023 were included. Patients underwent FDG-PET pre- and postsurgery. The maximum standardized uptake value (SUVmax) from FDG-PET was examined in relation to histological tumor response and prognosis. SUVmax decreased significantly after chemotherapy in all patients (p < 0.001), especially in those with Grade 1a, 2, and 3 tumors (p < 0.05). SUV reduction increased stepwise with the histological response grade. Optimal cut-off values for the percentage decrease in SUVmax (ΔSUVmax) predictive of histologic efficacy were identified as 53% (area under curve 0.855, p = 0.0018) for Grade 1b or higher and 75% (area under curve 0.806, p = 0.0044) for Grade 2 or higher. Patients with ΔSUVmax > 50% had improved recurrence-free survival (p = 0.027).

FDG-PET may be useful as a predictor of treatment response in neoadjuvant SOX therapy for gastric cancer. The determination of the optimal ΔSUVmax value may enhance the precision of histological tumor response prediction.

Patients with gastric cancer (GC) who experience early recurrence (ER) within 2 years postoperatively have poor prognoses. This study aimed to analyze and predict ER after curative surgery for patients with GC using machine learning (ML) methods.

This multicenter population-based cohort study included data from ten large tertiary regional medical centers in China. The clinical, pathological, and laboratory parameters were retrospectively collected from the records of 11,615 patients. The patients were randomly divided into training (70%) and test (30%) cohorts. A total of ten ML models were developed and validated to predict the ER. Model performance was evaluated using area under the receiver operating characteristic curve (AUC), calibration plots, and Brier score (BS). SHapley Additive exPlanations (SHAP) was used to rank the input features and interpret predictions.

ER was reported in 1794 patients (15%) during follow-up. The stacking ensemble model achieved AUCs of 1.0 and 0.8 in the training and testing cohorts, respectively, with a BS of 0.113. SHAP dependency plots revealed that tumor staging, elevated tumor marker levels, lymphovascular invasion, perineural invasion, and tumor size > 5 cm were associated with higher ER risk. The impact of age and the number of lymph nodes harvested on ER risk exhibited a "U-shaped distribution." Additionally, an online prediction tool based on the best model was developed to facilitate clinical applications.

We developed a robust clinical model for predicting the risk of ER after surgery for GC, which may aid in individualized clinical decision-making.

To improve the prognosis of clinically resectable type 4 or large type 3 gastric cancer (GC), we performed a phase I/II study of neoadjuvant-radiotherapy combined with S-1 plus cisplatin.

Phase I, with a standard 3 + 3 dose-escalation design, was performed to define the recommended phase II dose. Efficacy and safety were evaluated in phase II. The three dose levels were as follows: level 0, S-1 60 mg/m2 on days 1-14 plus cisplatin 60 mg/m2 on day 1; level 1, S-1 80 mg/m2 on days 1-14 plus cisplatin 60 mg/m2 on day 1; and level 2, S-1 80 mg/m2 on days 1-14 and 22-35, plus cisplatin 60 mg/m2 on days 1 and 22. The starting dose was level 1. Radiotherapy was delivered at a total dose of 40 Gy in fractions for 4 weeks.

A total of six patients were enrolled in the phase I study. Dose-limiting toxicity was observed at level 2; level 1 was established as the recommended phase II dose. In phase II, 20 patients were enrolled from November 2012 to April 2018. Grade 3/4 leukopenia and nonhematologic adverse events occurred in 35% and 5% of the patients, respectively. In total, 19 patients underwent the protocol surgery; 2 (10.5%) achieved a pathological complete response. There were no treatment-related deaths; 3- and 5-year overall survival rates were 70.0 and 50.0%, respectively.

Neoadjuvant chemoradiotherapy with S-1 plus cisplatin is a safe and promising treatment for clinically resectable type 4 or large type 3 GC.

Large type 3 (≥ 8 cm) and type 4 gastric cancers (GCs) have poor prognoses and necessitate multidisciplinary treatment. A multi-institutional phase II study (OGSG1902) was conducted to assess the efficacy and safety of neoadjuvant chemotherapy (NAC) with docetaxel, oxaliplatin, and S-1 (DOS) in these patients.

Patients with large type 3 or type 4 GC without distant metastasis, except for positive peritoneal cytology (CY), were enrolled. Patients received three courses of neoadjuvant DOS therapy (docetaxel 40 mg/m2 and oxaliplatin 100 mg/m2 on day 1 via intravenous infusion, and S-1 80 mg/m2 orally for 14 days, repeated every 3 weeks) followed by gastrectomy. After R0 resection, adjuvant docetaxel/S-1 therapy was administered for 1 year.

From October 2019 to February 2022, 48 patients were enrolled. NAC was completed in 91.7% of patients. The R0 resection rate was 89.6%. The pathological response rate (Grade 1b-3) was 66.7%. Among patients with measurable lesions, the response rate was 50.0%. The CY-negative conversion rate was 80.0%, and the protocol completion rate was 45.8%. Grade 3 or 4 adverse events during NAC, including neutropenia and appetite loss, occurred in 37.5% of patients. Major postoperative complications (Clavien-Dindo Grade IIIa or higher) were observed in 2.1% of patients.

NAC with DOS for large type 3 or type 4 GC followed by gastrectomy demonstrated promising efficacy, high pathological response rates, and an acceptable toxicity profile. Further evaluation of long-term survival outcomes is ongoing.

Gastric cancer ranks fifth as the most common cancer and third as the leading cause of death worldwide. Risk factors include advancing age, low-fiber diets, high salt intake and Helicobacter pylori infection. Diagnosis relies on histological examination following endoscopic biopsy with staging accomplished through various imaging modalities. Early gastric cancer is primarily managed via endoscopic resection, while non-early operable cases typically undergo surgery. Advanced cases are addressed through sequential chemotherapy lines, with initial treatment usually comprising a platinum and fluoropyrimidine combination. Linitis plastica (LP) is a rare, aggressive form of gastric cancer characterized by diffuse infiltration of the gastric wall, resulting in poor outcomes even after curative resection. The absence of a standardized definition contributes to uncertainty regarding the precise incidence of these tumors. LP is often diagnosed at advanced stages, with a reported median survival rate of approximately 4%-29%, despite "curative resection". Its distinctive biological behavior includes perineural invasion, nodal metastasis, and peritoneal dissemination. The bleak prognosis for LP patients partly stems from delayed diagnosis and its aggressive biological nature, posing significant challenges for clinical management. Currently, no specialized treatment strategy exists for LP, and clinical approaches typically align with those used for general gastric cancer treatment. Surgical resection is the primary treatment, but the optimal surgical approach remains contentious. Recent studies have investigated the efficacy of neoadjuvant chemotherapy and radiotherapy in improving survival outcomes for LP patients. However, controversies persist regarding the role of adjuvant chemotherapy and postoperative radiotherapy. LP requires a multidisciplinary approach and personalized treatment strategies tailored to each patient's condition. Further research is needed to elucidate optimal therapeutic interventions and improve outcomes for LP patients.

To systematically evaluate the efficacy and safety of combination therapy with toripalimab in the treatment of advanced gastric cancer (GC).

We conducted a thorough search for relevant studies in PubMed, Embase, Cochrane Library, and Web of Science. Effect estimates were computed utilizing Stata software (version 14.0) and either random or fixed effects models, as applicable. A subgroup analysis was undertaken to assess the effect of various combination therapies on overall response rate (ORR). Begg and Egger's tests were employed to assess publication bias.

The study consisted of 8 trials, which included 277 participants with advanced gastric cancer. The overall ORR was 41.4% (95% CI, 32.4%-50.3%), with a disease control rate (DCR) of 83.6% (95% CI, 74.6%-92.7%), a median overall survival (mOS) of 11.0 months (95% CI, 9.6-12.4), and a median progression-free survival (mPFS) of 4.2 months (95% CI, 2.5-6.0) for the combination therapy with toripalimab. Subgroup analysis revealed that the combination of toripalimab and chemotherapy achieved a greater ORR compared to the non-chemotherapy group, with ORR rates of 49.8% (95% CI, 42.2%-57.4%) and 31.9% (95% CI, 26.7%-37.1%), respectively. The combination therapy with toripalimab led to adverse events (AEs) of any grade at 94.0% of cases (95% CI, 89.5%-98.5%) and grade 3 AEs at 32.4% (95% CI, 17.8%-47.1%). The sensitivity analysis indicated that no single study affected the overall results.

Combination therapy of toripalimab can improve clinical efficacy, although with increased but manageable toxicity. Additional clinical trials are required to assess comprehensively the efficacy and safety of alternative toripalimab regimens. The review agreement has been recorded with PROSPERO (CRD42024585696).

To report the latest systematic review and meta-analysis of randomized controlled trials (RCT) to compare perioperative versus adjuvant chemotherapy for resectable gastric cancer.

We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until April, 2024 for RCT which compared perioperative versus adjuvant chemotherapy for resectable gastric cancer. Outcomes measured were overall survival (OS) and progression-free survival (PFS).

5 RCTs including 2,735 patients were included for meta-analysis. Meta-analysis revealed a significant longer PFS in the neoadjuvant chemotherapy (NAC) group (HR: 0.77; 95% CI: 0.69, 0.85; P<0.00001) compared with adjuvant chemotherapy (AC) group. Subgroup analysis found that there was still a significant superiority of NAC in female (HR: 0.53; 95% CI: 0.40, 0.70; P<0.0001) and cN+ (HR: 0.77; 95% CI: 0.67, 0.89; P=0.0005) patients, while the superiority disappeared in male (HR: 0.87; 95% CI: 0.74, 1.01; P=0.07) and cN- patients (HR: 0.91; 95% CI: 0.46, 1.78; P=0.77). In addition, meta-analysis observed a trend towards improved OS with NAC (HR: 0.86; 95% CI: 0.70, 1.07; P = 0.17), and sensitivity analysis demonstrated instability in OS.

NAC can significantly prolong PFS in patients with resectable gastric cancer compared to AC, and the benefit is more significant in women and cN+ patients. Besides, our analysis indicated that NAC has a potential to improve OS compared with AC.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024546165.

Patients with large Stage IV gastric cancer (GC) invading the proximal stomach find it difficult to receive not only bypass surgery but also S-1-based chemotherapy. This study aimed to show our treatment results for those GC patients using elementary diet (ED) tubes, which enabled S-1-based chemotherapy and nutrition support.

We evaluated 20 patients (13 men and 7 women; median age 70 years) with large Stage IV GCs (8.7-21.9 cm) invading the proximal stomach, who were admitted due to inability to eat, treated with S-1-based chemotherapy using an ED tube. The duration from the initiation of the chemotherapy to the improvement of oral intake, changes in nutritional status, and disease-specific survival (DSS) were retrospectively investigated. Two of the 20 patients failed to complete even one cycle of chemotherapy due to severe nausea or diarrhea. The other 18 patients improved oral liquid intake after 47.5 ± 18.8 days, and 17 patients improved oral solid food intake after 54.5 ± 19.6 days from the start of chemotherapy. In addition, three patients (16.7%) could receive conversion surgery after improvement of oral intake. The median DSS of those 18 patients was 13.1 months. Serum albumin level and prognostic nutritional index (PNI) were significantly improved after about 1 month of the treatment (both P <0.0001). Improvement of serum albumin level and PNI during the first 1 month of the treatment significantly correlated with better DSS (P = 0.006, 0.01, respectively).

Given a high oral intake success rate, S-1-based chemotherapy using an ED tube can be a promising treatment option for large Stage IV GC with poor oral intake.

Advanced gastric cancer with gastric outlet obstruction (GOO) causes malnutrition and medication adherence issues, leading to a poor prognosis. We developed a novel multimodal, less invasive treatment approach for gastric cancer patients with symptomatic GOO: laparoscopic stomach-partitioning gastrojejunostomy (LSPGJ) combined with neoadjuvant chemotherapy (NAC), followed by minimally invasive gastrectomy with reuse of gastrojejunostomy. This study is a retrospective analysis of the safety and feasibility of our treatment strategy.

In this single-institution retrospective study, we enrolled 54 patients (NAC group, n = 26; upfront gastrectomy group, n = 28) who achieved R0 resection through a minimally invasive approach between 2007 and 2020 and evaluated their short- and long-term outcomes.

After LSPGJ, the Gastric Outlet Obstruction Scoring System score significantly improved (p < 0.001). The median relative dose intensity of NAC was 88.2%. Regarding short-term outcomes, there were no differences in postoperative complications, length of postsurgical hospital stay, and adjuvant chemotherapy administration. Although overall survival and relapse-free survival showed trends toward improvement in the NAC group, these differences were not statistically significant. The cumulative incidence curve for recurrence in the NAC group was significantly lower than that of the upfront gastrectomy group (p = 0.041). Recurrence and hematogenous metastasis were significantly lower in the NAC group (p = 0.031 and 0.041, respectively) than in the upfront gastrectomy group. A forest plot revealed that NAC yielded favorable outcomes, particularly for patients with a body mass index (BMI) < 18.5 kg/m2, cT4, or cN1.

LSPGJ combined with NAC followed by minimally invasive gastrectomy was a safe and feasible treatment strategy for patients with advanced gastric cancer with symptomatic GOO. This procedure may contribute to the early recovery of oral intake and help maintain NAC dose intensity, potentially improving prognosis, particularly for patients with low BMI and advanced-stage disease.

Gastric cancer is prevalent worldwide and is a leading cause of cancer-related death. Patients with GC often present at advanced stages at diagnosis. Patients with locally advanced diseases experience poor survival rates with surgery alone. Multimodality therapy, including peri-operative therapy and adjuvant therapy, has improved outcomes. However, there is no consensus on the optimal treatment approach. Molecular characteristics of GC may help guide treatment choices and studies are currently underway to evaluate other treatment modalities including immunotherapy and targeted therapy.

Gastric cancer is one of the most common cancers in both Korea and worldwide. Since 2004, the Korean Practice Guidelines for Gastric Cancer have been regularly updated, with the 4th edition published in 2022. The 4th edition was the result of a collaborative work by an interdisciplinary team, including experts in gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology, and guideline development methodology. The current guideline is the 5th version, an updated version of the 4th edition. In this guideline, 6 key questions (KQs) were updated or proposed after a collaborative review by the working group, and 7 statements were developed, or revised, or discussed based on a systematic review using the MEDLINE, Embase, Cochrane Library, and KoreaMed database. Over the past 2 years, there have been significant changes in systemic treatment, leading to major updates and revisions focused on this area. Additionally, minor modifications have been made in other sections, incorporating recent research findings. The level of evidence and grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation system. Key factors for recommendation included the level of evidence, benefit, harm, and clinical applicability. The working group reviewed and discussed the recommendations to reach a consensus. The structure of this guideline remains similar to the 2022 version. Earlier sections cover general considerations, such as screening, diagnosis, and staging of endoscopy, pathology, radiology, and nuclear medicine. In the latter sections, statements are provided for each KQ based on clinical evidence, with flowcharts supporting these statements through meta-analysis and references. This multidisciplinary, evidence-based gastric cancer guideline aims to support clinicians in providing optimal care for gastric cancer patients.

Gastric cancer (GC) has benefited from treatment improvements such as minimally invasive surgery, molecular-targeted drugs, and immune check point inhibitors. However, the prognosis of advanced GC is still unfavorable. Minimally invasive pre-treatment detection of drug sensitivity (MI-PDDS) has increasing importance in view of improved chemotherapy. Gastric biopsy specimens are obtained with relative ease but have not been considered an appropriate source for generating cell lines because of their minute amounts. We therefore materialized the idea of MI-PDDS using biopsy-derived cell lines obtained from endoscopic biopsy specimens. Here, a cell line designated TCC-GC1-C1 was established from a biopsy specimen of a histologically confirmed adenocarcinoma of the stomach. The cell line showed the ability of forming spheroid with deeply stained nuclei and disturbed cellular morphology indicative of malignancy. Single-nucleotide polymorphism (SNP) genotyping of the cell line revealed a duplication of chromosome19q and a deletion of chromosome 8p. A drug screening test with 221 anticancer drugs showed that the cell line had high sensitivity to the proteasome inhibitor (Carfilzomib) and the fibroblast growth factor receptor inhibitor (Erdafitinib), with a low IC50 value of under 0.1 μM. Our MI-PDDS approach holds promise in making a treatment decision for advanced GC.

Differences in demographics, medical expertise, and patient healthcare resources across countries have led to significant variations in guidelines. In light of these differences, in this review, we aimed to explore and compare the most recent updates to gastric cancer treatment from five guidelines that are available in English. These English-version guidelines, which have been recently published and updated for journal publication, include those published in South Korea in 2024, Japan in 2021, China in 2023, the United States in 2024, and Europe in 2024. The South Korean and Japanese guidelines provide a higher proportion of content to endoscopic and surgical treatments, reflecting their focus on minimally invasive techniques, function-preserving surgeries, and systemic therapy. The Chinese guidelines provide recommendations addressing not only surgical approaches but also perioperative chemotherapy and palliative systemic therapy. Meanwhile, in the United States and European guidelines, a higher proportion of the content is dedicated to perioperative and palliative systemic therapy, aligning with their approaches to advanced-stage disease management. All guidelines address surgical and systemic chemotherapy treatments; however, the proportion and emphasis of content vary based on the patient distribution and treatment approaches specific to each country. With emerging research findings on gastric cancer treatment worldwide, the national guidelines are being progressively revised and updated. Understanding the commonalities and differences among national guidelines, along with the underlying evidence, can provide valuable insights into the treatment of gastric cancer.

Purpose The prognosis for type 4 and large type 3 gastric cancer (GC) is extremely poor, especially in elderly patients (≥ 75 years). To improve the prognosis of these types of GC, we performed a phase I study to determine the recommended dose (RD) of S-1 combined with neoadjuvant radiotherapy. Methods Patients with clinically resectable type 4 and large type 3 GC were enrolled to successive cohorts in a conventional 3 + 3 design. Three dose levels were designed, as follows: level 0: S-1 60 mg/m2/day on Days 1-14; level 1: S-1 80 mg/m2/day on Days 1 -14; level 2: S-1 80 mg/m2/day on Days 1-14 and Days 22-35. The starting dose was level 1. Radiotherapy was delivered at a total dose of 40 Gy in fractions for 4 weeks. Results Ten patients were enrolled from July 2014 to August 2018. Six patients were registered at level 1, and one patient developed a dose limiting toxicity as gastric stenosis (grade 3). Two of four patients enrolled at level 2 developed dose limiting toxicity (inability to receive S-1 for hematological reasons). Therefore, the RD was determined as level 1. All patients underwent the protocol surgery; one patient underwent R1 resection because of positive peritoneal washing cytology. There were no treatment-related deaths, and the pathological response rate was 80%. The 5-year overall- and progression-free survival rates were both 60.0%. Conclusion The RD was determined as level 1. A phase II trial using the RD should be initiated.

Surgical resection is the cornerstone of treatment for locally advanced gastric cancer (LAGC). Hence, downstaging of the tumor with neoadjuvant therapy is critical for R0 resection and prolongs the overall survival. Data from related studies are lacking, and the literature is scarce. Therefore, a single arm-study was performed on PD-1 inhibitor and apatinib plus S-1 and oxaliplatin as neoadjuvant chemotherapy for patients with LAGC. The findings are expected to serve as a reference for neoadjuvant therapy for LAGC. We assessed 130 LAGC patients using PD-1 inhibitor, apatinib plus S-1, and oxaliplatin as neoadjuvant chemotherapy from January 2021 to October 2022. A total of 104 patients received gastric transcatheter chemoembolization (GTC). The primary endpoint was the rate of clinical complete response, pathological complete response, and safety, while the secondary endpoints were the R0 resection rate and objective response rate of the disease and the disease control rate. A total of 130 patients completed the clinical assessment, of which 6 patients (4.6%) achieved clinical complete response, 87 patients (66.9%) achieved partial response, 30 patients (23.0%) achieved stable disease, and 7 patients (5.5%) experienced progressive disease. The overall response rate was 71.5% (93/130), and the disease control rate was 94.5% (123/130). A remarkable downstaging effect was observed in this study. Downstaging of the T stage and N stage was achieved in 71.5% and 80% of the patients, respectively, which translated into a high R0 resection rate. The findings revealed that 125 patients underwent R0 resection, and the R0 resection rate was 96.1%. According to the observed results, 21.6% of the patients achieved pathological complete response after neoadjuvant chemotherapy. Gastric transcatheter chemoembolization in the first cycle of neoadjuvant therapy was beneficial for tumor regression (P < .001). All adverse events were relieved and disappeared after symptomatic treatment, and no grade 4 adverse events were noted. PD-1 inhibitor and apatinib plus S-1 and oxaliplatin are safe and effective as neoadjuvant treatment of LAGC. Gastric transcatheter chemoembolization is useful for tumor regression during neoadjuvant therapy.

Large 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.

In 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.

Of 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).

Large 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.

Homologous recombination deficiency (HRD) is one of the crucial hallmarks of cancer. It is associated with a favorable response to platinum-based chemotherapy. We explored the distinctive clinicopathological features of gastric cancer (GC) with HRD and the clinical significance of HRD in platinum-based first-line chemotherapy for unresectable metastatic GC.

We enrolled 160 patients with GC in this study. Their tumor samples were subjected to genomic profiling utilizing targeted tumor sequencing. HRD was defined as the presence of alterations in any of 16 HR genes (BARD1, BLM, BRCA1, BRCA2, BRIP1, MRE11A, NBN, PALB2, PARP1, POLD1, RAD50, RAD51, RAD51C, RAD51D, WRN, and XRCC2). The clinicopathological features and treatment outcomes of first-line chemotherapy for unresectable metastatic GC were compared between HRD and non-HRD groups.

Forty-seven patients (29.4%) were classified into the HRD group. This group had a significantly lower proportion of macroscopic type 3 or 4 tumors and higher TMB than the non-HRD group. Among patients who underwent platinum-based first-line chemotherapy, the HRD group had a greater response rate and longer progression-free survival after treatment (median 8.0 months vs. 3.0 months, P = 0.010), with an adjusted hazard ratio of 0.337 (95% confidence interval 0.151-0.753). HRD status was not associated with treatment outcomes in patients who did not undergo platinum-based chemotherapy.

Low proportion of macroscopic type 3 or 4 tumors and a high TMB are distinctive features of GC with HRD. HRD status is a potential predictive marker in platinum-based first-line chemotherapy for unresectable metastatic GC.

Large type 3 and type 4 gastric cancers (GC) have a significantly poor prognosis, primarily due to their high predisposition for peritoneal dissemination. The application of intraperitoneal chemotherapy has emerged as a viable therapeutic strategy for managing GC patients with peritoneal metastasis. This study is planned to enroll 37 resectable large type 3 or type 4 GC patients. These patients are scheduled to undergo a treatment comprising preoperative chemotherapy with paclitaxel, oxaliplatin and S-1, followed by D2 gastrectomy, and concluding with postoperative treatments that include prophylactic intraperitoneal chemotherapy. The study's primary objective is to evaluate the 3-year peritoneal recurrence rate. Secondary objectives are to assess the 3-year disease-free survival, 3-year overall survival and to monitor the adverse events.Clinical trial registration number: ChiCTR2400083253 (https://www.chictr.org.cn).

To explore the feasibility of modified docetaxel, cisplatin, and capecitabine (mDCX) chemotherapy with a lower dose of docetaxel than previously reported for stage III resectable gastric cancer patients with a high risk of recurrence or for stage IV gastric cancer patients aiming for conversion surgery.

Patients with stage III resectable HER2-negative gastric cancer with large type 3 or type 4 tumors or extensive lymph node metastasis (bulky N or cN3) and those who had stage IV HER2-negative gastric cancer with distant metastasis were enrolled to receive 30 mg/m2 docetaxel and 60 mg/m2 cisplatin on day 1, followed by 2000 mg/m2 capecitabine per day for 2 weeks every 3 weeks.

Five patients with stage III gastric cancer with a high risk of recurrence received three courses of mDCX, and four patients with stage IV gastric cancer received three or four courses of mDCX. In terms of grade 3 or worse adverse events, leukopenia was observed in one (11%) patient, neutropenia in two (22%) patients, anemia in one (11%) patient, anorexia in two (22%) patients and nausea in two (22%) patients. All six patients with measurable lesions achieved a partial response. All nine patients underwent subsequent surgeries. The histological responses of the nine patients revealed grade 3 in one (11%) patient, grade 2 in five (56%) patients, and grade 1a in three (33%) patients. Three of the nine patients survived without recurrence, and two of them survived for more than four years.

mDCX seems to be feasible and may be helpful as neoadjuvant chemotherapy for patients at high risk of recurrence or as chemotherapy for patients who are likely to undergo conversion surgery.

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.

Whether patients with diffuse gastric cancer, which is insensitive to chemotherapy, can benefit from neoadjuvant or adjuvant chemotherapy has long been controversial.

To investigate whether perioperative chemotherapy can improve survival of patients with locally advanced diffuse gastric cancer.

A total of 2684 patients with locally advanced diffuse gastric cancer from 18 population-based cancer registries in the United States were analyzed.

Compared with surgery alone, perioperative chemotherapy improved the prognosis of patients with locally advanced gastric cancer. Before stabilized inverse probability of treatment weighting (IPTW), the median overall survival (OS) times were 40.0 months and 13.0 months (P < 0.001), respectively. After IPTW, the median OS times were 33.0 months and 17.0 months (P < 0.001), respectively. Neoadjuvant chemotherapy did not improve the prognosis of patients with locally advanced gastric cancer compared with adjuvant chemotherapy after IPTW. After IPTW, the median OS times were 38.0 months in the neoadjuvant chemotherapy group and 42.0 months in the adjuvant chemotherapy group (P = 0.472).

Patients with diffuse gastric cancer can benefit from perioperative chemotherapy. There was no significant difference in survival between patients who received neoadjuvant chemotherapy and those who received 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.

Post-operative infectious complication (IC) is a well-known negative prognostic factor, while showing neoadjuvant chemotherapy (NAC) may cancel out the negative influence of IC. This analysis compared the clinical impacts of IC according to the presence or absence of NAC in gastric cancer patients enrolled in the phase III clinical trial (JCOG0501) which compared upfront surgery (arm A) and NAC followed by surgery (arm B) in type 4 and large type 3 gastric cancer.

The subjects were 224 patients who underwent R0 resection out of 316 patients enrolled in JCOG0501. The prognoses of the patients with or without ICs in each arm were investigated by univariable and multivariable Cox regression analyses.

There were 21 (20.0%) IC occurrences in arm A and 15 (12.6%) in arm B. In arm A, the overall survival (OS) of patients with ICs was slightly worse than those without IC (3-year OS, 57.1% in patients with ICs, 79.8% in those without ICs; adjusted hazard ratio (95% confidence interval), 1.292 (0.655-2.546)). In arm B, patients with ICs showed a trend of better survival than those without ICs (3-year OS, 80.0% in patients with IC, 74.0% in those without IC; adjusted hazard ratio, 0.573 (0.226-1.456)).

This study could not indicate the negative prognostic influence of ICs in gastric cancer patients receiving NAC, which might be canceled by NAC. To build exact evidence, further investigation with prospective and large numbers of data might be expected.

This study evaluated pathologic response rate, overall survival (OS), and postoperative complications in locally advanced gastric cancer (GC) and esophagogastric junction (EGJ) adenocarcinoma patients who underwent curative gastric resection D2 lymph node dissection with neoadjuvant treatment.

We reviewed the medical records of 122 patients with locally advanced GC and EGJ adenocarcinoma who had neoadjuvant treatment and curative resection with D2 dissection between January 2014 and December 2022. Patients were divided into responders and nonresponders. Grades 1a-1b were responders, while 2-3 were non-responders. Patients' clinicopathological features, pathologic response rate, survival, and postoperative complications were evaluated. We assessed complications using the Clavien-Dindo (CD) classification. Total survival was assessed using the Kaplan-Meier model. Overall survival was assessed using univariate and multivariate Cox regression analysis.

The mean age of the study participants was 61 (N = 89 males; N = 33 females). There were 79 GC and 43 EGJ adenocarcinomas. Overall postoperative complications (CD ≥ II) were 27 %. Postoperative complications were similar in responders and non-responders (p = 0.316). YpT0N0 had a 2.5 % pathological complete response rate. Responders had better overall survival, but there was no statistical difference.

Both responder and non-responder groups have similar postoperative complications. A complete pathologic response is discouraging for assessing neoadjuvant chemotherapy for locally advanced gastric cancer, but a positive treatment response is acceptable. Pathologic response rate helps stage and predict gastric cancer prognosis. Responder groups survive slightly better.

Splenic hilar lymphadenectomy has been recommended for locally advanced proximal gastric cancer (APGC) involving the greater curvature. However, it is unclear whether laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) is associated with a long-term survival benefit for APGC without greater curvature invasion.

To present the 5-year follow-up data from a randomized clinical trial that compared laparoscopic total gastrectomy (D2 group) with D2 plus LSPSHL (D2 + No. 10 group) among patients with resectable APGC.

This is a post hoc secondary analysis of a randomized clinical trial that enrolled 536 patients with potentially resectable APGC (cT2-4a, N0 or N+, and M0) without greater curvature invasion from January 5, 2015, to October 10, 2018. All patients were tracked for at least 5 years. The final follow-up was on October 30, 2023.

Patients were randomly assigned in a 1:1 ratio to the D2 + No. 10 or D2 groups.

The 5-year disease-free survival (DFS) and overall survival (OS) rates were measured. Recurrence patterns and causes of death were compared.

A total of 526 patients (392 men [74.5%]; mean [SD] age, 60.6 [9.6] years) were included in the modified intent-to-treat analysis, with 263 patients in each group. The 5-year DFS rate was 63.9% (95% CI, 58.1%-69.7%) for the D2 + No. 10 group and 55.1% (95% CI, 49.1%-61.1%) for the D2 group (log-rank P = .04). A statistically significant difference was observed in the 5-year OS between the D2 + No. 10 group and the D2 group (66.2% [95% CI, 60.4%-71.9%] vs 57.4% [95% CI, 51.4%-63.4%]; log-rank P = .03). The No. 10 lymph node exhibited a therapeutic value index (TVI) of 6.5, surpassing that of Nos. 8a (TVI, 3.0), 11 (TVI, 5.8), and 12a (TVI, 0.8). A total of 86 patients in the D2 + No. 10 group (cumulative incidence, 32.7%) and 111 patients in the D2 group (cumulative incidence, 42.2%) experienced recurrence (hazard ratio, 0.72; 95% CI, 0.54-0.95; P = .02). The multivariable competing risk regression model demonstrated that D2 + No. 10 remained an independent protective factor for a lower 5-year cumulative recurrence rate after surgery (hazard ratio, 0.75; 95% CI, 0.56-1.00; P = .05). There was a significant difference in the 5-year cumulative recurrence rate at the No. 10 lymph node area between the 2 groups (D2 + No. 10 group vs D2 group: 0% vs 2.3% [n = 6]; P = .01).

This post hoc secondary analysis of a randomized clinical trial found that laparoscopic total gastrectomy with LSPSHL can improve the prognosis and reduce recurrence for APGC without greater curvature invasion. Future multicenter studies are warranted to validate these findings.

ClinicalTrials.gov Identifier: NCT02333721.