Postoperative adjuvant chemotherapy in older adults aged ≥ 80 years with locally advanced gastric cancer (LAGC) remains debated owing to concerns over treatment tolerance and limited data. We aimed to assess the effectiveness of postoperative adjuvant chemotherapy in adults aged ≥ 80 years with LAGC using data from the Surveillance, Epidemiology, and End Results database.

A total of 2395 patients with LAGC aged ≥ 80 years who underwent radical surgery between 2004 and 2015 were identified. Propensity score matching (1:1) was applied to pair 422 patients receiving adjuvant chemotherapy with 1973 patients who underwent surgery alone. Multivariate logistic regression identified independent predictors of adjuvant chemotherapy, including the period from 2012-2015, pN1-2 and pN3 stages, and radiation therapy. Conversely, age ≥ 85 years predicted decreased chemotherapy use. Cancer-specific survival (CSS) and overall survival (OS) were compared using multivariate Cox analysis, showing significantly longer OS and CSS in the adjuvant chemotherapy group, before and after matching. Subgroup analysis revealed that patients aged 80-84 years and those with N + stages benefited most from adjuvant chemotherapy, whereas patients aged ≥ 90 years did not show significant benefit.

Postoperative adjuvant chemotherapy should be considered for patients aged ≥ 80 years with LAGC, especially those with lymph node involvement, as it offers significant survival benefits. However, as age approaches 90 years, the benefits of adjuvant chemotherapy may diminish, warranting more cautious application.

Gastrointestinal (GI) cancers remain a leading cause of cancer-related mortality worldwide, with metabolic reprogramming recognized as a central driver of tumor progression and therapeutic resistance. Among the key regulatory layers, N6-methyladenosine (m6A) RNA modification-mediated by methyltransferases (writers such as METTL3/14), RNA-binding proteins (readers like YTHDFs and IGF2BPs), and demethylases (erasers including FTO and ALKBH5), plays a pivotal role in controlling gene expression and metabolic flux in the tumor context. Concurrently, the gut microbiota profoundly influences GI tumorigenesis and immune evasion by modulating metabolite availability and remodeling the tumor microenvironment. Recent evidence has uncovered a bidirectional crosstalk between microbial metabolites and m6A methylation: microbiota-derived signals dynamically regulate m6A deposition on metabolic and immune transcripts, while m6A modifications, in turn, regulate the stability and translation of key mRNAs such as PD-L1 and FOXP3. This reciprocal interaction forms self-reinforcing epigenetic circuits that drive tumor plasticity, immune escape, and metabolic adaptation. In this review, we dissect the molecular underpinnings of the microbiota-m6A-metabolism axis in GI cancers and explore its potential to inform novel strategies in immunotherapy, metabolic intervention, and microbiome-guided precision oncology.

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.

The incidence of gastric cancer in the elderly is increasing; however, standardized surgical approaches are lacking.

To investigate the effects of radical surgery on the trauma response, postoperative complications, and long-term prognosis in elderly patients with gastric cancer.

Between January 2020 and December 2023, 110 gastric cancer patients admitted to the Department of Oncology Jiangnan University Medical Center were categorized into a control group (40 cases) and an observation group (70 cases) based on surgical method differences. The control and observation group received palliative surgery and radical surgery, respectively, and were further divided into open (25 cases) and laparoscopic (45 cases) surgery. Surgical outcomes, trauma indicators, complication rates, and long-term survival at 6 months, 1-, and 2-years were compared.

Laparoscopic surgery showed superior surgical outcomes compared to the open surgery and control groups (P < 0.05). Trauma indicators were lowest in the laparoscopic group and highest in the control group (P < 0.05). No significant difference was observed in the complication rates between the open and laparoscopic groups (P > 0.05), but both were higher than those in the control group (P < 0.05). No significant differences were found in survival rates at different follow-up periods between the laparoscopic and open groups (P > 0.05); however, both groups showed higher survival rates than the control group (P < 0.05).

Radical surgery in elderly patients with gastric cancer reduces surgical trauma response, facilitates postoperative recovery, and improves long-term survival rates, albeit with an increased risk of complications. Laparoscopic radical surgery further minimizes postoperative trauma, with no significant difference in complication rates and survival prognosis compared with open radical surgery.

Gastric adenocarcinoma (GAC) has a different epidemiological profile in Egypt than in other countries. It ranks 11th in incidence, with 3,285 new cases and 10th in mortality, with 2,469 cases. This retrospective study aims to analyze gastric cancer epidemiology and clinical outcomes in Egyptian patients at Ain Shams University Clinical Oncology Department.

We conducted a retrospective analysis of the complete medical records of patients with confirmed GAC at the Ain Shams University Clinical Oncology Department from January 2017 to December 2020.

This study included 70 patients with GAC. The median age was 52.5 years, with nearly half of cases under 50 years and males representing 53% of the cohort. 70% of patients were from urban areas. Nearly one-third were smokers, with 57.1% having medical comorbidities, mainly diabetes mellitus, hypertension and viral hepatitis. Additionally, 25.7% had a positive family history of GAC. Most Common presenting symptoms were vomiting (42.9%) and abdominal pain (57.1%). 40% of tumours were in the gastric body, and 64.3% were diffuse-type GAC, with 64.3% classified as high grade (III). At presentation, the majority of cases were metastatic (55.7%), with 15.7% presenting with stage II disease and 28.6% with stage III. Most patients (72.8%) had an Eastern Cooperative Oncology Group ≤2. Only 18.6% received neoadjuvant chemotherapy, while 48.6% underwent surgical resection with adequate lymph node dissection in 55.9% of cases. Adjuvant chemotherapy or chemoradiation was administered to 19 patients. The median overall survival (OS) was 11 months, 36 months for stage II, 17 months for stage III and 7 months for stage IV. Univariate analysis indicated that female gender, higher stage (Stage III-IV), higher grade (G IV), absence of neoadjuvant chemotherapy and intestinal type were significantly associated with increased mortality. However, multivariate analysis adjusting for these factors identified the advanced stage as a significant independent predictor of mortality.

This study identified the distinct GAC profile of Egyptian patients, younger age, aggressive tumours and frequent metastases. These factors contributed to lower OS. Further research and targeted interventions are needed to improve outcomes.

Gastric cancer is often diagnosed at an advanced stage and at order age, identification of high-risk population is needed for detection of early-stage gastric cancer.

To examine whether clonal hematopoiesis of indeterminate potential (CHIP) is a risk factor of gastric cancer.

This cohort study used data from the UK Biobank collected from baseline (2006-2010) to the end of follow-up in March 2024.

Data on age, sex, race, alcohol consumption, smoking status and type 2 diabetes were collected at baseline interview. Previous and diagnosed cancer or diseases were collected from self-reported and in-hospital records.

Participants with no previous cancer or hematologic disorders were selected. Participants with gastric cancer cases were aged 60.7 (S.D. 6.62), 71.8 % male; controls were aged 56.1 (S.D. 8.11), 47.4 % male.

Whole-exome sequencing was performed on blood samples collected at baseline. A CHIP status was identified based on the mutations on 43 CHIP-related genes.

Odds ratio (OR) of CHIP with gastric cancer risk was estimated using multivariable logistic regression models. Participants were grouped based on age and CHIP status to examine if there are differences in the cumulative incidence of gastric cancer.

Among 402,253 participants, 1,070 incident gastric cancer cases were identified (mean age, 60.7 ± 6.62 years). The prevalence of CHIP at baseline was associated with an increased risk of gastric cancer (cases: 6.54 % vs. controls 5.14 %; OR without adjustment, 1.29; 95 % CI, 1.004 to 1.63). The stratified OR (95 % CI) of individuals aged ≥ 57 was 1.33 (1.02 to 1.72) for overall CHIP, whereas the OR for younger individuals was 0.79 (0.37 to 1.44). CHIP involving DNMT3A (OR, 1.81; 95 % CI, 1.05 to 2.88; P = 0.0193) and ASXL1 (OR, 2.43; 95 % CI, 0.95 to 4.99; P = 0.032) was associated with an increased risk of gastric cancer. These positive associations remained significantly in sensitivity analyses adjusted by known risk factors. Compared to younger individuals and non-CHIP carriers, older participants with CHIP exhibited a significantly higher cumulative incidence of gastric cancer (P < 0.0001).

CHIP is associated with gastric cancer in the elderly and contributes to the positive association between DNM3A and ASXL1 mutations and risk of gastric cancer.

The potential of the application of artificial intelligence and biochemical markers of oxidative stress to predict the prognosis of older patients with gastric cancer (GC) remains unclear.

This retrospective multicenter study included consecutive patients with GC aged ≥ 65 years treated between January 2012 and April 2018. The patients were allocated into three cohorts (training, internal, and external validation). The GC-Integrated Oxidative Stress Score (GIOSS) was developed using Cox regression to correlate biochemical markers with patient prognosis. Predictive models for five-year overall survival (OS) were constructed using random forest (RF), decision tree (DT), and support vector machine (SVM) methods, and validated using area under the curve (AUC) and calibration plots. The SHapley Additive exPlanations (SHAP) method was used for model interpretation.

This study included a total of 1,859 older patients. The results demonstrated that a low GIOSS was a predictor of poor prognosis. RF was the most efficient method, with AUCs of 0.999, 0.869, and 0.796 in the training, internal validation, and external validation sets, respectively. The DT and SVM models showed low AUC values. Calibration and decision curve analyses demonstrated the considerable clinical usefulness of the RF model. The SHAP results identified pN, pT, perineural invasion, tumor size, and GIOSS as key predictive features. An online web calculator was constructed based on the best model.

Incorporating the GIOSS, the RF model effectively predicts postoperative OS in older patients with GC and is a robust prognostic tool. Our findings emphasize the importance of oxidative stress in cancer prognosis and provide a pathway for improved management of GC.

Retrospectively registered at ClinicalTrials.gov (trial registration number: NCT06208046, date of registration: 2024-05-01).

Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023.

The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys.

Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023. Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014. The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023. However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively.

The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.

Background: Although the current literature has shown an increasing interest in surgical treatment of gastric cancer (GC) in older adults in recent years, there is still no consensus on proper management in this subgroup of patients. This study was designed with the objective of evaluating the current evidence that compares limited lymph node dissection with extended lymph node dissection in older adult patients (≥65 years) coursing with resectable GC. Methods: A systematic review of PubMed, Cochrane library, and ScienceDirect was performed according to PRISMA guidelines. All studies before 2018 were selected using a systematic review by Mogal et al. Studies were eligible for this meta-analysis if they were randomized controlled trials or non-randomized comparative studies comparing limited lymph node dissection versus extended lymph node dissection in patients with resectable GC taken to gastrectomy. Results: Seventeen studies and a total of 5056 patients were included. There were not any statistically significant differences in OS (HR = 1.04, CI95% = 0.72-1.51), RFS (HR = 0.92, CI95% = 0.62-1.38), or CSS (HR = 1.24, CI95% = 0.74-2.10) between older adult patients taken to limited and extended lymphadenectomy in addition to gastrectomy as the current surgical treatment for GC. Although a higher rate of major complications was observed in the extended lymphadenectomy group, this difference was not statistically significant in incidence between both groups of patients (OR = 1.92, CI95% = 0.75-4.91). Conclusions: Limited lymphadenectomy must be considered as the better recommendation for surgical treatment for GC in older adult patients, considering the oncological outcomes and lower rates of complications compared with more radical lymph node dissections.

Tumor imaging represents an ideal environment for collecting novel biomarkers from different technologies, as patients with tumors often undergo multiple imaging studies.With the aging of the Chinese population, the number of elderly patients with gastric cancer is also increasing. In the past, patients with gastric cancer in the elderly have been conservative in whether surgical treatment can be performed, and advanced age is regarded as a relative contraindication to the effect of surgical treatment on gastric cancer patients. To investigate the clinical characteristics of patients with upper gastrointestinal hemorrhage complicated by deep vein thrombosis in elderly patients with gastric cancer. One patient with upper gastrointestinal hemorrhage complicated by deep venous thrombosis, and elderly gastric cancer patients admitted to our hospital on 11 October 2020, were selected. After anti-shock symptomatic support, filter placement, prevention and treatment of thrombosis, gastric cancer eradication, anticoagulation, immune regulation, etc. Treatment and long-term follow-up observation. Long-term follow-up showed that the patient's condition was stable, there was no sign of metastasis or recurrence after radical gastrectomy for gastric cancer, and there were no serious pre- and post-operative complications such as upper gastrointestinal bleeding and deep vein thrombosis, and the prognosis was satisfactory. How to choose the appropriate operation timing and method for elderly gastric cancer patients with upper gastrointestinal bleeding and deep vein thrombosis at the same time to maximize benefits, clinical experience in this area is particularly valuable.

A single metric does not sufficiently capture the multidimensional and complex perioperative nature of treatment for patients with gastric cancer. There is a newly developed composite indicator, called textbook outcome, that reflects the "ideal" surgical outcome. However, limited evidence exists for the long-term prognosis of textbook outcome in patients with gastric cancer. Thus, this study was aimed at assessing the association between textbook outcome and long-term oncologic prognosis after gastrectomy.

In total, 2,658 consecutive patients who underwent gastrectomy between January 2004 and December 2017 were included. The primary endpoint was 5-year conditional survival (if the patient survived the first 30 days after surgery). Textbook outcome was defined as retrieved ≥15 lymph nodes, pR0 resection, complete-potentially curative resection during operation, hospitalization ≤21 days, no reinterventions, no severe postoperative complications, no hospital readmission ≤30 days after discharge, no unplanned intensive care unit treatment, and no 30-day postoperative mortality. Multivariable analysis was performed to evaluate the adjusted predictors of textbook outcome. A Cox regression analysis was used to analyze the relationship between achieving textbook outcome parameters and long-term oncologic prognosis.

A total of 1,770 (66.6%) of the 2,658 patients achieved all textbook outcome metrics in this study. The textbook outcome group displayed a greater 5-year conditional overall survival than the nontextbook outcome group (64.7% vs 40.2%, P < .001). The 5-year conditional disease-free survival of the patients with textbook outcomes was strongly superior to that of the patients without textbook outcomes (63.1% vs 37.6%, P < .001). Textbook outcome was independently associated with longer 5-year conditional overall survival and disease-free survival (hazard ratio 0.494 [0.439-0.557] and hazard ratio 0.487 [0.433-0.547], respectively).

Attaining textbook outcome is strongly related to an improved long-term oncologic prognosis for patients with gastric cancer, underscoring the need for continued efforts to enhance surgical care quality.

Older patients with gastroesophageal (GE) cancer are at increased risk of low treatment tolerability and poor outcome. Dose reduced chemotherapy has been shown to improve tolerability without compromising efficacy in advanced GE cancer. However, the impact of reduced dose preoperative chemotherapy in the curative setting of older patients is unknown. The primary aim of this study was to investigate if dose reduction during preoperative chemotherapy impacts survival in older patients aged≥70 years with resectable GE cancer.

This cohort study included consecutive patients referred to perioperative chemotherapy treated from November 2016 until October 2021. The primary endpoint was overall survival (OS) estimated by Kaplan-Meier analysis. The log-rank test was used to compare survival rates. A multivariate analysis was made to control for potentially interacting covariates.

A total of 548 patients (age ≥ 70, 179; age < 70, 369) were included. Fewer older compared to younger patients had Eastern Cooperative Oncology Group Performance Status 0 at baseline (50 % vs 63 %, p = 0.007). Preoperative chemotherapy was more often initiated at reduced dose in older patients compared to younger (37 % vs 14 %, p < 0.001). Older patients who did not receive a reduce dose in the second or subsequent cycles of preoperative chemotherapy were less likely to complete preoperative chemotherapy when compared to the younger patients (75 % vs 85 %, p = 0.03). Dose reduction in the second or subsequent preoperative chemotherapy cycles was associated with significantly better OS for the older patient population (HR = 0.54, 95 % CI: 1.2-2.9, p = 0.006) but not for the younger (HR = 0.97, 95 % CI: 0.75-1.4, p = 0.83). Dose reduction in the second or subsequent preoperative chemotherapy cycles was associated with lower mortality risk in the multivariate analysis for the older patients (HR = 0.56, 95 % CI: 0.33-0.97, p = 0.04).

Dose reduction in the second or subsequent preoperative chemotherapy cycles seems safe and feasible in older patients without compromising survival and may result in a benefit in OS. This finding should be validated in an independent cohort or a randomized trial.

Palladium (Pd) and zinc oxide (ZnO) (Pd/ZnO NPs) bimettalic nanocomposites still lag much too far behind other nanoparticles investigated for various biological uses in the area of cancer treatments. Chemically created nanoparticles agglomerate under physiological conditions, impeding their use in biomedical applications. In this study, a straightforward and environmentally friendly method for creating bimetallic nanoparticles (NPs) by combining palladium (Pd) and zinc oxide (ZnO) using Crocus sativus extract (CS-Pd/ZnO NCs) was reported; the bio-synthesize bimetallic palladium/zinc oxide nanocomposites and their antioxidant and anti-cancer properties were assessed. The developed Pd/ZnO NPs were characterized using different approaches, including UV-vis, DLS, FTIR, EDX, and SEM analyses. The present investigation shows how nanocomposites are made, their distinctive properties, antioxidant activity, anticancer mechanisms, and their potential therapeutic applications. DPPH and ABTS tests were used to investigate antioxidant activity. Further, the effects of CS-Pd/ZnO NCs on HeLa cells were assessed using the cell viability, ROS generation, MMP levels, and induced apoptosis. Apoptosis induction was measured using an Annexin V-fluorescein isothicyanate assay. Cell DNA was stained with propidium iodide to evaluate the impact upon this cell cycle. Time-dependent cell death was carried on by CS-Pd/ZnO NCs. The maximum inhibitory effect was 59 ± 3.2 when dosages of 4.5 µg/mL or higher were delivered after 24 h of treatment. Additionally, the CS-Pd/ZnO NCs caused HeLa cells to undergo apoptosis. Apoptotic HeLa cells were present in 35.64% of the treated cells at 4.5 µg/mL, and the cell cycle arrest at G0/G1 phase occurred concurrently. According to these findings, the CS-Pd/ZnO NCs may be a promising candidate for the creation of brand-new cervical cancer treatment.

Textbook outcome (TO) is widely recognized as a comprehensive prognostic indication for patients with gastric cancer (GC). This study aims to develop a modified TO (mTO) for elderly patients with GC.

Data from the elderly patients (aged ≥ 65 years) in two Chinese tertiary referral hospitals were analyzed. 1389 patients from Fujian Medical University Union Hospital were assigned as the training cohort and 185 patients from Affiliated Hospital of Putian University as the validation cohort. Nomogram was developed by the independent prognostic factors of Overall Survival (OS) based on Cox regression.

In the training cohort, laparoscopic surgery was significantly correlated with higher TO rate (P < 0.05). Cox regression analysis revealed that surgical approach was also an independent factor of OS (P < 0.001), distinct from the traditional TO. In light of these findings, TO parameters were enhanced by the inclusion of surgical approach, rendering a modified TO (mTO). Further analysis showed that mTO, tumor size, pTNM staging, and adjuvant chemotherapy were independent prognostic factors associated with OS (all P < 0.05). Additionally, the nomogram incorporating these four indicators accurately predicted 1-, 3-, and 5-year OS in the training cohort, with AUC values of 0.793, 0.814, and 0.807, respectively, and exhibited outstanding predictive performance within the validation cohort.

mTO holds a robust association with the prognosis of elderly patients with GC, meriting intensified attention in efforts aimed at enhancing surgical quality. Furthermore, the predictive model incorporating mTO demonstrates excellent predictive performance for elderly patients with GC.

Gastric cancer is a major health problem worldwide, with a high incidence among older adults. Given the aging overall population, it was crucial to understand the current burden and prospective trend of older gastric cancer. This study aimed to analyze the temporal trends of the incidence, mortality, and survival of older gastric cancer in the highest gastric cancer risk area in China from 2010 to 2019, and to predict the future burden of older gastric cancer up to 2024.

The study was conducted in Gansu province, an area characterized by the highest gastric cancer incidence and mortality in China. The registration data of gastric cancer incidence and mortality from 2010 to 2019 were pooled from registries in the Gansu Cancer Registration System, while survival data were collected from the First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Cancer Hospital. Chinese standard population in 2000 and the Segi's world standard population were applied to calculate the age-standardized rate. Joinpoint regression was used to analyze the average annual percentage change (AAPC) in cancer incidence and mortality. Autoregressive Integrated Moving Average (ARIMA) models were employed to generate forecasts for incidence and mortality from 2020 to 2024.

Based on registry data from 2010 to 2019, the incidence and mortality rates of gastric cancer among older adults remained stable. The incidence rates declined from 439.65 per 100,000 in 2010 to 330.40 per 100,000 in 2019, with an AAPC of -2.59% (95% confidence interval[CI], -5.14 to 0.04, P = 0.06). Similarly, the mortality rate changed from 366.98 per 100,000 in 2010 to 262.03 per 100,000 in 2019, with an AAPC of -2.55% (95% CI, -8.77-4.08%, P = 0.44). In the hospital-based cohort, the decline in survival rates was reported among older patients with gastric cancer in the highest gastric cancer risk area in China, with the 3-year overall survival (OS) decreasing from 58.5% (95% CI, 53.5-63.2%) in 2010 to 34.4% (95%CI, 32.1-36.7%) in 2019, and the 3-year progression-free survival (PFS) decreasing from 51.3% (95%CI, 47.5-55.1%) in 2010 to 34.2% (95%CI, 32.0-36.3%) in 2019, respectively. Moreover, forecasts generated by ARIMA models revealed a significant decline in the incidence and mortality of older gastric cancer in China from 2020 to 2024. Specifically, the incidence rate of older gastric cancer was expected to decrease from 317.94 per 100,000 population in 2020 to 205.59 per 100,000 population in 2024, while the anticipated mortality rate was estimated to decrease from 222.52 per 100,000 population in 2020 to 186.22 per 100,000 population in 2024.

From 2010 to 2019, the incidence and mortality of older gastric cancer remained stable in the highest gastric cancer risk area in China, while the survival rates showed a decline. Based on the ARIMA models, it was anticipated that there might be a continued decline in older gastric cancer incidence and mortality in the highest-risk area in China over the next five years.

For the elderly patients with gastric cancer, it may be more challenging to tolerate complete neoadjuvant therapy (NAT). The impact of discontinued NAT on the surgical safety and pathological outcomes of elderly patients with poor tolerance remains poorly understood.

Gastric cancer patients received gastrectomy with curative intent from the Dutch upper GI cancer audit (DUCA) database were included in this study. The independent association of age with not initiating and discontinuation of NAT was assessed with restricted cubic splines (RCS). According to the RCS results, age ≥ 70 years was defined as elderly. Short-term postoperative outcomes and pathological results were compared between elderly patients who completed and discontinued NAT.

Between 2011- 2021, total of 3049 patients were included. The risk of not initiating NAT increased from 70 years. In 1954 (64%) patients receiving NAT, the risk of discontinuation increased from 55 years, reaching the peak around 74 years. In the elderly, discontinued NAT was not independently associated with worse 30-day mortality, overall complications, anastomotic leakage, re-intervention, and pathologic complete response, but was associated with a higher risk of R1/2 resection (p-value = 0.001), higher ypT stage (p-value = 0.004), ypN + (p-value = 0.008), and non-response ( p-value = 0.012).

A decreased utilization of NAT has been observed in Dutch gastric cancer patients from 70 years due to old age considerations, possibly because of their high risk of discontinuation. Increasing the utilization of NAT may not adversely impact the surgical safety of gastric cancer population ≥ 70 years and may contribute to better pathological results.

Microtubule affinity regulating kinase 4 (MARK4), which is overexpressed in various tumors, is involved in the regulation of cell division, proliferation, migration, and the cell cycle, and has been considered a potential marker for cancer; however, its mechanism of action in gastric cancer (GC) remains unclear. This study aimed to investigate the role of MARK4 in the proliferation, migration, and invasion of GC cell through the MAPK/ERK signaling pathway by targeting MARK4 knockdown.

Using The Cancer Genome Atlas data and clinical information, MARK4 expression and its relationship with prognosis were analyzed. Possible pathways involving MARK4 were explored using enrichment analysis. Western blotting and real-time quantitative polymerase chain reaction were used to detect MARK4 expression in GC. After targeted transfection of siRNA, the transfection efficiency of the experimental group was detected in AGS and HGC-27 cells. The effects of knockdown MARK4 on the proliferation, migration, and invasion of GC cells were verified using CCK-8, colony formation, wound healing, and transwell assays. Finally, the relationship between MARK4, the MAPK/ERK pathway, and epithelial-mesenchymal transition in GC was verified by western blotting.

MARK4 expression was upregulated in GC and associated with poor prognosis in patients with GC. Enrichment analysis showed that MARK4 was involved in the activation of the MAPK signaling pathway. Western blotting results indicated that MARK4 overexpression promoted the proliferation, migration, and invasion of GC cells through the MAPK/ERK pathway.

MARK4 expression was upregulated in GC and promoted the proliferation, migration, and invasion of GC cells through the MAPK/ERK pathway.

This study examined temporal shifts in adjuvant therapy patterns in Japanese patients with resectable gastric cancer (GC) and treatment patterns of first-line and subsequent therapy among those with recurrent disease.

This retrospective analysis of hospital-based administrative claims data (April 1, 2008 to March 31, 2022) included adults (aged ≥ 20 years) with GC who started adjuvant therapy on or after October 1, 2008 (adjuvant cohort) and patients in the adjuvant cohort with disease recurrence (recurrent cohort), further defined by the time to recurrence (≤ 180 or > 180 days after adjuvant therapy).

In the adjuvant cohort (n = 17,062), the most common regimen during October 2008-May 2016 was tegafur/gimeracil/oteracil potassium (S-1; 95.7%). As new standard adjuvant regimen options were established, adjuvant S-1 use decreased to 65.0% and fluoropyrimidine plus oxaliplatin or docetaxel plus S-1 use increased to 15.0% and 20.0%, respectively, in September 2019-March 2022. In the recurrent cohort with no history of trastuzumab/trastuzumab deruxtecan treatment (n = 1257), the most common first-line regimens were paclitaxel plus ramucirumab (34.0%), capecitabine plus oxaliplatin (CapeOX; 17.0%), and nab-paclitaxel plus ramucirumab (10.1%) in patients with early recurrence, and S-1 plus oxaliplatin (26.3%), S-1 plus cisplatin (15.3%), CapeOX (14.0%), S-1 (13.2%), and paclitaxel plus ramucirumab (10.8%) in those with late recurrence.

This study demonstrated temporal shifts in adjuvant treatment patterns that followed the establishment of novel regimens, and confirmed that post-recurrent treatment patterns were consistent with the Japanese Gastric Cancer Association guideline recommendations.

Surgery is a standard treatment for early-stage gastrointestinal cancers, often preceded by neoadjuvant chemo(radio)therapy or followed by adjuvant therapy. While leading to cure in a proportion of patients, it has some drawbacks such as intra/post-operative complications, mutilation and life-long functional sequelae. Further to the unprecedented efficacy data from studies of immune checkpoint inhibitors for advanced mismatch repair deficient/microsatellite instable (dMMR/MSI-H) tumours, a strong interest has recently emerged for the investigation of such agents in the neoadjuvant setting. Although limited by the exploratory design and small sample size, trials of neoadjuvant immune checkpoint inhibitors for early-stage dMMR/MSI-H gastrointestinal cancers have consistently reported complete response rates ranging from 70 % to 100 %. As a result, the question has arisen as to whether surgery is still needed or organ-preserving strategies should be offered to this especially immuno-sensitive population. In this article, we discuss the available evidence for neoadjuvant immune checkpoint inhibitors in dMMR/MSI-H gastrointestinal cancers and analyse opportunities and challenges to the implementation of non-operative management approaches in this setting.

Bimetallic nanoparticles, specifically Zinc oxide (ZnO) and Silver (Ag), continue to much outperform other nanoparticles investigated for a variety of biological uses in the field of cancer therapy. This study introduces biosynthesis of bimetallic silver/zinc oxide nanocomposites (Ag@ZnO NCs) using the Crocus sativus extract and evaluates their anti-cancer properties against cervical cancer.

The process of generating bimetallic nanoparticles (NPs), namely Ag@ZnO NCs, through the utilization of Crocus sativus extract proved to be uncomplicated and eco-friendly. Various methods, such as UV-vis, DLS, FTIR, EDX, and SEM analyses, were utilized to characterize the generated Ag@ZnO NCs. The MTT assay was employed to assess the cytotoxic properties of biosynthesized bimetallic Ag@ZnO NCs against the HeLa cervical cancer cell line. Moreover, the impact of Ag@ZnO NCs on HeLa cells was assessed by examining cell survival, ROS production, MMP levels, and induced apoptosis. Through western blot analysis, the expression levels of the PI3K, AKT, mTOR, Cyclin D, and CDK proteins seemed to be ascertained. Using flow cytometry, the cancer cells' progression through necrosis and apoptosis, in addition to the cell cycle analysis, were investigated.

Bimetallic Ag@ZnO NCs that were biosynthesized showed a high degree of stability, as demonstrated by the physicochemical assessments. The median size of the particles in these NCs was approximately 80-90 nm, and their zeta potential was -14.70 mV. AgNPs and ZnO were found, according to EDX data. Further, Ag@ZnO NCs hold promise as a potential treatment for cervical cancer. After 24 hours of treatment, a dosage of 5 µg/mL or higher resulted in a maximum inhibitory effect of 58 ± 2.9. The concurrent application of Ag/ZnO NPs to HeLa cells resulted in elevated apoptotic signals and a significant generation of reactive oxygen species (ROS). As a result, the bimettalic Ag@ZnO NCs treatment has been recognized as a chemotherapeutic intervention by inhibiting the production of PI3K, AKT, and mTOR-mediated regulation of propagation and cell cycle-regulating proteins.

The research yielded important insights into the cytotoxic etiology of biosynthesized bimetallic Ag@ZnO NCs against HeLa cells. The biosynthesized bimetallic Ag@ZnO NCs have a significant antitumor potential, which appears to be associated with the development of oxidative stress, which inhibits the development of the cell cycle and the proliferation of cells. Therefore, in the future, biosynthesized bimetallic Ag@ZnO NCs may be used as a powerful anticancer drug to treat cervical cancer.

Lymph node (LN) status is a vital prognostic factor for patients. However, there has been limited focus on predicting the prognosis of patients with late-onset gastric cancer (LOGC). This study aimed to investigate the predictive potential of the log odds of positive lymph nodes (LODDS), lymph node ratio (LNR), and pN stage in assessing the prognosis of patients diagnosed with LOGC.

The LOGC data were obtained from the Surveillance, Epidemiology, and End Results database. This study evaluated and compared the predictive performance of three LN staging systems. Univariate and multivariate Cox regression analyses were carried out to identify prognostic factors for overall survival (OS). Three machine learning methods, namely, LASSO, XGBoost, and RF analyses, were subsequently used to identify the optimal LN staging system. A nomogram was built to predict the prognosis of patients with LOGC. The efficacy of the model was demonstrated through receiver operating characteristic (ROC) curve analysis and decision curve analysis.

A total of 4,743 patients with >16 removed lymph nodes were ultimately included in this investigation. Three LN staging systems demonstrated significant performance in predicting survival outcomes (P < 0.001). The LNR exhibited the most important prognostic ability, as evidenced by the use of three machine learning methods. Utilizing independent factors derived from multivariate Cox regression analysis, a nomogram for OS was constructed.

The calibration, C-index, and AUC revealed their excellent predictive performance. The LNR demonstrated a more powerful performance than other LN staging methods in LOGC patients after surgery. Our novel nomogram exhibited superior clinical feasibility and may assist in patient clinical decision-making.

The impact of achieving textbook oncological outcome (TOO) as a multimodal therapy quality indicator on the prognosis of advanced gastric cancer (AGC) remains inadequately assessed.

Patients with AGC who underwent curative gastrectomy between January 2010 and December 2017 at two East Asian medical centers were included. TOO was defined as achieving the textbook outcome (TO) and receiving neoadjuvant and/or adjuvant chemotherapy (NCT or ACT). Cox and logistic regression models were used to identify prognostic and non-TOO-associated risk factors.

Among 3626 patients, 57.6% achieved TOO (TOO group), exhibiting significantly better 5-year overall survival (OS) and disease-free survival (DFS) than the non-TOO group (both p < 0.05). Multivariate Cox regression identified TOO as an independent prognostic factor for 5-year OS (HR, 0.67; 95% CI, 0.61-0.74; p < 0.001) and DFS (HR, 0.73; 95% CI, 0.66-0.81; p < 0.001). Multivariate logistic regression showed that open gastrectomy, lack of health insurance, age ≥65 years, ASA score ≥ Ⅲ, and tumor size ≥50 mm are independent risk factors for non-achievement of TOO (all p < 0.05). On a sensitivity analysis of TOO's prognostic value using varying definitions of chemotherapy parameters, a stricter definition of chemotherapy resulted in a decrease in the TOO achievement rate from 57.6 to 22.3%. However, the associated reductions in the risk of death and recurrence fluctuated within the ranges of 33-39% and 28-37%, respectively.

TOO is a reliable and stable metric for favorable prognosis in AGC. Optimizing the surgical approach and improving health insurance status may enhance TOO achievement.

In this study, we sought to fabricate nickel/zinc oxide nanocomposites utilizing Citrus sinensis (C. sinensis) peel extract (CS-Ni/ZnO NCs) and investigate their ability to impede the JAK/STAT3 signaling pathway in gastric cancer AGS cells. Different methods, including UV-Vis spectral analysis, FT-IR, XRD, FE-SEM, EDAX, DLS, and zeta potential, were used to characterize the fabricated CS-Ni/ZnO NCs. By measuring ROS, MMP, and apoptotic cell death using the appropriate fluorescence describing procedures, the anticancer potential of CS-Ni/ZnO NCs was examined against AGS cells. The synthesized CS-Ni/ZnO NCs displayed a rod structure with a diameter of 74.76 nm. The cytotoxicity assay showed that the CS-Ni/ZnO NCs diminished the viability of the AGS cells in a dosage-dependent manner. Results from the fluorescence probe assay showed that the CS-Ni/ZnO NCs caused apoptosis in AGS cells. JAK/STAT-3 over expressions thought to expand the transcriptional regulation of proliferation and anti-apoptosis. Hence, inhibition of JAK/STAT-3 expression is considered a crucial target for impeding the expansion of gastric cancer proliferation. The JAK/STAT3 signaling cascade was successfully blocked by CS-Ni/ZnO NCs treatment, which also started the apoptotic pathway in the AGS cells. The findings conclude that CS-Ni/ZnO NCs might serve as a promising chemo-preventive agent for treating GC.

Gastric adenocarcinoma can present uncommonly. This emphasizes the need for intensified vigilance in the absence of typical gastrointestinal symptoms, particularly in areas where infectious diseases are common.

Gastric adenocarcinoma, a common advanced-age global malignancy is typically associated with abdominal symptoms. However, atypical presentations such as back pain and respiratory distress particularly in younger patients represent diagnostic challenges. We present a case of a late-30s male who presented initially with back pain, shortness of breath, and constitutional symptoms. A diagnosis of tuberculosis was established presumptively with immediate initiation of treatment. Later on, he presented with abdominal pain and intractable vomiting. Oesophagoduodenoscopy (OGD), tissue histology, and immunohistochemistry confirmed a diffuse type gastric adenocarcinoma. He died as a result of complications from an advanced disease. This particular instance emphasizes the importance of maintaining a high index of skepticism even in atypical presentations, as well as the significance of prompt OGD alongside potential genetic testing if any. Gastric adenocarcinoma should be contemplated by clinicians in a variety of clinical scenarios, especially when handling younger patients from settings with limited resources to facilitate timely diagnosis and effective treatment.

This investigation aimed to explore the prognostic factors in elderly patients with unresected gastric cancer (GC) who have received chemotherapy and to develop a nomogram for predicting their cancer-specific survival (CSS). Elderly gastric cancer patients who have received chemotherapy but no surgery in the Surveillance, Epidemiology, and End Results Database between 2004 and 2015 were included in this study. Cox analyses were conducted to identify prognostic factors, leading to the formulation of a nomogram. The nomogram was validated using receiver operating characteristic (ROC) and calibration curves. The findings elucidated six prognostic factors encompassing grade, histology, M stage, radiotherapy, tumor size, and T stage, culminating in the development of a nomogram. The ROC curve indicated that the area under curve of the nomogram used to predict CSS for 3, 4, and 5 years in the training queue as 0.689, 0.708, and 0.731, and in the validation queue, as 0.666, 0.693, and 0.708. The calibration curve indicated a high degree of consistency between actual and predicted CSS for 3, 4, and 5 years. This nomogram created to predict the CSS of elderly patients with unresected GC who have received chemotherapy could significantly enhance treatment accuracy.

Gastric cancer is one of the most frequent and deadly tumours worldwide. However, the evidence that currently exists for the treatment of older adults is limited and is derived mainly from clinical trials in which older patients are poorly represented. In this article, a group of experts selected from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Group for the Treatment of Digestive Tumours (TTD), and the Spanish Multidisciplinary Group on Digestive Cancer (GEMCAD) reviews the existing scientific evidence for older patients (≥65 years old) with gastric cancer and establishes a series of recommendations that allow optimization of management during all phases of the disease. Geriatric assessment (GA) and a multidisciplinary approach should be fundamental parts of the process. In early stages, endoscopic submucosal resection or laparoscopic gastrectomy is recommended depending on the stage. In locally advanced stage, the tolerability of triplet regimens has been established; however, as in the metastatic stage, platinum- and fluoropyrimidine-based regimens with the possibility of lower dose intensity are recommended resulting in similar efficacy. Likewise, the administration of trastuzumab, ramucirumab and immunotherapy for unresectable metastatic or locally advanced disease is safe. Supportive treatment acquires special importance in a population with different life expectancies than at a younger age. It is essential to consider the general state of the patient and the psychosocial dimension.

Robotic gastrectomy (RG) has been widely used to treat gastric cancer. However, whether the short-term outcomes of robotic gastrectomy are superior to those of laparoscopic gastrectomy (LG) for elderly patients with advanced gastric cancer has not been reported.

The study enrolled of 594 elderly patients with advanced gastric cancer who underwent robotic or laparoscopic radical gastrectomy. The RG cohort was matched 1:3 with the LG cohort using propensity score-matching (PSM).

After PSM, 121 patients were included in the robot group and 363 patients in the laparoscopic group. Excluding the docking and undocking times, the operation time of the two groups was similar (P = 0.617). The RG group had less intraoperative blood loss than the LG group (P < 0.001). The time to ambulation and first liquid food intake was significantly shorter in the RG group than in the LG group (P < 0.05). The incidence of postoperative complications did not differ significantly between the two groups (P = 0.14). Significantly more lymph nodes were dissected in the RG group than in the LG group (P = 0.001). Postoperative adjuvant chemotherapy was started earlier in the RG group than in the LG group (P = 0.02).

For elderly patients with advanced gastric cancer, RG is safe and feasible. Compared with LG, RG is associated with less intraoperative blood loss; a faster postoperative recovery time, allowing a greater number of lymph nodes to be dissected; and earlier adjuvant chemotherapy.

As a promising drug delivery system, the temperature-sensitive liquid embolic agent (TempSLE) has yet to be reported in animal experiments in treating gastric cancer. We observed and compared computed tomography (CT) imaging changes, tumor volume, HE staining, and immunohistochemistry after transcatheter arterial chemoembolization (TACE) treatment in rabbit VX2 gastric cancer models to clarify the effectiveness of TempSLE loaded with oxaliplatin (TempSLE/Oxa) in treating gastric cancer. One milliliter TempSLE can be loaded with 20 mg oxaliplatin. The accumulative drug release rate at 30 min was 38.76%, and after 24 h, it reached more than 90%. CT examination 1 week after TACE revealed that the TempSLE/Oxa group presents unenhanced hypodense necrotic foci, the iodinated oil loaded with oxaliplatin (Ioil/Oxa) group presents shrinking tumors but still visible speckled foci of enhancement, and the normal saline (NS) group presents heterogeneous enhancement with larger tumors than before. In the postoperative autopsy of TACE, the tumor volumes of TempSLE/Oxa, Ioil/Oxa, and NS groups were 0.15 ± 0.06 cm3, 0.37 ± 0.11 cm3, and 1.19 ± 0.16 cm3, respectively, all of which were statistically different. The positive vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) expression percentages in the TempSLE/Oxa, Ioil/Oxa, and NS groups were statistically different and lowest in the TempSLE/Oxa group. In conclusion, the TempSLE can load a high dose of oxaliplatin to meet the demand of clinical applications. TempSLE/Oxa could effectively inhibit tumor cell proliferation and angiogenesis. This study provides experimental evidence for the further clinical application of the TempSLE/Oxa.

Textbook outcome (TO) in gastric cancer surgery is a multidimensional measure of surgical quality. However, its impact on long-term survival after laparoscopic gastrectomy (LG) is unclear. This study aims to evaluate TO in LG, assess its hospital-level relevance, and examine its association with long-term survival.

In this retrospective cohort study, we analyzed 2278 consecutive gastric cancer patients who underwent laparoscopic gastrectomy (LG) from January 2004 to December 2017. We determined TO achievement rates, compared preoperative and intraoperative variables between TO and non-TO groups, identified independent predictors of TO, and assessed long-term oncologic outcomes using Kaplan-Meier analysis and Cox regression.

A total of 1540 LG patients were analyzed, with 994 (64.5%) achieving TO. The least frequently achieved metric was 'hospital stays ≤21 days' (83.4%), followed by 'lymph nodes retrieved ≥15' (84.0%). Factors independently associated with reduced TO likelihood included age ≥65 years, BMI ≥25, ASA III, conversion to open surgery, operation time ≥260 min, and estimated blood loss ≥150 ml. Furthermore, TO was independently linked to improved 5-year overall survival (OS) and disease-free survival (DFS) (HR 0.519 [0.443-0.609] and HR 0.517 [0.443-0.604], respectively).

Implementing the TO concept in LG provides a benchmark for achieving improved prognoses and empowers surgeons to devise strategies for enhancing surgical care quality.

The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis. SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.

To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.

This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years (median age 65) between July 2006 and April 2007. Patients were followed up until death or the study ended (median follow-up duration of 28.5 mo). The samples were used to generate tissue microarrays (TMAs) for immunohistochemical (IHC) staining. The expressions of TGF-β1, pSMAD3C(S423/425), pSMAD3L(S204), and VEGFR-1 in gastric cancer (GC) tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients. Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015. The relationship between TGF-β1, pSMAD3C(S423/425), pSMAD3L(S204), and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient. The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test. A survival curve was generated using the Kaplan-Meier survival analysis.

TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent non-cancerous tissue. The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site [pSMAD3C(S423/425): 51.0% and pSMAD3L(S204): 31.6%]. High expression of pSMAD3L(S204) was significantly correlated with larger tumors (P = 0.038) and later N stages (P = 0.035). Additionally, high expression of VEGFR-1 was closely correlated with tumor size (P = 0.015) and pathological grading (P = 0.013). High expression of both pSMAD3L(S204) and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival (OS). Multivariate analysis indicated that high expression of pSMAD3L(S204) and VEGFR-1 were independent risk factors for prognosis in GC patients. VEGFR-1 protein expression was correlated with TGF-β1 (r = 0.220, P = 0.029), pSMAD3C(S423/425) (r = 0.302, P = 0.002), and pSMAD3L(S204) (r = 0.201, P = 0.047), respectively. Simultaneous overexpression of pSMAD3L(S204) and VEGFR-1 was associated with poor OS in gastric cancer patients.

Co-upregulation of pSMAD3L(S204) and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis, and pSMAD3L(204) may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.

A significant proportion of locally-advanced esophago-gastric adenocarcinoma (EGA) is diagnosed in patients ≥70 years old (y.o.) who are commonly underrepresented in clinical trials.

The PubMed database was searched for phase 2/3 clinical trials enrolling patients ≥70 y.o and reporting efficacy/safety information of chemotherapy for resectable EGA. The main outcomes were overall survival (OS) and recurrence-free survival (RFS).

Among 6,128 records, only seven studies reported these outcomes (three peri-operative, three adjuvant, and one neoadjuvant), including 1004 older patients, <20% of the overall population. No significant benefit in terms of OS and RFS was observed for perioperative or adjuvant chemotherapy vs surgery alone. No trial reported safety endpoints in this subgroup.

This work did not show any significant benefit in OS or RFS for chemotherapy vs surgery alone or conventional vs de-escalated chemotherapy in the curative setting of EGA in ≥70 y.o patients. Specific ad hoc trials should be performed to derive reliable data.

The incidence of gastric cancer is known to be high in the elderly population. Identification of the best perioperative chemotherapy regimen is challenging in patients with resectable gastric cancer. In this study, we aimed to evaluate and compare the outcomes and safety of epirubicin, cisplatin, and 5-fluorouracil (ECF), docetaxel, cisplatin, and 5-fluorouracil (DCF), oxaliplatin plus 5-Fluorouracil and leucovorin (FOLFOX), and docetaxel, oxaliplatin, leucovorin, and 5-Fluorouracil (FLOT) chemotherapy regimens to identify the most appropriate treatment option for elderly patients with resectable gastric cancer.

In this retrospective observational cohort study, data were extracted from the medical archives (2017-2021) of Omid Hospital, which is a tertiary oncology referral hospital in Isfahan, Iran. Patients with resectable gastric cancer, above 60 years of age, who were perioperatively treated with one of the mentioned chemotherapy regimens and met the inclusion criteria, were enrolled in this study. The survival parameters and safety profile of the regimens were evaluated and compared in this population.

A total of 63 patients were included in this study. The median follow-up period of the patients was 24 months (range, 7-51 months). The results of survival analysis revealed that the FLOT and DCF regimens were significantly associated with longer overall survival (OS) as compared to the other regimens (median OS: 38 and 33 months, respectively). Based on the results, the progression-free survival was longer in the DCF regimen (median: 24 months) compared to the other regimens; however, only the difference with the ECF regimen (median: 14 months) was significant. The results of Cox regression analysis showed no significant difference in the overall adjusted hazard ratio of mortality between the FLOT and DCF regimens (P = 0.802). The DCF and FOLFOX regimens accounted for the highest and lowest rates of adverse events (e.g., neutropenia and mucositis), respectively.

Considering the higher rate of adverse events in the DCF group, besides the significant improvement of OS and the acceptable adverse event profile of patients treated with the FLOT regimen, it can be proposed that this chemotherapy regimen is the most appropriate treatment option for elderly patients with resectable gastric cancer.

With the aging of the population, the burden of elderly gastric cancer (EGC) increases worldwide. However, there is no consensus on the definition of EGC and the efficacy of adjuvant chemotherapy in patients with stage II EGC. Here, we investigated the effectiveness of adjuvant chemotherapy in defined EGC patients.

We enrolled 5762 gastric cancer patients of three independent cohorts from the Sixth Affiliated Hospital of Sun Yat-sen University (local), the Surveillance, Epidemiology, and End Results (SEER), and the Asian Cancer Research Group (ACRG). The optimal age cutoff for EGC was determined using the K-adaptive partitioning algorithm. The defined EGC group and the efficacy of adjuvant chemotherapy for them were confirmed by Cox regression and Kaplan-Meier survival analyses. Furthermore, gene set variation analyses (GSVA) were performed to reveal pathway enrichment between groups.

The optimal age partition value for EGC patients was 75. In the local, SEER, and ACRG cohorts, the EGC group exhibited significantly worse overall survival and cancer-specific survival than the non-EGC group (P < 0.05) and was an independent risk factor. Stratified analyses based on chemotherapy showed that EGC patients derived little benefit from adjuvant chemotherapy. Furthermore, GSVA analysis revealed the activation of DNA repair-related pathways and downregulation of the p53 pathway, which may partially contribute to the observed findings.

In this retrospective, international multi-center study, 75 years old was identified as the optimal age cutoff for EGC definition, and adjuvant chemotherapy proved to be unbeneficial for stage II EGC patients.