Resectable Gastric Cancer Research Articles

Evaluation of Pathological Response Rate and Complications of FOLFOX versus FLOT Regimen in Perioperative Chemotherapy for Resectable Gastric Cancer: A Prospective Study.

Previous studies have shown that the perioperative and postoperative chemotherapy can lead to an improvement in the prognosis of patients with resectable gastric cancer (GC). There is no preference for postoperative chemotherapy with the two common treatment regimens, FLOT and FOLFOX, in these patients. The aim of this study was to compare FOLFOX and FLOT regimens in perioperative chemotherapy in resectable GC based on pathological response and complications. This prospective cohort study was conducted on 112 patients with resectable GC who were admitted to Firozgar Hospital affiliated with Iran University of Medical Sciences, Tehran, Iran between 2021 to 2022. Given the inclusion criteria, 80 patients were enrolled in the present study. Patients were divided into 2 groups based on the type of treatment regimen, FOLFOX (40 patients) and FLOT (40 patients). Tumor response was classified using Mandard Tumor regression grading system criteria into five categories of TRG1 to 5. Also, the side effects were classified according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. The rate of complete pathological response in FOLT group was significantly higher than FOLFOX group (35.0% vs 2.5%, p: 0.001). The frequency of neurological complications and hair loss in the FOLT group was significantly higher than the FOLFOX group (P<0.05). While no significant difference was observed in the frequency of hematological, Gastroenterological, hepatic, renal and stomatitis complications in the both groups (p>0.05). Our study showed that perioperative FLOT regimen has a better pathological response than FOLFOX regimen. The frequency of neurological complications and hair loss was significantly higher in patients treated with FLOT regimen. Thus, perioperative FLOT regimen may be recommended for treating GC patients.

Neoadjuvant docetaxel, oxaliplatin, and S-1 plus surgery and adjuvant S-1 for resectable advanced gastric cancer: Final survival outcomes of the randomized phase 3 PRODIGY trial.

30 Background: The phase 3 PRODIGY study compared neoadjuvant docetaxel, oxaliplatin and S-1 (DOS) chemotherapy followed by surgery followed by adjuvant S-1 with surgery followed by adjuvant S-1 for Korean patients with resectable locally advanced gastric cancer (LAGC) (Kang et al. J Clin Oncol. 2021). The planned analysis of the primary endpoint of PRODIGY showed that the addition of neoadjuvant DOS to surgery and adjuvant S-1 improved progression-free survival (PFS). We herein report the long-term follow-up outcomes, including overall survival (OS), from this trial. Methods: Patients with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma with clinical T2-3N+ or T4Nany disease were enrolled from 18 Korean study sites. Patients were randomly assigned to D2 surgery followed by adjuvant S-1 (40–60 mg orally twice a day, days 1–28 q6w for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m2, oxaliplatin 100 mg/m2 intravenously day 1, S-1 40 mg/m2 orally twice a day, days 1–14 q3w for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary endpoint was PFS. OS was the secondary endpoint. This analysis presents the final assessment of the outcomes after 5 years. Results: A total of 266 and 264 patients were randomly assigned to the CSC and SC arms, respectively, among which 238 and 246 patients were treated and included in the full analysis set. As of the data cut-off date (SEP-2022), the median follow-up duration of the surviving patients was 99.5 months (range, 68.6–127.7 months). As compared to SC, CSC significantly increased the OS (adjusted hazard ratio, 0.72; 95% CI, 0.54 to 0.97; stratified log-rank P=0.028) with a 5-year OS rate of 66.8% and 63.0% for the CSC and SC arms, respectively. CSC also significantly improved the PFS (adjusted hazard ratio, 0.71; 95% CI, 0.53 to 0.94; stratified log-rank P=0.019) with a 5-year PFS rate of 60.6% and 56.9% for the CSC and SC arms, respectively. Among the patient subgroups determined based on different clinical T/N categories, a patient subgroup with cT4Nany disease showed the greatest relative risk reduction in OS with neoadjuvant chemotherapy (HR 0.69, 95% CI 0.51–0.95). Conclusions: The addition of neoadjuvant docetaxel, oxaliplatin and S-1 (DOS) chemotherapy, as part of perioperative chemotherapy, to surgery and adjuvant S-1 prolonged the OS and PFS of Asian patients with LAGC relative to patients treated with surgery and adjuvant S-1 alone. Neoadjuvant DOS chemotherapy should be considered one of the standard treatment options for patients with LAGC in Asia. Unlike in the Western setting, neoadjuvant chemotherapy may be preferentially considered for patients with cT4 disease in Asia. Clinical trial information: NCT01515748 .

Immunonutrition supplementation for resectable gastric cancer during standard perioperative chemotherapy (CT) FLOT: A pivotal study, I–SUPPLY.

57 Background: Gastric carcinomas (GC) can be divided into immunogenic and immune-resistant based on the infiltration of the tumour microenvironment (TME) from different immune cells (ICs) such as Natural Killer (NK), activated CD8+, CD3+ and CD4+ memory T cells. High ImmunoScore (IS) (positive cells/mm2 for each marker (CD8+, CD3+, Foxp3+) in the Core Tumour and Invasive Margins) is strongly related to better prognosis of GC patients in terms of Disease-Free Survival and Overall Survival. ICs activation and consequent immunogenic TME requires high nutrient absorption and synthesis accumulation of protein, lipid and nucleotides. However, tumour cells (TCs) promote their own proliferation by stealing the available micronutrients to ICs therefore leading to an immunosuppressive TME phenotype. Methods: This is a translational, prospective, non-randomized study. Primary endpoint is to assess if enteral immune nutrition (EIN) supplementation during the acme of the activity of cytotoxic of perioperative FLOT (docetaxel, oxaliplatin and 5-fluorouracil) in stage II-III GC can revert the TME in favour of ICs over TCs, witnessed by an increase of IS in surgical specimen over biopsy controls. A steady amount of EIN with Arginine, Omega-3-fatty acids, Glutamine and ribonucleic acid, will be added to patient’s diet from day 3 to 8 of each FLOT cycle, twice a day. We plan to use Image analysis software for automatic tumor detection and quantification of CD3+ and CD8+ stained cells whose densities will be converted into IS with pre-defined cutoffs. IS utilizes standardized percentile values (0 to 100%). We identify IS as Low, Intermediate (Int) and High with a mean percentile of 0-25%, &gt;25-70%, &gt;70-100% respectively. Two-group classifications are planned, corresponding to IS Low and Int-High. To better define the kind of tumor infiltrating cells (TILs) and assess the amount of immune suppressive cells, more IHC scoring will be evaluated: helper T-cells CD4+, CD8 T memory (CD 103+), T regulatory (both CD4+ and Foxp3+/CD105+), Macrophages M1 (CD 68+) and M2 (CD 163+). Results: Based on historical controls the rate of Int-High IS (&gt;25-70%, &gt;70% respectively) is about 64%, we expect to find a 20% increase of Int-High IS GC over biopsy control (internal validation cohort). To detect an increase in the percentage of high IS among patients treated with EIN (estimated around 85%) compared to biopsy controls (estimated around 64%) assuming a probability α and β of 0.2, the required sample size will be of 21 patients with resectable GC receiving EIN supplementation plus standard CT. To define the sample size a single proportion test was used. Conclusions: Our hypothesis is that EIN given during perioperative CT might prevent the establishment of an unfavourable TME for ICs in both auxotrophic and non-auxotrophic malignancies, thus leading to an increase of GC immunogenic pattern.

Gastrointestinal Symptoms After Resection of Esophagogastric Cancer: A Longitudinal Study on Their Incidence and Impact on Patient-Reported Outcomes.

This study assesses the incidence of gastrointestinal symptoms in the first year after resection of esophageal or gastric cancer and its association with health-related quality of life (HRQoL), functioning, work productivity, and daily activities. Patients diagnosed with esophageal or gastric cancer between 2015 and 2021, who underwent a resection, and completed ≥ 2 questionnaires from the time intervals prior to resection and 0-3, 3-6, 6-9, and 9-12 months after resection were included. Multivariable generalized linear mixed models were used to assess changes in gastrointestinal symptoms over time and the impact of the number of gastrointestinal symptoms on HRQoL, functioning, work productivity, and daily activities for patients who underwent an esophagectomy or gastrectomy separately. The study population consisted of 961 (78.8%) and 259 (21.2%) patients who underwent an esophagectomy and gastrectomy, respectively. For both groups, the majority of gastrointestinal symptoms changed significantly over time. Most clinically relevant differences were observed 0-3 after resection compared with prior to resection and included increased diarrhea, appetite loss, and eating restrictions, and specifically after esophagectomy dry mouth, trouble with coughing, and trouble talking. At 9-12 after resection one or more severe gastrointestinal symptoms were reported by 38.9% after esophagectomy and 33.7% after gastrectomy. A higher number of gastrointestinal symptoms was associated with poorer functioning, lower HRQoL, higher impairment in daily activities, and lower work productivity. This study shows that gastrointestinal symptoms are frequently observed and burdensome after esophagectomy or gastrectomy, highlighting the importance to address these sequelae for high quality survivorship.

Efficacy of chemotherapy combined with surgical resection for gastric cancer with synchronous ovarian metastasis: A propensity score matching analysis.

Ovarian metastasis from gastric cancer (GC) is characterized by aggressive biological behavior and poor outcome. Currently, there is no standard treatment mode for such patients. Thus, we evaluated the efficacy of conversion therapy in patients with synchronous ovarian metastasis from GC in this study. About 219 GC patients with ovarian metastasis in 2011-2020 were enrolled. Two groups were established based on the different treatment: the conversion therapy group (chemotherapy combined with surgical resection, CS group) and the non-conversion therapy group (NCS group). Propensity score matching (PSM) was used to analyze the efficacy of different treatment modes on the prognosis of these patients. Ninety-two patients were included according to PSM results, with 46 patients each in CS and NCS groups. The median overall survival (OS) in the CS group was notably better than that in the NCS group (p < 0.001). Twenty-six patients (56.52%) in the CS group achieved R0 resection, and they had a better prognosis (p = 0.003). Compared with patients who underwent simultaneous gastrectomy and ovarian metastasectomy (CSb group), those who underwent ovarian metastasectomy before systemic chemotherapy (CSa group) had a higher R0 resection rate (p = 0.016) and longer survival time (p = 0.002). A total of 38 patients (41.30%) across both groups received hyperthermic intraperitoneal chemotherapy (HIPEC), and these patients had a better survival (p = 0.043). The conversion therapy is safe and effective for patients with synchronous ovarian metastasis from GC and can improve their prognosis. However, our results need to be confirmed by more randomized controlled clinical studies.

Postoperative Early Body Weight Loss Is a Risk Factor for Recurrence in Patients with pStage III Gastric Cancer

Introduction: The goal of this study was to determine whether postoperative early body weight loss (EWL) after radical gastrectomy is a risk factor for recurrence in patients with pathological stage III (pStage III) gastric cancer who received postoperative adjuvant chemotherapy, which included tegafur/gimeracil/oteracil (S-1). Methods: Patients who underwent gastrectomy for gastric cancer were identified from a prospectively managed gastric cancer database. We analyzed 58 consecutive patients who underwent radical gastrectomy with D2 lymph node dissection for confirmed pStage III gastric cancer treated postoperatively with adjuvant chemotherapy including S-1 between 2010 and 2019. Clinical and pathologic characteristics, baseline body mass index (BMI), and postoperative weights were extracted. Weight changes were evaluated from the preoperative period to the start of adjuvant chemotherapy. EWL was defined as % BMI change = (preoperative BMI – postoperative BMI at the start of adjuvant chemotherapy) × 100/preoperative BMI. Results: Of the 58 consecutive patients who underwent radical resection for gastric cancer, 72.4% were male, with a mean age of 65.5 years, and a mean preoperative BMI of 21.2 (range: 15.4–29.1) kg/m². The degree of EWL was found to be closely correlated to compliance with adjuvant chemotherapy. Multivariate analysis by Cox proportional hazard analysis revealed that EWL was an independent factor for relapse-free survival (RFS), and patients with an EWL of 15.9% or more severe had poorer RFS. Conclusion: EWL above a certain rate at the start of adjuvant chemotherapy was a predictor of poor compliance with adjuvant chemotherapy and a high risk of disease recurrence in patients with pStage III gastric cancer.

Impact of Skeletal Muscle Mass Reduction on Long-term Survival After Radical Resection of Gastric Cancer.

This study aimed to investigate the effect of preoperative skeletal muscle mass and muscle mass loss after surgery on overall survival in patients with gastric cancer who underwent radical resection. We also examined factors involved in postoperative skeletal muscle loss. One hundred fifty gastric cancer patients who underwent radical resection were retrospectively examined. Skeletal muscle index (SMI) was measured using computed tomography before surgery and 1 year after. Degree of muscle reduction (MR) was calculated. Patients were stratified according to preoperative SMI (high/low) and MR (high/low) for analysis. In addition, patients were grouped according to SMI and MR stratification as follows: group A, low SMI/high MR; group B, low SMI/low MR; group C, high SMI/high MR; and group D, high SMI/low MR. In multivariate analysis, preoperative SMI and MR were independent predictors of overall survival. Overall survival significantly differed among groups A, B, C, and D (p<0.0001). The list of groups in order of worsening overall survival was as follows: group D, group C, group B, and group A. In multivariate analysis, patient group according to SMI and MR stratification was an independent predictor of overall survival. MR was affected by operation time (>430 min) and surgical procedure (total gastrectomy). Preoperative SMI and reduction in skeletal muscle mass after gastric cancer surgery were significantly associated with overall survival. Long-term management of these patients should focus on maintenance of postoperative skeletal muscle mass.

Prognostic Value of Tumor Markers in Gastric Cancer: A Tertiary Cancer Centre Experience.

Gastric cancer is a heterogeneous malignancy in terms of stage-wise prognosis. This study aimed at finding any prognostic significance of preoperative carcinoembryonic antigen (CEA) and cancer antigen (CA) 19-9 in resectable gastric cancer. A total of 57 patients at Kidwai Memorial Institute of Oncology, Bengaluru, India from January 2022 to March 2023 were included in this observational prospective study. Included patients had a resectable tumor at clinical staging. Patients were divided into two categories (raised and non-raised) based on serum tumor marker (CEA and CA 19-9) levels. Their relationship with clinicopathological features was studied. The association was studied using chi-square test, and p-value <0.05 was considered significant. The mean age of the study group was 55.47 years with male predominance (63.2%, n=36). Raised CEA and CA 19-9 were seen in 15.8% (n=9) and 10.5% (n=6) patients, respectively, while both markers were raised in 5.3% (n=3). Raised CEA was found significantly associated with grade 3 adenocarcinoma stomach (OR 7.825, 95%CI: 1.374-44.562; p= 0.020) and intraoperative finding of inoperability due to occult intra-abdominal disease (p<0.05). CA 19-9 (pre- and post-operative levels) had no statistically significant association (p>0.05) with the grade of adenocarcinoma. This study indicates a benefit in estimating CEAfor the prediction of prognosis in gastric cancer. CEA levels have been found to predict chances of finding occult intra-abdominal metastasis in gastric cancer.

Prediction of overall survival after radical gastrectomy using nomograms created by tumor markers.

Prediction of prognosis after radical resection of gastric cancer has not been well established. Therefore, we aimed to establish a prognostic model based on a new score system of patients with gastric cancer. A total of 1235 patients who underwent curative gastrectomy at our hospital from October 2015 to April 2017 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. Construction of the nomogram was based on Cox proportional hazard regression models. The construction of the new score models was analyzed by the receiver operating characteristic curve (ROC curve), calibration curve, and decision curve. Multivariate analysis showed that tumor size, T, N, carcinoembryonic antigen, CA125, and CA19-9 were independent prognostic factors. The new score model had a greater AUC (The area under the ROC curve) than other systems, and the C-index of the nomogram was highly reliable for evaluating the survival of patients with gastric cancer. Based on the tumor markers and other clinical indicators, we developed a precise model to predict the prognosis of patients with gastric cancer after radical surgery. This score system can be helpful to both surgeons and patients.

High expression of death-associated protein 5 promotes glucose metabolism in gastric cancer cells and correlates with poor survival outcomes

To investigate the prognostic value of death-associated protein 5 (DAP5) in gastric cancer (GC) and its regulatory effect on aerobic glycolysis in GC cells. We analyzed DAP5 expression levels in GC and adjacent tissues and its association with survival outcomes of GC patients using public databases. We collected paired samples of GC and adjacent tissues from 102 patients undergoing radical resection of GC in our hospital from June, 2012 to July, 2017, and analyzed the correlation of DAP5 expression level detected immunohistochemically with the clinicopathological parameters of the patients. Cox regression analysis, Kaplan-Meier analysis, and ROC curves were used to explore the independent risk factors and the predictive value of DAP5 expression for 5-year survival of the patients. In the cell experiments, we observed the changes in aerobic glycolysis in MGC-803 cells following lentivirus-mediated DAP5 knockdown or overexpression by measuring glucose uptake and cellular lactate level and using qRT-PCR and Western blotting. Analysis using the public databases showed that DAP5 was highly expressed in GC and correlated with tumor progression and poor survival outcomes of the patients (P < 0.05). In the clinical samples, DAP5 expression was significantly higher in GC than in the adjacent tissues (3.19±0.60 vs 1.00±0.12; t=36.863, P < 0.01), and a high expression of DAP5 was associated with a reduced 5-year survival rate of the patients (17.6% vs 72.5%; χ2=29.921, P < 0.05). A high DAP5 expression, T3-4, N2-3, and CEA≥5 ng/mL were identified as independent risk factors affecting 5-year survival outcomes of GC (P < 0.05), for which DAP5 expression showed a prediction sensitivity, specificity and accuracy of 73.2%, 80.4% and 79.0%, respectively. In MGC-803 cells, DAP5 knockdown significantly reduced glucose uptake, lactate level and the expressions of GLUT1, HK2 and LDHA, and DAP5 overexpression produced the opposite effects (P < 0.05). A high expression of DAP5 in GC, which enhances cellular aerobic glycolysis to promote cancer progression, is correlated with a poor survival outcome and may serve as a biomarker for evaluating long-term prognosis of GC patients.

3D versus 2D laparoscopic distal gastrectomy in patients with gastric cancer: a systematic review and meta-analysis.

While laparoscopic gastrectomy is a prominent therapeutic approach for distal gastric cancer, the clinical benefits of 3D laparoscopy over 2D laparoscopy remain unclear. We aimed to compare the clinical outcomes of 3D laparoscopy and 2D laparoscopy for distal gastric cancer resection through a systematic review and meta-analysis. We searched PubMed/MEDLINE, EMBASE, and Cochrane Library databases for studies published from inception through January 2023, according to the PRISMA guidelines. The MD or RR was used to compare 3D and 2D distal gastrectomy. Random-effects meta-analysis was estimated using the inverse variance and Mantel-Haenszel method for binary outcomes and the DerSimonian-Laird estimator for continuous outcomes. After reviewing 559 studies, 6 manuscripts met the inclusion criteria. The analysis included 689 patients, with 348 (50.5%) in the 3D group and 341 (49.5%) in the 2D group. 3D laparoscopic gastrectomy reduces the operative time (WMD - 28.57min, 95% CI - 50.70 to - 6.44, p = 0.011), intraoperative blood loss (WMD - 6.69mL, 95% CI - 8.09 to - 5.29, p < 0.001), and postoperative hospital stay (WMD - 0.92days, 95% CI - 1.43 to - 0.42, p < 0.001). There were no significant differences in time to first postoperative flatus (WMD - 0.22days, 95% CI - 0.50 to 0.05, p = 0.110), postoperative complications (Relative Risk 0.56, 95% CI 0.22 to 1.41, p = 0.217), and the number of retrieved lymph nodes (WMD 1.25, 95% CI - 0.54 to 3.03, p = 0.172) between 3 and 2D laparoscopic distal gastrectomy. Our study highlights the potential advantages of 3D laparoscopy in distal gastrectomy, including shorter operative time, postoperative hospital stay, and decreased intraoperative blood loss.

A feasibility study of modified docetaxel, cisplatin, and capecitabine for advanced gastric cancer followed by gastrectomy.

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 30mg/m2 docetaxel and 60mg/m2 cisplatin on day 1, followed by 2000mg/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.

Integration of endoscopic screening, magnification, and resection for early gastric cancer: advantages of underwater EMR (with video)

Integration of endoscopic screening, magnification, and resection for early gastric cancer: advantages of underwater EMR (with video)

Regional Lymph Node Metastasis Distribution in Resectable Middle-Third Gastric Cancer: A Cross-Sectional Study.

Introduction Lymph node (LN) metastasis happens even in early gastric cancer (GC) even in LN stations that are not adjacent to the primary tumor. Total or subtotal gastrectomy (TG or sTG) can be performed in the middle third of the GC if the negative proximal margin is maintained. These procedures differed in the extent of LN dissection; therefore, oncology considerations must be taken into consideration when selecting the appropriate procedure. Methods This was a cross-sectional study involving 98 patients suffering from middle-third GC. The metastatic lymph nodes (mLN) ratio was calculated in each case by the ratio between the number of mLN and the number of total LNs retrieved. We compare the difference in the total LN retrieved, number of mLN, and rate of positive LN (N+) between the two groups TG and sTG. Results The majority of patients had advanced GC (82.7% pT2-4). About 65.3% of patients had metastasis LN. The events of LN metastasis and skipped LN metastasis happened even in tumors contained in the submucosal layer. The metastasis rates in each LN station were also increasing in correlation with the depth of tumor invasion. For LN station No. 2, 4sa, 10, 11d (which are not mandatory) in sTG, the rate of mLN was 0% for the pT1-3 tumor, regardless of tumor longitudinal location. The rate of mLN for each station was higher in adjacent stations of the tumor (No. 1-3-5-7 in lesser curvature, No. 4sb-4d-6 in greater curvature, No.1-3-4sb in the anterior wall, No. 3-7-12a in the posterior wall). The total LN retrieved, number of mLN, and rate of positive LN were statistically higher in the TG group compared to the sTG group. However, the mean mLN ratios between the two groups were comparable (p = 0.116). Conclusion In accordance with the macroscopic and microscopic characteristics, we observed a stratified distribution of mLN in the middle third of the GC. With these early results, sTG combined with standard lymphadenectomy was an acceptable treatment for T1-T3 middle-third GC in terms of mLN distribution. Total No. 4sb LN dissection might also be reserved in gastrectomy for T1-T3 GC.

The results of treatment for resectable gastric cancer with microsatellite instability

Background. microsatellite instability (MSI) is a prognostic marker of survival in many malignant diseases and show resistance to chemotherapy at early stages of colorectal cancer and show no benefits from chemotherapy at early stages of colorectal cancer. However, the role of MSI in resectable gastric cancer (GC) remains unknown.Aim. To study the results of treatment of resectable gastric cancer with microsatellite instability.Materials and methods. The study included 286 patients with resectable gC who received treatment at the N. N. Blokhin national medical Research Center of Oncology. All patients underwent PCR testing for MSI-H in 5 markers (BAT25, BAT26, NR21, NR24, NR27). Tumor regression grades (TRG) were evaluated according to the mandard tumour regression score, including disease-free survival and overall survival.Results. MSI indicated in 27 cases (9.44 %) out of 286 resectable gastric cancer. In group patients who received only surgical treatment, 2-year disease-free survival in patients with MSI-H was 77.80 % versus 88.29 % in MSS patients (hazard ratio (HR) 1.82, 95 % confidence interval (CI) 0.37–8.82, p = 0.45), 2-year overall survival in patients with MSI-H was 88.90 % versus 95.36 % in MSS patients (HR 2.03, 95 % CI 0.20–19.8, p = 0.54). In patients who received perioperative chemotherapy, 28.57 % (4 / 14) had progression in MSI-H tumor versus 3.61 % (6 / 166) in MSS tumor (p &lt;0.001). In group patients who received treatment combined with chemotherapy, 2-year disease-free survival in patients with MSI-H was 59.60 % versus 67.36 % (HR 1.96, CI 95 % 0.88–4.35, p = 0.09), 2-year overall survival in patients with MSI-H was 67.30 % versus 85.86 % in MSS patients (HR 1.86, 95 % CI 0.64–5.41, p = 0.25)Conclusion. MSI-H is not a favorable prognosis factor in patients with resectable GC who are treated surgically combined with chemotherapy. The prevalence of progression in patients with MSI-H-status is higher than MSS-status with perioperative chemotherapy (FLOT / FOLFIRINOX).

Evaluation of neoadjuvant immunotherapy plus chemotherapy in Chinese surgically resectable gastric cancer: a pilot study by meta-analysis.

Recently, the use of immunochemotherapy in the treatment of advanced gastric cancer (GC) has been increasing and programmed cell death protein 1 (PD-1) inhibitors combined with chemotherapy has become the first-line treatment for advanced GC. However, few studies with small sample sizes have examined this treatment regimen to assess its effectiveness and safety in the neoadjuvant treatment phase of resectable local advanced GC. Herein, we systematically searched PubMed, Cochrane CENTRAL, and Web of Science for clinical trials on neoadjuvant immunochemotherapy (nICT) in advanced GC. The primary outcomes were effectiveness [evaluated by major pathological response (MPR) and pathological complete response (pCR)] and safety [assessed by grade 3-4 treatment-related adverse events (TRAEs) and postoperative complications]. A meta-analysis of non-comparative binary results was performed to aggregate the primary outcomes. Direct comparative analysis was used to compare pooled results of neoadjuvant chemotherapy (nCT) with nICT. The outcomes emerged as risk ratios (RR). Five articles with 206 patients were included, and all of them were from the Chinese population. The pooled pCR and MPR rates were 26.5% (95% CI: 21.3%-33.3%) and 49.0% (95% CI: 42.3%-55.9%), while grade 3-4 TRAEs and post-operative complication rates were 20.0% (95% CI: 9.1%-39.8%) and 30.1% (95% CI: 23.1%-37.9%), respectively. Direct comparison showed that with the exception of grade 3-4 TRAEs and postoperative complications, all outcomes including pCR, MPR, and R0 resection rate favoured nICT to nCT. nICT is a promising strategy for use as an advisable neoadjuvant treatment for patients with advanced GC in Chinese population. However, more phase III randomized controlled trials (RCTs) will be required to further consolidate the efficacy and safety of this regimen.

#4577 RENAL SAFETY OF FLOT REGIMEN FOR GASTROESOPHAGEAL CANCER

Abstract Background and Aims Currently, peri-operative docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) chemotherapy is the gold standard treatment for patients with locally advanced gastric cancer (LAGC), who undergo peri-operative chemotherapy and surgery. The known nephrotoxicity of both docetaxel and oxaliplatin compounds may limit the its application in CKD population. Nevertheless, limited evidence is available regarding the effects of FLOT regimen on renal function. In our analysis we evaluated the renal safety of FLOT regimen in LAGC population. Method Retrospective data on patient with resectable gastric cancer in four tertiary referral hospital between jan/2018 to jan/2022 have been analyzed. Patient have been treated with docetaxel (60 mg/m2), oxaliplatin (85 mg/m2), leucovorin (200 mg/m2), and 5-fluorouracil (2,600 mg/m2 as a 24 hr infusion), all given on day 1 and administered every 2 weeks in 4 administrations before surgery. Serum creatinine, hemoglobin, lymphocytes and CKD-EPI eGFR were detected at baseline and before each cycle. AKI and CKD onset/prevalence were determined according to K-DIGO criteria. Results A consecutive cohort of 90 patients was enrolled. At baseline CKD was present in 16 pts (21.9%). Median eGFR was 84,9 ml/min. In terms of eGFR decay and CKD onset during the treatment cycle, the result of ANOVA indicated no significant differences or relationship with FLOT; Wilks’ Lambda = 0.94, p = 0.354 (Table 1 and Figure 1). AKI incidence was very low with one episode of stage 2 AKI (0,7%) between the 2nd and the 4th treatment cycle. New onset anemia between the 1st and the 2nd cycle was the only significant adverse event observed (p = 0.003). Conclusion According to our results, the pre-operative FLOT regimen seems to have a negligible impact on renal function with very low rate of renal toxicity suggesting the possibility to extend its use even in patient with advanced CKD.

LAG3 in gastric cancer: it’s complicated

PurposeLymphocyte activation gene 3 (LAG3) is thought to contribute to T cell exhaustion within the tumor microenvironment of solid tumors. This study aimed to analyze the spatial distribution of LAG3 + cells in relation to clinicopathological and survival data in a large set of 580 primary resected and neoadjuvantly treated gastric cancers (GC).MethodsLAG3 expression was evaluated in tumor center and invasive margin using immunohistochemistry and whole-slide digital image analysis. Cases were divided into LAG3-low and LAG3-high expression groups based on (1) median LAG3 + cell density, (2) cut-off values adapted to cancer-specific survival using Cutoff Finder application.ResultsSignificant differences in spatial distribution of LAG3 + cells were observed in primarily resected GC, but not in neoadjuvantly treated GC. LAG3 + cell density showed evident prognostic value at following cut-offs: in primarily resected GC, 21.45 cells/mm2 in tumor center (17.9 vs. 10.1 months, p = 0.008) and 208.50 cells/mm2 in invasive margin (33.8 vs. 14.7 months, p = 0.006); and in neoadjuvantly treated GC, 12.62 cells/mm2 (27.3 vs. 13.2 months, p = 0.003) and 123.00 cells/mm2 (28.0 vs. 22.4 months, p = 0.136), respectively. Significant associations were found between LAG3 + cell distribution patterns and various clinicopathological factors in both cohorts. In neoadjuvantly treated GC, LAG3 + immune cell density was found to be an independent prognostic factor of survival (HR = 0.312, 95% CI 0.162–0.599, p < 0.001).ConclusionIn this study, a higher density of LAG3 + cells was associated with favorable prognosis. Current results support the need for extended analysis of LAG3. Differences in the distribution of LAG3 + cells should be considered, as they could influence clinical outcomes and treatment responses.Graphical abstract

Indocyanine Green Tracer-Guided Radical Robotic Distal Gastrectomy Using the Firefly™ System Improves the Quality of Lymph Node Dissection in Patients with Gastric Cancer

BackgroundThis study investigated indocyanine green (ICG) as an intraoperative tool for improving lymph node dissection quality in radical robotic distal gastrectomy (RDG) for gastric cancer by comparing the rate of lymph node (LN) noncompliance with or without use of the Firefly™ system. MethodsPatients with potentially resectable gastric cancer including cT1-T4a, N0/ + , M0 were registered in a prospective nonrandomized cohort study at our institution between March 2019 and December 2022. Patients were assigned to the da Vinci surgical system with Firefly system (F group) or that without Firefly system (non-F group). F group patients received endoscopic peritumoral injection of ICG to the submucosa one day before surgery. Rate of LN noncompliance, number of harvested LNs, and short-term outcomes were compared. ResultsOf the 94 patients in this study, 55 underwent Firefly system-guided RDG and 39 underwent conventional RDG. The mean [SD] total number of harvested lymph nodes in F group, 31.2 [10.2], was significantly higher than that harvested in non-F group (25.6 [12.6]; p = 0.026). The LN noncompliance rate in F group was lower than that in non-F group (32.7% vs. 61.5%, p = 0.006). The mean number of LNs harvested in F group was significantly higher than that harvested in non-F group (31.2 [10.2] vs. 25.7 [12.6], p = 0.02). Significant differences were found between the F vs. non-F groups in blood loss and postoperative hospital stay (83.9 [75.1] vs. 301.9 [766.7] mL; p = 0.003 and 13.4 vs. 17.4 days, p = 0.049). ConclusionThe Firefly system-assisted ICG tracer improved LN dissection quality without compromising safety.

Endoscopic Resection of Early Gastric Cancer and Pre-Malignant Gastric Lesions.

Early gastric cancer comprises gastric malignancies that are confined to the mucosa or submucosa, irrespective of lymph node metastasis. Endoscopic resection is currently pivotal for the management of such early lesions, and it is the recommended treatment for tumors presenting a very low risk of lymph node metastasis. In general, these lesions consist of two groups of differentiated mucosal adenocarcinomas: non-ulcerated lesions (regardless of their size) and small ulcerated lesions. Endoscopic submucosal dissection is the technique of choice in most cases. This procedure has high rates of complete histological resection while maintaining gastric anatomy and its functions, resulting in fewer adverse events than surgery and having a lesser impact on patient-reported quality of life. Nonetheless, approximately 20% of resected lesions do not fulfill curative criteria and demand further treatment, highlighting the importance of patient selection. Additionally, the preservation of the stomach results in a moderate risk of metachronous lesions, which underlines the need for surveillance. We review the current evidence regarding the endoscopic treatment of early gastric cancer, including the short-and long-term results and management after resection.