Resectable Gastric Cancer Research Articles

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 <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.

Contemporary Cancer Program Practice Profile Report Compliance Rates for Gastric Cancer: A National Cancer Database Analysis.

The Commission on Cancer (CoC) established quality measures to be reported in National Cancer Database (NCDB) Quality Reporting Tools. Compliance is provided to accredited cancer programs as Cancer Program Practice Profile Reports (CP3R). At the time of this study, the quality metric for gastric cancer (GC) was removal and pathologic examination of 15 regional lymph nodes for resected GC (G15RLN). This study evaluates national trends in quality metric compliance for GC based on CoC CP3R. The National Cancer Database (NCDB) was queried from 2004-2017 to identify patients with stage I-III GC who met criteria for inclusion. National trends in compliance were compared. Overall survival (OS) was compared stage for stage. Overall, 42997 patients with GC qualified. In 2017, 64.5% of patients met compliance with G15RLN compared to 31.4% in 2004. When comparing academic and non-academic institutions, compliance was met 67.0% vs 60.0% of the time in 2017 (P < .01) and 36% vs 30.6% of the time in 2004 (P < .01). On multivariate logistic regression, patients receiving care at academic institutions (OR 1.5, 95% CI 1.4-1.5) and who underwent surgery at institutions in the >75th percentile for case volume (OR 1.5, 95% CI 1.4-1.6) had higher odds of compliance. When stratified by stage, median OS was better across all stages when compliance was met. Compliance rates with GC quality measures have improved over time. Compliance with the G15RLN metric is associated with improved OS, stage for stage. Continued efforts to improve compliance rates across all institutions are critical.

Comparison of the effects of remimazolam and dexmedetomidine on early postoperative cognitive function in elderly patients with gastric cancer.

To compare the effects of remimazolam and dexmedetomidine on early postoperative cognitive dysfunction (POCD) in aged gastric cancer patients. From June to December 2022, 104 elderly patients (aged 65-80 years) received laparoscopic radical resection of gastric cancer at the First Affiliated Hospital of Nanchang University. Using the random number table approach, the patients were separated into three groups: remimazolam (Group R), dexmedetomidine (Group D), and saline (Group C). The primary outcome was the incidence of POCD, and secondary outcomes included TNF-α and S-100β protein concentrations, hemodynamics, VAS scores, anesthesia recovery indicators, and the occurrence of adverse events within 48 h postoperatively. At 3 and 7 days after surgery, there were no statistically significant differences in the incidence of POCD, the MMSE and MoCA scores between groups R and D (p > 0.05). However, compared to the saline group, both groups had higher MMSE and MoCA scores and decreased incidences of POCD. These differences were statistically significant (p < 0.05). Between group R and group D, there were no statistically significant changes (p > 0.05) in the levels of TNF-α and S-100β protein at the three time points (at the end of the surgery, 1 day later, and 3 days later). Even though neither group's concentration of the two factors was as high as that of the saline group, the differences were statistically significant (p < 0.05). At all three time points-following induction (T2), 30 min into the operation (T3), and at the conclusion of the surgery (T4)-the heart rate and blood pressure in group R were greater than those in groups D and C. Statistics showed that the differences were significant (p < 0.05). The incidence of intraoperative hypotension was highest in group D and lowest in group R (p < 0.05). The dose of propofol and remifentanil, group C > group R > group D. Extubation and PACU residence times did not differ statistically significantly (p > 0.05) between the three groups. There was no significant difference in VAS scores between groups R and D after 24 h postoperatively (p > 0.05), although both had lower scores than group C, and the difference was statistically significant (p < 0.05). The VAS scores between the three groups at 72 h (T6) and 7 days (T7) were not statistically significant (p > 0.05). Adverse reactions such as respiratory depression, hypotension, bradycardia, agitation, drowsiness, and nausea and vomiting had the lowest incidence in group R and the highest incidence in group C (p < 0.05). Remimazolam is similarly beneficial as dexmedetomidine in lowering the incidence of early POCD in aged patients after radical gastric cancer resection, probably due to reduced inflammatory response.

Perioperative PD-1 antibody toripalimab plus SOX or XELOX chemotherapy versus SOX or XELOX alone for locally advanced gastric or gastro-oesophageal junction cancer: Results from a prospective, randomized, open-label, phase II trial.

4001 Background: The combination of PD-1 antibody and chemotherapy was shown to be effective in advanced gastric or gastro-oesophageal junction (GEJ) cancer, but has not yet been investigated in the context of locally advanced patients. In this study, we conducted a prospective, randomized, open-label phase II trial to evaluate the effectiveness of adding PD-1 antibody to perioperative chemotherapy in patients with locally advanced resectable gastric or GEJ cancer. Methods: In this randomized, open-label, phase II study, patients with resectable gastric or GEJ cancer clinically staged as cT3-4a N+M0 were randomized (1:1) to three preoperative and five postoperative 3-week cycles of SOX/XELOX (C arm) or PD-1 antibody toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for 6 months (C+T arm). The primary endpoint was pathological complete regression/moderate regression rate (TRG 0/1). The secondary endpoints were pathological complete response (pCR), R0 resection rate, recurrence-free survival, event-free survival, objective response rate, disease control rate, overall survival and treatment safety. The study had been completed enrollment, and here, we analyzed the primary endpoint. Mantel-Haenszel test was used to test the difference of pathological regression between the two arms. The trial was registered at ClinicalTrials.gov, identifier: NCT04250948. Results: Between Oct 2019 and June 2022, 108 patients (C+T arm, n=54; C arm, n=54) were enrolled and assessed using intention-to-treat analysis. Patients in the toripalimab plus chemotherapy arm achieved higher proportion of TRG 0/1 than those in the chemotherapy arm (44.4% [24/54, 95% CI: 30.9%-58.6%] vs 20.4% [11/54, 95% CI: 10.6%-33.5%]; P=0.009). A higher pCR rate was observed in the C+T arm (24.1% [13/54, 95% CI:13.5%-37.6%] vs 9.3% [5/54, 95% CI: 3.1%-20.3%]; P=0.039). Preoperative therapies (3 cycles) were completed in 96.3% of patients and postoperative cycles (&gt;3 cycles) in 81.5%, with no significant differences observed between these two arms. A higher proportion of downstaging was observed in the C+T arm (ypT0-2: 46.3% vs 22.2% [P=0.002]; ypstage 0-1: 38.9% vs 16.7% [P=0.024]). Surgical morbidity (11.8% in the C+T arm vs 13.5% in the C arm) and mortality (1.9% vs 0%) and treatment-related grade 3-4 adverse events (27.8% vs 25.9%) were comparable between the arms. Conclusions: Perioperative PD-1 antibody toripalimab plus chemotherapy demonstrated a significantly improved pathological regression and might be a promising option for patients with locally advanced resectable gastric or GEJ cancer. Clinical trial information: NCT04250948 .

Right axillopopliteal artery bypass using a combined transiliac and lateral popliteal approach for groin infection and lymph fistula.

Wound infection in the groin is a serious complication after vascular bypass surgery. The combined treatment of critical limb ischemia and recurrent infection presents challenges for vascular surgery(1Lounes Y. Ozdemir B. Alric P. Canaud L. Trans-iliac Bypass for Critical Limb Ischaemia with Groin Necrosis: A Case Report.EJVES Short Reports. 2019; 42: 31-33https://doi.org/10.1016/j.ejvssr.2019.01.002Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar, 2Multon S. Jayet J. Javerliat I. Coscas R. Coggia M. Aortic–tibial transiliac wing extra-anatomic bypass with distal fistula for treatment of an infected deep femoral pseudoaneurysm.J Vasc Surg Cases, Innov Tech. 2022; 8: 201https://doi.org/10.1016/j.jvscit.2022.02.008Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 3Engin C, Posacioglu H, Ayik F, Apaydin A . Management of vascular infection in the groin. Texas Hear Inst J (2005) 32:529–534.Google Scholar). In this case, we successfully managed the wound infection in the groin after axillofemoral artery bypass grafting, using a combination of trans-iliac bypass and lateral popliteal approach(4Enzmann F.K. Nierlich P. Eder S. Aspalter M. Dabernig W. Aschacher T. et al.Trans-Iliac Bypass Grafting for Vascular Groin Complications.Eur J Vasc Endovasc Surg. 2019; 58: 930-935https://doi.org/10.1016/j.ejvs.2018.11.003Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar, 5Benzing C. Fellmer P. Lateral Approach to the Distal Femoral Artery in Femoro-Anterior-Tibial Bypass Surgery.Eur J Vasc Endovasc Surg. 2016; 52: 267https://doi.org/10.1016/j.ejvs.2016.04.024Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar). A 74-year-old man, having Buerger's disease and arteriosclerosis obliterans, presented with extensive lymphatic fistula and necrosis of the groin (Fig.1) after right axillary artery to the right deep femoral artery bypass, which had been patented for last five years after the several revascularizations of iliac arteries and femoral arteries. Due to the several open surgeries, such as aorto-right external iliac artery bypass, aorto-left popliteal artery bypass, cholecystectomy and resection of gastric cancer, we chose right axillopopliteal artery bypass grafting, through the iliac wing. The skin incision was made along the iliac crest and the external oblique muscle fascia was separated to reach the pelvis, and a longitudinal incision was made anterosuperior to the greater trochanter to create a gluteal pathway to bypass the infected groin. 10-mm hole was made by shaving the bone about 4 cm from the iliac crest, and the graft was passed through the hole. (Fig 2). A lateral popliteal approach was selected for revascularization owing to extensive groin and medial thigh infective wounds. After that the extensive lymphatic fistula and necrosis were controlled with using negative pressure wound therapy.Figure 2View Large Image Figure ViewerDownload Hi-res image Download (PPT) The postoperative course was uneventful, and contrast-enhanced computed tomography confirmed proper arrangement of the graft, without bending (Fig 3 and Fig 4). He was discharged from the hospital on the 14th postoperative day. The computed tomography which was taken one year later showed the patency of this graft. The combination of trans - iliac bypass and lateral popliteal approach was shown to be effective in this case of extensive groin and medial compartment infection, and can potentially be applied in similar future cases.Figure 4View Large Image Figure ViewerDownload Hi-res image Download (PPT)

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.

4067 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. 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. Clinical trial information: NCT01515748 .

PD-5 MONEO: Phase II study of avelumab (Av) plus FLOT in the peri-operative treatment for patients (pts) with resectable gastric or gastroesophageal junction cancer (GC)

PD-5 MONEO: Phase II study of avelumab (Av) plus FLOT in the peri-operative treatment for patients (pts) with resectable gastric or gastroesophageal junction cancer (GC)

P-33 The role of preoperative immune-chemotherapy in locally advanced resectable gastric cancer with microsatellite instability

P-33 The role of preoperative immune-chemotherapy in locally advanced resectable gastric cancer with microsatellite instability

P-211 Factors predicting nodal spread in curatively resected gastric cancer – analysis from a tertiary care center in India

P-211 Factors predicting nodal spread in curatively resected gastric cancer – analysis from a tertiary care center in India

Risk stratification for predicting postoperative recurrence of gastric cancer by grade of venous invasion

BackgroundVenous invasion (VI) in pathological examination of surgically resected gastric cancer (GC) may predict postoperative recurrence, but there are no objective criteria for VI grading.Methods157 GC patients (pathological stages I 82, II 34, and III 41) who underwent surgery with curative intent were analyzed. VI was graded in pathological examination by elastica van Gieson staining based on the number of VIs per glass slide as follows: v0, 0; v1, 1−3; v2, 4−6; and v3, ≥ 7. Filling-type invasion in veins with a minor axis of ≥ 1 mm increased the grade by 1. The association of VI grade with prognosis was statistically analyzed.ResultsRecurrence increased with VI grade (v0 1.5%, v1 29.6%, v2 41.7%, v3 78.6%). VI grade as well as pathological (p) tumor, node, metastasis (TNM) stage was a significant recurrence predictor by the multivariate Cox analysis. VI grade was implicated in hematogenous and peritoneal recurrences independent of pTNM stage but not in nodal recurrence. GC was then divided into two tiers, without indication of adjuvant chemotherapy (AC) (pStage I, pT1 and pT3N0) and with AC indication (pStages remaining II/III), based on the ACTS-GC trial, which is common in Japan and East Asia. VI grade was a significant recurrence predictor in both tiers. v2/v3 revealed a significantly worse recurrence-free survival (RFS) than v0/v1 in GC without AC indication. v0/v1 exhibited RFS rate exceeding 95% even after 5 years but that of v2/v3 fell around 70% within one year postoperatively, suggesting that AC may be considered for this tier with v2/v3. GC with AC indication exhibited dismal RFS according to the VI grade. RFS rate fell below 80% within one year postoperatively when VI was positive, while recurrence was not observed in v0, which was, however, rare in this tier (10.9%). Differentiation grade did not significantly affect postoperative prognosis in both tiers.ConclusionsVI grade was a significant predictor of postoperative GC recurrence irrespective of the AC indication based on the ACTS-GC study and this VI grading system could be applied in future studies of adjuvant therapy in GC presently deemed without AC indication in Japan.

Linear EUS Accuracy in Preoperative Staging of Gastric Cancer: A Retrospective Multicenter Study.

Preoperative gastric cancer (GC) staging is the most reliable prognostic factor that affects therapeutic strategies. Contrast-enhanced computed tomography (CECT) and radial endoscopic ultrasound (R-EUS) scans are the most commonly used staging tools for GC. The accuracy of linear EUS (L-EUS) in this setting is still controversial. The aim of this retrospective multicenter study was to evaluate the accuracy of L-EUS and CECT in preoperative GC staging, with regards to depth of tumor invasion (T staging) and nodal involvement (N staging). 191 consecutive patients who underwent surgical resection for GC were retrospectively enrolled. Preoperative staging had been performed using both L-EUS and CECT, and the results were compared to postoperative staging by histopathologic analysis of surgical specimens. L-EUS diagnostic accuracy for depth of invasion of the GC was 100%, 60%, 74%, and 80% for T1, T2, T3, and T4, respectively. CECT accuracy for T staging was 78%, 55%, 45%, and 10% for T1, T2, T3, and T4, respectively. L-EUS diagnostic accuracy for N staging of GC was 85%, significantly higher than CECT accuracy (61%). Our data suggest that L-EUS has a higher accuracy than CECT in preoperative T and N staging of GC.

Defining a Nomogram for Predicting Early Recurrence in Gastric Cancer Patients After Neoadjuvant Chemotherapy and Radical Gastrectomy

PurposeTo define and predict early recurrence (ER) in patients with gastric cancer (GC) who underwent radical gastrectomy after neoadjuvant chemotherapy (NAC). MethodsThe present study included 573 patients who underwent NAC followed by curative resection for GC between January 2014 and December 2019. The patients were randomly divided into the training (n = 382) and validation (n = 191) cohorts in a 2:1 ratio. The optimal cut-off value of recurrence-free survival for defining ER was determined based on post-recurrence survival (PRS). Risk factors for ER were identified by logistic regression. A nomogram was further constructed and evaluated. ResultsThe optimal cut-off value for defining ER was 12 months. Overall, 136 patients (23.7%) experienced ER and had significantly shorter median PRS (4 vs. 13 months, P < 0.001). In the training cohort, factors independently associated with ER included age (P = 0.026), Lauren classification (P < 0.001), preoperative carcinoembryonic antigen (P = 0.029), ypN staging (P < 0.001), major pathological regression (P = 0.004), and postoperative complications (P < 0.001). A nomogram integrating these factors exhibited higher predictive accuracy than the ypTNM stage alone in both the training and validation cohorts. Moreover, the nomogram enabled significant risk stratification in both cohorts; only the high-risk patients could benefit from adjuvant chemotherapy (ER rate: 53.9% vs. 85.7%, P = 0.007). ConclusionA nomogram involving preoperative factors can accurately predict the risk of ER and guide individualized treatment strategies for GC patients following NAC, which may assist in clinical decision-making.

The 'double‑track sign': A novel CT finding suggestive of the diagnosis of T1a gastric cancer.

Effective identification of T1a stage cancer is crucial for planning endoscopic resection for early gastric cancers. The present study aimed to determine the diagnostic value of the double-track sign in patients with T1a gastric cancer using computed tomography (CT) imaging. A total of 152 patients diagnosed with pathologically proven T1a gastric cancer at The First Affiliated Hospital of Zhengzhou University (Zhengzhou, China) between July 2011 and August 2021 were retrospectively reviewed. The control group consisted of 2,926 patients with gastritis. Clinical data, including patient characteristics and preoperative CT imaging findings with gastric morphological features, were reviewed and analyzed. Out of 51 patients with T1a gastric cancer finally included, 31 (60.8%) exhibited local double-track enhancement changes of the stomach, referred to as the 'double-track sign', on CT images. In addition, four patients (7.8%) had well-enhanced mucosal thickening of the gastric wall. Of the 2,926 control subjects, none had any double-track sign and six patients (0.2%) had local gastric wall thickening with abnormally strengthened enhancement. In conclusion, a double-track sign on CT images is beneficial in the diagnostic differentiation of T1a gastric cancer.

Prognostic Value of T-Cell Density in the Tumor Center and Outer Margins in Gastric Cancer

Tumor-infiltrating lymphocytes are associated with the survival of gastric cancer patients. T-cell densities in the tumor and its periphery were previously identified as prognostic T-cell markers for resectable gastric cancer. Immunohistochemistry for 5 T-cell markers, CD3, CD45RO, CD8, FOXP3, and granzyme B was performed on serial sections of N = 251 surgical resection specimens of patients treated with surgery only in the D1/D2 trial. Positive T cells were digitally quantified into tiles of 0.25 mm2 across 3 regions: the tumor center (TC), the inner invasive margin, and the outer invasive margin (OIM). A classification and regression tree model was employed to identify the optimal combination of median T-cell densities per region with cancer-specific survival (CSS) as the outcome. All statistical tests were 2-sided. CD8OIM was identified as the most dominant prognostic factor, followed by FOXP3TC, resulting in a decision tree containing 3 prognostically distinct subgroups with high (Hi) or low (Lo) density of the markers: CD8OIMHi, CD8OIMLo/FOXP3TCHi, and CD8OIMLo/FOXP3TCLo. In a multivariable Cox regression analysis, which included pathological T and N stages, Lauren histologic types, EBV status, microsatellite instability, and type of surgery, the immune subgroups were independent predictors for CSS. CSS was lower for CD8OIMLo/FOXP3TCHi (HR: 5.02; 95% CI: 2.03-12.42) and for CD8OIMLo/FOXP3TCLo (HR: 7.99; 95% CI: 3.22-19.86), compared with CD8OIMHi (P < .0001). The location and density of both CD8+ and FOXP3+ T cells in resectable gastric cancer are independently associated with survival. The combination of CD8OIM and FOXP3TC T-cell densities is a promising stratification factor that should be validated in independent studies.