Adjuvant Chemotherapy For Gastric Cancer Research Articles

Diallyl disulfide antagonizes DJ-1 mediated proliferation, epithelial-mesenchymal transition, and chemoresistance in gastric cancer cells.

Diallyl disulfide (DADS), an organic component of allicin abstracted from garlic, possesses multi-target antitumor activity. DJ-1 performs a vital function in promoting AKT aberrant activation via down-regulating phosphatase and tensin homologue (PTEN) in tumors. It is unknown the involvement of DJ-1 in epithelial-mesenchymal transition (EMT) of gastric cancer (GC) cells. The purpose of this study is to investigate whether diallyl disulfide (DADS) intervenes in the role of DJ-1 in GC. Based on the identification that the correlation between high DJ-1 and low PTEN expression in GC was implicated in clinical progression, we illuminated that down-regulation of DJ-1 by DADS aided in an increase in PTEN expression and a decrease in phosphorylated AKT levels, which was in line with the results manifested in the DJ-1 knockdown and overexpressed cells, concurrently inhibiting proliferation, EMT, migration, and invasion. Furthermore, the antagonistic effects of DADS on DJ-1 were observed in in vivo experiments. Additionally, DADS mitigated the DJ-1-associated drug resistance. The current study revealed that DJ-1 is one of potential targets for DADS, which hopefully provides a promising strategy for prevention and adjuvant chemotherapy of GC.

A Retrospective Analysis of the Lauren Classification in the Choice of XELOX or SOX as an Adjuvant Chemotherapy for Gastric Cancer.

We aim to retrospectively explore the guiding value of the Lauren classification for patients who have undergone D2 gastrectomy to choose oxaliplatin plus capecitabine (XELOX) or oxaliplatin plus S-1 (SOX) as a further systemic treatment after the operation. We collected data of 406 patients with stage III gastric cancer(GC)after radical D2 resection and regularly received XELOX or SOX adjuvant treatment after surgery and followed them for at least five years. According to the Lauren classification, we separated patients out into intestinal type (IT) GC together with non-intestinal type(NIT) GC. According to the chemotherapy regimen, we separated patients into the SOX group together with the XELOX group. Among non-intestinal type patients, the 3-year DFS rates in the SOX group and the XELOX group were 72.5%, respectively; 54.5% (P=0.037); The 5-year OS rates were 66.8% and 51.8% respectively (P=0.038), both of which were statistically significant. The patients of non-intestinal type GC may benefit from the SOX regimen. Differences were counted without being statistically significant with intestinal-type GC in the SOX or XELOX groups.

Updated Adjuvant Chemotherapy for Gastric Cancer.

Surgical resection is currently the best curative approach for gastric cancer (GC); however, the prognosis of patients with advanced GC remains poor even with curative resection. For this reason, perioperative chemotherapy has been combined with surgery to reduce the risk of postoperative recurrence. Standard perioperative chemotherapy for resectable advanced GC varies from region to region. Postoperative S-1 therapy was standardized via the ACTS-GC study in East Asia, perioperative ECF (Epirubicin + Cisplatin + Fluorouracil) was standardized via the MAGIC study in Europe, and postoperative chemoradiotherapy was standardized via the US intergroup study in North America. Since then, more intensive regimens have been developed. In recent years, perioperative therapy using novel agents, such as molecular-targeted drugs and immune checkpoint inhibitors (ICIs), has also been tested and evaluated in the three major regions (East Asia, Europe, and North America) with promising results. Perioperative chemotherapy has become an integral part of many treatment strategies and requires continued research and evaluation.

Thromboembolic events in patients who received adjuvant chemotherapy for gastric cancer: a single-center retrospective study.

Thromboembolic events (TEEs) are significant adverse events that can cause serious morbidities and mortality in cancer patients receiving chemotherapy. Patients with gastric cancer (GC) treated with palliative chemotherapy have been reported to experience a TEE incidence of 5-27%. However, very few reports have addressed TEEs in adjuvant chemotherapy (AC) for GC. This study retrospectively analyzed 611 GC patients (stage II: 309, III: 302) who started AC with capecitabine/oxaliplatin (167 patients) or S-1 (444 patients) after undergoing curative resection between January 2013 and June 2020 at a single center. The incidence of TEEs during AC or within 1year after AC completion was investigated, while analyzing the factors that influenced the TEEs' occurrence. TEEs were confirmed in 20 patients (3.3%), and TEEs occurred in almost all patients in the S-1 group (19 patients). The most common TEE types were cerebral infarction and pulmonary thromboembolism (five patients each). Although old age (≥ 70years, p < 0.0001), S-1 treatment (p = 0.021), and hypertension (p = 0.017) were identified as significant risk factors for TEEs in univariate analysis, only old age showed a statistically significant correlation with TEEs' occurrence in multivariate analysis (odds ratio: 3.07; 95% confidence interval 1.11-8.48; p = 0.031). TEEs occurred in fewer patients with GC who had been treated with AC than patients who had received palliative chemotherapy in previous reports. However, elderly GC patients who are undergoing AC require more careful surveillance for possible TEEs, considering relatively higher incidence of them.

Solitary living worsens the continuation of adjuvant chemotherapy for gastric cancer.

No studies have reported the effect of solitary living on adjuvant chemotherapy continuation in patients with gastric cancer. This study aimed to investigate the influence of solitary living on the efficacy of adjuvant chemotherapy after curative gastrectomy. We enrolled 155 patients with pathological stage II/III gastric cancer who underwent gastrectomy and adjuvant chemotherapy between January 2013 and March 2020. The patients were divided into two groups according to their living conditions, the solitary group (n=34) versus the non-solitary group (n=121). Clinicopathological features, predictive factors for the continuation of adjuvant chemotherapy, and long-term survival were compared between the two groups. The median body weight loss (BWL) at one month after surgery (8.9% vs. 7.0%, p=0.01), and the rates of failure to continue six courses of chemotherapy were higher in the solitary group (41.2% vs. 14.9%, p=0.002) than in the non-solitary group. Multivariate analysis revealed that solitary living was an independent predictive factor for discontinuing adjuvant chemotherapy (odds ratio 3.36, 95% confidence interval [CI; 1.32-8.58], p=0.01) as well as 10% BWL at one month after surgery (odds ratio 3.99, 95% CI [1.57-10.2], p=0.004). The relapse-free survival was significantly worse in the solitary group (p=0.03). Solitary living may be an independent risk factor for discontinuation of adjuvant chemotherapy in patients with gastric cancer. It is necessary to examine whether social and medical support organized by medical institutes and the government improves the continuation of adjuvant chemotherapy in patients living alone.

Optimizing the Choice for Adjuvant Chemotherapy in Gastric Cancer.

Simple SummaryGastric cancer is the fourth largest cause of tumor-related death worldwide. Despite advances in the management of resectable cancer and improvements in early diagnosis, especially in east Asia where screening campaigns are actively performed, many patients experience recurrence and die because of the disease. Adjuvant systemic chemotherapy is administered after radical surgery in order to reduce the risk of recurrence and death. The modality of administration and regimens of chemotherapy in this setting are different between Eastern and Western countries. In Asia, adjuvant chemotherapy is traditionally given after surgery, while in Europe it is commonly scheduled after preoperative chemotherapy and surgery (perioperative chemotherapy), and in Northern America it is usually combined with radiotherapy (chemoradiotherapy). All these approaches are sustained by well-designed phase III clinical studies, and none may be considered superior to the others in the absence of head-to-head comparisons. The identification of predictive and/or prognostic factors could help to select patients at higher risk of recurrence and those more likely to receive a benefit from the adjuvant treatment. This would allow clinicians to avoid the administration of undue toxicity to non-responder patients and even to reduce the cost of unnecessary treatment.Advances in the management of gastric cancer have improved patient survival in the last decade. Nonetheless, the number of patients relapsing and dying after a diagnosis of localized gastric cancer is still too high, even in early stages (10% in stage I). Adjuvant systemic chemotherapy has been proven to significantly improve outcomes. In the present article we have critically reviewed the clinical trials that guide the current clinical practice in the adjuvant treatment of patients affected by resectable gastric cancer, focusing on the different approaches worldwide, i.e., adjuvant chemotherapy, adjuvant chemoradiotherapy, and perioperative chemotherapy. We also delineate the clinical–pathological characteristics that are commonly taken into account to identify patients at a higher risk of recurrence and requiring adjuvant chemotherapy, and also describe novel biomarkers and therapeutic agents that might allow personalization of the treatment.

Analysis of treatment outcomes according to the cycles of adjuvant chemotherapy in gastric cancer: a retrospective nationwide cohort study

BackgroundOne-year S-1 or six-month capecitabine/oxaliplatin (CAPOX) has been the standard adjuvant chemotherapy for gastric cancer (GC). We investigated outcomes according to the cycles of adjuvant chemotherapy, using data from the Korean Health Insurance and Assessment Service.MethodsA total of 20,552 patients, including 13,614 patients who received S-1 and 6,938 patients who received CAPOX extracted from 558,442 patients were retrospectively analyzed. The five-year overall survival rate was evaluated according to the duration of adjuvant chemotherapy.ResultsThe five-year overall survival rate gradually increased according to the increase in adjuvant chemotherapy cycles in both the S-1 (≤ 5 cycles: 48.4%, hazard ratio [HR] 4.06, 95% confidence interval [CI] 3.74–4.40, P < 0.0001; 5 < cycles ≤ 6: 55.4%, HR 3.08, 95% CI 2.65–3.57, P < 0.0001; 6 < cycles ≤ 7: 64.1%, HR 2.11, 95% CI 1.84–2.41, P < 0.0001; 7 < cycles < 8: 71.1%, HR 1.60, 95% CI 1.39–1.84, P < 0.0001; ≥ 8 cycles: 77.9%) and the CAPOX groups (≤ 4 cycles: 43.5%, HR 3.20, 95% CI 2.84–3.61, P < 0.0001; 5 cycles: 45.3%, HR 2.63, 95% CI 2.11–3.27, P < 0.0001; 6 cycles: 47.1%, HR 2.09, 95% CI 1.76–2.49, P < 0.0001; 7 cycles: 55.3%, HR 1.63, 95% CI 1.35–1.96, P < 0.0001; ≥ 8 cycles: 67.2%).ConclusionsReducing the treatment cycles of adjuvant chemotherapy in GC with S-1 or CAPOX showed inferior survival outcomes. Completing the standard duration of adjuvant chemotherapy with S-1 or CAPOX would be strongly recommended.

Usefulness of an S-1 dosage formula: An exploratory analysis of randomized clinical trial (JCOG1001).

288 Background: Although the S-1 dose is determined by body surface area (BSA), its blood concentration and adverse events are affected by renal function. One study had reported the clinical utility of an S-1 dosage formula for calculating the dose for target blood concentration based on renal function (Booka E. Gastric Cancer 2016;19:876-86.). The present study aimed to explore the usefulness of this formula in adjuvant chemotherapy for gastric cancer. Methods: Ad hoc analyses was performed using data from patients enrolled in a phase III trial, JCOG1001, to evaluate the role of bursectomy for resectable advanced gastric cancer. In the abovementioned trial, patients with stage II/III received adjuvant S-1 chemotherapy based on BSA. The present study calculated the S-1 dose using the following formula: 1447.8 * (14.5+0.301*CLcr+8.23*SEX [male=1, female=0])*BSA (mg/day). Patients were divided into three groups, overdosed (OD), equal dosed (ED), and underdosed (UD), by comparing the initial dosage administered with that recommended by the formula. Results: Among the 686 eligible pts, 324, 304, and 58 were respectively classified as OD/ED/UD, with the following characteristics: median age, 67.5/64/53.5 years; men 188/229/57 (58%/75%/98%); undifferentiated type, 168/172/38 (52%/57%/66%); and pStage III, 212/200/41 (65%/66%/71%). Median relative dose intensity in OD/ED/UD pts was 93.8%/108.8%/75.0% based on the formula-recommended dose. The planned adjuvant S-1 therapy was completed in 69%/74%/74%, dose reduction and treatment schedule alteration were required in 31%/21%/9% and 20%/17%/9%, and treatment was terminated due to adverse events in 25%/18%/12%. The 5-year relapse-free (RFS) and overall survival (OS) OD/ED/UD patients were 66.6%/69.2%/74.0% and 77.0%/74.3%/77.3%, in pStage II 80.2%/85.6%/93.8% and 88.3%/90.1%/100%, and pStage III 59.6%/60.4%/65.8% and 67.0%/70.0%/67.7%, respectively. OD pts had significantly higher incidences of grade 3 or higher anemia, thrombocytopenia, diarrhea, stomatitis than ED and UD pts. Conclusions: Despite no difference in survival, this formula improved treatment compliance in OD patients receiving adjuvant S-1 chemotherapy for gastric cancer.[Table: see text]

Low CBS expression can identify patients who benefit from adjuvant chemotherapy in gastric cancer

ABSTRACT Aim: To explore the clinical significance of Cystathionine beta-synthase (CBS) expression in gastric cancer (GC). Research design and methods: CBS expression and clinicopathological/follow-up information of patients with gastric cancer undergoing operation were collected from The Cancer Genome Atlas (TCGA) database. The association of CBS expression with patients’ overall survival (OS) was determined in the entire cohort and different subgroups. Validation was performed in two external cohorts from NCBI Gene Expression Omnibus (GEO) database. The estimated drug response of the tumors with different CBS expressions was characterized. The potential CBS-related cellular pathways in chemoresistance were explored. Results: High CBS was associated with poor OS in patients receiving adjuvant chemotherapy (ACT) but not those without ACT. And ACT was associated with favorable OS in patients with low CBS expression but not those with high CBS expression. The results were verified in two external cohorts. Drug response prediction suggested that patients with low CBS expression showed high sensitivity to 5-Fluorouracil. Gene Set Enrichment Analysis (GSEA) suggested that CBS might contribute to GC chemoresistance via modulating many cellular pathways, including down-regulating apoptosis and P53 pathways while up-regulating DNA repair pathway. Conclusion: Low CBS expression can predict the benefit from ACT in GC.

Clinical biomarkers in adjuvant chemotherapy for gastric cancer after D2 dissection by a pooled analysis of individual patient data from large randomized controlled trials.

Adjuvant therapy for gastric cancer is a standard among the world with no regimen selection criteria. Also, prognostic factors except for tumor staging have not been established. We aimed to identify prognostic and predictive markers for gastric cancer adjuvant therapy from large randomized controlled trials with standard lymph node dissection. Three studies: ACTS-GC, CLASSIC, and SAMIT were found and selected for a pooled analysis, following PRISMA guideline. The integrity of individual participant data (IPD) was verified in the eligible 3527 patients registered, and fixed-effect model was used. The primary endpoint was relapse-free survival (RFS) and the secondary endpoint was overall survival (OS). Age was a significant prognostic factor in addition to tumor stages both in "surgery alone" and "adjuvant" groups. Adjuvant therapy was effective for every TN stage; however, it tended to be more effective in T1-2 than in T3-4. Also, it was more effective in low- or middle-BMI than in high-BMI group with Hazard ratio [HR]s: 0.58, 0.58, and 1.05, respectively. Capecitabine plus oxaliplatin (CAPOX) was more effective than S-1 for T1-2, N2-3, and differentiated type with HRs between 0.59 and 0.70, but with no difference among TNM stages. Combining histology to TN; the HRs in differentiated T1-2 N1-3 groups were between 0.29 and 0.45. For T3-4 N0-1 group, S-1 was likely to be effective, not significant. Age is a significant prognostic factor both in surgery alone and adjuvant group. CAPOX is more effective for differentiated T1-2 tumors with lymph node metastasis.

THE ROLE OF ADJUVANT CHEMOTHERAPY IN THE TREATMENT OF LOCALLY ADVANCED GASTRIC CANCER

The purpose of the study was a systemic literature review on data regarding the efficacy, safety and prospects for the use of adjuvant chemotherapy for locally advanced gastric cancer.Material and Methods. The study contained a thorough literary analysis of the results of international studies on the use of preoperative and postoperative chemotherapy for locally advanced gastric cancer. Relevant sources were searched in Medlin and Cochrane Library databases, and publications from 2001 to 2019 were included. Of all the studies analyzed, 28 were used to write the systematic review.Results. The increase in survival rates was mainly achieved due to the use of a multimodal approach to the treatment of gastric cancer. The effectiveness of this approach, which combined surgery with chemotherapy or chemoradiotherapy, was proven in several large clinical studies. However, despite the large number of treatment options for locally advanced gastric cancer, there is still no single standard for the management of patients with this disease. One of the treatment options successfully practiced in a number of leading countries is the use of adjuvant chemo/chemoradiation therapy.Conclusion. Analysis of the literature data of the last 18 years has shown the high relevance of studies on adjuvant chemotherapy for gastric cancer and the need to continue further study of this problem.

Risk factors for the continuation of S-1 adjuvant chemotherapy for gastric cancer analyzed from the JCOG1104 phase III trial.

196 Background: The phase III trial (JCOG1104), comparing between 4- (6 months) and 8-course (1 year) of S-1 as the adjuvant chemotherapy for pathological stage II gastric cancer, registered a total of 590 patients between Feb. 2012 and Mar. 2017 until the study was terminated due to futility at the interim analysis (relapse-free survival at 3 years: 93.1% in the 8-course group and 89.8% in the 4-course group). Non-inferiority of the 4-course to the 8-course was not shown, highlighting a continuation of S-1 adjuvant chemotherapy for one year. This preplanned exploratory study investigated the risk factors for time to treatment failure (TTF). Methods: TTF was defined as the time from randomization to the date of termination of S-1 before the planned treatment period, relapse, or any cause of death, whichever came first, and censored on the last date of contact for a surviving patient after completing the planned treatment or the last date of S-1 in the patients under the protocol treatment when the trial was closed. The risk factor of TTF was analyzed by Cox proportional hazard model using the variables of the planned treatment period, PS, age, sex, body weight loss (percentile of the body weight loss at the registration compared with that before surgery: BWL), albumin, lymphocyte count, creatinine clearance (Ccr), extent of gastrectomy (total gastrectomy vs. others), surgical approach (open vs. laparoscopic approach), and blood loss during surgery. As TTF did not reach 50%, proportion of treatment completion was compared. Results: Among 590 registered patients, this study included 530 patients (273 in the 8-course group and 257 in the 4-course group) by excluding 24 ineligible patients, 7 patients who did not start the protocol treatment, and 29 patients with unavailable data for variables. Proportion of treatment completion at 6 months estimated by Kaplan-Meier method were 89.2% in the 4-course group and 84.6% in the 8-course group ( P=0.1204), and that at 1 year was 73.6% in the 8-course group. Risk factors of TTF before 6M identified by multivariable analysis with stepwise selection method including both groups, in which all patients completed treatment were censored at 6 months, were the planned treatment period (4-courses vs. 8-course, HR 0.611, 95% Confidence interval (CI) 0.375-0.996, P=0.0482), age (continuous value, HR 1.039, 95% CI 1.004-1.074, P=0.0266), and Ccr (&lt;80 vs. &gt;80 ml/min, HR 1.943, 95% CI 1.105-3.415, P=0.0211). As for the TTF in the 8-course group, BWL (&gt;10% vs &lt;10%, HR 2.167, 95% CI 1.269-3.703, P=0.0046) and Ccr (&lt;80 vs. &gt;80 ml/min, HR 1.900, 95% CI 1.186-3.045, P=0.0076) were independent risk factors. Conclusions: Compared to 8-course, 4-course of S-1 adjuvant chemotherapy was associated with a higher 6-month proportion of treatment completion. When planning the adjuvant chemotherapy with S-1 for one year, BWL (&gt;10%) and low Ccr (&lt;80 ml/min) were risk factors for treatment failure. Clinical trial information: UMIN000007306.

An immune checkpoint score system for prognostic evaluation and adjuvant chemotherapy selection in gastric cancer

Immunosuppressive molecules are extremely valuable prognostic biomarkers across different cancer types. However, the diversity of different immunosuppressive molecules makes it very difficult to accurately predict clinical outcomes based only on a single immunosuppressive molecule. Here, we establish a comprehensive immune scoring system (ISSGC) based on 6 immunosuppressive ligands (NECTIN2, CEACAM1, HMGB1, SIGLEC6, CD44, and CD155) using the LASSO method to improve prognostic accuracy and provide an additional selection strategy for adjuvant chemotherapy of gastric cancer (GC). The results show that ISSGC is an independent prognostic factor and a supplement of TNM stage for GC patients, and it can improve their prognosis prediction accuracy; in addition, it can distinguish GC patients with better prognosis from those with high prognostic nutritional index score; furthermore, ISSGC can also be used as a tool to select GC patients who would benefit from adjuvant chemotherapy independent of their TNM stages, MSI status and EBV status.

Optimal time interval from surgery to adjuvant chemotherapy in gastric cancer.

The effect of adjuvant chemotherapy (AC) for resected gastric cancer is well established; however, delays in treatment and its impact on clinical outcomes have not yet been determined. The current study analyzed the survival rates based on time interval (TI) between surgery and AC administration to evaluate a potential association between the two variables. Patients diagnosed with stage II–III gastric adenocarcinoma between 2009 and 2016 at the Kyung Hee University Hospital were included. Patients' data including demographics, TNM stage, types of AC, and TI retrospectively collected from surgery to the start of AC. Patients were dichotomized based on the TI, which was predetermined at 3, 4, 5, 6, 7 or 8 weeks. Median disease-free survival (DFS) and overall survival (OS) were analyzed according to TI. In total, 172 patients were identified. The median follow-up duration was 40.8 (3–109) months. The median TI was 4.1 (2.1-9.8) weeks. DFS in patients with TI ≥4 weeks (n=106, 61.6%) was significantly lower compared with patients with TI <4 weeks (n=66, 38.4%), with a median DFS of TI < vs. ≥4 weeks of 8.1 vs. 6.0 years [hazard ratio (HR)=1.80, 95% confidence interval (CI): 1.067-3.045, P=0.0277]. OS was also significantly reduced in patients with TI ≥4 weeks, favoring TI <4 weeks [median OS of TI < vs. ≥4 weeks: Not reached (NR) vs. 7.0 years, HR=2.15, 95% CI: 1.173-3.939, P=0.0133]. Other predetermined TIs were not associated with survival outcomes. The current study demonstrated that AC within 4 weeks of surgery should be recommended for gastric cancer, and delays of >4 weeks may be detrimental to patients' survival.

P-229 Elderly population do benefit from adjuvant chemotherapy in gastric cancer: Experience in a single institution

Gastric cancer in Peru represents the 4th most common cause of cancer and the second most deadly. In elderly people, defined as people 65 years old or more, it is one of the most frequent malignant diseases and the age-adjusted mortality rate was reported to increase with age. Adjuvant chemotherapy showed survival benefit compared to surgery alone. Because of comorbidities or age-related toxicities, some oncologists hesitate to recommend elderly patients receive additional adjuvant chemotherapy.

Adjuvant chemotherapy in gastric cancer

Adjuvant chemotherapy in gastric cancer

Adjuvant Chemotherapy in Microsatellite Instability-High Gastric Cancer.

PurposeMicrosatellite instability (MSI) status may affect the efficacy of adjuvant chemotherapy in gastric cancer. In this study, the clinical characteristics of MSI-high (MSI-H) gastric cancer and the predictive value of MSI-H for adjuvant chemotherapy in large cohorts of gastric cancer patients were evaluated.Material and MethodsThis study consisted of two cohorts. Cohort 1 included gastric cancer patients who received curative resection with pathologic stage IB-IIIC. Cohort 2 included patients with MSI-H gastric cancer who received curative resection with pathologic stage II/III. MSI was examined using two mononucleotide markers and three dinucleotide markers.ResultsOf 359 patients (cohort 1), 41 patients (11.4%) had MSI-H. MSI-H tumors were more frequently identified in older patients (p < 0.001), other histology than poorly cohesive, signet ring cell type (p=0.005), intestinal type (p=0.028), lower third tumor location (p=0.005), and absent perineural invasion (p=0.027). MSI-H status has a tendency of better disease-free survival (DFS) and overall survival (OS) in multivariable analyses (hazard ratio [HR], 0.4; p=0.059 and HR, 0.4; p=0.063, respectively). In the analysis of 162 MSI-H patients (cohort 2), adjuvant chemotherapy showed a significant benefit with respect to longer DFS and OS (p=0.047 and p=0.043, respectively). In multivariable analysis, adjuvant chemotherapy improved DFS (HR, 0.4; p=0.040).ConclusionMSI-H gastric cancer had distinct clinicopathologic findings. Even in MSI-H gastric cancer of retrospective cohort, adjuvant chemotherapy could show a survival benefit, which was in contrast to previous prospective studies and should be investigated in a further prospective trial.

Development and Validation of a Deep Learning CT Signature to Predict Survival and Chemotherapy Benefit in Gastric Cancer: A Multicenter, Retrospective Study.

We aimed to develop a deep learning-based signature to predict prognosis and benefit from adjuvant chemotherapy using preoperative computed tomography (CT) images. Current staging methods do not accurately predict the risk of disease relapse for patients with gastric cancer. We proposed a novel deep neural network (S-net) to construct a CT signature for predicting disease-free survival (DFS) and overall survival in a training cohort of 457 patients, and independently tested it in an external validation cohort of 1158 patients. An integrated nomogram was constructed to demonstrate the added value of the imaging signature to established clinicopathologic factors for individualized survival prediction. Prediction performance was assessed with respect to discrimination, calibration, and clinical usefulness. The DeLIS was associated with DFS and overall survival in the overall validation cohort and among subgroups defined by clinicopathologic variables, and remained an independent prognostic factor in multivariable analysis (P< 0.001). Integrating the imaging signature and clinicopathologic factors improved prediction performance, with C-indices: 0.792-0.802 versus 0.719-0.724, and net reclassification improvement 10.1%-28.3%. Adjuvant chemotherapy was associated with improved DFS in stage II patients with high-DeLIS [hazard ratio = 0.362 (95% confidence interval 0.149-0.882)] and stage III patients with high- and intermediate-DeLIS [hazard ratio = 0.611 (0.442-0.843); 0.633 (0.433-0.925)]. On the other hand, adjuvant chemotherapy did not affect survival for patients with low-DeLIS, suggesting a predictive effect (Pinteraction = 0.048, 0.016 for DFS in stage II and III disease). The proposed imaging signature improved prognostic prediction and could help identify patients most likely to benefit from adjuvant chemotherapy in gastric cancer.

Efficacy of capecitabine and oxaliplatin versus S-1 as adjuvant chemotherapy in gastric cancer after D2 lymph node dissection according to lymph node ratio and N stage

BackgroundWe sought to assess the prognostic significance of lymph node ratio (LNR) and N stage in patients undergoing D2 gastrectomy and adjuvant chemotherapy, S-1, and XELOX and to compare the efficacy of them according to LNRs and N stages to evaluate the clinical impact of using LNRs compared with using N staging.MethodsPatients undergoing D2 gastrectomy with adequate lymph node dissection and adjuvant chemotherapy for stage II/III gastric cancer between Mar 2011 and Dec 2016 were analysed. Of the 477 patients enrolled, 331 received S-1 and 146 received XELOX. LNR groups were segregated as 0, 0–0.1, 0.1–0.25, and > 0.25 (LNR0, 1, 2, and 3, respectively). Propensity score matching (PSM) was used to minimise potential selection bias and compare DFS and OS stratified by LNRs and N stages in the two treatment groups.ResultsAfter PSM, the sample size of each group was 110 patients, and variables were well balanced. All patients had more than 15 examined lymph nodes (median 51, range 16~124). In multivariate analysis, LNR (> 0.25) and N stage (N3) showed independent prognostic value in OS and DFS, but LNR (> 0.25) showed better prognostic value. In subgroup analysis, the LNR3 group showed better 5-year DFS (20% vs 54%; HR 0.29; p = 0.004) and 5-year OS (26% vs 67%; HR 0.28; p = 0.020) in the XELOX group. The N3 group showed better 5-year DFS (38% vs 66%; HR 0.40; p = 0.004) and 5-year OS (47% vs 71%; HR 0.45; p = 0.019) in the XELOX group. Stage IIIC showed better 5-year DFS (22% vs 57%; HR 0.32; p = 0.004) and 5-year OS (27% vs 68%; HR 0.32; p = 0.009) in the XELOX group. The LNR3 group within N3 patients showed better 5-year DFS (21% vs 55%; HR 0.31; p = 0.004) and 5-year OS (27% vs 68%; HR 0.34; p = 0.018) in the XELOX group.ConclusionsLNR showed better prognostic value than N staging. LNR3, N3 and stage IIIC groups showed the superior efficacy of XELOX to that of S-1. And the LNR3 group within N3 patients showed more survival benefit from XELOX. LNR > 0.25, N3 stage and stage IIIC were the discriminant factors for selecting XELOX over S-1.Trial registrationNot applicable (retrospective study).

148P - Efficacy of capecitabine and oxaliplatin versus S-1 as adjuvant chemotherapy in gastric cancer after D2 lymph node dissection according to lymph node ratio and N stage

BackgroundThe purpose of this study was to compare Capecitabine and Oxaliplatin (XELOX) with S-1, based on disease-free survival (DFS) and overall survival (OS) in gastric cancer (GC). In addition, clinical impact of using lymph node ratios and compare it with N stage was investigated. MethodsPatients who had curative resection and received either S-1 or XELOX as adjuvant chemotherapy for advanced gastric cancer between Jan, 2011 and Dec, 2015, were analysed. Of the 412 patients enrolled, 301 received S-1 and 111 received XELOX. Lymph node ratio (LNR) groups were segregated as 0, 0-0.1, 0.1-0.25, and > 0.25 and named LNR 0,1,2 and 3, respectively. Propensity score matching (PSM) was used to minimize the influence of potential selection bias. The PSM compared DFS and OS in the two treatment groups, and enabled subgroup analysis according to clinical variables including the lymph node ratio group (LNR group) and N stage. ResultsIn PSM cohort, the sample size of each group was 86 patients and variables are well balanced. The XELOX group showed significantly better DFS (26.9% vs 59.3%, HR 0.43, 95% CI 0.20-0.90; p = 0.025) and better OS(30.8% vs 63.0%, HR 0.44, 95% CI 0.20-0.99; 0.045) in stage IIIC. The XELOX group showed significantly better DFS in all stage III. (54.7% vs 61.6%, HR 0.57,95% CI 0.33-0.99; p = 0.045). The N3 group showed significantly better DFS (40% vs 65.8%, HR 0.45, 95% CI, 0.23-0.86; p = 0.017) and better OS (44.7% vs 68.4%, HR 0.48, 95% CI, 0.24-0.97; p = 0.040) in the XELOX group. The LNR 3 group showed significantly better DFS in the XELOX group (26.3% vs 52.9% with HR 0.41 (95% CI, 0.17-0.97; p = 0.042). ConclusionsOur data suggested that current N staging and LNR could be a useful tool for selecting patients who can benefit from adjuvant XELOX after D2 gastrectomy when compared with S-1. When patients who are designated N3 or LNR > 0.25 or at stage IIIC, XELOX should be recommended over S-1. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.