Prognostic and predictive value of immunoscore signature in gastric cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15594-e15594 ◽  
Author(s):  
Xiaolong Qi ◽  
Yuming Jiang ◽  
Qi Zhang ◽  
Yanfeng Hu ◽  
Tuanjie Li ◽  
...  

e15594 Background: TNM staging system is not adequate to define the prognosis of patients with gastric cancer (GC). This system is also unable to predict whether the GC patients are likely to benefit from adjuvant chemotherapy. We postulated that ImmunoScore of GC (ISGC) could markedly improve the prediction of postsurgical survival and adjuvant chemotherapeutic benefits. Methods: 125 GC patients were enrolled as a training cohort to detect the expression of 27 immune features using immunohistochemistry and then constructed a five-feature-based ISGC using the LASSO Cox regression model. Internal validation cohort (126 specimens) and two external validation cohorts (628 specimens) were utilized to validate the prognostic and predictive value of ISGC. Results: We established the ISGC classifier based on the five features: CD3invasive margin (IM), CD3center of tumor (CT), CD8IM, CD45ROCT, and CD66bIM. The ISGC classifier could distinguish GC patients with high-ISGC from those with low-ISGC with significant differences in 5-year disease-free survival (45.0% v.s. 4.4%, p < 0.001) and 5-year overall survival (48.8% v.s. 6.7%, p < 0.001). According to the multivariate analysis, the ISGC classifier was proved to be an independent prognostic factor. A combination of ISGC and TNM had better prognostic value than TNM stage alone. In a further analysis, stage II and III GC patients with high-ISGC exhibited a favorable response to adjuvant chemotherapy. To provide a quantitative method to predict stage II and III GC patients’ probability of 3- and 5-year overall survival, we constructed two nomograms that integrated the ISGC and clinicopathological risk factors. Calibration plots showed that the nomograms performed well compared with an ideal model. The predictive accuracy and clinical usefulness of the nomograms were also demonstrated. Conclusions: The ISGC classifier could effectively predict recurrence and survival of GC, and complemented the prognostic value to TNM system. Moreover, the classifier might be a useful predictive tool to identify candidates with stage II and III GC who would benefit from adjuvant chemotherapy. Therefore, the ISGC might facilitate the counseling and personalize the postoperative management of GC patients.

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lei Chen ◽  
Chenghai Zhang ◽  
Zhendan Yao ◽  
Ming Cui ◽  
Jiadi Xing ◽  
...  

Abstract Background This study compared the long-term efficacy of different durations of adjuvant chemotherapy for patients with gastric cancer after radical gastrectomy with D2 lymphadenectomy. Methods We retrospectively identified 428 patients with stage II–III gastric cancer who underwent D2 gastrectomy between 2009 and 2016. Patients were divided into four groups according to the duration of adjuvant chemotherapy, including 0 week (no adjuvant, group A), 20 to 24 weeks (completed 7–8 cycles every 3 weeks or 10–12 cycles every 2 weeks, group B), and 12 to18 weeks (completed 4–6 cycles every 3 weeks or 6–9 cycles every 2 weeks, group C), and less than 12 weeks (received up to 3 cycles every 3 weeks or 5 cycles every 2 weeks, group D). The chemotherapy regimens included XELOX, SOX, and FOLFOX. 5-year overall survival (OS) and disease-free survival (DFS) were analyzed. Results The 5-year OS rates for groups A, B, C, and D were 52.3, 73.7, 72.0, and 53.3%, respectively, and the 5-year DFS rates were 50.0, 68.0, 65.4, and 50.0%, respectively. OS and DFS were higher in group B than in groups A and D. Similarly, patients in group C were more likely to have higher OS and DFS than those in groups A and D. Meanwhile, there were no significant differences in OS and DFS between groups B and C. The multivariate analysis confirmed with high statistical significance the efficacy of complete courses of adjuvant chemotherapy, and, among them, the similar impact of 4–6/6–9 and 7–8/10–12 cycles, resulting in similar HRs vs Group A (0.52 and 0.42, respectively). Conclusions To reduce toxicity and maintain efficacy, XELOX or SOX chemotherapy regimens administered for 4–6 cycles every 3 weeks or FOLFOX regimen for 6–9 cycles every 2 weeks might be a favorable option for patients with stage II–III gastric cancer after D2 gastrectomy. Prospective multicenter clinical trials with adequate sample sizes are necessary to verify these findings.


1999 ◽  
Vol 17 (12) ◽  
pp. 3810-3815 ◽  
Author(s):  
Lluís Cirera ◽  
Anna Balil ◽  
Eduard Batiste-Alentorn ◽  
Ignasi Tusquets ◽  
Teresa Cardona ◽  
...  

PURPOSE: The efficacy of adjuvant chemotherapy in gastric cancer is controversial. We conducted a phase III, randomized, multicentric clinical trial with the goal of assessing the efficacy of the combination of mitomycin plus tegafur in prolonging the disease-free survival and overall survival of patients with resected stage III gastric cancer. PATIENTS AND METHODS: Patients with resected stage III gastric adenocarcinoma were randomly assigned, using sealed envelopes, to receive either chemotherapy or no further treatment. Chemotherapy was started within 28 days after surgery according to the following schedule: mitomycin 20 mg/m2 intravenously (bolus) at day 1 of chemotherapy; 30 days later, oral tegafur at 400 mg bid daily for 3 months. Disease-free survival and overall survival were estimated using the Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: Between January 1988 and September 1994, 148 patients from 10 hospitals in Catalonia, Spain, were included in the study. The median follow-up period was 37 months. The tolerability of the treatment was excellent. The overall survival and disease-free survival were higher in the group of patients treated with chemotherapy (P = .04 for survival and P = .01 for disease-free survival in the log-rank test). The overall 5-year survival rate and the 5-year disease-free survival rate were, respectively, 56% and 51% in the treatment group and 36% and 31% in the control group. CONCLUSION: Our positive results are consistent with the results of recent studies; which conclude that there is a potential benefit from adjuvant chemotherapy in resected gastric cancer.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3548-3548
Author(s):  
Brandon Matthew Meyers ◽  
Humaid Obaid Al-Shamsi ◽  
Alvaro Tell Figueredo

3548 Background: Colon cancer is potentially curable by surgery in the early stages of the disease. Adjuvant chemotherapy improves disease-free and overall survival in patients with stage III disease, but the magnitude of benefit in stage II colon cancer is less clear. A previous Cochrane systematic review and meta-analysis (SR/MA) found improved disease-free, but not overall survival (Figueredo et al., 2008). An updated SR/MA was performed to determine the effects of adjuvant chemotherapy on disease-free and overall survival in patients with stage II colon cancer. Methods: Relevant databases (MEDLINE, EMBASE, and Cochrane) were independently searched by all authors, using the same search strategy employed in the original study (1/1988 to 9/2012). Randomized trials containing data on stage II colon cancer patients undergoing adjuvant 5-fluorouracil (5FU) chemotherapy versus observation were included. Pooled results were expressed as hazard ratios (HR) whenever possible, or risk ratios (RR), with 95% confidence intervals (95%CI) using a random effects model. Results: Seven studies were identified, and included in the final SR/MA. Six of the 7 studies were included in the disease-free survival analysis (n=4587). Adjuvant 5FU was associated with better disease-free survival (RR 0.84 (95%CI 0.75-0.94)). All 7 studies (n=5353) were included in the overall survival analysis showing an improvement with adjuvant 5FU (HR 0.87 (95%CI 0.78-0.97)). There was no evidence of heterogeneity across the studies (I2 = 0% for all analyses). Conclusions: In stage II colon cancer, adjuvant 5FU chemotherapy statistically improves both disease-free and overall survival. Our SR/MA demonstrates, for the first time, an overall survival advantage with adjuvant chemotherapy in stage II colon cancer.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 181-181
Author(s):  
Chun-Xia Du ◽  
Xiao-Yan Liu ◽  
Hong-Gang Zhang ◽  
Ai-Ping Zhou

181 Background: To compare the efficacy of docetaxel plus FOLFOX4 to FOLFOX4 as adjuvant chemotherapy for gastric cancer patients. Methods: 320 patients with stage IB-IV (M0) gastric cancer were enrolled into the retrospective study. All patients received a total or subtotal gastrectomy with at least D1 lymph nodes dissection. 193 patients received FOLFOX4 as adjuvant chemotherapy. 127 patients received biweekly docetaxel plus FOLFOX4 (DOF regimen) as adjuvant chemotherapy. Docetaxel was administered at 40 mg/m2 on day 1, followed by FOLFOX4 regimen. Both of the regimens were repeated every 2 weeks for a maximum of 12 cycles. Results: In comparison with patients in FOLFOX4 group, patients in DOF group were relatively younger (p=.001), with more advanced disease in pN stage (p=.035) and pTNM stage (p=.031), received more cycles of adjuvant chemotherapy (p=.004), and had a higher percentage of adjuvant radiation (p =.002). After adjustment of unbalanced variables as mentioned above, no statistical difference was observed between DOF group and FOLFOX4 group in terms of 3-year disease-free survival (54% vs 69%, p = 0.100, HR 1.362, 95% CI (0.943-1.967)) and 3-year overall survival(70% vs 72%, p = 0.810, HR 1.049, 95% CI (0.711-1.548)). Stratified analysis according to clinicopathologic characters showed that there were almost no statistical differences of 3-year overall survival rates between two groups, except the primary site (middle 1/3) (p =.025) and pTNM stage (IIb stage) (p =.035) in favor of FOLFOX4 group. The incidences of grade 3/4 adverse events were obviously higher in DOF group than in FOLFOX4 group,including decreased appetite (18.1% V 10.4%, P = 0.046), diarrhea (4.7% V 0%, p=0.004 ), hypersensitivity reactions to oxaliplatin (3.1% V 0%, p=0.024) and neutropenia (47.3% V 31.6%, p=0.004). Conclusions: Compared to FOLFOX4 regimen, adjuvant docetaxel plus FOLFOX4 did not show significant survival advantages in gastric cancer patients. However, a more serious toxicity profile was observed in docetaxel plus FOLFOX4 arm. Further studies are needed to decide whether triplet regimen is appropriate as adjuvant chemotherapy of gastric cancer.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 105-105
Author(s):  
Yukio Maezawa ◽  
Tsutomu Sato ◽  
Toru Aoyama ◽  
Kazuki Kano ◽  
Kenki Segami ◽  
...  

105 Background: ACTS-GC trial demonstrated that S-1 is effective as adjuvant chemotherapy for Japanese patients who have undergone curative D2 gastrectomy for gastric cancer and were diagnosed with pathological stage II disease. However, stages T1N2M0 and T1N3M0, which are classified as part of Stage II, were excluded from the ACTS-GC trial. The aim of the present study was to identify the unfavorable subset of patients with T1N2M0 and T1N3M0 gastric cancer for whom surgery alone is the standard treatment. Methods: The present study examined 59 patients who were diagnosed with T1N2M0 or T1N3M0 gastric cancer at Kanagawa Cancer Center and Yokohama City University Hospital between January 2000 and June 2010. Univariate and multivariate analyses were performed to identify risk factors for overall survival using a Cox proportional hazards model. Results: When overall survival was compared by the log-rank test, a significant difference was observed with regard to macroscopic tumor diameter. A macroscopic tumor diameter greater than 30mm was regarded as a critical point of classification considering the survival. Mulitivariate Cox’s proportional hazard analyses demonstrated that macroscopic tumor diameter was the only significant independent prognosticator. The five-year survival was 60.0% in patients with a macroscopic tumor diameter < 30mm, and 84.6% in those with a macroscopic tumor diameter > 30mm (P = 0.027). Conclusions: Among T1N2M0 and T1N3M0 gastric cancer patients for whom surgery alone is the standard treatment, having a small T1N2-3 tumor of less than 30 mm in diameter was the sole risk factor for gastric cancer survival. These tumors might be another target for adjuvant chemotherapy.


1995 ◽  
Vol 13 (11) ◽  
pp. 2757-2763 ◽  
Author(s):  
M Lise ◽  
D Nitti ◽  
A Marchet ◽  
T Sahmoud ◽  
M Buyse ◽  
...  

PURPOSE In a randomized clinical trial (European Organization for the Research and Treatment of Cancer [EORTC] no. 40813) on adjuvant chemotherapy in gastric cancer, results obtained after administration of the FAM2 regimen (fluorouracil [5-FU], doxorubicin, and mitomycin) were compared with results obtained after surgery alone to assess the effect of this regimen on overall survival, time to progression, and disease-free interval. PATIENTS AND METHODS Three hundred fourteen patients who had undergone curative resection for stage II or stage III (International Union Against Cancer [UICC] 1978) gastric adenocarcinoma were randomized to receive chemotherapy (treatment arm) or no further treatment (control arm). The chemotherapy schedule was repeated every 43 days for seven cycles. The log-rank test and the Cox model were used for statistical analysis. RESULTS Of 314 patients, 159 comprised the control group and 155 the FAM2 group. Nineteen FAM2 patients never received chemotherapy. The median number of cycles was five. Of the patients started on adjuvant treatment, severe hematologic and nonhematologic toxicity (grades 3 or 4, World Health Organization [WHO] scale) occurred, respectively, in 6% to 9% and in 1% to 29% of cases. The overall 5-year survival rate was 70% for stage II and 32% for stage III patients. No statistically significant difference was found between overall survival of the two treatment arms (P = .295). However, time to progression was significantly delayed in the FAM2 arm (P = .020) and disease-free survival showed borderline significance (P = .068). CONCLUSION FAM2, in view of its high toxicity, cannot be advocated as standard adjuvant treatment for gastric cancer. Large-scale clinical trials using more active, less toxic regimens are required to demonstrate whether adjuvant chemotherapy provides any real benefit.


2011 ◽  
Vol 29 (33) ◽  
pp. 4387-4393 ◽  
Author(s):  
Mitsuru Sasako ◽  
Shinichi Sakuramoto ◽  
Hitoshi Katai ◽  
Taira Kinoshita ◽  
Hiroshi Furukawa ◽  
...  

Purpose The first planned interim analysis (median follow-up, 3 years) of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer confirmed that the oral fluoropyrimidine derivative S-1 significantly improved overall survival, the primary end point. The results were therefore opened at the recommendation of an independent data and safety monitoring committee. We report 5-year follow-up data on patients enrolled onto the ACTS-GC study. Patients and Methods Patients with histologically confirmed stage II or III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive S-1 after surgery or surgery only. S-1 (80 to 120 mg per day) was given for 4 weeks, followed by 2 weeks of rest. This 6-week cycle was repeated for 1 year. The primary end point was overall survival, and the secondary end points were relapse-free survival and safety. Results The overall survival rate at 5 years was 71.7% in the S-1 group and 61.1% in the surgery-only group (hazard ratio [HR], 0.669; 95% CI, 0.540 to 0.828). The relapse-free survival rate at 5 years was 65.4% in the S-1 group and 53.1% in the surgery-only group (HR, 0.653; 95% CI, 0.537 to 0.793). Subgroup analyses according to principal demographic factors such as sex, age, disease stage, and histologic type showed no interaction between treatment and any characteristic. Conclusion On the basis of 5-year follow-up data, postoperative adjuvant therapy with S-1 was confirmed to improve overall survival and relapse-free survival in patients with stage II or III gastric cancer who had undergone D2 gastrectomy.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 164-164 ◽  
Author(s):  
Woo Jin Hyung ◽  
Taeil Son ◽  
Minseok Park ◽  
Hansang Lee ◽  
Youn Nam Kim ◽  
...  

164 Background: Staging systems for cancer are critical to predict the prognosis of patients. Current staging systems for gastric cancer have limitations to predict individualized and precise prediction of patient’s survival after treatment. We aimed to develop prediction model based on deep learning by estimating the survival probability of patients who underwent gastrectomy. Methods: To predict the survival probability, we used a deep neural network model which consisted of 5 layers: input layer, 3 fully connected layer, and output layer with 8 characteristics (age, sex, histology, depth of tumor, number of metastatic and examined lymph node, presence of distant metastasis, and resection extent) of patients which was previously published Yonsei prediction model using Cox regression. Each layer functioned as the nonlinear weighted sum of lower layer. Five-year overall survival was predicted using the deep learning method and it was compared to Yonsei prediction model. The average area under the curve (AUC) was compared between the models. For internal validation, 5-fold cross validations were carried out. We also performed external validation with a dataset from another hospital (n = 1549). . Results: Deep learning predicted 5-year overall survival of patients with an average accuracy of 83.5% in the test set. The average AUC of deep learning by integrating 8 characteristics was significantly higher than that of Yonsei prediction model (AUC: 0.844 vs. 0.831, P < 0.001) with the same variables. In the external validation the average accuracy of survival prediction was 84.1%. The AUC was also greater in a dataset from other hospital in Korea (AUC: 0.852 vs. 0.847, P = 0.023) Conclusions: Prognosis prediction with deep learning showed superior survival predictive power compared to prediction model using Cox regression. It can provide individualized and precise stratification based on the risk using characteristics of gastric cancer patients.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 294-294
Author(s):  
Chul Hyo Jeon ◽  
Han Hong Lee

294 Background: The role of controlling nutritional status (CONUT) score in predicting cancer survival remains uncertain. This study aimed to investigate the predictive value of the CONUT score and to develop a more appropriate scoring system beyond CONUT for gastric cancer (GC). Methods: We retrospectively reviewed 1307 patients who underwent curative gastrectomy between 2009 and 2015. The CONUT and three modified scores with modified lipid components (L-CONUT: albumin/total lymphocyte count [TLC]/low density lipoprotein, H-CONUT: albumin/TLC/high density lipoprotein, and T-CONUT: albumin/TLC/triglyceride) were calculated. The predictive value of each scoring system on long-term survival was assessed. Results: The values of the four nutritional scores were categorized into three groups (low, medium, and high). The CONUT (P < 0.001), L-CONUT (P < 0.001), H-CONUT (P < 0.001), and T-CONUT (P < 0.001) scores showed significant differences in overall survival in the three groups. Survival analysis according to the pathological stage showed that advanced age, Eastern Cooperative Oncology Group performance status, male sex, and high H-CONUT score (HR, 3.93; 95% CI, 1.81–8.55; P = 0.001) were independent worse prognostic factors for overall survival in the stage I group. In the stage II group, CONUT score (HR, 5.077; 95% CI, 1.65–15.65; P = 0.005) was significantly associated with poor prognosis. In the stage III group, no scoring system showed significant results. Conclusions: In advanced GC (beyond stage II), the prognostic impact of the nutritional scoring system was uncertain. However, the H-CONUT score is a promising indicator of prognosis in stage I GC, and the CONUT score is useful for predicting long-term survival in stage II GC.


Sign in / Sign up

Export Citation Format

Share Document