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      Indications for adjuvant chemotherapy in patients with AJCC stage IIa T3N0M0 and T1N2M0 gastric cancer—an east and west multicenter study

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          Abstract

          Purpose

          To determine the indications for adjuvant chemotherapy (AC) in patients with stage IIa gastric cancer (T3N0M0 and T1N2M0) according to the 7th American Joint Committee on Cancer (AJCC).

          Methods

          A total of 1593 patients with T3N0M0 or T1N2M0 stage gastric cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database for the period 1988.1–2012.12. Cox multiple regression, nomogram and decision curve analyses were performed. External validation was performed using databases of the Fujian Medical University Union Hospital (FJUUH) ( n = 241) and Italy IMIGASTRIC center ( n = 45).

          Results

          Cox multiple regression analysis showed that the risk factors that affected OS in patients receiving AC were age > 65 years old, T1N2M0, LN dissection number ≤ 15, tumor size > 20 mm, and nonadenocarcinoma. A nomogram was constructed to predict 5-year OS, and the patients were divided into those predicted to receive a high benefit (points ≤ 188) or a low benefit from AC (points > 188) according to a recursive partitioning analysis. OS was significantly higher for the high-benefit patients in the SEER database and the FJUUH dataset than in the non-AC patients (Log-rank < 0.05), and there was no significant difference in OS between the low-benefit patients and non-AC patients in any of the three centers (Log-rank = 0.154, 0.470, and 0.434, respectively). The decision curve indicated that the best clinical effect can be obtained when the threshold probability is 0–92%.

          Conclusion

          Regarding the controversy over whether T3N0M0 and T1N2M0 gastric cancer patients should be treated with AC, this study presents a predictive model that provides concise and accurate indications. These data show that high-benefit patients should receive AC.

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          Most cited references24

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          Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial.

          After curative resection, the prognosis of gastroesophageal adenocarcinoma is poor. This phase III trial was designed to evaluate the benefit in overall survival (OS) of perioperative fluorouracil plus cisplatin in resectable gastroesophageal adenocarcinoma. Overall, 224 patients with resectable adenocarcinoma of the lower esophagus, gastroesophageal junction (GEJ), or stomach were randomly assigned to either perioperative chemotherapy and surgery (CS group; n = 113) or surgery alone (S group; n = 111). Chemotherapy consisted of two or three preoperative cycles of intravenous cisplatin (100 mg/m(2)) on day 1, and a continuous intravenous infusion of fluorouracil (800 mg/m(2)/d) for 5 consecutive days (days 1 to 5) every 28 days and three or four postoperative cycles of the same regimen. The primary end point was OS. Compared with the S group, the CS group had a better OS (5-year rate 38% v 24%; hazard ratio [HR] for death: 0.69; 95% CI, 0.50 to 0.95; P = .02); and a better disease-free survival (5-year rate: 34% v 19%; HR, 0.65; 95% CI, 0.48 to 0.89; P = .003). In the multivariable analysis, the favorable prognostic factors for survival were perioperative chemotherapy (P = .01) and stomach tumor localization (P < .01). Perioperative chemotherapy significantly improved the curative resection rate (84% v 73%; P = .04). Grade 3 to 4 toxicity occurred in 38% of CS patients (mainly neutropenia) but postoperative morbidity was similar in the two groups. In patients with resectable adenocarcinoma of the lower esophagus, GEJ, or stomach, perioperative chemotherapy using fluorouracil plus cisplatin significantly increased the curative resection rate, disease-free survival, and OS.
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            Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial.

            D2 gastrectomy is recommended in US and European guidelines, and is preferred in east Asia, for patients with resectable gastric cancer. Adjuvant chemotherapy improves patient outcomes after surgery, but the benefits after a D2 resection have not been extensively investigated in large-scale trials. We investigated the effect on disease-free survival of adjuvant chemotherapy with capecitabine plus oxaliplatin after D2 gastrectomy compared with D2 gastrectomy only in patients with stage II-IIIB gastric cancer. The capecitabine and oxaliplatin adjuvant study in stomach cancer (CLASSIC) study was an open-label, parallel-group, phase 3, randomised controlled trial undertaken in 37 centres in South Korea, China, and Taiwan. Patients with stage II-IIIB gastric cancer who had had curative D2 gastrectomy were randomly assigned to receive adjuvant chemotherapy of eight 3-week cycles of oral capecitabine (1000 mg/m(2) twice daily on days 1 to 14 of each cycle) plus intravenous oxaliplatin (130 mg/m(2) on day 1 of each cycle) for 6 months or surgery only. Block randomisation was done by a central interactive computerised system, stratified by country and disease stage. Patients, and investigators giving interventions, assessing outcomes, and analysing data were not masked. The primary endpoint was 3 year disease-free survival, analysed by intention to treat. This study reports a prespecified interim efficacy analysis, after which the trial was stopped after a recommendation by the data monitoring committee. The trial is registered at ClinicalTrials.gov (NCT00411229). 1035 patients were randomised (520 to receive chemotherapy and surgery, 515 surgery only). Median follow-up was 34·2 months (25·4-41·7) in the chemotherapy and surgery group and 34·3 months (25·6-41·9) in the surgery only group. 3 year disease-free survival was 74% (95% CI 69-79) in the chemotherapy and surgery group and 59% (53-64) in the surgery only group (hazard ratio 0·56, 95% CI 0·44-0·72; p<0·0001). Grade 3 or 4 adverse events were reported in 279 of 496 patients (56%) in the chemotherapy and surgery group and in 30 of 478 patients (6%) in the surgery only group. The most common adverse events in the intervention group were nausea (n=326), neutropenia (n=300), and decreased appetite (n=294). Adjuvant capecitabine plus oxaliplatin treatment after curative D2 gastrectomy should be considered as a treatment option for patients with operable gastric cancer. F Hoffmann-La Roche and Sanofi-Aventis. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Decision curve analysis.

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                Author and article information

                Contributors
                +86-591-83363366 , hcmlr2002@163.com
                Journal
                BMC Gastroenterol
                BMC Gastroenterol
                BMC Gastroenterology
                BioMed Central (London )
                1471-230X
                2 December 2019
                2 December 2019
                2019
                : 19
                : 205
                Affiliations
                [1 ]ISNI 0000 0004 1758 0478, GRID grid.411176.4, Department of Gastric Surgery, Fujian Medical University Union Hospital, ; No. 29 Xinquan Road, Fuzhou, 350001 Fujian Province China
                [2 ]ISNI 0000 0004 1758 0478, GRID grid.411176.4, Department of General Surgery, , Fujian Medical University Union Hospital, ; Fuzhou, China
                [3 ]ISNI 0000 0004 1797 9307, GRID grid.256112.3, Key Laboratory of Ministry of Education of Gastrointestinal Cancer, , Fujian Medical University, ; Fuzhou, China
                [4 ]ISNI 0000 0004 1757 3630, GRID grid.9027.c, Department of Digestive Surgery, , St. Mary’s Hospital, University of Perugia, ; Terni, Italy
                Article
                1096
                10.1186/s12876-019-1096-8
                6889451
                31791240
                b5da51e2-9f12-45ed-8bbc-1b020eacdaf3
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 5 July 2019
                : 22 October 2019
                Funding
                Funded by: Scientific and technological innovation joint capital projects of Fujian Province
                Award ID: 2016Y9031
                Award Recipient :
                Funded by: Hubei Technological Innovation Special Fund (CN)
                Award ID: [2017]171
                Award Recipient :
                Funded by: General project of Miaopu scientific research fund of Fujian Medical University
                Award ID: 2015MP021
                Award Recipient :
                Funded by: Fujian province medical innovation project
                Award ID: 2015-CXB-16
                Award Recipient :
                Funded by: CARIT Foundation (Fondazione Cassa di Risparmio di Terni e Nami)
                Award ID: No.0024137
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Gastroenterology & Hepatology
                gastric cancer,adjuvant chemotherapy,t3n0m0 and t1n2m0,decision curve

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