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      Recent advances in treating oesophageal cancer

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          Abstract

          Esophageal cancer (EC) is an aggressive malignancy with an increasing incidence and a poor prognosis. EC is histologically divided into two major categories: adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). EAC and ESCC are molecularly different and therefore treatments should reflect the respective histological subtype. Combined modality therapy is needed for localized EC. When EC is advanced (stage 4), systemic therapy is the mainstay treatment for palliation. For localized EC, several strategies are considered standard, and more trials are necessary to determine a unified and more effective approach. The management for advanced EC is slowly evolving as immunotherapy is showing some promise for ESCC, but more data from ongoing studies are anticipated. Treatment advances will be based on high-definition genomic investigation of individual tumors. Herein, we review the contemporary trends in diagnosing and treating EAC and ESCC.

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          Most cited references43

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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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            Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

            This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system 1 2 was adopted to define the strength of recommendations and the quality of evidence.
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              A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907).

              Patients with esophageal carcinoma receiving postoperative chemotherapy showed superior disease-free survival than those receiving surgery alone in a Japan Clinical Oncology Group trial (JCOG9204). The purpose of this study was to evaluate optimal perioperative timing-that is, before or after surgery-for providing chemotherapy in patients with locally advanced esophageal squamous cell carcinoma. Eligible patients with clinical stage II or III, excluding T4, squamous cell carcinoma were randomized to undergo surgery followed (group 1) or preceded (group 2) by chemotherapy consisting of two courses of cisplatin plus 5-fluorouracil. The primary end point was progression-free survival. We randomized 330 patients, with 166 assigned to group 1 and 164 to group 2, between May 2000 and May 2006. The planned interim analysis was conducted after completion of patient accrual. Progression-free survival did not reach the stopping boundary, but overall survival in group 2 was superior to that of group 1 (P = 0.01). Therefore, the Data and Safety Monitoring Committee recommended early publication. Updated analyses showed the 5-year overall survival to be 43% in group 1 and 55% in group 2 (hazard ratio 0.73, 95% confidence interval 0.54-0.99, P = 0.04), where the median follow-up of censored patients was 61.6 months. Concerning operative morbidity, renal dysfunction after surgery in group 2 was slightly higher than in group 1. Preoperative chemotherapy with cisplatin plus 5-fluorouracil can be regarded as standard treatment for patients with stage II/III squamous cell carcinoma.
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                Author and article information

                Contributors
                Role: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: Writing – Review & Editing
                Role: Writing – Review & Editing
                Role: Writing – Review & Editing
                Role: Writing – Review & Editing
                Role: SupervisionRole: Writing – Review & Editing
                Journal
                F1000Res
                F1000Research
                F1000Research
                F1000 Research Limited (London, UK )
                2046-1402
                1 October 2020
                2020
                : 9
                : F1000 Faculty Rev-1189
                Affiliations
                [1 ]Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
                [2 ]Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
                [3 ]Department of Pharmacy Clinical Program, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
                Author notes

                KH, JR, and JA conceived the review. KH prepared the first draft of the manuscript. All authors contributed to the preparation of the manuscript. All authors were involved in the revision of the draft manuscript and have agreed to the final content.

                No competing interests were disclosed.

                Author information
                https://orcid.org/0000-0001-5818-7072
                Article
                10.12688/f1000research.22926.1
                7531047
                33042518
                f0f3f88e-18c6-449d-aba5-3ad6f27a89ce
                Copyright: © 2020 Harada K et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 September 2020
                Funding
                Funded by: University of Texas MD Anderson Cancer Center
                Funded by: Japan Society for the Promotion of Science Overseas Research Fellowships
                Funded by: Department of Defense
                Award ID: CA150334andCA162445
                Funded by: Schecter Private Foundation
                Funded by: Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers
                Funded by: Kevin Fund
                Funded by: Rivercreek Foundation
                Funded by: Dio Fund
                Funded by: Myer Fund
                Funded by: Milrod Fund
                Funded by: National Cancer Institute
                Award ID: CA129906
                Award ID: CA127672
                Award ID: CA138671
                Award ID: CA172741
                This work was supported by generous grants from the Caporella, Dallas, Sultan, Park, Smith, Frazier, Oaks, Vanstekelenberg, Planjery, and Cantu families, as well as from the Schecter Private Foundation, Rivercreek Foundation, Kevin Fund, Myer Fund, Dio Fund, Milrod Fund, and The University of Texas MD Anderson Cancer Center (Houston, Texas, USA) multidisciplinary grant program. This research was also supported in part by National Cancer Institute grants CA129906, CA127672, CA138671, and CA172741; by Department of Defense grants CA150334 and CA162445 (J.A.A.); and by a grant from the Japan Society for the Promotion of Science Overseas Research Fellowships and Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers (K.H.).
                The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Review
                Articles

                esophageal cancer,esophageal adenocarcinoma,esophageal squamous cell carcinoma

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