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      Lymph Node Involvement in Advanced Gastric Cancer in the Era of Multimodal Treatment—Oncological and Surgical Perspective

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          Abstract

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          Gastric cancer (GC) continues to be one of the major oncological challenges on a global scale. The role of neoadjuvant chemotherapy (NAC) in GC is to downstage primary tumour, eliminate potential micrometastases, and increase the chance for radical resection. Although systemic treatment prolongs the survival in advanced GC, persistent lymph node (LN) metastases indicate poor prognosis. Therefore, further identification of prognostic factors after NAC is urgent and could positively influence clinical outcomes. This article aimed to review the actual trends and future perspectives in multimodal therapy of advanced GC, with a particular interest in the post-neoadjuvant pathological nodal stage. Since downstaged and primarily node-negative patients show a similar prognosis, the main target for NAC in advanced GC should be nodal clearance. Adequate staging and personalised perioperative therapy seem to be of great importance in the multimodal treatment of GC.

          Abstract

          Gastric cancer (GC) continues to be one of the major oncological challenges on a global scale. The role of neoadjuvant chemotherapy (NAC) in GC is to downstage primary tumour, eliminate potential micrometastases, and increase the chance for radical resection. Although systemic treatment prolongs the survival in advanced GC, persistent lymph node (LN) metastases indicate poor prognosis. Further identification of prognostic factors after NAC is urgent and could positively influence clinical outcomes. This article aimed to review the actual trends and future perspectives in multimodal therapy of advanced GC, with a particular interest in the post-neoadjuvant pathological nodal stage. A favourable prognostic impact for ypN0 patients is observed, either due to truly negative LN before the start of therapy or because preoperative therapy achieved a pathologically complete nodal response. Ongoing trials investigating the extent of lymphadenectomy after neoadjuvant therapy will standardise the LN dissection from the multimodal therapy perspective. Since downstaged and primarily node-negative patients show a similar prognosis, the main target for NAC in advanced GC should be nodal clearance. Adequate staging and personalised perioperative therapy seem to be of great importance in the multimodal treatment of GC.

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          Most cited references111

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          The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging.

          The American Joint Committee on Cancer (AJCC) staging manual has become the benchmark for classifying patients with cancer, defining prognosis, and determining the best treatment approaches. Many view the primary role of the tumor, lymph node, metastasis (TNM) system as that of a standardized classification system for evaluating cancer at a population level in terms of the extent of disease, both at initial presentation and after surgical treatment, and the overall impact of improvements in cancer treatment. The rapid evolution of knowledge in cancer biology and the discovery and validation of biologic factors that predict cancer outcome and response to treatment with better accuracy have led some cancer experts to question the utility of a TNM-based approach in clinical care at an individualized patient level. In the Eighth Edition of the AJCC Cancer Staging Manual, the goal of including relevant, nonanatomic (including molecular) factors has been foremost, although changes are made only when there is strong evidence for inclusion. The editorial board viewed this iteration as a proactive effort to continue to build the important bridge from a "population-based" to a more "personalized" approach to patient classification, one that forms the conceptual framework and foundation of cancer staging in the era of precision molecular oncology. The AJCC promulgates best staging practices through each new edition in an effort to provide cancer care providers with a powerful, knowledge-based resource for the battle against cancer. In this commentary, the authors highlight the overall organizational and structural changes as well as "what's new" in the Eighth Edition. It is hoped that this information will provide the reader with a better understanding of the rationale behind the aggregate proposed changes and the exciting developments in the upcoming edition. CA Cancer J Clin 2017;67:93-99. © 2017 American Cancer Society.
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            Gastric cancer

            Gastric cancer is the fifth most common cancer and the third most common cause of cancer death globally. Risk factors for the condition include Helicobacter pylori infection, age, high salt intake, and diets low in fruit and vegetables. Gastric cancer is diagnosed histologically after endoscopic biopsy and staged using CT, endoscopic ultrasound, PET, and laparoscopy. It is a molecularly and phenotypically highly heterogeneous disease. The main treatment for early gastric cancer is endoscopic resection. Non-early operable gastric cancer is treated with surgery, which should include D2 lymphadenectomy (including lymph node stations in the perigastric mesentery and along the celiac arterial branches). Perioperative or adjuvant chemotherapy improves survival in patients with stage 1B or higher cancers. Advanced gastric cancer is treated with sequential lines of chemotherapy, starting with a platinum and fluoropyrimidine doublet in the first line; median survival is less than 1 year. Targeted therapies licensed to treat gastric cancer include trastuzumab (HER2-positive patients first line), ramucirumab (anti-angiogenic second line), and nivolumab or pembrolizumab (anti-PD-1 third line).
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              Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer.

              A regimen of epirubicin, cisplatin, and infused fluorouracil (ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma. We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer. We randomly assigned patients with resectable adenocarcinoma of the stomach, esophagogastric junction, or lower esophagus to either perioperative chemotherapy and surgery (250 patients) or surgery alone (253 patients). Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin (50 mg per square meter of body-surface area) and cisplatin (60 mg per square meter) on day 1, and a continuous intravenous infusion of fluorouracil (200 mg per square meter per day) for 21 days. The primary end point was overall survival. ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer. Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group (46 percent and 45 percent, respectively), as were the numbers of deaths within 30 days after surgery. The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group. With a median follow-up of four years, 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died. As compared with the surgery group, the perioperative-chemotherapy group had a higher likelihood of overall survival (hazard ratio for death, 0.75; 95 percent confidence interval, 0.60 to 0.93; P=0.009; five-year survival rate, 36 percent vs. 23 percent) and of progression-free survival (hazard ratio for progression, 0.66; 95 percent confidence interval, 0.53 to 0.81; P<0.001). In patients with operable gastric or lower esophageal adenocarcinomas, a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival. (Current Controlled Trials number, ISRCTN93793971 [controlled-trials.com].). Copyright 2006 Massachusetts Medical Society.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                20 May 2021
                May 2021
                : 13
                : 10
                : 2509
                Affiliations
                Department of Surgical Oncology, Medical University of Lublin, Radziwiłłowska 13 St, 20-080 Lublin, Poland; zuzanna.torun@ 123456gmail.com (Z.P.); magdalenaskorzewska@ 123456umlub.pl (M.S.); wojciech.polkowski@ 123456umlub.pl (W.P.P.)
                Author notes
                [* ]Correspondence: karolrawiczpruszynski@ 123456umlub.pl ; Tel.: +48-81-531-81-26
                Author information
                https://orcid.org/0000-0002-2555-2114
                Article
                cancers-13-02509
                10.3390/cancers13102509
                8160868
                34065596
                3f2da156-c000-4c90-b0f4-3052b1dce5e0
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 09 May 2021
                : 19 May 2021
                Categories
                Review

                advanced gastric cancer,neoadjuvant chemotherapy,lymph node metastases

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