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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="Table of Contents Page" href="/books/n/pdqcis/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-pdqcis-lrg.png" alt="Cover of PDQ Cancer Information Summaries" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>PDQ Cancer Information Summaries [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK65766_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK65766_dtls__"><div>Bethesda (MD): <a href="http://www.cancer.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Cancer Institute (US)</a>; 2002-.</div></div><div class="half_rhythm"></div><div class="bk_noprnt"><form method="get" action="/books/n/pdqcis/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK65766_"><span class="title" itemprop="name">Gastric Cancer Treatment (PDQ®)</span></h1><div class="subtitle whole_rhythm">Health Professional Version</div><p class="contrib-group"><span itemprop="author">PDQ Adult Treatment Editorial Board</span>.</p><p class="small">Published online: February 2, 2018.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="_abs_rndgid_" itemprop="description"><p id="CDR0000062911__345">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of gastric cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.</p><p id="CDR0000062911__346">This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p></div><div id="CDR0000062911__1"><h2 id="_CDR0000062911__1_">General Information About Gastric Cancer</h2><div id="CDR0000062911__163"><h3>Incidence and Mortality</h3><p id="CDR0000062911__164">Estimated new cases and deaths from gastric cancer in the United States in 2018:[<a class="bk_pop" href="#CDR0000062911_rl_1_1">1</a>]</p><ul id="CDR0000062911__165"><li class="half_rhythm"><div>New cases: 26,240.</div></li><li class="half_rhythm"><div>Deaths: 10,800.</div></li></ul></div><div id="CDR0000062911__255"><h3>Epidemiology</h3><p id="CDR0000062911__256">Management of adenocarcinoma histology, which accounts for 90% to 95% of all gastric malignancies,
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is discussed in this summary. There are changing epidemiologic patterns in the United States regarding the anatomic location of esophagogastric cancers, with a trend of decreased occurrence of distal or noncardia gastric cancers.[<a class="bk_pop" href="#CDR0000062911_rl_1_2">2</a>] However, in persons aged 25 to 39 years, there has been an increase in the incidence of noncardia gastric cancers from 0.27 cases per 100,000 individuals (1977–1981) to 0.45 cases per 100,000 individuals (2002–2006).[<a class="bk_pop" href="#CDR0000062911_rl_1_2">2</a>] Additional studies are needed to confirm the observed increases in noncardia gastric cancers in this specific age group. </p><p id="CDR0000062911__340">In contrast to the overall stable trend for noncardia gastric cancers, earlier studies demonstrated an increased incidence of adenocarcinomas of the gastric cardia of 4% to 10% per year from the mid-1970s to the late 1980s.[<a class="bk_pop" href="#CDR0000062911_rl_1_3">3</a>] Similarly, the incidence of gastroesophageal junction adenocarcinomas increased sharply, from 1.22 cases per 100,000 individuals (1973–1978) to 2.00 cases per 100,000 individuals (1985–1990).[<a class="bk_pop" href="#CDR0000062911_rl_1_4">4</a>] Since that time, the incidence has remained steady at 1.94 cases per 100,000 individuals (2003–2008).[<a class="bk_pop" href="#CDR0000062911_rl_1_4">4</a>] More recent data demonstrate that the incidence of gastric cardia cancers has been relatively stable, although an increase has been observed, from 2.4 cases per 100,000 individuals (1977–1981) to 2.9 cases per 100,000 individuals (2001–2006) in the Caucasian population.[<a class="bk_pop" href="#CDR0000062911_rl_1_2">2</a>] The reasons for these temporal changes in incidence are unclear.</p></div><div id="CDR0000062911__166"><h3>Risk Factors</h3><p id="CDR0000062911__3">In the United States, gastric cancer ranks 14th in incidence among the major
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types of cancer. While the precise etiology is unknown,
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acknowledged risk factors for gastric cancer include the following:[<a class="bk_pop" href="#CDR0000062911_rl_1_5">5</a>-<a class="bk_pop" href="#CDR0000062911_rl_1_7">7</a>]
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</p><ul id="CDR0000062911__125"><li class="half_rhythm"><div><i>Helicobacter pylori</i>
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gastric infection. </div></li><li class="half_rhythm"><div>Advanced age. </div></li><li class="half_rhythm"><div>Male gender. </div></li><li class="half_rhythm"><div>Diet low in fruits and vegetables.</div></li><li class="half_rhythm"><div>Diet high in salted, smoked, or preserved foods.
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</div></li><li class="half_rhythm"><div>Chronic atrophic gastritis. </div></li><li class="half_rhythm"><div>Intestinal metaplasia.</div></li><li class="half_rhythm"><div>Pernicious anemia. </div></li><li class="half_rhythm"><div>Gastric adenomatous polyps.</div></li><li class="half_rhythm"><div>Family history of gastric cancer.</div></li><li class="half_rhythm"><div>Cigarette smoking. </div></li><li class="half_rhythm"><div>Menetrier disease (giant hypertrophic gastritis).
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</div></li><li class="half_rhythm"><div>Familial adenomatous polyposis.</div></li></ul></div><div id="CDR0000062911__167"><h3>Prognosis and Survival</h3><p id="CDR0000062911__5">The prognosis of patients with gastric cancer is related to tumor extent and
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includes both nodal involvement and direct tumor extension beyond the gastric
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wall.[<a class="bk_pop" href="#CDR0000062911_rl_1_8">8</a>,<a class="bk_pop" href="#CDR0000062911_rl_1_9">9</a>] Tumor grade may also provide some prognostic information.[<a class="bk_pop" href="#CDR0000062911_rl_1_10">10</a>]
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</p><p id="CDR0000062911__6">In localized distal gastric cancer, more than 50% of patients can be cured.
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However, early-stage disease accounts for only 10% to 20% of all cases
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diagnosed in the United States. The remaining patients present with metastatic
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disease in either regional or distant sites. The overall survival rate in
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these patients at 5 years ranges from almost no survival for patients with
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disseminated disease to almost 50% survival for patients with localized distal
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gastric cancers confined to resectable regional disease. Even with apparent
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localized disease, the 5-year survival rate of patients with proximal gastric
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cancer is only 10% to 15%. Although the treatment of patients with
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disseminated gastric cancer may result in palliation of symptoms and some
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prolongation of survival, long remissions are uncommon.
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</p><p id="CDR0000062911__9">Gastrointestinal stromal tumors occur most commonly in the stomach. (Refer to
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the PDQ summary on <a href="/books/n/pdqcis/CDR0000639481/">Gastrointestinal Stromal Tumors Treatment</a> for more information.)
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</p></div><div id="CDR0000062911__315"><h3>Related Summaries</h3><p id="CDR0000062911__316">Other PDQ summaries containing information related to gastric cancer include the following:</p><ul id="CDR0000062911__317"><li class="half_rhythm"><div><a href="/books/n/pdqcis/CDR0000062830/">Stomach (Gastric) Cancer Prevention</a>.</div></li><li class="half_rhythm"><div><a href="/books/n/pdqcis/CDR0000062757/">Stomach (Gastric) Cancer Screening</a>.</div></li><li class="half_rhythm"><div><a href="/books/n/pdqcis/CDR0000062872/#CDR0000062872__58">Unusual Cancers of Childhood</a> (childhood cancer of the stomach).</div></li></ul></div><div id="CDR0000062911_rl_1"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062911_rl_1_1">American Cancer Society: Cancer Facts and Figures 2018. Atlanta, Ga: American Cancer Society, 2018. <a href="https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-2018.pdf" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Available online</a>. Last accessed August 3, 2018.</div></li><li><div class="bk_ref" id="CDR0000062911_rl_1_2">Anderson WF, Camargo MC, Fraumeni JF Jr, et al.: Age-specific trends in incidence of noncardia gastric cancer in US adults. JAMA 303 (17): 1723-8, 2010. [<a href="/pmc/articles/PMC3142962/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3142962</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20442388" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20442388</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_1_3">Blot WJ, Devesa SS, Kneller RW, et al.: Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 265 (10): 1287-9, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/1995976" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1995976</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_1_4">Buas MF, Vaughan TL: Epidemiology and risk factors for gastroesophageal junction tumors: understanding the rising incidence of this disease. Semin Radiat Oncol 23 (1): 3-9, 2013. [<a href="/pmc/articles/PMC3535292/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3535292</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23207041" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23207041</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_1_5">Kurtz RC, Sherlock P: The diagnosis of gastric cancer. Semin Oncol 12 (1): 11-8, 1985. [<a href="https://pubmed.ncbi.nlm.nih.gov/3975641" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3975641</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_1_6">Scheiman JM, Cutler AF: Helicobacter pylori and gastric cancer. Am J Med 106 (2): 222-6, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10230753" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10230753</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_1_7">Fenoglio-Preiser CM, Noffsinger AE, Belli J, et al.: Pathologic and phenotypic features of gastric cancer. Semin Oncol 23 (3): 292-306, 1996. [<a href="https://pubmed.ncbi.nlm.nih.gov/8658213" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8658213</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_1_8">Siewert JR, Böttcher K, Stein HJ, et al.: Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study. Ann Surg 228 (4): 449-61, 1998. [<a href="/pmc/articles/PMC1191515/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1191515</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/9790335" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9790335</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_1_9">Nakamura K, Ueyama T, Yao T, et al.: Pathology and prognosis of gastric carcinoma. Findings in 10,000 patients who underwent primary gastrectomy. Cancer 70 (5): 1030-7, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1515980" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1515980</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_1_10">Adachi Y, Yasuda K, Inomata M, et al.: Pathology and prognosis of gastric carcinoma: well versus poorly differentiated type. Cancer 89 (7): 1418-24, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/11013353" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11013353</span></a>]</div></li></ol></div></div><div id="CDR0000062911__10"><h2 id="_CDR0000062911__10_">Cellular Classification of Gastric Cancer</h2><p id="CDR0000062911__243">There are two major types of gastric adenocarcinoma including the following:</p><ul id="CDR0000062911__244"><li class="half_rhythm"><div>Intestinal.</div></li><li class="half_rhythm"><div>Diffuse.</div></li></ul><p id="CDR0000062911__245"> Intestinal adenocarcinomas are well differentiated, and the cells tend to arrange themselves in tubular or glandular structures. The terms tubular, papillary, and mucinous are assigned to the various types of intestinal adenocarcinomas. Rarely, adenosquamous cancers can occur. </p><p id="CDR0000062911__246">Diffuse adenocarcinomas are undifferentiated or poorly differentiated, and they lack a gland formation. Clinically, diffuse adenocarcinomas can give rise to infiltration of the gastric wall (i.e., linitis plastica). </p><p id="CDR0000062911__247">Some tumors can have mixed features of intestinal and diffuse types.</p></div><div id="CDR0000062911__17"><h2 id="_CDR0000062911__17_">Stage Information for Gastric Cancer</h2><p id="CDR0000062911__383"><i>Note: The American Joint Committee on Cancer (AJCC) has published the 8<sup>th</sup> edition of the AJCC Cancer Staging Manual, which includes revisions to the staging for this disease. Implementation of the 8<sup>th</sup> edition began in January 2018. The PDQ Adult Treatment Editorial Board, which maintains this summary, is reviewing the revised staging and will make appropriate changes as needed.</i></p><div id="CDR0000062911__288"><h3>Definitions of TNM</h3><p id="CDR0000062911__290">The AJCC has designated staging by TNM (tumor, node, metastasis)
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classification to define gastric cancer.[<a class="bk_pop" href="#CDR0000062911_rl_17_1">1</a>-<a class="bk_pop" href="#CDR0000062911_rl_17_3">3</a>]</p><div id="CDR0000062911__284" class="table"><h3><span class="title">Table 1. Primary Tumor (T)<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65766.5/table/CDR0000062911__284/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062911__284_lrgtbl__"><table class="no_margin"><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">TX</td><td colspan="1" rowspan="1" style="vertical-align:top;">Primary tumor cannot be assessed.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T0</td><td colspan="1" rowspan="1" style="vertical-align:top;">No evidence of primary tumor.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Tis</td><td colspan="1" rowspan="1" style="vertical-align:top;">Carcinoma <i>in situ</i>: intraepithelial tumor without invasion of the lamina propria.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor invades lamina propria, muscularis mucosae, or submucosa.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1a</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor invades lamina propria or muscularis mucosae.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1b</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor invades submucosa.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor invades muscularis propria.<sup>b</sup></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor penetrates subserosal connective tissue without invasion of visceral peritoneum or adjacent structures.<sup>c,</sup><sup>d</sup></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T4</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor invades serosa (visceral peritoneum) or adjacent structures.<sup>c,</sup><sup>d</sup></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T4a</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor invades serosa (visceral peritoneum).</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T4b</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor invades adjacent structures.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Stomach. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 117-26.</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>b</sup>A tumor may penetrate the muscularis propria with extension into the gastrocolic or gastrohepatic ligaments, or into the greater or lesser omentum, without perforation of the visceral peritoneum covering these structures. In this case, the tumor is classified T3. If there is perforation of the visceral peritoneum covering the gastric ligaments or the omentum, the tumor should be classified T4.</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>c</sup>The adjacent structures of the stomach include the spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine, and retroperitoneum.</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>d</sup>Intramural extension to the duodenum or esophagus is classified by the depth of the greatest invasion in any of these sites, including the stomach.</p></div></dd></dl></div></div></div><div id="CDR0000062911__279" class="table"><h3><span class="title">Table 2. Regional Lymph Nodes (N)<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65766.5/table/CDR0000062911__279/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062911__279_lrgtbl__"><table class="no_margin"><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">NX</td><td colspan="1" rowspan="1" style="vertical-align:top;">Regional lymph node(s) cannot be assessed.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N0</td><td colspan="1" rowspan="1" style="vertical-align:top;">No regional lymph node metastasis.<sup>b</sup></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N1</td><td colspan="1" rowspan="1" style="vertical-align:top;">Metastases in 1–2 regional lymph nodes.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N2</td><td colspan="1" rowspan="1" style="vertical-align:top;">Metastases in 3–6 regional lymph nodes.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N3</td><td colspan="1" rowspan="1" style="vertical-align:top;">Metastases in ≥7 regional lymph nodes.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N3a</td><td colspan="1" rowspan="1" style="vertical-align:top;">Metastases in 7–15 regional lymph nodes.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N3b</td><td colspan="1" rowspan="1" style="vertical-align:top;">Metastases in ≥16 regional lymph nodes.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Stomach. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 117-26.</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>b</sup>A designation of pN0 should be used if all examined lymph nodes are negative, regardless of the total number removed and examined.</p></div></dd></dl></div></div></div><div id="CDR0000062911__280" class="table"><h3><span class="title">Table 3. Distant Metastasis<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65766.5/table/CDR0000062911__280/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062911__280_lrgtbl__"><table class="no_margin"><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td><td colspan="1" rowspan="1" style="vertical-align:top;">No distant metastasis.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M1</td><td colspan="1" rowspan="1" style="vertical-align:top;">Distant metastasis.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Stomach. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 117-26.</p></div></dd></dl></div></div></div><div id="CDR0000062911__281" class="table"><h3><span class="title">Table 4. Anatomic Stage/Prognostic Groups<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65766.5/table/CDR0000062911__281/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062911__281_lrgtbl__"><table class="no_margin"><thead><tr><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Stage</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">T</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">N</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">M</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">0</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tis</td><td colspan="1" rowspan="1" style="vertical-align:top;">N0</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"> IA</td><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">N0</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="2" style="vertical-align:top;">IB</td><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">N0</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="3" style="vertical-align:top;">IIA</td><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">N0</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">N2</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="4" style="vertical-align:top;"> IIB</td><td colspan="1" rowspan="1" style="vertical-align:top;">T4a</td><td colspan="1" rowspan="1" style="vertical-align:top;">N0</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">N2</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">N3</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="3" style="vertical-align:top;">IIIA</td><td colspan="1" rowspan="1" style="vertical-align:top;">T4a</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">N2</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">N3</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="4" style="vertical-align:top;"> IIIB</td><td colspan="1" rowspan="1" style="vertical-align:top;">T4b</td><td colspan="1" rowspan="1" style="vertical-align:top;">N0</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T4b</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T4a</td><td colspan="1" rowspan="1" style="vertical-align:top;">N2</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">N3</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="3" style="vertical-align:top;">IIIC</td><td colspan="1" rowspan="1" style="vertical-align:top;">T4b</td><td colspan="1" rowspan="1" style="vertical-align:top;">N2</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T4b</td><td colspan="1" rowspan="1" style="vertical-align:top;">N3</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T4a</td><td colspan="1" rowspan="1" style="vertical-align:top;">N3</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">IV</td><td colspan="1" rowspan="1" style="vertical-align:top;">Any T</td><td colspan="1" rowspan="1" style="vertical-align:top;">Any
|
|
N</td><td colspan="1" rowspan="1" style="vertical-align:top;">M1</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Stomach. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 117-26.</p></div></dd></dl></div></div></div></div><div id="CDR0000062911_rl_17"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062911_rl_17_1">Stomach. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, p 120.</div></li><li><div class="bk_ref" id="CDR0000062911_rl_17_2">Roder JD, Böttcher K, Busch R, et al.: Classification of regional lymph node metastasis from gastric carcinoma. German Gastric Cancer Study Group. Cancer 82 (4): 621-31, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9477092" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9477092</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_17_3">Ichikura T, Tomimatsu S, Uefuji K, et al.: Evaluation of the New American Joint Committee on Cancer/International Union against cancer classification of lymph node metastasis from gastric carcinoma in comparison with the Japanese classification. Cancer 86 (4): 553-8, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10440681" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10440681</span></a>]</div></li></ol></div></div><div id="CDR0000062911__49"><h2 id="_CDR0000062911__49_">Treatment Option Overview</h2><p id="CDR0000062911__253">Radical surgery represents the standard form of therapy that has curative intent.
|
|
However, the incidences of local failure in the tumor bed and regional lymph
|
|
nodes, and distant failures via hematogenous or peritoneal routes, remain
|
|
high.[<a class="bk_pop" href="#CDR0000062911_rl_49_1">1</a>] As such, adjuvant external-beam radiation therapy with combined chemotherapy has been
|
|
evaluated in the United States.</p><p id="CDR0000062911__168"> In a phase III Intergroup trial (SWOG-9008),
|
|
556 patients with completely resected stage IB to stage IV (M0) adenocarcinoma of
|
|
the stomach and gastroesophageal junction were randomly assigned to receive surgery
|
|
alone or surgery plus postoperative chemotherapy (5-fluorouracil [5-FU] and leucovorin) and
|
|
concurrent radiation therapy (45 Gy). With 5 years' median follow-up, a
|
|
significant survival benefit was reported for patients who received adjuvant combined modality
|
|
therapy.[<a class="bk_pop" href="#CDR0000062911_rl_49_2">2</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] Median survival was 36 months for the adjuvant chemoradiation
|
|
therapy group and 27 months for the surgery-alone arm (<i>P </i>= .005). Three-year
|
|
overall survival (OS) rates were 50%, and relapse-free survival rates were 48% with adjuvant
|
|
chemoradiation therapy versus 3-year OS rates of 41% and relapse-free survival rates of 31% for surgery alone (<i>P </i>= .005). The rate of distant metastases was 18% for the surgery-alone arm and 33% for the chemoradiation-therapy arm. Because distant disease remains a significant concern, the aim of the Cancer and Leukemia Group B study (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=258787" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CALGB-80101</a>) was to augment the postoperative chemoradiation therapy regimen used in INT-0116. Neoadjuvant
|
|
chemoradiation therapy such as in the <a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=67026" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RTOG-9904</a> trial, which is completed, and the SWOG-S0425 (<a href="https://clinicaltrials.gov/show/NCT00335959" title="Study NCT00335959" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT00335959</a>) trial, which is closed, was clinically evaluated.[<a class="bk_pop" href="#CDR0000062911_rl_49_3">3</a>]</p><p id="CDR0000062911__170">Investigators in Europe evaluated the role of preoperative and postoperative chemotherapy without radiation therapy.[<a class="bk_pop" href="#CDR0000062911_rl_49_4">4</a>] In the randomized phase III trial (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=63914" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MRC-ST02</a>), patients with stage II or higher adenocarcinoma of the stomach or of the lower third of the esophagus were assigned to receive three cycles of epirubicin, cisplatin, and continuous infusion 5-FU before and after surgery or to receive surgery alone. Compared with the surgery group, the perioperative chemotherapy group had a significantly higher likelihood of progression-free survival (hazard ratio [HR] for progression, 0.66; 95% confidence interval [CI], 0.53–0.81; <i>P</i> < .001) and of OS (HR<sub>death</sub>, 0.75; 95% CI, 0.60–0.93; <i>P</i> = .009). Five-year OS was 36.3%; 95% CI, 29 to 43 for the perioperative chemotherapy group and 23%; 95% CI, 16.6 to 29.4 for the surgery group.[<a class="bk_pop" href="#CDR0000062911_rl_49_4">4</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>]</p><div id="CDR0000062911_rl_49"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062911_rl_49_1">Gunderson LL, Sosin H: Adenocarcinoma of the stomach: areas of failure in a re-operation series (second or symptomatic look) clinicopathologic correlation and implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 8 (1): 1-11, 1982. [<a href="https://pubmed.ncbi.nlm.nih.gov/7061243" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7061243</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_49_2">Macdonald JS, Smalley SR, Benedetti J, et al.: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345 (10): 725-30, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11547741" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11547741</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_49_3">Ajani JA, Winter K, Okawara GS, et al.: Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol 24 (24): 3953-8, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16921048" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16921048</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_49_4">Cunningham D, Allum WH, Stenning SP, et al.: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355 (1): 11-20, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16822992" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16822992</span></a>]</div></li></ol></div></div><div id="CDR0000062911__51"><h2 id="_CDR0000062911__51_">Stage 0 Gastric Cancer</h2><p id="CDR0000062911__388"><div class="milestone-start" id="CDR0000062911__387"></div>Standard treatment options:</p><ul id="CDR0000062911__389"><li class="half_rhythm"><div>Surgery.</div></li></ul><div id="CDR0000062911__390"><h3>Surgery</h3><p id="CDR0000062911__391">Stage 0 is gastric cancer confined to mucosa. Experience in Japan, where stage
|
|
0 is diagnosed frequently, indicates that more than 90% of patients treated
|
|
by gastrectomy with lymphadenectomy will survive beyond 5 years. An American
|
|
series has confirmed these results.<div class="milestone-end"></div>[<a class="bk_pop" href="#CDR0000062911_rl_51_1">1</a>]</p></div><div id="CDR0000062911__TrialSearch_51_sid_5"><h3>Current Clinical Trials</h3><p id="CDR0000062911__TrialSearch_51_22">Use our <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/advanced-search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">advanced clinical trial search</a> to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General information</a> about clinical trials is also available.</p></div><div id="CDR0000062911_rl_51"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062911_rl_51_1">Green PH, O'Toole KM, Slonim D, et al.: Increasing incidence and excellent survival of patients with early gastric cancer: experience in a United States medical center. Am J Med 85 (5): 658-61, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3189369" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3189369</span></a>]</div></li></ol></div></div><div id="CDR0000062911__53"><h2 id="_CDR0000062911__53_">Stage I Gastric Cancer</h2><p id="CDR0000062911__393"><div class="milestone-start" id="CDR0000062911__392"></div>Standard treatment options:</p><ol id="CDR0000062911__394"><li class="half_rhythm"><div class="half_rhythm">One of the following surgical procedures:<ul id="CDR0000062911__395"><li class="half_rhythm"><div>Distal subtotal gastrectomy (if the lesion is not in the fundus or at the
|
|
cardioesophageal junction).
|
|
</div></li><li class="half_rhythm"><div>Proximal subtotal gastrectomy or total gastrectomy, both with distal
|
|
esophagectomy (if the lesion involves the cardia). These tumors often
|
|
involve the submucosal lymphatics of the esophagus.
|
|
</div></li><li class="half_rhythm"><div>Total gastrectomy (if the tumor involves the stomach diffusely or arises
|
|
in the body of the stomach and extends to within 6 cm of the
|
|
cardia or distal antrum).
|
|
</div></li></ul></div><div class="half_rhythm">Regional lymphadenectomy is recommended with all of the above procedures.
|
|
Splenectomy is not routinely performed.[<a class="bk_pop" href="#CDR0000062911_rl_53_1">1</a>]</div></li><li class="half_rhythm"><div class="half_rhythm">Postoperative chemoradiation therapy for patients with node-positive (T1 N1)
|
|
and muscle-invasive (T2 N0) disease.[<a class="bk_pop" href="#CDR0000062911_rl_53_2">2</a>]</div></li></ol><p id="CDR0000062911__398"><div class="milestone-start" id="CDR0000062911__397"></div>Surgical resection including regional lymphadenectomy is the treatment of
|
|
choice for patients with stage I gastric cancer.[<a class="bk_pop" href="#CDR0000062911_rl_53_1">1</a>] If the lesion is not in
|
|
the cardioesophageal junction and does not diffusely involve the stomach,
|
|
subtotal gastrectomy is the procedure of choice, because it has been demonstrated
|
|
to provide equivalent survival when compared with total gastrectomy and is
|
|
associated with decreased morbidity.[<a class="bk_pop" href="#CDR0000062911_rl_53_3">3</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] When the
|
|
lesion involves the cardia, proximal subtotal gastrectomy or total gastrectomy
|
|
(including a sufficient length of esophagus) may be performed with curative
|
|
intent. If the lesion diffusely involves the stomach, total gastrectomy is
|
|
required. At a minimum, surgical resection includes greater and lesser
|
|
curvature perigastric regional lymph nodes. Note that in patients with stage I
|
|
gastric cancer, perigastric lymph nodes may contain cancer.
|
|
<div class="milestone-end"></div></p><p id="CDR0000062911__400"><div class="milestone-start" id="CDR0000062911__399"></div>In patients with node-positive (T1 N1) and muscle-invasive (T2 N0) disease,
|
|
postoperative chemoradiation therapy may be considered. </p><ol id="CDR0000062911__405"><li class="half_rhythm"><div class="half_rhythm">A prospective
|
|
multi-institution phase III trial (SWOG-9008) evaluated postoperative combined
|
|
chemoradiation therapy versus surgery alone in 556 patients with completely resected
|
|
stage IB to stage IV (M0) adenocarcinoma of the stomach and gastroesophageal
|
|
junction and reported a significant survival benefit with adjuvant combined
|
|
modality therapy.[<a class="bk_pop" href="#CDR0000062911_rl_53_2">2</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] <ul id="CDR0000062911__406"><li class="half_rhythm"><div>With a median follow-up of 5
|
|
years, median survival was 36 months for the adjuvant chemoradiation therapy group and 27 months for the surgery-alone arm (<i>P </i>= .005). </div></li><li class="half_rhythm"><div>Three-year
|
|
overall survival (OS) rates were 50%, and relapse-free survival rates were 48% with adjuvant
|
|
chemoradiation therapy versus 3-year OS rates of 41% and relapse-free survival rates of 31% for surgery alone (<i>P </i>= .005). However, only
|
|
36 patients in the trial had stage IB tumors (18 patients in each arm).[<a class="bk_pop" href="#CDR0000062911_rl_53_4">4</a>] </div></li></ul></div><div class="half_rhythm">Since the
|
|
prognosis is relatively favorable for patients with completely resected stage
|
|
IB disease, the effectiveness of adjuvant chemoradiation therapy for this group is
|
|
less clear.<div class="milestone-end"></div></div></li></ol><div id="CDR0000062911__TrialSearch_53_sid_6"><h3>Current Clinical Trials</h3><p id="CDR0000062911__TrialSearch_53_22">Use our <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/advanced-search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">advanced clinical trial search</a> to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General information</a> about clinical trials is also available.</p></div><div id="CDR0000062911_rl_53"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062911_rl_53_1">Brennan MF, Karpeh MS Jr: Surgery for gastric cancer: the American view. Semin Oncol 23 (3): 352-9, 1996. [<a href="https://pubmed.ncbi.nlm.nih.gov/8658219" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8658219</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_53_2">Macdonald JS, Smalley SR, Benedetti J, et al.: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345 (10): 725-30, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11547741" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11547741</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_53_3">Bozzetti F, Marubini E, Bonfanti G, et al.: Subtotal versus total gastrectomy for gastric cancer: five-year survival rates in a multicenter randomized Italian trial. Italian Gastrointestinal Tumor Study Group. Ann Surg 230 (2): 170-8, 1999. [<a href="/pmc/articles/PMC1420871/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1420871</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/10450730" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10450730</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_53_4">Kelsen DP: Postoperative adjuvant chemoradiation therapy for patients with resected gastric cancer: intergroup 116. J Clin Oncol 18 (21 Suppl): 32S-4S, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/11060322" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11060322</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_53_5">Ajani JA, Winter K, Okawara GS, et al.: Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol 24 (24): 3953-8, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16921048" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16921048</span></a>]</div></li></ol></div></div><div id="CDR0000062911__63"><h2 id="_CDR0000062911__63_">Stage II Gastric Cancer</h2><p id="CDR0000062911__409"><div class="milestone-start" id="CDR0000062911__408"></div>Standard treatment options:</p><ol id="CDR0000062911__410"><li class="half_rhythm"><div class="half_rhythm">One of the following surgical procedures:<ul id="CDR0000062911__411"><li class="half_rhythm"><div>Distal subtotal gastrectomy (if the lesion is not in the fundus or at the
|
|
cardioesophageal junction).
|
|
</div></li><li class="half_rhythm"><div>Proximal subtotal gastrectomy or total gastrectomy (if the lesion
|
|
involves the cardia).
|
|
</div></li><li class="half_rhythm"><div>Total gastrectomy (if the tumor involves the stomach diffusely or arises
|
|
in the body of the stomach and extends to within 6 cm of the
|
|
cardia).
|
|
</div></li></ul></div><div class="half_rhythm">Regional lymphadenectomy is recommended with all of the above procedures.
|
|
Splenectomy is not routinely performed.[<a class="bk_pop" href="#CDR0000062911_rl_63_1">1</a>]</div></li><li class="half_rhythm"><div class="half_rhythm">Postoperative chemoradiation therapy.[<a class="bk_pop" href="#CDR0000062911_rl_63_2">2</a>]</div></li><li class="half_rhythm"><div class="half_rhythm">Perioperative chemotherapy.[<a class="bk_pop" href="#CDR0000062911_rl_63_3">3</a>]</div></li><li class="half_rhythm"><div class="half_rhythm"> Postoperative chemotherapy.</div></li></ol><p id="CDR0000062911__414"><div class="milestone-start" id="CDR0000062911__413"></div>Surgical resection with regional lymphadenectomy is the treatment of choice for
|
|
patients with stage II gastric cancer.[<a class="bk_pop" href="#CDR0000062911_rl_63_1">1</a>] If the lesion is not in the
|
|
cardioesophageal junction and does not diffusely involve the stomach, subtotal
|
|
gastrectomy is the procedure of choice. When the lesion involves the cardia,
|
|
proximal subtotal gastrectomy or total gastrectomy may be performed with
|
|
curative intent. If the lesion diffusely involves the stomach, total
|
|
gastrectomy and appropriate lymph node resection may be required. The role of
|
|
extended lymph node (D2) dissection is uncertain [<a class="bk_pop" href="#CDR0000062911_rl_63_4">4</a>] and in some series is
|
|
associated with increased morbidity.<div class="milestone-end"></div>[<a class="bk_pop" href="#CDR0000062911_rl_63_5">5</a>,<a class="bk_pop" href="#CDR0000062911_rl_63_6">6</a>]</p><p id="CDR0000062911__416"><div class="milestone-start" id="CDR0000062911__415"></div>Postoperative chemoradiation therapy may be considered for patients with stage II
|
|
gastric cancer. </p><ol id="CDR0000062911__418"><li class="half_rhythm"><div>A prospective
|
|
multi-institution phase III trial (SWOG-9008) evaluated postoperative combined chemoradiation therapy versus surgery alone in
|
|
556 patients with completely resected stage IB to stage IV (M0) adenocarcinoma of
|
|
the stomach and gastroesophageal junction and reported a significant survival
|
|
benefit with adjuvant combined modality therapy.[<a class="bk_pop" href="#CDR0000062911_rl_63_2">2</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] <ul id="CDR0000062911__419"><li class="half_rhythm"><div>With a median follow-up of
|
|
5 years, median survival was 36 months for the adjuvant chemoradiation therapy group and 27 months for the surgery-alone arm (<i>P</i> = .005). </div></li><li class="half_rhythm"><div>Three-year overall
|
|
survival (OS) rates were 50%, and relapse-free survival rates were 48% with adjuvant
|
|
chemoradiation therapy versus 3-year OS rates of 41% and relapse-free survival rates of 31% for surgery alone (<i>P </i>= .005).</div></li><li class="half_rhythm"><div>The rate of distant metastases was 32% for the surgery-alone arm and 40% for the chemoradiation therapy arm. Because distant disease remains a significant concern, the aim of the closed Cancer and Leukemia Group B study (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=258787" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CALGB-80101</a>) was to augment the postoperative chemoradiation therapy regimen used in SWOG-9008.[<a class="bk_pop" href="#CDR0000062911_rl_63_7">7</a>] </div></li></ul></div><div>Neoadjuvant
|
|
chemoradiation therapy remains under clinical evaluation, such as in the SWOG-S0425 (<a href="https://clinicaltrials.gov/show/NCT00335959" title="Study NCT00335959" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT00335959</a>) trial, which is closed and the <a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=67026" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RTOG-9904</a> trial, which is completed.<div class="milestone-end"></div>[<a class="bk_pop" href="#CDR0000062911_rl_63_8">8</a>]</div></li></ol><p id="CDR0000062911__422"><div class="milestone-start" id="CDR0000062911__421"></div>Investigators in Europe evaluated the role of preoperative and postoperative chemotherapy without radiation therapy.[<a class="bk_pop" href="#CDR0000062911_rl_63_3">3</a>] </p><ol id="CDR0000062911__424"><li class="half_rhythm"><div>In the randomized phase III trial (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=63914" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MRC-ST02</a>), patients with stage II or higher adenocarcinoma of the stomach or of the lower third of the esophagus were assigned to receive three cycles of epirubicin, cisplatin, and continuous infusion fluorouracil (ECF) before and after surgery or to receive surgery alone.<ul id="CDR0000062911__425"><li class="half_rhythm"><div>Compared with the surgery group, the perioperative chemotherapy group had a significantly higher likelihood of progression-free survival (hazard ratio [HR] for progression, 0.66; 95% confidence interval [CI], 0.53–0.81; <i>P </i>< .001) and of OS (HR for death, 0.75; 95% CI, 0.60–0.93; <i>P </i>= .009). </div></li><li class="half_rhythm"><div>Five-year OS was 36.3%, 95% CI, 29 to 43 for the perioperative chemotherapy group and 23%, 95% CI, 16.6 to 29.4 for the surgery group.[<a class="bk_pop" href="#CDR0000062911_rl_63_3">3</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>]</div></li></ul></div></li><li class="half_rhythm"><div>Japanese investigators randomly assigned 1,059 patients with stage II or III gastric cancer who had undergone a D2 gastrectomy to receive either 1 year of S-1, an oral fluoropyrimidine not available in the United States, or follow-up after surgery alone.[<a class="bk_pop" href="#CDR0000062911_rl_63_9">9</a>] Patients were randomly assigned in a 1:1 fashion. <ul id="CDR0000062911__426"><li class="half_rhythm"><div>The 3-year OS rate was 80.1% in the S-1 group and 70.1% in the surgery-only group. The HR for death in the S-1 group, as compared with the surgery-only group, was 0.68 (95% CI, 0.52–0.87; <i>P</i> = .003).[<a class="bk_pop" href="#CDR0000062911_rl_63_9">9</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>]</div></li></ul></div></li><li class="half_rhythm"><div>Subsequently, investigators in Asia evaluated the role of capecitabine/oxaliplatin as adjuvant therapy after gastric cancer resection. In the <a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=526882" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CLASSIC</a> (<a href="https://clinicaltrials.gov/show/NCT00411229" title="Study NCT00411229" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT00411229</a>) trial, 37 centers in South Korea, China, and Taiwan randomly assigned 1,035 patients with stage IIA, IIB, IIIA, or IIIB gastric cancer who had undergone a curative D2 gastrectomy to receive adjuvant chemotherapy (eight 3-week cycles of capecitabine plus oxaliplatin) or follow-up post-surgery alone.[<a class="bk_pop" href="#CDR0000062911_rl_63_10">10</a>] <ul id="CDR0000062911__427"><li class="half_rhythm"><div>The 3-year disease-free survival rate was 74% in the chemotherapy group and 59% in the surgery-alone group (HR, 0.56; 95% CI, 0.44–0.72; <i>P</i> < .0001). </div></li><li class="half_rhythm"><div>The 3-year OS was 83% in the chemotherapy group and 78% in the surgery-alone group (HR, 0.72; 95% CI, 0.52–1.00; <i>P</i> = .0493).[<a class="bk_pop" href="#CDR0000062911_rl_63_10">10</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] </div></li><li class="half_rhythm"><div>Further follow-up is anticipated.<div class="milestone-end"></div></div></li></ul></div></li></ol><div id="CDR0000062911__TrialSearch_63_sid_7"><h3>Current Clinical Trials</h3><p id="CDR0000062911__TrialSearch_63_22">Use our <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/advanced-search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">advanced clinical trial search</a> to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General information</a> about clinical trials is also available.</p></div><div id="CDR0000062911_rl_63"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062911_rl_63_1">Brennan MF, Karpeh MS Jr: Surgery for gastric cancer: the American view. Semin Oncol 23 (3): 352-9, 1996. [<a href="https://pubmed.ncbi.nlm.nih.gov/8658219" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8658219</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_63_2">Macdonald JS, Smalley SR, Benedetti J, et al.: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345 (10): 725-30, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11547741" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11547741</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_63_3">Cunningham D, Allum WH, Stenning SP, et al.: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355 (1): 11-20, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16822992" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16822992</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_63_4">Kitamura K, Yamaguchi T, Sawai K, et al.: Chronologic changes in the clinicopathologic findings and survival of gastric cancer patients. J Clin Oncol 15 (12): 3471-80, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/9396400" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9396400</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_63_5">Bonenkamp JJ, Songun I, Hermans J, et al.: Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients. Lancet 345 (8952): 745-8, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7891484" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7891484</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_63_6">Cuschieri A, Fayers P, Fielding J, et al.: Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial.The Surgical Cooperative Group. Lancet 347 (9007): 995-9, 1996. [<a href="https://pubmed.ncbi.nlm.nih.gov/8606613" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8606613</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_63_7">Fuchs C, Tepper JE, Niedwiecki D, et al.: Postoperative adjuvant chemoradiation for gastric or gastroesophageal adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and after CI 5-FU and radiotherapy (RT): interim toxicity results from Intergroup trial CALGB 80101. [Abstract] American Society of Clinical Oncology 2006 Gastrointestinal Cancers Symposium, 26-28 January 2006, San Francisco, California. A-61, 2006.</div></li><li><div class="bk_ref" id="CDR0000062911_rl_63_8">Ajani JA, Winter K, Okawara GS, et al.: Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol 24 (24): 3953-8, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16921048" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16921048</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_63_9">Sakuramoto S, Sasako M, Yamaguchi T, et al.: Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357 (18): 1810-20, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17978289" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17978289</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_63_10">Bang YJ, Kim YW, Yang HK, et al.: Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet 379 (9813): 315-21, 2012. [<a href="https://pubmed.ncbi.nlm.nih.gov/22226517" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22226517</span></a>]</div></li></ol></div></div><div id="CDR0000062911__73"><h2 id="_CDR0000062911__73_">Stage III Gastric Cancer</h2><p id="CDR0000062911__433"><div class="milestone-start" id="CDR0000062911__432"></div>Standard treatment options:</p><ol id="CDR0000062911__434"><li class="half_rhythm"><div> Radical surgery. Curative resection procedures are confined to patients who
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do not have extensive nodal involvement at the time of surgical exploration.</div></li><li class="half_rhythm"><div>Postoperative chemoradiation therapy.[<a class="bk_pop" href="#CDR0000062911_rl_73_1">1</a>]</div></li><li class="half_rhythm"><div>Perioperative chemotherapy.[<a class="bk_pop" href="#CDR0000062911_rl_73_2">2</a>]</div></li><li class="half_rhythm"><div>Postoperative chemotherapy.</div></li></ol><p id="CDR0000062911__436"><div class="milestone-start" id="CDR0000062911__435"></div>Surgery is the treatment of choice for all patients who have tumors that can be resected. As many as
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15% of selected stage III patients can be cured by surgery alone, particularly
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if lymph node involvement is minimal (<7 lymph nodes).
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<div class="milestone-end"></div></p><p id="CDR0000062911__438"><div class="milestone-start" id="CDR0000062911__437"></div>Postoperative chemoradiation therapy may be considered for patients with stage III
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gastric cancer. </p><ol id="CDR0000062911__472"><li class="half_rhythm"><div>A prospective
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multi-institution phase III trial (SWOG-9008) evaluating postoperative combined chemoradiation therapy versus surgery alone in
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556 patients with completely resected stage IB to stage IV (M0) adenocarcinoma of
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the stomach and gastroesophageal junction reported a significant survival
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benefit with adjuvant combined modality therapy.[<a class="bk_pop" href="#CDR0000062911_rl_73_1">1</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] <ul id="CDR0000062911__473"><li class="half_rhythm"><div>With a median follow-up of
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5 years, median survival was 36 months for the adjuvant chemoradiation therapy group and 27 months for the surgery-alone arm (<i>P </i>= .005).
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</div></li><li class="half_rhythm"><div>Three-year overall
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survival (OS) rates were 50%, and relapse-free survival rates were 48% with adjuvant
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chemoradiation therapy versus 3-year OS rates of 41% and relapse-free survival rates of 31% for surgery alone (<i>P </i>= .005). Because distant disease remains a significant concern, the aim of the Cancer and Leukemia Group B study (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=258787" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CALGB-80101</a>), which is closed, was to augment the postoperative chemoradiation therapyregimen used in the SWOG-9008 trial, for example, and the preoperative chemotherapy and chemoradiation therapy regimen used, for example, in the <a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=67026" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RTOG-9904</a> trial, which is now completed.<div class="milestone-end"></div></div></li></ul></div></li></ol><p id="CDR0000062911__440"><div class="milestone-start" id="CDR0000062911__439"></div>Investigators in Europe evaluated the role of preoperative and postoperative chemotherapy without radiation therapy.[<a class="bk_pop" href="#CDR0000062911_rl_73_2">2</a>]</p><ol id="CDR0000062911__442"><li class="half_rhythm"><div> In the randomized phase III trial (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=63914" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MRC-ST02</a>), patients with stage II or higher adenocarcinoma of the stomach or of the lower third of the esophagus were assigned to receive three cycles of epirubicin, cisplatin, and continuous infusion 5-fluorouracil (ECF) before and after surgery or to receive surgery alone. <ul id="CDR0000062911__443"><li class="half_rhythm"><div>Compared with the surgery group, the perioperative chemotherapy group had a significantly higher likelihood of progression-free survival (hazard ratio [HR] for progression, 0.66; 95% confidence interval [CI], 0.53–0.81; <i>P </i>< .001) and of OS (HR<sub>death</sub>, 0.75; 95% CI, 0.60–0.93; <i>P </i>= .009). </div></li><li class="half_rhythm"><div>Five-year OS was 36.3%; 95% CI, 29 to 43 for the perioperative chemotherapy group and 23%; 95% CI, 16.6 to 29.4 for the surgery group.[<a class="bk_pop" href="#CDR0000062911_rl_73_2">2</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>]</div></li></ul></div></li><li class="half_rhythm"><div>Japanese investigators randomly assigned 1,059 patients with stage II or III gastric cancer who had undergone a D2 gastrectomy to receive either 1 year of S-1, an oral fluoropyrimidine not available in the United States, or follow-up after surgery alone.[<a class="bk_pop" href="#CDR0000062911_rl_73_3">3</a>] Patients were randomly assigned in a 1:1 fashion. <ul id="CDR0000062911__444"><li class="half_rhythm"><div>The 3-year OS rate was 80.1% in the S-1 group and 70.1% in the surgery-only group. </div></li><li class="half_rhythm"><div>The HR<sub>death</sub> in the S-1 group, as compared with the surgery-only group, was 0.68 (95% CI, 0.52–0.87; <i>P</i> = .003).[<a class="bk_pop" href="#CDR0000062911_rl_73_3">3</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>]</div></li></ul></div></li><li class="half_rhythm"><div>Subsequently, investigators in Asia evaluated the role of capecitabine/oxaliplatin as adjuvant therapy after gastric cancer resection. In the <a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=526882" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CLASSIC</a> (<a href="https://clinicaltrials.gov/show/NCT00411229" title="Study NCT00411229" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT00411229</a>) trial , 37 centers in South Korea, China, and Taiwan randomly assigned 1,035 patients with stage IIA, IIB, IIIA, or IIIB gastric cancer who had undergone a curative D2 gastrectomy to receive adjuvant chemotherapy (eight 3-week cycles of capecitabine plus oxaliplatin) or follow-up post-surgery alone.[<a class="bk_pop" href="#CDR0000062911_rl_73_4">4</a>] <ul id="CDR0000062911__445"><li class="half_rhythm"><div>The 3-year disease-free survival rate was 74% in the chemotherapy group and 59% in the surgery-alone group (HR, 0.56; 95% CI, 0.44–0.72; <i>P</i> < .0001). </div></li><li class="half_rhythm"><div>The 3-year OS was 83% in the chemotherapy group and 78% in the surgery-alone group (HR, 0.72; 95% CI, 0.52–1.00; <i>P</i> = .0493).[<a class="bk_pop" href="#CDR0000062911_rl_73_4">4</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] </div></li><li class="half_rhythm"><div>Further follow-up is anticipated.<div class="milestone-end"></div></div></li></ul></div></li></ol><div id="CDR0000062911__TrialSearch_73_sid_8"><h3>Current Clinical Trials</h3><p id="CDR0000062911__TrialSearch_73_22">Use our <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/advanced-search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">advanced clinical trial search</a> to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General information</a> about clinical trials is also available.</p></div><div id="CDR0000062911_rl_73"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062911_rl_73_1">Macdonald JS, Smalley SR, Benedetti J, et al.: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345 (10): 725-30, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11547741" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11547741</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_73_2">Cunningham D, Allum WH, Stenning SP, et al.: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355 (1): 11-20, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16822992" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16822992</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_73_3">Sakuramoto S, Sasako M, Yamaguchi T, et al.: Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357 (18): 1810-20, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17978289" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17978289</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_73_4">Bang YJ, Kim YW, Yang HK, et al.: Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet 379 (9813): 315-21, 2012. [<a href="https://pubmed.ncbi.nlm.nih.gov/22226517" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22226517</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_73_5">Fuchs C, Tepper JE, Niedwiecki D, et al.: Postoperative adjuvant chemoradiation for gastric or gastroesophageal adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and after CI 5-FU and radiotherapy (RT): interim toxicity results from Intergroup trial CALGB 80101. [Abstract] American Society of Clinical Oncology 2006 Gastrointestinal Cancers Symposium, 26-28 January 2006, San Francisco, California. A-61, 2006.</div></li><li><div class="bk_ref" id="CDR0000062911_rl_73_6">Ajani JA, Winter K, Okawara GS, et al.: Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol 24 (24): 3953-8, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16921048" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16921048</span></a>]</div></li></ol></div></div><div id="CDR0000062911__81"><h2 id="_CDR0000062911__81_">Stage IV and Recurrent Gastric Cancer</h2><p id="CDR0000062911__451"><div class="milestone-start" id="CDR0000062911__450"></div>Standard treatment options:</p><ol id="CDR0000062911__452"><li class="half_rhythm"><div>Palliative chemotherapy with:<ul id="CDR0000062911__453"><li class="half_rhythm"><div>Fluorouracil (5-FU).[<a class="bk_pop" href="#CDR0000062911_rl_81_1">1</a>-<a class="bk_pop" href="#CDR0000062911_rl_81_3">3</a>]
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</div></li><li class="half_rhythm"><div>Epirubicin, cisplatin, and 5-FU (ECF).[<a class="bk_pop" href="#CDR0000062911_rl_81_4">4</a>,<a class="bk_pop" href="#CDR0000062911_rl_81_5">5</a>]
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</div></li><li class="half_rhythm"><div>Epirubicin, oxaliplatin, and capecitabine (EOX).[<a class="bk_pop" href="#CDR0000062911_rl_81_6">6</a>]</div></li><li class="half_rhythm"><div>Cisplatin and 5-FU (CF).[<a class="bk_pop" href="#CDR0000062911_rl_81_7">7</a>
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,<a class="bk_pop" href="#CDR0000062911_rl_81_3">3</a>]</div></li><li class="half_rhythm"><div>Docetaxel, cisplatin, and 5-FU.[<a class="bk_pop" href="#CDR0000062911_rl_81_8">8</a>]</div></li><li class="half_rhythm"><div>Etoposide, leucovorin, and 5-FU (ELF).[<a class="bk_pop" href="#CDR0000062911_rl_81_9">9</a>]
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</div></li><li class="half_rhythm"><div>5-FU, doxorubicin, and methotrexate (FAMTX).[<a class="bk_pop" href="#CDR0000062911_rl_81_7">7</a>]
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</div></li></ul>
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</div></li><li class="half_rhythm"><div>Trastuzumab, cisplatin, and either 5-FU or capecitabine in patients with HER2-positive tumors (3+ on immunohistochemistry [IHC] or fluorescence <i>in situ</i> hybridization [FISH]-positive). </div></li><li class="half_rhythm"><div>Endoluminal laser therapy, endoluminal stent placement, or gastrojejunostomy, may be helpful to
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patients with gastric obstruction.[<a class="bk_pop" href="#CDR0000062911_rl_81_10">10</a>]</div></li><li class="half_rhythm"><div>Palliative radiation therapy may alleviate bleeding, pain, and obstruction.
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</div></li><li class="half_rhythm"><div>Palliative resection is reserved for patients with continued bleeding
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or obstruction.
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</div></li></ol><p id="CDR0000062911__455"><div class="milestone-start" id="CDR0000062911__454"></div>Standard chemotherapy versus best supportive care for patients with metastatic gastric cancer has been tested in several clinical trials, and there is general agreement that patients who receive chemotherapy live for several months longer on average than patients who receive supportive care.[<a class="bk_pop" href="#CDR0000062911_rl_81_11">11</a>-<a class="bk_pop" href="#CDR0000062911_rl_81_13">13</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] During the last 20 years, multiple randomized studies evaluating different treatment regimens (monotherapy vs. combination chemotherapy) have been performed in patients with metastatic gastric cancer with no clear consensus emerging as to the best management approach. A meta-analysis of these studies demonstrated a hazard ratio (HR) of 0.83 for overall survival (OS) (95% confidence interval [CI], 0.74–0.93) in favor of combination chemotherapy.[<a class="bk_pop" href="#CDR0000062911_rl_81_14">14</a>]</p><ol id="CDR0000062911__475"><li class="half_rhythm"><div>Of all the combination regimens, ECF is often considered the reference standard in the United States and Europe. In one European trial, 274 patients with metastatic esophagogastric cancer were randomly assigned to receive either ECF or FAMTX.[<a class="bk_pop" href="#CDR0000062911_rl_81_15">15</a>] <ul id="CDR0000062911__476"><li class="half_rhythm"><div>The group who received ECF had a significantly longer median survival (8.9 vs. 5.7 months, <i>P</i> = .0009) than the FAMTX group.[<a class="bk_pop" href="#CDR0000062911_rl_81_15">15</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] </div></li></ul></div></li><li class="half_rhythm"><div>In a second trial that compared ECF with mitomycin, cisplatin, and 5-FU (MCF), there was no statistically significant difference in median survival (9.4 vs. 8.7 months, <i>P</i> = .315).[<a class="bk_pop" href="#CDR0000062911_rl_81_5">5</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] </div></li><li class="half_rhythm"><div>Oxaliplatin and capecitabine are often substituted for cisplatin and 5-FU within the ECF regimen on the basis of results from the REAL-2 trial (<a href="http://www.isrctn.com/ISRCTN51678883" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ISRCTN51678883</a>).[<a class="bk_pop" href="#CDR0000062911_rl_81_6">6</a>] This randomized trial of 1,002 patients with advanced esophageal, gastroesophageal (GE) junction, or gastric cancer utilized a 2 × 2 design to demonstrate noninferior median OS in patients treated with capecitabine rather than 5-FU (HR<sub>death</sub> = 0.86; 95% CI, 0.82–0.99) and in patients treated with oxaliplatin in place of cisplatin (HR<sub>death</sub> = 0.92; 95% CI, 0.80–1.10). </div></li><li class="half_rhythm"><div>An international collaboration of investigators randomly assigned 445 patients with metastatic gastric cancer to receive docetaxel, cisplatin, and 5-FU (DCF) or CF.[<a class="bk_pop" href="#CDR0000062911_rl_81_16">16</a>] Time-to-treatment progression (TTP) was the primary endpoint. <ul id="CDR0000062911__477"><li class="half_rhythm"><div>Patients who received DCF experienced a significantly longer TTP (5.6 months; 95% CI, 4.9–5.9; vs. 3.7 months; 95% CI, 3.4–4.5; HR, 1.47; 95% CI, 1.19–1.82; log-rank <i>P</i> < .001; risk reduction 32%). </div></li><li class="half_rhythm"><div>The median OS was significantly longer for patients who received DCF versus patients who received CF (9.2 months; 95% CI, 8.4–10.6; vs. 8.6 months; 95% CI, 7.2–9.5; HR, 1.29; 95% CI, 1.0–1.6; log-rank <i>P</i> = .02; risk reduction = 23%).[<a class="bk_pop" href="#CDR0000062911_rl_81_16">16</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] </div></li><li class="half_rhythm"><div>There were high toxicity rates in both arms.[<a class="bk_pop" href="#CDR0000062911_rl_81_17">17</a>] </div></li><li class="half_rhythm"><div>Febrile neutropenia was more common in patients who received DCF (29% vs. 12%), and the death rate on the study was 10.4% for patients on the DCF arm and 9.4% for patients on the CF arm.</div></li></ul></div></li><li class="half_rhythm"><div>Whether the CF regimen should be considered as an index regimen for the treatment of patients with metastatic gastric cancer is the subject of debate.[<a class="bk_pop" href="#CDR0000062911_rl_81_17">17</a>] The results of a study that randomly assigned 245 patients with metastatic gastric cancer to receive CF, FAMTX, or ELF demonstrated no significant difference in response rate, progression-free survival, or OS between the arms.[<a class="bk_pop" href="#CDR0000062911_rl_81_7">7</a>] <ul id="CDR0000062911__478"><li class="half_rhythm"><div>Grades 3 and 4 neutropenia occurred in 35% to 43% of patients on all arms, but severe nausea and vomiting was more common in patients in the CF arm and occurred in 26% of those patients.[<a class="bk_pop" href="#CDR0000062911_rl_81_7">7</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587983/" class="def">Level of evidence: 1iiDiv</a>]<div class="milestone-end"></div></div></li></ul></div></li></ol><div id="CDR0000062911__460"><h3>Trastuzumab</h3><ol id="CDR0000062911__480"><li class="half_rhythm"><div>In the open-label, international phase III <a href="https://clinicaltrials.gov/ct2/show/NCT01041404" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ToGA (Trastuzumab for Gastric Cancer</a> [<a href="https://clinicaltrials.gov/show/NCT01041404" title="Study NCT01041404" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT01041404</a>]) trial, patients with HER2-positive metastatic, inoperable locally advanced, or recurrent gastric or GE junction cancer were randomly assigned to chemotherapy with or without the anti-HER2 monoclonal antibody trastuzumab.[<a class="bk_pop" href="#CDR0000062911_rl_81_18">18</a>] HER2 positivity was defined as either 3+ staining by IHC or a HER2 to CEP17 ratio of two or more using FISH. Tumors from 3,665 patients were HER2 tested; of the patients, 810 were positive (22%) and 594 met eligibility criteria for randomization. Chemotherapy consisted of cisplatin plus 5-FU or capecitabine chosen at the investigator’s discretion. The study treatment was administered every 3 weeks for six cycles, and trastuzumab was continued every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. Crossover to trastuzumab at disease progression was not permitted. <ul id="CDR0000062911__481"><li class="half_rhythm"><div>Median OS was 13.8 months (95% CI, 12–16) in patients assigned to trastuzumab and 11.1 months (95% CI, 10–13) in patients assigned to chemotherapy alone (HR, 0.74; 95% CI, 0.60–0.91; <i>P</i> = .0046).[<a class="bk_pop" href="#CDR0000062911_rl_81_18">18</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] </div></li><li class="half_rhythm"><div>There was no significant difference in rates of any adverse event, and cardiotoxic effects were equally rare in both arms.</div></li></ul></div></li></ol></div><div id="CDR0000062911__462"><h3>Second-line Chemotherapy</h3><p id="CDR0000062911__463">When patients develop progression of disease after first-line chemotherapy, there is no standard treatment option. </p><ol id="CDR0000062911__483"><li class="half_rhythm"><div>Investigators in Korea randomly assigned patients with advanced gastric cancer who had received one or two prior chemotherapy regimens involving both a fluoropyrimidine and a platinum agent to either salvage chemotherapy or best supportive care in a 2:1 fashion.[<a class="bk_pop" href="#CDR0000062911_rl_81_19">19</a>] Salvage chemotherapy consisted of either docetaxel (60 mg/m<sup>2</sup> every 3 weeks) or irinotecan (150 mg/m<sup>2</sup> every 2 weeks) and was left to the discretion of the treating physicians. Of the 202 patients enrolled, 133 received salvage chemotherapy and 69 received best supportive care. <ul id="CDR0000062911__484"><li class="half_rhythm"><div>Median OS was 5.3 months in the group that received salvage chemotherapy and 3.8 months in the group that received best supportive care (HR, 0.657; <i>P</i> = .007). </div></li><li class="half_rhythm"><div>There was no difference in median OS between
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docetaxel and irinotecan (5.2 months vs. 6.5 months, <i>P</i> = .116).[<a class="bk_pop" href="#CDR0000062911_rl_81_19">19</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>]</div></li></ul></div></li></ol></div><div id="CDR0000062911__464"><h3>Ramucirumab</h3><p id="CDR0000062911__465">Ramucirumab is a fully humanized monoclonal antibody directed against the vascular endothelial growth factor receptor-2. </p><ol id="CDR0000062911__486"><li class="half_rhythm"><div class="half_rhythm">In the international, phase III, placebo-controlled, <a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=647442" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">REGARD</a> trial (<a href="https://clinicaltrials.gov/show/NCT00917384" title="Study NCT00917384" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT00917384</a>), 355 patients with stage IV gastric or GE junction cancer who had progressed on a first-line fluorouracil- or platinum-containing regimen were randomly assigned in a 2:1 fashion to ramucirumab or placebo.[<a class="bk_pop" href="#CDR0000062911_rl_81_20">20</a>] <ul id="CDR0000062911__487"><li class="half_rhythm"><div>Patients who were assigned to ramucirumab had a significantly improved median OS of 5.2 months compared with patients assigned to the placebo who had a median OS of 3.8 months (HR, 0.776; <i>P</i> = .047). </div></li><li class="half_rhythm"><div>Rates of hypertension were higher in the ramucirumab group than in the placebo group.[<a class="bk_pop" href="#CDR0000062911_rl_81_20">20</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] </div></li></ul></div><div class="half_rhythm">Ramucirumab is an acceptable treatment in cisplatin or 5-FU refractory, stage IV, gastric cancer.</div></li><li class="half_rhythm"><div class="half_rhythm">In the international, double-blinded, phase III <a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=682676" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RAINBOW</a> trial (<a href="https://clinicaltrials.gov/show/NCT01170663" title="Study NCT01170663" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT01170663</a>), 665 patients were randomly assigned to receive paclitaxel (80 mg/m<sup>2</sup>) on days 1, 8, and 15 every 28 days with ramucirumab (8 mg/kg) added on days 1 and 15 or a placebo added on days 1 and 15.[<a class="bk_pop" href="#CDR0000062911_rl_81_21">21</a>] <ul id="CDR0000062911__489"><li class="half_rhythm"><div>Patients assigned to ramucirumab had a significant improvement in median OS of 9.6 months compared with patients assigned to a placebo who had a median OS of 7.4 months (HR, 0.807; <i>P</i> = .017). </div></li><li class="half_rhythm"><div>Grade 3 or higher neutropenia, fatigue, hypertension, and abdominal pain were more common in the ramucirumab group.[<a class="bk_pop" href="#CDR0000062911_rl_81_21">21</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335106/" class="def">Level of Evidence: 1iA</a>]</div></li></ul>
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</div><div class="half_rhythm">The combination of paclitaxel and ramucirumab is an acceptable second-line-chemotherapy regimen in patients with stage IV gastric or GE junction cancer.<div class="milestone-end"></div></div></li></ol><p id="CDR0000062911__468"><div class="milestone-start" id="CDR0000062911__467"></div>Treatment options under clinical evaluation:</p><ul id="CDR0000062911__469"><li class="half_rhythm"><div>Palliative chemotherapy with:<ul id="CDR0000062911__470"><li class="half_rhythm"><div>Irinotecan and cisplatin.</div></li><li class="half_rhythm"><div>Folic acid, 5-FU, and irinotecan (FOLFIRI).</div></li><li class="half_rhythm"><div>Leucovorin, 5-FU, and oxaliplatin (FOLFOX).</div></li></ul></div></li></ul><p id="CDR0000062911__471">Phase II studies evaluating irinotecan-based or oxaliplatin-based regimens demonstrate similar response rates and TTP to those found with ECF or CF, but the former may be less toxic.[<a class="bk_pop" href="#CDR0000062911_rl_81_22">22</a>-<a class="bk_pop" href="#CDR0000062911_rl_81_27">27</a>] There are conflicting data regarding relative efficacy of any one regimen. Ongoing studies are evaluating these newer regimens. <div class="milestone-end"></div></p></div><div id="CDR0000062911__TrialSearch_81_sid_9"><h3>Current Clinical Trials</h3><p id="CDR0000062911__TrialSearch_81_22">Use our <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/advanced-search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">advanced clinical trial search</a> to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General information</a> about clinical trials is also available.</p></div><div id="CDR0000062911_rl_81"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062911_rl_81_1">Comis RL, Carter SK: Integration of chemotherapy into combined modality therapy of solid tumors. IV. Malignant melanoma. Cancer Treat Rev 1 (4): 285-304, 1974. [<a href="https://pubmed.ncbi.nlm.nih.gov/4619579" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4619579</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_81_2">Cullinan SA, Moertel CG, Fleming TR, et al.: A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma. Fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. JAMA 253 (14): 2061-7, 1985. [<a href="https://pubmed.ncbi.nlm.nih.gov/2579257" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2579257</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_81_3">Ohtsu A, Shimada Y, Shirao K, et al.: Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol 21 (1): 54-9, 2003. 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[<a href="/pmc/articles/PMC2033628/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2033628</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/7533517" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7533517</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_81_13">Glimelius B, Ekström K, Hoffman K, et al.: Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol 8 (2): 163-8, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/9093725" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9093725</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_81_14">Wagner AD, Grothe W, Haerting J, et al.: Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol 24 (18): 2903-9, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16782930" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16782930</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_81_15">Webb A, Cunningham D, Scarffe JH, et al.: Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 15 (1): 261-7, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/8996151" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8996151</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_81_16">Ajani JA, Moiseyenko VM, Tjulandin S, et al.: Clinical benefit with docetaxel plus fluorouracil and cisplatin compared with cisplatin and fluorouracil in a phase III trial of advanced gastric or gastroesophageal cancer adenocarcinoma: the V-325 Study Group. J Clin Oncol 25 (22): 3205-9, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17664467" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17664467</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_81_17">Ilson DH: Docetaxel, cisplatin, and fluorouracil in gastric cancer: does the punishment fit the crime? J Clin Oncol 25 (22): 3188-90, 2007. 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J Clin Oncol 30 (13): 1513-8, 2012. [<a href="https://pubmed.ncbi.nlm.nih.gov/22412140" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22412140</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_81_20">Fuchs CS, Tomasek J, Yong CJ, et al.: Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 383 (9911): 31-9, 2014. [<a href="https://pubmed.ncbi.nlm.nih.gov/24094768" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24094768</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_81_21">Wilke H, Muro K, Van Cutsem E, et al.: Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 15 (11): 1224-35, 2014. [<a href="https://pubmed.ncbi.nlm.nih.gov/25240821" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25240821</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_81_22">Ilson DH, Saltz L, Enzinger P, et al.: Phase II trial of weekly irinotecan plus cisplatin in advanced esophageal cancer. J Clin Oncol 17 (10): 3270-5, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10506629" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10506629</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_81_23">Beretta E, Di Bartolomeo M, Buzzoni R, et al.: Irinotecan, fluorouracil and folinic acid (FOLFIRI) as effective treatment combination for patients with advanced gastric cancer in poor clinical condition. Tumori 92 (5): 379-83, 2006 Sep-Oct. [<a href="https://pubmed.ncbi.nlm.nih.gov/17168428" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17168428</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_81_24">Pozzo C, Barone C, Szanto J, et al.: Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study. Ann Oncol 15 (12): 1773-81, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15550582" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15550582</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_81_25">Bouché O, Raoul JL, Bonnetain F, et al.: Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol 22 (21): 4319-28, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15514373" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15514373</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_81_26">Ajani JA, Baker J, Pisters PW, et al.: CPT-11 plus cisplatin in patients with advanced, untreated gastric or gastroesophageal junction carcinoma: results of a phase II study. Cancer 94 (3): 641-6, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/11857295" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11857295</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062911_rl_81_27">Cavanna L, Artioli F, Codignola C, et al.: Oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic gastric cancer (MGC). Am J Clin Oncol 29 (4): 371-5, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16891864" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16891864</span></a>]</div></li></ol></div></div><div id="CDR0000062911__122"><h2 id="_CDR0000062911__122_">Changes to This Summary (02/02/2018)</h2><p id="CDR0000062911__123">The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.</p><p id="CDR0000062911__384"><b><a href="#CDR0000062911__1">General Information About Gastric Cancer</a></b></p><p id="CDR0000062911__385">Updated <a href="#CDR0000062911__164">statistics</a> with estimated new cases and deaths for 2018 (cited American Cancer Society as reference 1).</p><p id="CDR0000062911__381"><b><a href="#CDR0000062911__17">Stage Information for Gastric Cancer</a></b></p><p id="CDR0000062911__386">An editorial change was made to this section.</p><p id="CDR0000062911__disclaimerHP_3">This summary is written and maintained by the <a href="http://www.cancer.gov/publications/pdq/editorial-boards/adult-treatment" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Adult Treatment Editorial Board</a>, which is
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editorially independent of NCI. The summary reflects an independent review of
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the literature and does not represent a policy statement of NCI or NIH. More
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information about summary policies and the role of the PDQ Editorial Boards in
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maintaining the PDQ summaries can be found on the <a href="#CDR0000062911__AboutThis_1">About This PDQ Summary</a> and <a href="http://www.cancer.gov/publications/pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ® - NCI's Comprehensive Cancer Database</a> pages.
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</p></div><div id="CDR0000062911__AboutThis_1"><h2 id="_CDR0000062911__AboutThis_1_">About This PDQ Summary</h2><div id="CDR0000062911__AboutThis_2"><h3>Purpose of This Summary</h3><p id="CDR0000062911__AboutThis_3">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of gastric cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.</p></div><div id="CDR0000062911__AboutThis_4"><h3>Reviewers and Updates</h3><p id="CDR0000062911__AboutThis_5">This summary is reviewed regularly and updated as necessary by the <a href="http://www.cancer.gov/publications/pdq/editorial-boards/adult-treatment" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Adult Treatment Editorial Board</a>, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p><p id="CDR0000062911__AboutThis_22"> Board members review recently published articles each month to determine whether an article should:</p><ul id="CDR0000062911__AboutThis_6"><li class="half_rhythm"><div>be discussed at a meeting,</div></li><li class="half_rhythm"><div>be cited with text, or</div></li><li class="half_rhythm"><div>replace or update an existing article that is already cited.</div></li></ul><p id="CDR0000062911__AboutThis_7">Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.</p><p>The lead reviewers for Gastric Cancer Treatment are:</p><ul><li class="half_rhythm"><div>Valerie Lee, MD (Johns Hopkins University)</div></li><li class="half_rhythm"><div>Jennifer Wo, MD (Massachusetts General Hospital)</div></li></ul><p id="CDR0000062911__AboutThis_9">Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.</p></div><div id="CDR0000062911__AboutThis_10"><h3>Levels of Evidence</h3><p id="CDR0000062911__AboutThis_11">Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a <a href="/books/n/pdqcis/CDR0000062796/">formal evidence ranking system</a> in developing its level-of-evidence designations.</p></div><div id="CDR0000062911__AboutThis_12"><h3>Permission to Use This Summary</h3><p id="CDR0000062911__AboutThis_13">PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”</p><p id="CDR0000062911__AboutThis_14">The preferred citation for this PDQ summary is:</p><p id="CDR0000062911__AboutThis_15">PDQ® Adult Treatment Editorial Board. PDQ Gastric Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: <a href="https://www.cancer.gov/types/stomach/hp/stomach-treatment-pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://www.cancer.gov/types/stomach/hp/stomach-treatment-pdq</a>. Accessed <MM/DD/YYYY>. [PMID: 26389209]</p><p id="CDR0000062911__AboutThis_16">Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in <a href="https://visualsonline.cancer.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Visuals Online</a>, a collection of over 2,000 scientific images.
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</p></div><div id="CDR0000062911__AboutThis_17"><h3>Disclaimer</h3><p id="CDR0000062911__AboutThis_18">Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the <a href="https://www.cancer.gov/about-cancer/managing-care" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Managing Cancer Care</a> page.</p></div><div id="CDR0000062911__AboutThis_20"><h3>Contact Us</h3><p id="CDR0000062911__AboutThis_21">More information about contacting us or receiving help with the Cancer.gov website can be found on our <a href="https://www.cancer.gov/contact" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Contact Us for Help</a> page. Questions can also be submitted to Cancer.gov through the website’s <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>.</p></div></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK65766.5/?report=reader">PubReader</a></li><li><a href="/books/NBK65766.5/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK65766" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK65766" style="display:none" title="Cite this Page"><div class="bk_tt">PDQ Adult Treatment Editorial Board. Gastric Cancer Treatment (PDQ®): Health Professional Version. 2018 Feb 2. In: PDQ Cancer Information Summaries [Internet]. 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ref="log$=inpage&link_id=inpage">Stage IV and Recurrent Gastric Cancer</a></li><li><a href="#CDR0000062911__122" ref="log$=inpage&link_id=inpage">Changes to This Summary (02/02/2018)</a></li><li><a href="#CDR0000062911__AboutThis_1" ref="log$=inpage&link_id=inpage">About This PDQ Summary</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related publications</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="document-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK65889/">Patient Version</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" 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class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/31661203" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Pediatric Gastric Cancer Treatment (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Pediatric Gastric Cancer Treatment (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Pediatric Treatment Editorial Board. </em><em 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