Approach Considerations

Studies for staging of stomach cancer may include the following^[4]:

Upper gastrointestinal (GI) tract endoscopy and biopsy
Chest/abdomen/pelvic computed tomography (CT) with oral and intravenous contrast
Positron emission tomography (PET) – CT evaluation if no evidence of M1 disease is found, and if clinically indicated
Complete blood cell count (CBC) and comprehensive chemistry profile
Endoscopic ultrasound if no evidence of M1 disease is found
Endoscopic resection for early-stage cancers
Biopsy of metastatic disease as clinically indicated
Microsatellite instability (MSI) and deficient mismatch repair (dMMR) testing if metastatic disease is documented/suspected
HER2-neu and programmed death ligand 1 (PD-L1) testing if metastatic adenocarcinoma is documented or suspected

Imaging Studies

Esophagogastroduodenoscopy has a diagnostic accuracy of 95%. This relatively safe and simple procedure provides a permanent color photographic record of the lesion. This procedure is also the primary method for obtaining a tissue diagnosis of suspected lesions. Biopsy of any ulcerated lesion should include at least 6 specimens taken from around the lesion because of variable malignant transformation. In selected cases, endoscopic ultrasound may be helpful in assessing depth of penetration of the tumor or involvement of adjacent structures.

Double-contrast upper GI series and barium swallows may be helpful in delineating the extent of disease when obstructive symptoms are present or when bulky proximal tumors prevent passage of the endoscope to examine the stomach distal to an obstruction (more common with gastroesophageal [GE]-junction tumors). These studies are only 75% accurate and should for the most part be used only when upper GI endoscopy is not feasible.

Chest radiograph is done to evaluate for metastatic lesions.

CT scan or MRI of the chest, abdomen, and pelvis assess the local disease process as well as evaluate potential areas of spread (ie, enlarged lymph nodes, possible liver metastases).

Endoscopic ultrasound allows for a more precise preoperative assessment of the tumor stage. Endoscopic sonography is becoming increasingly useful as a staging tool when the CT scan fails to find evidence of T3, T4, or metastatic disease. Institutions that favor neoadjuvant chemoradiotherapy for patients with locally advanced disease rely on endoscopic ultrasound data to improve patient stratification.

In a study of peritoneal cancer (PC) diagnosis, investigators found that the administration of carbonated water for dual-time point imaging may improve the accuracy of FDG PET/CT scanning for PC in patients previously diagnosed with colorectal cancer (CRC).^[27]

Histologic Findings

Adenocarcinoma of the stomach constitutes 90-95% of all gastric malignancies. The second most common gastric malignancies are lymphomas. Gastrointestinal stromal tumors formerly classified as either leiomyomas or leiomyosarcomas account for 2% of gastric neoplasms (see Gastric Stromal Tumors). Carcinoids (1%), adenoacanthomas (1%), and squamous cell carcinomas (1%) are the remaining tumor histologic types.^[3]

Adenocarcinoma of the stomach is subclassified according to histologic description as follows: tubular, papillary, mucinous, or signet-ring cells, and undifferentiated lesions.

Pathology specimens are also classified by gross appearance. In general, researchers consider gastric cancers ulcerative, polypoid, scirrhous (ie, diffuse linitis plastica), superficial spreading, multicentric, or Barrett ectopic adenocarcinoma.

Researchers also employ a variety of other classification schemes. The Lauren system classifies gastric cancer pathology as either type I (intestinal) or type II (diffuse). An appealing feature of classifying patients according to the Lauren system is that the descriptive pathologic entities have clinically relevant differences.

Intestinal, expansive, epidemic-type gastric cancer is associated with chronic atrophic gastritis, retained glandular structure, little invasiveness, and a sharp margin. The pathologic presentation classified as epidemic by the Lauren system is associated with most environmental risk factors, carries a better prognosis, and shows no familial history.

The second type, diffuse, infiltrative, endemic cancer, consists of scattered cell clusters with poor differentiation and dangerously deceptive margins. Margins that appear clear to the operating surgeon and examining pathologist often are determined retrospectively to be involved. The endemic-type tumor invades large areas of the stomach. This type of tumor is also not recognizably influenced by environment or diet, is more virulent in women, and occurs more often in relatively young patients. This pathologic entity is associated with genetic factors (such as E-cadherin), blood groups, and a family history of gastric cancer.

In 2013, researchers identified a possible third type of gastric adenocarcinoma. In an analysis of 248 gastric tumors using microarray-based gene-expression profiling, Lei et al found that this third subtype of gastric adenocarcinoma (which they termed the "metabolic" subtype; the other 2 subtypes are mesenchymal and proliferative) preferentially responds to 5-fluorouracil (5-FU). The researchers validated their findings in an independent set of 70 gastric tumors.^{[28, 29, 30]}They believe that the preferential sensitivity of metabolic-subtype gastric cancers to 5-FU may be due to their significantly lower expression of thymidylate synthase and dihydropyrimidine dehydrogenase relative to the other 2 subtypes.^[28]

Staging

The 2017 American Joint Committee on Cancer (AJCC) Cancer Staging Manual presents the following TNM classification system for staging gastric carcinoma^[31]:

Primary tumor (T)

See the list below:

TX - Primary tumor cannot be assessed
T0 - No evidence of primary tumor
Tis - Carcinoma in situ, intraepithelial tumor without invasion of lamina propria
T1 - Tumor invades lamina propria, muscularis mucosae, or submucosa
T1a - Tumor invades lamina propria or muscularis mucosae
T1b - Tumor invades submucosa
T2 - Tumor invades muscularis propria
T3 - Tumor penetrates subserosal connective tissue without invasion of visceral peritoneum or adjacent structures
T4 - Tumor invades serosa (visceral peritoneum) or adjacent structures
T4a - Tumor invades serosa (visceral peritoneum)
T4b - Tumor invades adjacent structures/organs

Regional lymph nodes (N)

See the list below:

NX - Regional lymph node(s) cannot be assessed
N0 - No regional lymph node metastases
N1 - Metastases in 1-2 regional lymph nodes
N2 - Metastases in 3-6 regional lymph nodes
N3 - Metastases in 7 or more regional lymph nodes
N3a - Metastases in 7-15 regional lymph nodes
N3b - Metastases in 16 or more regional lymph nodes

Distant metastasis

See the list below:

M0 - No distant metastasis
M1 - Distant metastasis

Prognostic features

Two important factors influencing survival in resectable gastric cancer are depth of cancer invasion through the gastric wall and presence or absence of regional lymph node involvement.

In about 5% of primary gastric cancers, a broad region of the gastric wall or even the entire stomach is extensively infiltrated by malignancy, resulting in a rigid thickened stomach, termed linitis plastica. Patients with linitis plastica have an extremely poor prognosis.^[32]

Margins positive for presence of cancer are associated with a very poor prognosis.

The greater the number of involved lymph nodes, the more likely the patient is to develop local and systemic failure after surgery.

In a study by Shen and colleagues,^[33]the depth of tumor invasion and gross appearance, size, and location of the tumor were 4 pathologic factors independently correlated with the number of metastatic lymph nodes associated with gastric cancer.

Lee and colleagues found that surgical stage, as estimated during curative resection for gastric cancer, complemented the pathologically determined stage for determining prognosis. Survival was significantly poorer among patients with pathologic Stages II, IIIa, and IIIb disease in whom intraoperative staging overestimated the extent of pathological stage.^[34]

Clinical Staging

See the list below:

Stage 0 - Tis, N0, M0
Stage I - T1-2, N0, M0
Stage IIA - T1-2, N1-3, M0
Stage IIB - T3, N0, M0 or T4a, N0, M0
Stage III - T3, N0, M0 or; T4a, N1-3, M0
Stage IVA - T4b, any N, M0
Stage IVB - Any T, any N, M1

For pathologic and post-neoadjuvant therapy stage grouping, see Gastric Cancer Staging

Survival rates

See the list below:

Stage IA - 94%
Stage IB - 88%
Stage IIA - 82%
Stage IIB - 68%
Stage IIIA - 54%
Stage IIIB - 36%
Stage IIIC - 18%
Stage IV - 5%

Spread patterns

Cancer of the stomach can spread directly, via lymphatics, or hematogenously. Features of spread include the following:

Direct extension into the omenta, pancreas, diaphragm, transverse colon or mesocolon, and duodenum is common
If the lesion extends beyond the gastric wall to a free peritoneal (ie, serosal) surface, then peritoneal involvement is frequent
The visible gross lesion frequently underestimates the true extent of the disease
The abundant lymphatic channels within the submucosal and subserosal layers of the gastric wall allow for easy microscopic spread
The submucosal plexus is prominent in the esophagus and the subserosal plexus is prominent in the duodenum, allowing proximal and distal spread
Lymphatic drainage is through numerous pathways and can involve multiple nodal groups (eg, gastric, gastroepiploic, celiac, porta hepatic, splenic, suprapancreatic, pancreaticoduodenal, paraesophageal, and paraaortic lymph nodes)
Hematogenous spread commonly results in liver metastases

Laboratory Studies

The goal of obtaining laboratory studies is to assist in determining optimal therapy. Useful studies may include the following:

A complete blood cell count (CBC) can identify anemia, which is present in approximately 30% of patients and may be caused by bleeding, liver dysfunction, or poor nutrition
Electrolyte panels and liver function tests also are essential to better characterize the patient's clinical state
Carcinoembryonic antigen (CEA) is increased in 45-50% of cases
Cancer antigen (CA) 19-9 is elevated in about 20% of cases

Distinctive serum glycan patterns may have the potential to serve as markers for gastric cancer risk. In a study of 72 serum samples from patients with gastric cancer, nonatrophic gastritis, or duodenal ulcer, Ozcan and colleagues found that abnormal patterns of serum glycans (sugars attached to proteins) may be useful as a screening tool for identifying patients with Helicobacter pylori infection who are at risk for stomach cancer.^{[35, 36]}

A total of 19 significant differences in serum glycan expression were found between gastric cancer patients and individuals with asymptomatic nonatrophic gastritis. High-mannose–type glycans, glycans with 1 complex type antenna, and bigalactosylated biantennary glycans tended to be lower in gastric cancer patients, whereas levels of nongalactosylated biantennary glycans were higher. Altered serum glycan levels were also seen in study patients with ulcers.^{[35, 36]}

Treatment & Management

World Health Organization. Cancer. WHO. Available at http://www.who.int/mediacentre/factsheets/fs297/en/. February 3, 2022; Accessed: April 17, 2023.
Surveillance, Epidemiology, and End Results Program. SEER Stat Fact Sheets: Stomach Cancer. National Cancer Institute. Available at http://seer.cancer.gov/statfacts/html/stomach.html. Accessed: April 17, 2023.
Avital I, Stojadinovic A, Pisters PWT, Kelsen DP, Willett CG. Cancer of the Stomach. DeVita VT, Lawrence TS, Rosenberg SA. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, PA: Wolters Kluwer; 2015. 613-42.
[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer. NCCN. Available at http://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf. Version 1.2023 — March 10, 2023; Accessed: April 17, 2023.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May. 71 (3):209-249. [QxMD MEDLINE Link]. [Full Text].
Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6. 345(10):725-30. [QxMD MEDLINE Link].
Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6. 355(1):11-20. [QxMD MEDLINE Link].
Ooi CH, Ivanova T, Wu J, Lee M, Tan IB, Tao J, et al. Oncogenic pathway combinations predict clinical prognosis in gastric cancer. PLoS Genet. 2009 Oct. 5(10):e1000676. [QxMD MEDLINE Link]. [Full Text].
Song H, Ekheden IG, Zheng Z, Ericsson J, Nyrén O, Ye W. Incidence of gastric cancer among patients with gastric precancerous lesions: observational cohort study in a low risk Western population. BMJ. 2015 Jul 27. 351:h3867. [QxMD MEDLINE Link]. [Full Text].
Correa P. Diet modification and gastric cancer prevention. J Natl Cancer Inst Monogr. 1992. 75-8. [QxMD MEDLINE Link].
Buiatti E, Palli D, Decarli A, Amadori D, Avellini C, Bianchi S, et al. A case-control study of gastric cancer and diet in Italy. Int J Cancer. 1989 Oct 15. 44(4):611-6. [QxMD MEDLINE Link].
Steevens J, Schouten LJ, Goldbohm RA, van den Brandt PA. Alcohol consumption, cigarette smoking and risk of subtypes of oesophageal and gastric cancer: a prospective cohort study. Gut. 2010 Jan. 59(1):39-48. [QxMD MEDLINE Link].
González CA, Pera G, Agudo A, Palli D, Krogh V, Vineis P, et al. Smoking and the risk of gastric cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC). Int J Cancer. 2003 Nov 20. 107(4):629-34. [QxMD MEDLINE Link].
Wu X, Zeng Z, Chen B, Yu J, Xue L, Hao Y, et al. Association between polymorphisms in interleukin-17A and interleukin-17F genes and risks of gastric cancer. Int J Cancer. 2009 Nov 10. [QxMD MEDLINE Link].
Usui Y, Taniyama Y, Endo M, et al. Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer. N Engl J Med. 2023 Mar 30. 388 (13):1181-1190. [QxMD MEDLINE Link].
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, Schistosom. Vol 61 of IARC monographs on the evaluation of carcinogenic risks to humans. International Agency for Research on Cancer, Lyon, 1994. J Clin Oncol. 2004. 22:2069.
Harrison P. H pylori Therapy Reduces Gastric Cancer in High-Risk Patients. Medscape Medical News. Available at https://www.medscape.com/viewarticle/924545. January 30, 2020; Accessed: February 5, 2020.
Choi IJ, Kim CG, Lee JY, Kim YI, Kook MC, Park B, et al. Family History of Gastric Cancer and Helicobacter pylori Treatment. N Engl J Med. 2020 Jan 30. 382 (5):427-436. [QxMD MEDLINE Link].
Cheung KS, Chan EW, Wong AYS, Chen L, Wong ICK, Leung WK. Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study. Gut. Available at http://gut.bmj.com/content/early/2017/09/18/gutjnl-2017-314605. October 31, 2017; Accessed: November 1, 2017.
Stomach (Gastric) Cancer Prevention (PDQ®) - Health Professional Version. National Cancer Institute. Available at http://www.cancer.gov/cancertopics/pdq/prevention/gastric/HealthProfessional. September 21, 2018; Accessed: February 27, 2019.
Neugut AI, Hayek M, Howe G. Epidemiology of gastric cancer. Semin Oncol. 1996 Jun. 23(3):281-91. [QxMD MEDLINE Link].
Guilford P, Hopkins J, Harraway J, et al. E-cadherin germline mutations in familial gastric cancer. Nature. 1998. 392:402. [QxMD MEDLINE Link].
Cardwell CR, Abnet CC, Cantwell MM, Murray LJ. Exposure to oral bisphosphonates and risk of esophageal cancer. JAMA. 2010 Aug 11. 304(6):657-63. [QxMD MEDLINE Link]. [Full Text].
American Cancer Society. Key statistics about stomach cancer. American Cancer Society. Available at http://www.cancer.org/cancer/stomachcancer/detailedguide/stomach-cancer-key-statistics. January 12, 2023; Accessed: April 17, 2023.
Arnold M, Park JY, Camargo MC, Lunet N, Forman D, Soerjomataram I. Is gastric cancer becoming a rare disease? A global assessment of predicted incidence trends to 2035. Gut. 2020 Jan 30. [QxMD MEDLINE Link].
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. 1982 Jan. 8(1):1-11. [QxMD MEDLINE Link].
Filippi L, D'Arienzo M, Scopinaro F, Salvatori R, Bagni O. Usefulness of dual-time point imaging after carbonated water for the fluorodeoxyglucose positron emission imaging of peritoneal carcinomatosis in colon cancer. Cancer Biother Radiopharm. 2013 Jan. 28(1):29-33. [QxMD MEDLINE Link].
Brooks M. A new gastric cancer subtype responds to 5-FU. Medscape Medical News. September 4, 2013. [Full Text].
Lei Z, Tan IB, Das K, et al. Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil. Gastroenterology. 2013 Sep. 145(3):554-65. [QxMD MEDLINE Link].
Turner ES, Turner JR. Expanding the lauren classification: a new gastric cancer subtype? [editorial]. Gastroenterology. 2013 Sep. 145(3):505-8. [QxMD MEDLINE Link].
American Joint Committee on Cancer. Stomach. Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, et al, eds. AJCC Cancer Staging Manual. 8th ed. New York: Springer; 2017.
Najam AA, Yao JC, Lenzi R, et al. Linitis plastica is common in women and in poorly differentiated and signet ring cell histologies: an analysis of 217 patients (abstract). Proc Am Soc Clin Oncol. 2002. 21:166a.
Shen KH, Wu CW, Lo SS, et al. Factors correlated with number of metastatic lymph nodes in gastric cancer. Am J Gastroenterol. 1999 Jan. 94(1):104-8. [QxMD MEDLINE Link].
Lee SE, Ryu KW, Nam BH, Lee JH, Choi IJ, Kook MC, et al. Prognostic significance of intraoperatively estimated surgical stage in curatively resected gastric cancer patients. J Am Coll Surg. 2009 Oct. 209(4):461-7. [QxMD MEDLINE Link].
Ozcan S, Barkauskas DA, Ruhaak LR, Javier Torres J, Cooke CL, An H, et al. Serum glycan signatures of gastric cancer. Cancer Prev Res (Phila). 2013 Dec 10. [QxMD MEDLINE Link].
Waknine Y. Researchers Discover 'Glycan Fingerprint' for Gastric Cancer. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/818637. January 3, 2014; Accessed: April 24, 2018.
Bozzetti F, Marubini E, Bonfanti G, Miceli R, Piano C, Gennari L. Subtotal versus total gastrectomy for gastric cancer: five-year survival rates in a multicenter randomized Italian trial. Italian Gastrointestinal Tumor Study Group. Ann Surg. 1999 Aug. 230(2):170-8. [QxMD MEDLINE Link].
Bonenkamp JJ, Hermans J, Sasako M, van de Velde CJ, Welvaart K, Songun I, et al. van de Velde, CJ. Extended lymph node dissection for gastric cancer. N Engl J Med. 1999 Mar 25. 340:908. [QxMD MEDLINE Link].
Hartgrink HH, van de Velde CJ, Putter H, Bonenkamp JJ, Klein Kranenbarg E, Songun I, et al. Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch gastric cancer group trial. J Clin Oncol. 2004 Jun 1. 22(11):2069-77. [QxMD MEDLINE Link].
Degiuli M, Sasako M, Ponti A. Morbidity and mortality in the Italian Gastric Cancer Study Group randomized clinical trial of D1 versus D2 resection for gastric cancer. Br J Surg. 2010 May. 97(5):643-9. [QxMD MEDLINE Link].
Memon MA, Subramanya MS, Khan S, et al. Meta-analysis of D1 versus D2 gastrectomy for gastric adenocarcinoma. Ann Surg. 2011 May. 253(5):900-11. [QxMD MEDLINE Link].
Coccolini F, Nardi M, Montori G, Ceresoli M, Celotti A, Cascinu S, et al. Neoadjuvant chemotherapy in advanced gastric and esophago-gastric cancer. Meta-analysis of randomized trials. Int J Surg. 2018 Mar. 51:120-127. [QxMD MEDLINE Link].
Sindelar WG, Kinsella TJ. Randomized trial of resection and intraoperative radiotherapy in locally advanced gastric cancer. Proc Ann Meet Am Soc Clin Oncol. 1987. 6:A357.
Moertel CG, Childs DS, Reitemeier RJ, et al. Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet. 1969 Oct 25. 2(7626):865-7. [QxMD MEDLINE Link].
Hallissey MT, Dunn JA, Ward LC, Allum WH. The second British Stomach Cancer Group trial of adjuvant radiotherapy or chemotherapy in resectable gastric cancer: five-year follow-up. Lancet. 1994 May 28. 343(8909):1309-12. [QxMD MEDLINE Link].
Gastrointestinal Tumor Study Group. The concept of locally advanced gastric cancer. Effect of treatment on outcome. The Gastrointestinal Tumor Study Group. Cancer. 1990 Dec 1. 66(11):2324-30. [QxMD MEDLINE Link].
Moertel CG, Childs DS, O'Fallon JR, et al. Combined 5-fluorouracil and radiation therapy as a surgical adjuvant for poor prognosis gastric carcinoma. J Clin Oncol. 1984 Nov. 2(11):1249-54. [QxMD MEDLINE Link].
Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, et al. Updated Analysis of SWOG-Directed Intergroup Study 0116: A Phase III Trial of Adjuvant Radiochemotherapy Versus Observation After Curative Gastric Cancer Resection. J Clin Oncol. 2012 Jul 1. 30(19):2327-33. [QxMD MEDLINE Link].
Earle CC, Maroun JA. Adjuvant chemotherapy after curative resection for gastric cancer in non-Asian patients: revisiting a meta-analysis of randomised trials. Eur J Cancer. 1999 Jul. 35(7):1059-64. [QxMD MEDLINE Link].
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. 2012 Jan 28. 379(9813):315-21. [QxMD MEDLINE Link].
Fuchs CS, Niedzwiecki D, Mamon HJ, Tepper JE, Ye X, Swanson RS, et al. Adjuvant Chemoradiotherapy With Epirubicin, Cisplatin, and Fluorouracil Compared With Adjuvant Chemoradiotherapy With Fluorouracil and Leucovorin After Curative Resection of Gastric Cancer: Results From CALGB 80101 (Alliance). J Clin Oncol. 2017 Nov 10. 35 (32):3671-3677. [QxMD MEDLINE Link]. [Full Text].
Narahara H, Koizumi T, Hara A, et al. Randomized phase III study of S-1 alone versus S-1+cisplatin in the treatment for advanced gastric cancer. J Clin Oncol. June 2007. 25:201s.
Wagner AD, Syn NL, Moehler M, Grothe W, Yong WP, Tai BC, et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2017 Aug 29. 8:CD004064. [QxMD MEDLINE Link].
Hartgrink HH, Jansen EP, van Grieken NC, van de Velde CJ. Gastric cancer. Lancet. 2009 Aug 8. 374(9688):477-90. [QxMD MEDLINE Link].
Kim HK, Choi IJ, Kim CG, Oshima A, Green JE. Gene expression signatures to predict the response of gastric cancer to cisplatin and fluorouracil. J Clin Oncol. 2009/05. 27:[Full Text].
Ishido K, Azuma M, Koizumi W, Takeuchi A, Sakuramoto S, Watanabe M, et al. Evaluation of prognostic factors for the response to S-1 in patients with stage II or III advanced gastric cancer who underwent gastrectomy. Pharmacogenet Genomics. 2009 Nov 5. [QxMD MEDLINE Link].
US Food and Drug Administration. FDA approves Cyramza for stomach cancer [press release]. April 21, 2014. Available at https://wayback.archive-it.org/7993/20170112023840/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm394107.htm. April 21, 2014; Accessed: April 24, 2018.
Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, et al. Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncol. 2018 Mar 15. [QxMD MEDLINE Link]. [Full Text].
Young KD. FDA Panel Votes Against Two Cancer Indications but Backs 4 of 6. Medscape Medical News. Available at https://www.medscape.com/viewarticle/950247. April 30, 2021; Accessed: May 4, 2021.
Kamada T, Togashi Y, Tay C, Ha D, Sasaki A, Nakamura Y, et al. PD-1⁺ regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer. Proc Natl Acad Sci U S A. 2019 May 14. 116 (20):9999-10008. [QxMD MEDLINE Link]. [Full Text].
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28. 376 (9742):687-97. [QxMD MEDLINE Link].
Shitara K, Bang YJ, Iwasa S, Sugimoto N, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18. 382 (25):2419-2430. [QxMD MEDLINE Link]. [Full Text].
Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau HT, Prokharau A, et al. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Nov. 19 (11):1437-1448. [QxMD MEDLINE Link].
Davenport L. 'Paradigm Shift' in Gastric Junction Cancers With Nivolumab. Medscape Medical News. Available at https://www.medscape.com/viewarticle/937916. September 23, 2020; Accessed: October 10, 2020.
Moehler M, Shitara K, Garrido M, Salman P, Shen L, Wyriwicz L, et al. Nivolumab (nivo) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC)/esophageal adenocarcinoma (EAC): First results of the CheckMate 649 study (abstract). Presented at the European Society of Medical Oncology Virtual Congress; September 21, 2020. Ann Oncol. 2020. 31(suppl 4):S1142-S-1215. [Full Text].
Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20. 29(30):3968-76. [QxMD MEDLINE Link]. [Full Text].
Van Cutsem E, de Haas S, Kang YK, Ohtsu A, Tebbutt NC, Ming Xu J, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. J Clin Oncol. 2012 Jun 10. 30(17):2119-27. [QxMD MEDLINE Link].
Rothwell PM, Fowkes GR, Belch JF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomized trials. Lancet. Dec 7/2010; Early online publication. [Full Text].
Stomach (Gastric) Cancer Screening (PDQ®) Health Professional Version. National Cancer Institute. Available at http://www.cancer.gov/cancertopics/pdq/screening/gastric/HealthProfessional. February 20, 2020; Accessed: February 22, 2021.
[Guideline] Dinis-Ribeiro M, Areia M, de Vries AC, et al. Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED). Endoscopy. 2012 Jan. 44 (1):74-94. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Chey WD, Wong BC, Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007 Aug. 102 (8):1808-25. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, et al. Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report. Gut. 2012 May. 61 (5):646-64. [QxMD MEDLINE Link].
[Guideline] Fallone CA, Chiba N, van Zanten SV, Fischbach L, Gisbert JP, Hunt RH, et al. The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults. Gastroenterology. 2016 Jul. 151 (1):51-69.e14. [QxMD MEDLINE Link]. [Full Text].
[Guideline] National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Genetic/Familial High Risk Assessment: Colorectal. NCCN. Available at https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf. Version 3.2019 — December 13, 2019; Accessed: February 24, 2020.
[Guideline] Fitzgerald RC, Hardwick R, Huntsman D, Carneiro F, Guilford P, Blair V, et al. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet. 2010 Jul. 47 (7):436-44. [QxMD MEDLINE Link]. [Full Text].
[Guideline] van der Post RS, Vogelaar IP, Carneiro F, et al. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet. 2015 Jun. 52 (6):361-74. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Giardiello FM, Allen JI, Axilbund JE, Boland CR, Burke CA, Burt RW, et al. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on colorectal cancer. Am J Gastroenterol. 2014 Aug. 109 (8):1159-79. [QxMD MEDLINE Link].
[Guideline] Lordick F, et al, on behalf of the ESMO Guidelines Committee. Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022 Oct. 33 (10):1005-1020. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Vasen HF, Blanco I, Aktan-Collan K, et al. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut. 2013 Jun. 62 (6):812-23. [QxMD MEDLINE Link].
Japanese Research Society for Gastric cancer. The general rules for the gastric cancer study in surgery and pathology. 12 ed. Tokyo: Kanahara Shuppan; 1993.