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Gastric Cancer: Local and Global Burden
Lynne Lederman, PhD
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Michael R. Page, PharmD, RPh; and Shriya Patel, PharmD
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David H. Ilson, MD, PhD

Gastric Cancer: Local and Global Burden

Lynne Lederman, PhD
Introduction and Epidemiology
Cancer is a leading cause of death worldwide in both developed and developing countries. In 2012, 14.1 million new cases of cancer were diagnosed and 8.2 million deaths were estimated to have occurred worldwide.1 In the United States alone, 1,688,780 new cases of cancer and 600,920 deaths are estimated for 2017.2 As populations grow and age, the burden of cancer will increase, particularly for less developed countries.1

Here, we will look at the changing burden of gastric cancer worldwide and in the United States. The incidence of some types of cancers, including gastric cancer, is different in developed versus developing countries; rates also vary between men and women and by ethnicity.1 Gastric cancer occurs about twice as frequently in men than in women, and it leads to more deaths in men.1,2 It is the third leading cause of cancer deaths in men worldwide, after lung cancer and liver cancer. In women, it is the fifth leading cause of cancer deaths, after breast, lung, colorectal, and cervical cancer.1

The estimated numbers of new cases, by sex, of gastric cancer and of gastric cancer deaths worldwide, in developed versus developing countries, and in the United States, are summarized in the Table.1,2

The occurrence of gastric cancer is highest in Eastern Asia, especially in Korea, Mongolia, Japan, and China, as well as in Central and Eastern Europe, and South America. The lowest incidence is in North America and most of Africa.1

In the United States, the incidence of gastric cancer is highest in non-Hispanic blacks, individuals of Asian and Pacific Island descent, and Hispanic and Latino individuals; in these populations, the incidence is nearly twice that of non-Hispanic white individuals, who have the lowest incidence. Native American and Alaskan populations have an incidence of gastric cancer higher than that of non-Hispanic whites, but lower than that of other ethnic populations. Although death rates related to gastric cancer are similar among all ethnic populations, among non-Hispanic whites, rates of death related to gastric cancer occur at approximately half the rate observed in other ethnic populations.2

In general, staging of cancer is based on the size and location of the primary tumor, whether the tumor has spread locally or invaded adjacent structures, if local lymph nodes are involved, or if the tumor has spread distantly (ie, metastasized). Clinical staging is based on the results of physical examinations, imaging tests, and biopsies. The pathologic or surgical stage can be determined if surgery is performed to remove the tumor and/or lymph nodes, or to take a biopsy. When the clinical and pathologic stages differ, the pathologic stage is more accurate for determining treatment options and prognosis.3

Expected survival is related to the stage at diagnosis. The 5-year relative survival rates for all stages of gastric cancer at diagnosis were 30% over the last decade in the United States. For gastric cancer diagnosed as local (confined entirely to the stomach), the 5-year relative survival rate is 67%; for gastric cancer diagnosed at a regional stage (because it has extended beyond the stomach into adjacent tissues, or involves regional lymph nodes, or both), or at a distant stage (having spread to sites distant from the stomach by extension or metastasis), the 5-year relative survival rates drop to 31% and 5%, respectively.2

The risk factor for gastric cancer that has been most clearly identified is chronic infection with Helicobacter pylori (H. pylori).1 Other general risk factors for gastric cancer include being overweight or obese, heavy drinking, and cigarette smoking. Cigarette smoking is estimated to contribute to 20% of gastric cancer deaths.2

In the United States, the rate of gastric cancer has declined steadily since the 1930s. For all ethnicities, the 5-year relative survival rate has increased over the last 4 decades.2 A steady decline in gastric cancer’s incidence and mortality has also been observed in other parts of North America and in Europe. This decline is thought to be due to reduction in chronic infection with H. pylori as well as to the increased availability of fresh fruits and vegetables and decreased use of salt-preserved food.1

Strategies to prevent gastric cancer include increased intake of fresh fruits and vegetables; reduced intake of salted, smoked, or preserved foods; and reduction of H. pylori infection through improved sanitation and antibiotic use.1,2 Clinical trials of screening for and treatment of H. pylori infection to prevent gastric cancer are ongoing. However, additional studies may be needed to determine how to best implement prevention programs, to establish which populations should be treated, and to identify possible negative effects of gastric cancer preventive measures. For instance, measures taken such as the elimination of H. pylori might result in the elimination of the possible protective effects of H. pylori against other health conditions. In addition, alteration of the gut microbiome could have unforeseen detrimental effects, and could result in proliferation of antibiotic-resistant strains of bacteria, and alteration of the gut microbiome.4
Historical Perspectives on Treatment
Gastric cancer was first recognized millennia ago, as early as 1600 BC, but not until the late 1800s was surgery used to treat it. The first surgeries defined as successful, meaning survival of the patients past the perioperative period, were performed by 2 different surgeons; they included a subtotal resection with gastroduodenal anastomosis in 1881, and a total gastrectomy with an esophagojejunostomy for reconstruction in 1897. Although both patients subsequently died of recurrences, refinements of the surgical procedures led to the eventual adoption of surgery as an accepted treatment modality for gastric cancer.5

In the early 1950s, the chemotherapeutic agent nitromin was used to treat advanced gastric cancer in Japan. Relatively primitive, nitromin was a derivative of nitrogen mustard, a chemical weapon, and its use resulted in minimal therapeutic benefit and serious adverse events. The late 1950s saw the introduction of mitomycin C and 5-fluorouracil (5-FU),6 agents still used today against advanced gastric cancer.7 Agents introduced in the late 1960s include tegafur, the prodrug of fluorouracil, and adriamycin; these agents resulted in response rates of 20% with little survival benefit. However, the combination of 5-FU, adriamycin, and mitomycin C, used as a standard regimen in Western countries, resulted in response rates of 50%, although not in all settings.6 In the late 1970s, the use of cisplatin in combination therapy resulted in improved responses. More recently, higher response rates and survival benefits have been obtained with combinations such as cisplatin plus 5-FU or irinotecan; and with tegafur, gimeracil, and oteracil, known as S-1. S-1 is approved and used in Japan and Europe, but in the United States it is still considered investigational and is not used.6,7

While chemotherapy was being introduced as a treatment regimen for advanced gastric cancer, it was also being investigated as adjuvant therapy after curative gastrectomy to prevent recurrence—mixed results occurred. As better chemotherapy agents for advanced gastric cancer were developed, they were also used for neoadjuvant therapy » preoperatively as an alternative to surgery for patients with locally advanced gastric cancer. Chemotherapy agents were also used for those with inoperable advanced gastric cancer, with the goal of downstaging tumors to render them operable.6

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