GASTROESOPHAGEAL CANCER EPIDEMIOLOGY AND CLINICAL PRESENTATION Priv. Doz. Dr. Dr. med. T.O. Götze Institute of Clinical Cancer Research Director: Prof. Dr. S.-E. Al- Batran University Cancer Center Frankfurt
Tumor Site • Anatomic regions of the stomach Al-Batran et al. Best Practice in Gastric Cancer and Adenocarcinoma of the Esophagogastric Junction. 1th edition 2010, Rs media GmbH, Regensburg
Tumor Site • Anatomic regions in the EGJ Al-Batran et al. Best Practice in Gastric Cancer and Adenocarcinoma of the Esophagogastric Junction. 1th edition 2010, Rs media GmbH, Regensburg
Increasing incidence of adenocarcinoma of esophagogastric junction
30 25 Rate pro 1.000.000
Kardia 20 15 10 5 Adenokarzinom Ösophagus 0 1975
1980
1985
1990
1995
2000
Relative Incidance to 1975
Pohl H, Welch HG: J Natl Cancer 97(2):142–146, 2005 Al-Batran et al. Best Practice in Gastric Cancer and Adenocarcinoma of the Esophagogastric Junction. 1th edition 2010, Rs media GmbH, Regensburg
Gastric cancer - general data Source: GLOBOCAN 2012 •
952,000 (6.8% of the total) new cases of stomach cancer in 2012
•
making it the fifth most common malignancy in the world
•
after cancers of the lung, breast, colorectum and prostate
•
represents a substantive change since the very first estimates in 1975 when stomach cancer was the most common neoplasm
•
More than 70% of cases (677,000 cases) occur in developing countries
•
456,000 in men, 221,000 in women
•
half the world total occurs in Eastern Asia (mainly in China)
incidence rates are about twice as high in men as in women ranging from 3.3 in Western Africa to 35.4 in Eastern Asia for men from 2.6 in Western Africa to 13.8 in Eastern Asia for women
Gastric cancer - general data Source: GLOBOCAN 2012 •
952,000 (6.8% of the total) new cases of stomach cancer in 2012
•
making it the fifth most common malignancy in the world
•
after cancers of the lung, breast, colorectum and prostate
•
represents a substantive change since the very first estimates in 1975 when stomach cancer was the most common neoplasm
•
More than 70% of cases (677,000 cases) occur in developing countries
•
456,000 in men, 221,000 in women
•
half the world total occurs in Eastern Asia (mainly in China)
incidence rates are about twice as high in men as in women ranging from 3.3 in Western Africa to 35.4 in Eastern Asia for men from 2.6 in Western Africa to 13.8 in Eastern Asia for women
Gastric cancer- general data Source: GLOBOCAN 2012 •
Stomach cancer is the third leading cause of cancer death in both sexes worldwide
723,000 deaths, 8.8% of the total
•
highest estimated mortality rates are in Eastern Asia
24 per 100,000 in men, 9.8 per 100,000 in women •
lowest in Northern America
2.8 and 1.5, respectively •
High mortality rates are also present in both sexes in
Central and Eastern Europe Central and South America
Esophageal cancer- general data Source: GLOBOCAN 2012 •
eighth most common cancer worldwide
•
456,000 new cases in 2012 (3.2% of the total),
•
sixth most common cause of death from cancer with an estimated 400,000 deaths (4.9% of the total)
figures of GLOBOCAN 2012 include both adenocarcinoma and squamous cell carcinoma sub-types •
Around 80% of the cases worldwide occur in less developed regions
•
Oesophageal cancer incidence rates worldwide in men are more than double those in women (male:female ratio 2.4:1).
•
In both sexes there are more than 20-fold differences in incidence between the different regions of the world,
rates ranging from 0.8 per 100,000 in Western Africa to 17.0 per 100,000 in Eastern Asia in men
0.2 per 100,000 in Micronesia/Polynesia to 7.8 per 100,000 in Eastern Africa in women
Esophageal cancer- general data Source: GLOBOCAN 2012 • very poor survival • overall ratio of mortality to incidence of 0.88 • mortality closely follows the geographical patterns for incidence • with the highest mortality rates occurring in Eastern Asia (14.1 per 100,000) and Southern Africa (12.8) in men Eastern Asia (7.3) and Southern Africa (6.2) in women
Ten leading cancer types for the estimated new cases in USA by sex in 2016.
Siegel RL et al. Cancer Statistics, 2016. CA Cancer J Clin 2016; 66; 7-30
Ten leading cancer types for the estimated deaths in USA by sex in 2016.
Siegel RL et al. Cancer Statistics, 2016. CA Cancer J Clin 2016; 66; 7-30
Estimated New Cancer Cases and Deaths by Sex, United States, 2016
Siegel RL et al. Cancer Statistics, 2016. CA Cancer J Clin 2016; 66; 7-30
Gastric / Esophagus Cancer
Siegel RL et al. Cancer Statistics, 2016. CA Cancer J Clin 2016; 66; 7-30
Trends in Death Rates Overall and for Selected Sites by Sex, United States, 1930 to 2012.
Siegel RL et al. Cancer Statistics, 2016. CA Cancer J Clin 2016; 66; 7-30
Siegel RL et al. Cancer Statistics, 2016. CA Cancer J Clin 2016; 66; 7-30
Siegel RL et al. Cancer Statistics, 2016. CA Cancer J Clin 2016; 66; 7-30
Trends in 5-Year Relative Survival Rates (%)
Siegel RL et al. CA Cancer J Clin 2016; 66; 7-30
Incidence and Death Rates by Site, Race, and Ethnicity, United States, 2008 to 2012
Siegel RL et al. CA Cancer J Clin 2016; 66; 7-30
Estimated Number of New Cancer Cases in 21 World Areas, 2012. Source: GLOBOCAN 2012
Torre LA et al. Global Cancer Statistics, 2012. CA Cancer J Clin 2015; 65; 87-108.
Incidence of gastric cancer in men 1975- 2010: (Source: GLOBOCAN 2012)
Mortality of gastric cancer in men 1975- 2010: (Source: GLOBOCAN 2012)
Incidence of gastric cancer in women 1975- 2010: (Source: GLOBOCAN 2012)
Mortality of gastric cancer in women 19752010: (Source: GLOBOCAN 2012)
Estimated New Cancer Cases and Deaths Worldwide by Sex and Level of Economic Development (Source: GLOBOCAN 2012)
Gastric cancer •
951,600 new stomach cancer cases in 2012
•
723,100 deaths occurred in 2012
•
Stomach cancer rates are generally about twice as high in men as in women
•
Stomach cancer rates vary widely across countries. Torre LA et al. Global Cancer Statistics, 2012. CA Cancer J Clin 2015; 65; 87-108
Stomach Cancer Incidence Rates by Sex and World Area incidence rates are highest •
Eastern Asia
•
particularly in Korea, Mongolia, Japan, and China
•
Central and Eastern Europe, and South America
incidence rates are lowest •
Northern America and most parts of Africa
Regional variations in part reflect differences •
dietary patterns
•
food storage
•
availability of fresh produce
•
the prevalence of Helicobacter pylori infection
Chronic infection with H. pylori •
the strongest identified risk factor
•
with about 90% of new cases of non-cardia gastric cancer worldwide attributed to this bacteria
Torre LA et al. Global Cancer Statistics, 2012. CA Cancer J Clin 2015; 65; 87-108
Estimated New Cancer Cases and Deaths Worldwide by Sex and Level of Economic Development (Source: GLOBOCAN 2012)
Torre LA et al. Global Cancer Statistics, 2012. CA Cancer J Clin 2015; 65; 87-108
Estimated New Cancer Cases and Deaths Worldwide by Sex and Level of Economic Development (Source: GLOBOCAN 2012)
Torre LA et al. Global Cancer Statistics, 2012. CA Cancer J Clin 2015; 65; 87-108
decline in stomach cancer •
A steady decline in stomach cancer incidence and mortality rates
•
since the middle of the 20th century in the majority of more developed countries
Northern America
Europe
•
similar decreasing trends have been noted in more recent years in areas with historically high rates, several countries in :
Asia (Japan, China, and Korea) Latin America (Colombia and Ecuador) Europe (Ukraine)
Torre LA et al. Global Cancer Statistics, 2012. CA Cancer J Clin 2015; 65; 87-108
Factors that have contributed to these declines • increased availability of fresh fruits and vegetables • decreased reliance on salt preserved foods • reduction in chronic H. pylori infection due to improved sanitation and antibiotics • In more developed countries, decreases in smoking prevalence may also account for some of the decline
Torre LA et al. Global Cancer Statistics, 2012. CA Cancer J Clin 2015; 65; 87-108
adenocarcinoma of the gastric cardia • Although stomach cancer is declining overall • adenocarcinoma of the gastric cardia is increasing in North America and Europe • increased obesity • perhaps improvement in classification
Torre LA et al. Global Cancer Statistics, 2012. CA Cancer J Clin 2015; 65; 87-108
The primary prevention strategies for stomach cancer •
reducing intake of foods preserved by salting, pickling
•
increasing consumption of fresh fruits and vegetables
•
not smoking
•
reducing prevalence of H. pylori infection through improvement of socioeconomic conditions
•
Screening for and eradication of H. pylori using antibiotics has been shown to reduce the risk of stomach cancer in recent randomized trials
•
Although this approach requires further study in additional settings and populations
•
it could represent a promising intervention for the prevention of stomach cancer. Torre LA et al. Global Cancer Statistics, 2012. CA Cancer J Clin 2015; 65; 87-108
Risk of Gastric Cancer Gene-environment interaction H. pylori strain virulence
(vacA s1, m1, cagA+)
Environment
(Epi) Genetic alterations
Host susceptibility
(IL1B-511*T / IL1RN*2/*2) (TNFA-308*A)
Gastric Carcinoma
Parameter
Risk x fold
H. Pylori virulent genotypes (VacA; CagA) IL-1 gene polymorphism H. Pylori virulence & IL-1B polymorphism
15 to 17 3.3 87
Machado et al. Gastroenterology 2001; Figueiredo et al, JNCI 2002
Risk of Gastric Cancer • Sporadic (90%) • Familial Aggregation (10%) – Familial Gastric Cancer (FGC) – Familial Intestinal Gastric Cancer (FIGC) – Familial Diffuse Gastric Cancer (FDGC)
• Hereditary (1%)* – Hereditary Diffuse Gastric Cancer (HDGC) *Most caused by E-cadherin alterations
Gastric Cancer Further Risk factors Low risk • Diet – Vegetables, fruits – Vitamin C – Vitamin E – betacaroten • High socio-economic level
High risk • Diet – Salt – Nitrosamins (nitrates) • Alcohol, tobacco, obesity • Low socio-economic level
Stage at time of diagnosis of gastric cancer Japan1
17% 15%
Resectable
68%
Locally advanced Metastatic
Western countries2
10–15%
Resectable
25−30%
25–30%
Locally advanced
30–35%
Metastatic Unstaged 1. http://www.ncc.go.jp/en/ncch/annrep/2000; 2. sanofi-aventis Internal Epidemiology Data.
Risk of esophageal adenocarcinoma 10
Reflux esophagitis
Relative Incidence of Event
Barrett’s esophagus (BE)
8
Adenocarcinoma of the esophagus
6
H pylori colonization
4 2 0
1910
1930
1950
1970
1990
Years Blaser. J Infect Dis. 1999;179:1523-1530.
Incidence of oesophageal cancer in men 19752010 (Source: GLOBOCAN 2012)
Mortality of oesophageal cancer in men 19752010 (Source: GLOBOCAN 2012)
Incidence of oesophageal cancer in women 1975- 2010 (Source: GLOBOCAN 2012)
Mortality of oesophageal cancer in women 1975- 2010 (Source: GLOBOCAN 2012)
Estimated New Cancer Cases and Deaths Worldwide by Sex and Level of Economic Development (Source: GLOBOCAN 2012)
Esophageal cancer • • •
455,800 new esophageal cancer cases cancer cases in 2012 400,200 deaths occurred in 2012 worldwide 3 to 4 times more common among men than women.
Estimated New Cancer Cases and Deaths Worldwide by Sex and Level of Economic Development (Source: GLOBOCAN 2012)
80%
Torre LA et al. Global Cancer Statistics, 2012. CA Cancer J Clin 2015; 65; 87-108
Esophageal Cancer Incidence Rates by Sex and World Area • incidence rates vary internationally by more than 21-fold highest incidence rates • Eastern Asia • Eastern • Southern Africa lowest incidence rates • Western Africa
Torre LA et al. Global Cancer Statistics, 2012. CA Cancer J Clin 2015; 65; 87-108
squamous cell and adenocarcinoma • The 2 main types : SC and AC highest-risk area: “esophageal cancer belt” stretches from • Northern Iran -Central Asian republics - North-Central China • 90% of cases are squamous cell carcinomas compared with • 26% in the United States (among white individuals)
Torre LA et al. Global Cancer Statistics, 2012. CA Cancer J Clin 2015; 65; 87-108
risk factors: squamous cell carcinomas • contributing risk factors are not well understood In high-risk areas (e.g.Golestan (Iran) , Linxan (China)) • thought to include poor nutritional status • low intake of fruits and vegetables • drinking beverages at high temperatures • HPV infection particularly in high risk areas in Asia • more research is needed to determine HPV or other infectious agents increase risk primary risk factors in Western countries • alcohol and tobacco use • account for almost 90% of total cases. Torre LA et al. Global Cancer Statistics, 2012. CA Cancer J Clin 2015; 65; 87-108
risk factors for esophageal adenocarcinoma main known risk factors • overweight and obesity • chronic gastroesophageal reflux disease (GERD) - Barrett esophagus • However, only a small percentage of those with Barrett esophagus go on to develop esophageal cancer • GERD is most common in overweight men and women
• Smoking and low intake of fruits and vegetables are also risk factors for adenocarcinoma of the esophagus.
Torre LA et al. Global Cancer Statistics, 2012. CA Cancer J Clin 2015; 65; 87-108
Temporal trends in esophageal cancer • vary greatly incidence rates of esophageal squamous cell carcinoma • have been increasing in some Asian countries, such as Taiwan • they have been steadily declining in Northern America and Europe due to reductions in alcohol and tobacco use incidence of esophageal adenocarcinoma • increasing rapidly in Western countries such as the United States, Australia, France, and England in recent decades most likely as a result of increases in the prevalence of overweight/obesity, chronic GERD, and Barrett esophagus This trend may related to the declining prevalence of H. pylori infection which may protect against esophageal adenocarcinoma Torre LA et al. Global Cancer Statistics, 2012. CA Cancer J Clin 2015; 65; 87-108
Preventive measures for esophageal cancer •
Maintaining a healthy body weight
•
eliminating the use of tobacco,
•
reducing alcohol
•
being physically active
•
healthy diet (fruits and vegetables)
•
Research to determine whether surveillance of Barrett esophagus - method to reduce esophageal cancer mortality
•
treating gastric reflux (ppi or surgery) may prevent Barrett esophagus / esophageal cancer
•
although once Barrett esophagus has developed, preventive measures have not been shown to prevent esophageal cancer
•
Further risk factor studies are necessary to elucidate primary prevention measures in high-risk areas (Northern Iran and Central Asia) because
•
the prevalence of established major risk factors for esophageal cancer is low in those regions.
Torre LA et al. Global Cancer Statistics, 2012. CA Cancer J Clin 2015; 65; 87-108
Gastric cancer - facts Source: GLOBOCAN 2012 Incidence: •
952,000 (6.8% of the total) new cases of stomach cancer in 2012
•
5th most common malignancy in the world
•
>70% of cases (677,000 cases) occur in developing countries 456,000 in men, 221,000 in women
•
50% of the world total occurs in Eastern Asia (mainly in China)
•
2.6 per 100,000 to 35.4 per 100,000 in Eastern Asia
Mortality •
Stomach cancer is the 3rd leading cause of cancer death in both sexes worldwide
723,000 deaths (8.8% of the total) •
highest estimated mortality rates are in Eastern Asia
•
lowest in Northern America
Esophageal cancer - facts Source: GLOBOCAN 2012 Incidence: •
456,000 (3.2% of the total) new cases of stomach cancer in 2012
•
8th most common malignancy in the world
•
0.2 per 100,000 to 17.0 per 100,000 in Eastern Asia
Mortality •
6th most common cause of death from cancer with an estimated 400,000 deaths (4.9% of the total)
figures of GLOBOCAN 2012 include both adenocarcinoma and squamous cell carcinoma sub-types •
80% of the cases worldwide occur in less developed regions
•
male:female ratio 2.4 : 1
•
overall ratio of mortality to incidence of 0.88
•
mortality closely follows the geographical patterns for incidence
