Population Dynamics

4.1.2.1 Primary cancer of the liver

Cancer of the liver is one of only a few cancers known to be increasing in Alberta.

The major risk factors for HCC are HBV and HCV infection. Over 2 billion people will have serological evidence of hepatitis and 400 million will become chronic carriers.

Worldwide between 0.5 and 1.2 million individuals succumb to either cirrhosis or HCC annually⁴⁶. The number of newly diagnosed patients with HCC is paralleled by the number of deaths attributed to HCC. Other risk factors include hereditary hemochromatosis, almost any kind of cirrhosis and diabetes mellitus but these are over shadowed in importance by viral hepatitis.

In the Far East, HBV infection may become chronic in children and HCC can develop in a non-cirrhotic liver, although patients with cirrhosis are at increased risk for the

malignancy. Studies have shown that prevention of neonatal HBV infection will prevent development of cirrhosis and HCC. A vaccine is now available for the prevention of HBV infection. The American Association for the Study of Liver Disease (AASLD)⁴⁷

recommends screening certain high risk groups and vaccinating those who are not already immune or infected. This includes (in addition to pregnant women), persons born in hyperendemic areas, men having sex with men, intravenous drug users, patients on dialysis, HIV infected patients, healthcare workers, and family and household contacts of HBV infected persons.

In Alberta routine vaccination is offered to all Grade 5 students. Those falling into high risk groups are also offered vaccination. While Canadian provinces have done a good job of vaccinating their citizens, the future does not look as positive. It has been estimated that by the year 2040 one third of the Canadian population will be immigrants, many coming from endemic areas of the world. High incidence areas include Sub-Saharan Africa, the People’s Republic of China, Hong Kong and Taiwan. Over 40% of all cases of HCC are diagnosed in the People’s Republic of China. The availability of less expensive vaccines may eventually reduce the pool of infected individuals and hence the burden of HCC.

HCV infection accounts for one third of HCC cases annually. Many patients have no recollection of contracting HCV and only present with end stage liver disease 20-30 years after the fact. The acute phase is often asymptomatic, and by the time the patient is aware of the symptoms, they may have developed cirrhosis and HCC. Ultimately 20-56% of patients with chronic HCV infection will develop HCC. There is no vaccine available against HCV.

Men are far more likely to develop HCC. This disparity is more pronounced in high incidence regions. Although not fully understood, differences in sex distribution are thought to be due to variations in hepatitis virus carrier states, exposure to environmental toxins, and the trophic effect of androgens⁴⁸. Older patients, with long standing liver disease, are most likely to develop HCC. A population based study in the US identified racial and ethnic variations in the incidence of HCC. The incidence of HCC was highest among Asians, nearly double that of Hispanics and four times higher than Caucasians⁴⁹. Cirrhosis and HCC often occur in vulnerable populations within our society, as viral hepatitis is often seen in

immigrants or intravenous drug users. In terms of education level of infected individuals, evidence suggests that having less than 12 years of education is associated with an increased risk of infection⁵⁰. Language barriers, mental health and addiction issues (intravenous drug users and alcoholics) and poorer socioeconomic status are often barriers to treating patients with viral hepatitis, cirrhosis and HCC.

The number of patients with end stage liver disease is growing in Alberta. Screening for HCC is recommended for patients with cirrhosis⁵¹. The combination of ultrasound of the liver with or without monitoring of the serum marker AFP is recommended for screening for HCC in the hope of detecting tumours when they are small and amenable to curative therapy. There has been an increasing utilization of liver resection and liver transplantation in Alberta in the past several years (See Appendix VIII). Liver resections for both primary liver cancer and colorectal carcinoma metastasis have increased steadily in the Calgary Health Region between 1991 and 2004⁵². The percentage of adult liver transplants performed at the University of Alberta Hospital in Edmonton increased from an average of 7.5% between

1990-1999 to an average of 19.9% between 2000-2009 (p<0.001). There has also been an increase in the number of new HCC patients requiring TACE at the Foothills Medical Centre in Calgary with an average of 0.61 new TACE patients per month from 2003-2005 compared to 1.11 new patients per month from 2006-2008. Using Alberta Health and Wellness data it is clear to see this pattern of increasing incidence of HCC in Alberta. From 2004 to 2008 the incidence of HCC has increased from approximately 11 to 15 per 100,000 Albertans (see Tables 2c and 2d).

4.1.2.2 Secondary cancer of the liver

Colorectal cancer is the most common gastrointestinal malignancy and the second most common cause of cancer death in Alberta. It is estimated that the lifetime risk of an individual developing colorectal cancer is about 1 in 14 men and 1 in 17 women in Alberta.

In recent years there have been 560 deaths annually and more than 1,400 new cases each year in Alberta⁵³. In about 50-60% of CRC cases the cancer spreads to the liver and results in CRCLM. While resection surgery can be curative, only 20% of patients will be surgical candidates. Most patients with CRCLM are not candidates for surgery because of tumour size, location, multifocal nature or inadequate hepatic capacity.

With improved commitment to screening programs for CRC incidence rates have declined in the past 15 years. Although incidence rates of CRC have fallen, over 90% of CRC cases are diagnosed in patients over the age of 50 years. With the prevalence of CRC higher in elderly patients, it is estimated that incidence rates will rise in the future alongside the aging population. In Alberta the incidence of CRC in 2008 was approximately 36 per 100, 000 Albertans (See Table 2c and 2d).

Several risk factors exist for the development of CRC. Approximately 25% of CRC cases can be attributed to family history; as such, patients with a family history of CRC should be screened regularly. Inflammatory bowel disease is also associated with a higher risk of developing CRC. Modifiable risk factors include smoking, alcohol use, diet, and activity levels.

Information on the burden of illness for CRCLM was limited and gaps existed. It was difficult to address issues such as psycho-social, economic and physical activity and lifestyle effects of CRCLM. However, as most cases of CRCLM are not curable, and involve chemotherapy as treatment, the burden of illness is very high.

NETs can, and do, metastasize to the liver as a result of portal venous drainage of the gut, a common primary site for NETs. The term carcinoid syndrome or carcinoid tumours of the liver refer to hepatic metastases that are a result of mNET. NETs of the

gastrointestinal (GI) tract are rare. They vary with respect to location and each are associated with distinct clinical settings. Carcinoid tumours, resulting from the spread of GI NETs, are also rare and account for less than 1% of all malignant disorders in the United States. It is estimated that mNET account for 10% of all metastatic liver lesions⁵⁴. The rate of carcinoid tumours has increased in the US from 1.09 cases per 100,000 in 1973, to 5.25 cases per 100,000 in 2004⁵⁵. Alberta incidence rates for 2004 were approximately 2 per 100, 000, slightly below the US rate. This rate has increased slightly in the province with 2008

incidence rates being 2.64 per 100, 000 (See Table 2c and 2d). The median age at diagnosis is 64 years and the median survival for patients with grade 3 or 4 tumours is 10 months⁴⁴.

Family history of cancer and a long-term history of diabetes mellitus are risk factors for developing NETs⁴³.

Information on the burden of illness for mNET patients was limited and addressing issues such as psycho-social, economic, physical activity and lifestyle effects of mNET was difficult. However, as most mNET patients are in advanced stages of disease the burden of illness is very high.

4.2. Patterns of Care