Chapter 15 Cancer

Written by Jormain Cady, Joyce A. Jackowski

1. Describe the prevalence, incidence, survival and mortality rates of cancer in Australia and New Zealand.

2. Outline the processes involved in the biology of cancer.

3. Explain the three phases of cancer development.

4. Describe the role of the immune system related to cancer.

5. Differentiate between the uses of the classification systems for cancer.

6. Discuss the role of the nurse in the prevention and detection of cancer.

7. Explore the use of surgery, chemotherapy, radiation therapy and biological and targeted therapy in the treatment of cancer.

8. Identify the classifications of chemotherapeutic agents and methods of administration.

9. Differentiate between teletherapy (external beam radiation) and brachytherapy.

10. Evaluate the effects of radiation therapy and chemotherapy on normal tissues.

11. Identify the types and effects of biological and targeted therapy agents.

12. Analyse the nursing management of patients receiving chemotherapy, radiation therapy and biological and targeted therapy.

13. Describe the nutritional therapy for patients with cancer.

14. Differentiate between the various complications associated with advanced cancer.

15. Describe the psychological support interventions for cancer patients, cancer survivors and their carers.

Cancer is a group of more than 200 diseases characterised by uncontrolled and unregulated growth of cells. It is a major health problem that occurs in people of all ethnicities. Although cancer is often considered a disease of ageing—for example, 69% of all cancers diagnosed in Australia in 2007 (the latest available data) occurred in those over 60 years of age—it occurs in people of all ages. An estimated 108,000 new cases of cancer are diagnosed in Australia every year (excluding non-melanocytic skin cancer).¹ From a survey in 2002 it was expected that around 451,000 new cases of non-melanocytic skin cancers would be diagnosed in Australia in 2010.² Overall, cancer incidence rates are slightly higher than a decade ago, although with the ageing population, it is estimated that the number of cancer cases diagnosed in Australia will rise by more than 3000 cases per year in the next five years.³ The incidence of some cancers, such as cervical and ovarian cancers in women, lung cancer in men, and bladder and stomach cancer in men and women, has declined (largely as a result of preventative efforts). However, the incidence of other types of cancers, such as breast and uterine cancers in women, bowel, prostate and testicular cancers in males, and non-Hodgkin’s lymphoma and skin cancers in men and women, is on the rise. Notably, the incidence of melanoma is one of the fastest rising of all cancers in Australia, almost doubling since 1982,¹ due to the combined result of genetic predisposition and sun exposure.⁴ Reasons for the rise in non-Hodgkin’s lymphoma are not fully understood. In New Zealand, similar cancer incidence rates and trends are found, with about 19,736 New Zealanders diagnosed with cancer in 2007.⁵

Cancer incidence overall is higher in men than in women. Gender differences in incidence and death rates for specific cancers are presented in Tables 15-1 and 15-2. Although mortality rates from all cancers combined are on the decline, cancer is still the second most common cause of death in Australia and New Zealand. In 2007, there were an estimated 39,884 deaths from cancer in Australia¹ and about 8519 deaths from cancer in New Zealand.⁵

TABLE 15-1 Gender differences: new cancer cases by site and gender, 2007

* Australian Institute of Health & Welfare (AIHW). Cancer in Australia, 2010. Canberra: AIHW; 2010.

† New Zealand Ministry of Health (NZMOH). Cancer: new registrations and deaths, 2007. Wellington: NZMOH; 2010.

TABLE 15-2 Gender differences: cases of cancer deaths by site and gender

N/A: not available

* Australian Institute of Health & Welfare (AIHW). Cancer in Australia, 2010. Canberra: AIHW; 2010.

† New Zealand Ministry of Health (NZMOH). Cancer: new registrations and deaths, 2007. Wellington: NZMOH; 2010.

Reliable national data on the risk of cancer in Indigenous Australians is not available. While cancer rates appear to be similar to that in non-Indigenous Australians, the incidence rate of cancer is significantly higher for Indigenous than non-Indigenous Australians for cervical cancer, lung cancer and cancer of unknown primary site. Mortality from all cancers combined is also much higher for Indigenous than non-Indigenous Australians (230 and 178 deaths per 100,000, respectively, in 2007).¹ Both cancer incidence and death rates are disproportionately higher in Māori than in non-Māori groups in New Zealand. In 2007, Māori were 21.3% more likely to be diagnosed with cancer overall than non-Maori, with this disparity being greater for females than for males. Age standardised mortality rates were 59.8% higher for Māori compared to non-Māori groups.⁵ (See the Health disparities box.) Differences in survival from cancer are attributed primarily to a combination of several factors, including poverty, difficult access to services, as well as later stage disease at presentation for Indigenous and Māori groups.^6,⁷

Considerable progress has been made in controlling cancer and people are surviving for long periods of time. In Australia at the end of 2004, there were 297,142 people alive who had been diagnosed with cancer in the preceding 5 years. In the most recent national report, the 5-year relative survival rate was reported as 58% for men and 64% for women in Australia (up from 41% for males and 53% for females in the 5-year period 1982–1986).¹ In New Zealand, 5-year relative survival rates are 59.6% for men and 61.9% for women.⁸ These statistics represent those Australians and New Zealanders living with cancer, including those who are disease-free, in remission or undergoing treatment. (Cancer survivors are discussed later in the chapter.)

Cancer

HEALTH DISPARITIES

Australia

• There are currently no national data on cancer incidence in Indigenous Australians due to poor data quality in several jurisdictions. For those Indigenous patients who are registered, there is concern that not all are correctly identified as Indigenous.

• Although Indigenous Australians are less likely to have some types of cancer than other Australians, Indigenous Australians are significantly more likely to have cancers that have a poor prognosis but are largely preventable, such as liver and lung cancers. The patterns of incidence and mortality are largely explained by the higher prevalence of risk factors, especially smoking, among Indigenous Australians.

• Indigenous Australians are usually diagnosed with cancer at a later stage, are less likely to receive adequate treatment and are more likely to die from cancers than other Australians.

• Common perceptions among Indigenous Australians about cancer, such as fearing cancer as a death sentence, can have an important effect on the use of health services.

• Remoteness has implications for access to preventative, diagnostic, curative, palliative and other support services, as well as to basic health infrastructure.

New Zealand

• Māori have higher cancer incidence rates and mortality rates than non-Māori.

• In the case of Māori men, the age-standardised cancer mortality rates are 2.0 times greater than for non-Māori and non-Pacific Islander men, while mortality from cancer among Māori women is 2.1 times greater than for non-Māori women.

• Generally, prostate cancer mortality rates among non-Māori and non-Pacific Islander men have been half those of Māori men, while breast cancer mortality rates in the wider population were 60% lower than those of Māori women.

• Among those for whom cancer stage was recorded at diagnosis, Māori were more likely to be diagnosed at a more advanced stage of disease for breast, lung, colon, rectum, cervix, prostate, testis, kidney and oral cancers and melanoma.

• Stomach cancer was the only cancer for which Māori were more likely than non-Māori to be diagnosed at an earlier stage.

• For some cancers, Māori were more likely to die from their cancers even when detected at the same stage as non-Māori.

Source: Cunningham J, Rumbold AR, Zhang X, Condon JR. Incidence, aetiology, and outcomes of cancer in Indigenous peoples in Australia. Lancet Oncology 2008; 9(6):585–595. Robson B, Purdie G, Cormack D. Unequal impact: Māori and non-Māori cancer statistics, 1996–2001. Wellington: NZMOH; 2004.

Statistics are helpful in describing the scope of cancer as a public health problem but they cannot describe the combined physiological, psychological and social impact of cancer on individual patients and their families. There is considerable apprehension associated with a cancer diagnosis, proportionally more so than with other chronic diseases, such as heart disease. Despite advances in treatment and care, there continues to be a great deal of anxiety and fear associated with a diagnosis of cancer. Education of healthcare professionals and the public is essential to promote realistic attitudes about cancer and cancer treatment.

Nurses have a key role in leading efforts aimed at changing attitudes and behaviours about cancer. It is clearly an important nursing responsibility to provide education that will assist individuals to: (1) understand, reduce or eliminate their risk of cancer developing; (2) comply with cancer management regimens; and (3) cope with the effects of cancer and related treatment. Nurses need to be knowledgeable about specific types of cancer, treatment options and protocols for the management of side effects of therapy, as well as supportive therapies for individuals who are diagnosed with cancer. Understanding the principles of palliative and end-of-life care can position nurses to help patients maintain function and quality of life through all phases of the cancer trajectory.

Biology of cancer

Cancer encompasses a broad range of diseases with multiple causes. It can arise in any cell of the body capable of evading regulatory controls over proliferation and differentiation. The two major dysfunctions present in the process of cancer development are defective cellular proliferation (growth) and defective cellular differentiation. These are described below.

DEFECT IN CELLULAR PROLIFERATION

Normally, most tissues of the human adult contain a population of predetermined, undifferentiated cells known as stem cells. Predetermined means that the stem cells of a particular tissue will ultimately differentiate and become mature, functioning cells of that tissue and only that tissue. Cell proliferation originates in the stem cell and begins when the stem cell enters the cell cycle (see Fig 15-1). The time from when a cell enters the cell cycle to the time the cell divides into two identical cells is called the generation time of the cell. A mature cell continues to function until it degenerates and dies.

Figure 15-1 Cell life cycle and metabolic activity. Generation time is the period from M phase to M phase. Cells not in the cycle but capable of division are in the resting phase (G₀).

All cells of the body are controlled by an intracellular mechanism that determines when cellular proliferation is necessary. Under normal conditions, a state of dynamic equilibrium is constantly maintained (i.e. cellular proliferation equals cellular degeneration or death). Normally, the process of cellular division and proliferation is activated only in the presence of cellular degeneration or death. Cellular proliferation will also occur if the body has a physiological need for more cells. For example, a normal increase in the white blood cell (WBC) count occurs in the presence of infection.

Another explanation for the phenomenon of proliferation control of normal cells is contact inhibition. Normal cells respect the boundaries and territory of the cells surrounding them. They will not invade a territory that is not their own. The neighbouring cells are thought to inhibit cellular growth through the physical contact of the surrounding cell membranes. Cancer cells grown in tissue culture are characterised by loss of contact inhibition. These cells have no regard for cellular boundaries and will grow on top of one another and also on top of, or between, normal cells.

The rate of normal cellular proliferation (from the time of cellular birth to the time of cellular death) differs in each body tissue. In some tissues, such as bone marrow, hair follicles and the epithelial lining of the gastrointestinal (GI) tract, the rate of cellular proliferation is rapid. In other tissues, such as myocardium and cartilage, cellular proliferation does not occur or is slow.

Cancer cells usually proliferate at the same rate as the normal cells of the tissue from which they arise. However, cancer cells respond differently from normal cells to the intracellular signals that regulate the state of dynamic equilibrium. Cancer cells divide indiscriminately and haphazardly. Sometimes they produce more than two cells at the time of mitosis.

The stem cell theory proposes that the loss of intracellular control of proliferation results from a mutation of the stem cells. The stem cells are viewed as the target or the origin of cancer development.⁹ The deoxyribonucleic acid (DNA) of the stem cell is substituted or permanently rearranged. When this happens, the stem cell has mutated. Once the cell has mutated, one of three things can occur: (1) the cell can die, either from the damage resulting from the mutation or by initiating a programmed cellular suicide called apoptosis; (2) the cell can recognise the damage and repair itself; or (3) the mutated cell can survive and pass along the damage to its daughter cells. Mutated cells that survive have the potential to become malignant (i.e. cells with invasive and metastatic potential). The stem cell theory of cancer development is not complete because malignant stem cells can differentiate to form normal tissue cells.⁹

A common misconception about the characteristics of cancer cells is that the rate of proliferation is more rapid than that of any normal body cell. This is not true; in most situations, cancer cells proliferate at the same rate as the normal cells of the tissue from which they originate. The difference is that proliferation of the cancer cells is indiscriminate and continuous. In this way, with each cell division creating two or more offspring cells, there is continuous growth of a tumour mass: 1 → 2 → 4 → 8 → 16 and so on. This is termed the pyramid effect. The time required for a tumour mass to double in size is known as its doubling time.

DEFECT IN CELLULAR DIFFERENTIATION

Cellular differentiation is normally an orderly process that progresses from a state of immaturity to a state of maturity. Because all body cells are derived from the fertilised ova, all cells have the potential to perform all body functions. As cells differentiate, this potential is repressed and the mature cell is capable of performing only specific functions (see Fig 15-2). With cellular differentiation there is a stable and orderly phasing out of cellular potential. Under normal conditions the differentiated cell is stable and will not dedifferentiate (i.e. revert to a previous undifferentiated state).

Figure 15-2 Normal cellular differentiation.

The exact mechanism that controls cellular differentiation and proliferation is not completely understood. Two types of normal genes that can be affected by mutation are protooncogenes and tumour suppressor genes. Protooncogenes are normal cellular genes that are important regulators of normal cellular processes. Protooncogenes promote growth whereas tumour suppressor genes, such as the gene for the tumour protein p53, suppress growth. Mutations that alter the expression of protooncogenes can activate them to function as oncogenes (tumour-inducing genes).

The protooncogene has been described as the genetic lock that keeps the cell in its mature functioning state. When this lock is ‘unlocked’, as may occur through exposure to carcinogens (cancer-causing agents capable of producing cellular alterations) or oncogenic viruses, genetic alterations and mutations occur. The abilities and properties that the cell had in fetal development are again expressed. Oncogenes interfere with normal cell expression under some conditions, causing the cell to become malignant. This cell regains a fetal appearance and function. For example, some cancer cells produce new proteins, such as those characteristic of the embryonic and fetal periods of life. These proteins, located on the cell membrane, include carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP). They can be detected in human blood by laboratory studies (see the section on the role of the immune system later in the chapter). Other cancer cells, such as small cell carcinoma of the lung, produce hormones (see the section on complications resulting from cancer later in the chapter) that are ordinarily produced by cells arising from the same embryonic cells as the tumour cells.

Tumour suppressor genes function to regulate cell growth. Mutations that alter tumour suppressor genes render them inactive, resulting in a loss of their tumour suppressing action. Examples of tumour suppressor genes are BRCA1 and BRCA2. Alterations in these genes increase a person’s risk of breast and ovarian cancer. Another tumour suppressor gene is the APC gene. Alterations in this gene increase a person’s risk of familial adenomatous polyposis, which is a precursor for colorectal cancer (see Ch 42). Mutations in the p53 tumour suppressor gene have been found in many cancers, including bladder, breast, colorectal, oesophageal, liver, lung and ovarian cancers.¹⁰

Tumours can be classified as benign or malignant. In general, benign neoplasms are well-differentiated and malignant neoplasms range from well-differentiated to undifferentiated. The ability of malignant tumour cells to invade and metastasise is the major difference between benign and malignant neoplasms. Other differences between benign and malignant neoplasms are presented in Table 15-3.

TABLE 15-3 Comparison of benign and malignant neoplasms

Characteristic	Malignant	Benign
Encapsulated	Rarely	Usually
Differentiated	Poorly	Normally
Metastasis	Capable	Absent
Recurrence	Possible	Rare
Vascularity	Moderate to marked	Slight
Mode of growth	Infiltrative and expansive	Expansive
Cell characteristics	Cells abnormal, become more unlike parent cells	Fairly normal; similar to parent cells

DEVELOPMENT OF CANCER

The following is a theoretical model of the development of cancer. The cause and development of each type of cancer are thought to be multifactorial. It is not known how many tumours have a chemical, environmental, genetic, immunological or viral origin. Cancers may arise spontaneously from causes that are thus far unexplained.

It is a common belief that the development of cancer is a rapid, haphazard event. However, the natural history of cancer is an orderly process comprising several stages and occurring over a period of time. These stages include initiation, promotion and progression (see Fig 15-3).

Figure 15-3 Process of cancer development.

Ultraviolet (UV) radiation has long been associated with melanoma and squamous and basal cell carcinoma of the skin. Because of excessive sun exposure, Australia and New Zealand have by far the highest incidence and mortality rates from skin cancer in the world.¹ This is of great concern, as melanoma is a skin cancer that is poorly responsive to systemic treatment. Although the cause of melanoma is probably multifactorial, mounting evidence suggests that UV radiation secondary to sunlight exposure is linked to the development of melanoma.

Viral carcinogens

Certain DNA and ribonucleic acid (RNA) viruses, termed oncogenic viruses, can transform the cells they infect and induce malignant transformation. Viruses have been identified as causative agents of cancer in animals and humans. Burkitt’s lymphoma has consistently shown evidence of the presence of the Epstein-Barr virus (EBV) in vitro. This virus is also present in infectious mononucleosis, but the explanation of why an infectious disease develops in some persons while a lymphoma develops in others is not known. Persons with acquired immunodeficiency syndrome (AIDS), which is caused by a virus, have a high incidence of Kaposi’s sarcoma (see Ch 14). Other viruses that have been linked to the development of cancer include hepatitis B virus, which is associated with hepatocellular carcinoma, and human papillomavirus, which is believed to be capable of inducing lesions that progress to squamous cell carcinomas, such as cervical and head and neck cancers.

Genetic susceptibility

Promotion

A single alteration of the genetic structure of the cell is not sufficient to result in cancer. However, the odds of cancer development are increased with the presence of promoting agents. Promotion, the second stage in the development of cancer, is characterised by the reversible proliferation of the altered cells. Consequently, with an increase in the altered cell population, the likelihood of additional mutations is increased.

An important distinction between initiation and promotion is that the activity of promoters is reversible. This is a key concept in cancer prevention. Promoting factors include such agents as dietary fat, obesity, cigarette smoking and alcohol consumption. Changing a person’s lifestyle to modify these risk factors can reduce the chance of cancer development. In Australia, it is estimated that more that 20–30% of all cancers are due to smoking.¹ Other risk factors for promotion of cancer include alcohol consumption, physical inactivity and obesity, sun exposure and poor diet.¹ Around one-third of cancer deaths can be attributed to avoidable risk factors.¹¹

Several promoting agents exert activity against specific types of body tissues or organs. Therefore, these agents tend to promote specific kinds of cancer. For example, cigarette smoke is a promoting agent in bronchogenic carcinoma and, in conjunction with alcohol intake, promotes oesophageal and bladder cancers. Some carcinogens (complete carcinogens) are capable of both initiating and promoting the development of cancer. Cigarette smoke is an example of a complete carcinogen that is capable of initiating and promoting cancer.

A period of time, ranging from 1 to 40 years, elapses between the initial genetic alteration and the actual clinical evidence of cancer. This period, called the latent period, is now theorised to comprise both the initiation and the promotion stages in the natural history of cancer. The variation in the length of time that elapses before the cancer becomes clinically evident is associated with the mitotic rate of the tissue of origin and environmental factors. In most cancers, the process of developing cancer is years or even decades in length.

For the disease process to become clinically evident, the cells must reach a critical mass. A 1-cm tumour (the size usually detectable by palpation) contains 1 billion cancer cells. A 0.5-cm tumour is the smallest that can be detected by current diagnostic measures, such as magnetic resonance imaging (MRI).

Progression

Progression is the final stage in the natural history of a cancer. This stage is characterised by an increased growth rate of the tumour, increased invasiveness and spread of the cancer to a distant site (metastasis). Certain cancers seem to have an affinity for a particular tissue or organ as a site of metastasis (e.g. colon cancer spreads to the liver). Other cancers are unpredictable in their pattern of metastasis (e.g. melanoma). The most frequent sites of metastasis are the lungs, brain, bone, liver and adrenal glands (see Fig 15-4).

Figure 15-4 Main sites of metastasis. A, Sites of haematogenous metastasis. B, Metastasis in bone. C, Metastasis in brain. D, Metastasis in liver. E, Metastasis in adrenals. F, Metastasis in lungs. M, lesion in vertebrae; S, metastasis from neoplasm in the stomach.

Source: Stevens A, Lowe J. Pathology: an illustrated review in color. 2nd edn. London: Mosby; 2000.

Metastasis is a multistep process beginning with the rapid growth of the primary tumour (see Fig 15-5). As the tumour increases in size, development of its own blood supply is critical to its survival and growth. The process of the formation of blood vessels within the tumour itself is termed tumour angiogenesis and is facilitated by tumour angiogenesis factors produced by the cancer cells. As the tumour grows, it can begin to mechanically invade surrounding tissues, growing into areas of least resistance.

Figure 15-5 The pathogenesis of cancer metastasis. To produce metastases, tumour cells must detach from the primary tumour and enter the circulation, survive in the circulation to arrest in the capillary bed, adhere to capillary basement membrane, gain entrance into the organ parenchyma, respond to growth factors, proliferate and induce angiogenesis, and evade host defences.

Source: Adapted from DeVita VT, Helman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. Philadelphia: Lippincott-Raven; 1997.

Certain subpopulations (segments) of tumour cells are able to detach from the primary tumour, invade the tissue surrounding the tumour and penetrate the walls of lymph or vascular vessels for metastasis to a distant site. Unique capabilities of some tumour cells facilitate this process. First, proliferation of malignant cells causes mechanical pressure, leading to penetration of surrounding tissues. Second, certain cells have decreased cell-to-cell adhesion in comparison with normal cells. This property equips these cancer cells with the mobility needed to move to the exterior of the primary tumour and to move within other vascular and organ structures. Some cancer cells produce metalloproteinase enzymes (a family of enzymes) that are capable of destroying the basement membrane (a tough barrier surrounding tissues and blood vessels) not only of the tumour itself, but also of lymph and blood vessels, muscles, nerves and most epithelial boundaries. Once free from the primary tumour, metastatic tumour cells frequently travel to distant organ sites via lymphatic and haematogenous routes. These two routes of metastasis are interconnected. Thus, it is theorised that tumour cells metastasise via both routes.

Haematogenous metastasis involves several steps beginning with the penetration of blood vessels by primary tumour cells via the release of metalloproteinase enzymes. These tumour cells then enter the circulation and adhere to small blood vessels of distant organs. Tumour cells are then able to penetrate the blood vessels of distant organs by releasing the same types of enzymes. Most tumour cells do not survive this process and are destroyed by mechanical mechanisms (e.g. turbulence of blood flow) and cells of the immune system. However, the formation of a combination of tumour cells, platelets and fibrin deposits may protect some tumour cells from destruction in blood vessels.

In the lymphatic system, tumour cells may be ‘trapped’ in the first lymph node confronted or they may bypass regional lymph nodes and travel to more distant lymph nodes, a phenomenon termed skip metastasis. This phenomenon is exhibited in malignancies such as oesophageal cancers and is the basis for questions about the effectiveness of dissection of regional lymph nodes for the prevention of some distant metastases.¹² Tumour cells that do survive the process of metastasis must create an environment in the distant organ site that is conducive to their growth and development. This growth and development is facilitated by the ability of tumour cells to evade cells of the immune system and to produce a vascular supply within the metastatic site that is similar to that developed in the primary tumour site. Vascularisation is critical to the supply of nutrients to the metastatic tumour and to the removal of waste products. Vascularisation of the metastatic site is also facilitated by tumour angiogenesis factors produced by the cancer cells.

ROLE OF THE IMMUNE SYSTEM

This section is limited to a discussion of the role of the immune system in the recognition and destruction of tumour cells. (For a detailed discussion of immune system function, see Ch 13.) The immune system has the potential to distinguish cells that are normal (self) from abnormal (non-self) cells. For example, cells of transplanted organs can be recognised by the immune system as non-self and thus elicit an immune response. This response can ultimately result in the rejection of the organ. Similarly, cancer cells can be perceived as non-self and elicit an immune response resulting in their rejection and destruction. However, unlike transplanted cells, cancer cells arise from normal, human cells and although they are mutated and thus different, the immune response that is mounted against cancer cells may be inadequate to effectively kill them.

Cancer cells may display altered cell surface antigens as a result of malignant transformation. These antigens are termed tumour-associated antigens (TAAs) (see Fig 15-6). It is believed that one of the functions of the immune system is to respond to TAAs. The response of the immune system to antigens of the malignant cells is termed immunological surveillance. In this process lymphocytes continually check cell surface antigens and detect and destroy cells with abnormal or altered antigenic determinants. It has been proposed that malignant transformation occurs continuously and that the malignant cells are destroyed by the immune response. Under most circumstances, immune surveillance will prevent these transformed cells from developing into clinically detectable tumours.

Figure 15-6 Tumour-associated antigens appear on the cell surface of malignant cells.

Immune response to malignant cells involves cytotoxic T cells, natural killer (NK) cells, macrophages and B lymphocytes. Cytotoxic T cells play a dominant role in resisting tumour growth. These cells are capable of killing tumour cells. T cells are also important in the production of cytokines (e.g. interleukin-2 [IL-2] and gamma-interferon), which stimulate T cells, NK cells, B cells and macrophages. NK cells are able to directly lyse tumour cells spontaneously without any prior sensitisation. These cells are stimulated by gamma-interferon and IL-2 (released from T cells), resulting in increased cytotoxic activity. Monocytes and macrophages have several important roles in tumour immunity. Macrophages can be activated by gamma-interferon (produced by T cells) to become non-specifically lytic for tumour cells. Macrophages also secrete cytokines, including interleukin-1 [IL-1], tumour necrosis factor (TNF) and colony-stimulating factors. The release of IL-1, coupled with the presentation of the processed antigen, stimulates T lymphocyte activation and production. α-interferon augments the killing ability of NK cells. TNF causes haemorrhagic necrosis of tumours and exerts cytocidal or cytostatic actions against tumour cells. Colony-stimulating factors regulate the production of various blood cells in the bone marrow and stimulate the function of various WBCs. B lymphocytes can produce specific antibodies that bind to tumour cells and can kill these cells by complement fixation and lysis (see Ch 13). These antibodies are often detectable in the serum and saliva of the patient.

Escape mechanisms from immunological surveillance

The process by which cancer cells evade the immune system is termed immunological escape. Theorised mechanisms by which cancer cells can escape immunological surveillance include: (1) suppression of factors that stimulate T cells to react to cancer cells; (2) weak surface antigens, allowing cancer cells to ‘sneak through’ immunological surveillance; (3) the development of tolerance of the immune system to some tumour antigens; (4) suppression of the immune response by products secreted by cancer cells; (5) the induction of suppressor T cells by the tumour; and (6) blocking antibodies that bind TAAs, thus preventing their recognition by T cells (see Fig 15-7).

Figure 15-7 Blocking antibodies prevent T cells from interacting with tumour-associated antigens and from destroying the malignant cell.

Oncofetal antigens

Oncofetal antigens are a type of tumour antigen. They are found both on the surfaces of and inside cancer cells, as well as fetal cells. These antigens are an expression of the shift of cancerous cells to a more immature metabolic pathway, an expression usually associated with embryonic or fetal periods of life. The reappearance of fetal antigens in malignant disease is not well understood but it is believed to occur as a result of the cell regaining its embryonic capability to differentiate into many different cell types.

Examples of oncofetal antigens are CEA and AFP. CEA is found on the surfaces of cancer cells derived from the GI tract and from normal cells from the fetal gut, liver and pancreas. Normally, it disappears during the last 3 months of fetal life. CEA was originally isolated from colorectal cancer cells. However, elevated CEA levels have also been found in non-malignant conditions (e.g. cirrhosis of the liver, ulcerative colitis and heavy smoking). These oncofetal antigens can be used as tumour markers that may be clinically useful to monitor the effect of therapy and indicate tumour recurrence. For example, the persistence of elevated CEA titres after surgery indicates that the tumour has not been completely removed. A rise in CEA levels after chemotherapy or radiation therapy may indicate recurrence or spread of the cancer.

AFP is produced by malignant liver cells, as well as fetal liver cells. AFP levels have also been found to be elevated in some cases of testicular carcinoma, viral hepatitis and non-malignant liver disorders. AFP has diagnostic value in primary cancer of the liver (hepatocellular cancer), but it is also produced when metastatic liver growth occurs. The detection of AFP is of value in tumour detection and determination of tumour progression.

Other oncofetal antigens currently being studied are CA-125 (found in ovarian carcinoma), CA-19-9 (found in pancreatic and gall bladder cancer), prostate-specific antigen (PSA; found in prostate cancer) and CA 15-3 and CA27-29 (found in breast cancer). Additional tumour markers for specific tumours include kRAS (expression of oncogene in colon cancer) and human epidermal growth factor receptor 2 (HER-2) expression in breast cancer.

Classification of cancer

Tumours can be classified according to anatomical site, histological grading and extent of disease (staging). Tumour classification systems are intended to provide a standardised way to: (1) communicate the status of the cancer to all members of the healthcare team; (2) assist in determining the most effective treatment plan; (3) evaluate the treatment plan; (4) predict prognosis; and (5) compare like groups of patients for statistical purposes.

ANATOMICAL SITE CLASSIFICATION

In the anatomical classification of tumours, the tumour is identified by the tissue of origin, the anatomical site and the behaviour of the tumour (i.e. benign or malignant; see Table 15-4). Carcinomas originate from embryonal ectoderm (skin and glands) and endoderm (mucous membrane linings of the respiratory tract, GI tract and genitourinary tract). Sarcomas originate from embryonal mesoderm (connective tissue, muscle, bone and fat). Lymphomas and leukaemias originate from the haematopoietic system.

TABLE 15-4 Anatomical classification of tumours

Site	Benign	Malignant
Epithelial tissue tumours^*	-oma	-carcinoma
Surface epithelium	Papilloma	Carcinoma
Glandular epithelium	Adenoma	Adenocarcinoma
Connective tissue tumours^†	-oma	-sarcoma
Fibrous tissue	Fibroma	Fibrosarcoma
Cartilage	Chondroma	Chondrosarcoma
Striated muscle	Rhabdomyoma	Rhabdomyosarcoma
Bone	Osteoma	Osteosarcoma
Nervous tissue tumours	-oma	-oma
Meninges	Meningioma	Meningeal sarcoma
Nerve cells	Ganglioneuroma	Neuroblastoma
Haematopoietic tissue tumours
Lymphoid tissue		Hodgkin’s lymphoma, non-hodgkin’s lymphoma
Plasma cells		Multiple myeloma
Bone marrow		Lymphocytic and myelogenous leukaemia

^*Body surfaces, lining of body cavities and glandular structures.

^†Supporting tissue, fibrotic tissue and blood vessels.

HISTOLOGICAL CLASSIFICATION

In histological grading of tumours, the appearance of cells and the degree of differentiation are evaluated pathologically. For many tumour types, four grades are used to evaluate abnormal cells based on the degree to which the cells resemble the tissue of origin. Tumours that are poorly differentiated (undifferentiated) have a worse prognosis than those that are closer in appearance to the normal tissue of origin:

EXTENT OF DISEASE CLASSIFICATION

Classifying the extent and spread of disease is termed staging. This classification system is based on a description of the extent of the disease rather than on cell appearance. Although there are similarities in the staging of cancers, there are many differences based on a thorough knowledge of the natural history of each specific type of cancer.

Clinical staging

The clinical staging classification system determines the anatomical extent of the malignant disease process by stages:

Stage 0: cancer in situ

Stage I: tumour limited to the tissue of origin; localised tumour growth

Stage II: limited local spread

Stage III: extensive local and regional spread

Stage IV: metastasis

Clinical staging has been used as a basis for staging a variety of tumour types, including cancer of the cervix (see Ch 53) and Hodgkin’s lymphoma (see Ch 30). Other malignant diseases (e.g. leukaemia) do not use this staging approach. Clinical staging assignment is completed after the diagnostic assessment and determines treatment options.

TNM classification system

The TNM classification system (see Box 15-1) is used to determine the anatomical extent of the disease involvement according to three parameters: tumour size and invasiveness (T); the presence or absence of regional spread to the lymph nodes (N); and metastasis to distant organ sites (M). TNM staging cannot be applied to all malignancies. For example, the leukaemias are not solid tumours and therefore cannot be staged using these guidelines. Carcinoma in situ has its own designation in the system (T_is) since it has all the histological characteristics of cancer except invasion, which is a primary feature of the TNM staging system.

BOX 15-1 TNM classification system

Note: For examples of the TNM classification system applied to diseases, see Fig 30-15, Table 27-10 and Table 51-8.

Staging of the disease can be performed initially and at several evaluation points. Clinical diagnostic staging is done at the completion of the diagnostic assessment to guide the most effective treatment selection. Examples of diagnostic studies that may be performed to assess the extent of disease include radiological studies, such as bone and liver scans, ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) scans.

Surgical staging refers to the extent of the disease as determined by surgical excision, exploration and/or lymph node sampling. For example, a laparotomy and a splenectomy may be performed in the staging of Hodgkin’s lymphoma. During a staging laparotomy, lymph node biopsies may be done and margins of any masses may be marked with metal clips. These clips are used as markers when radiotherapy is used as a treatment modality. Exploratory surgical staging is, however, being used less frequently as non-invasive diagnostic technology becomes increasingly sophisticated.

After the extent of the disease is determined, the stage classification is not changed. The original description of the extent of the tumour remains part of the original record. If additional treatment is needed, or if treatment fails, re-treatment staging is done to determine the extent of the disease process prior to re-treatment. ‘Restaging’ classification (rTNM) is differentiated from stage at diagnosis as the clinical significance may be quite different.

In addition to tumour classification systems, other rating scales can be used to describe and document the status of patients with cancer at the time of diagnosis, treatment and re-treatment and at each follow-up examination. For example, the Karnofsky Functional Performance Scale and the Katz Index of Independence in Activities of Daily Living describe patient performance in terms of their function. (The Karnofsky Functional Performance Scale is shown in Table 15-5.)

TABLE 15-5 Karnofsky Performance Scale

Prevention of cancer

Nurses play a prominent role in the prevention and detection of cancer. Elimination of modifiable predisposing risk factors reduces the incidence of cancers and may favourably affect the survival of patients who have cancer. An important aspect of nursing care is to educate the public about cancer prevention and early detection, including the following:

1. Reduce or avoid exposure to known or suspected carcinogens and cancer-promoting agents, including cigarette smoke and sun exposure.

2. Eat a balanced diet that includes vegetables and fresh fruits (see Ch 39), wholegrains and adequate amounts of fibre, and reduce the amount of fat and preservatives, including smoked and salt-cured meats containing high nitrite concentrations.

3. Participate in a regular exercise regimen (i.e. ≥30 minutes of moderate physical activity five times per week).

4. Obtain adequate, consistent periods of rest (at least 6–8 hours of sleep per night).

5. Have a health examination on a regular basis that includes a health history, a physical examination and specific diagnostic tests for common cancers in accordance with the guidelines published by the Cancer Council Australia and the Cancer Society of New Zealand (see Table 15-6).

6. Eliminate, reduce or change your perceptions of stressors and enhance your ability to effectively cope with stressors.

7. Know the warning signs of cancer (see Box 15-2). (These actually detect fairly advanced disease.)

8. Learn and practise recommended cancer screenings on a timely basis (e.g. in Australia and New Zealand, screening mammography is recommended for asymptomatic women at average risk at 2-yearly intervals from 50 years to 69 years and access on request is available to women over 70 years and in the 40–49 years age group).

9. Learn and practise self-examination (e.g. breast or testicular self-examination).

10. Seek immediate medical care if you notice a change in what is normal for you and if cancer is suspected. Early detection of cancer has a positive impact on prognosis.

TABLE 15-6 Screening guidelines for early detection of cancer in asymptomatic people ^*

* These recommendations are for people at average risk of cancer. People at increased risk may need to follow a different screening schedule, such as starting at an earlier age or being screened more often.

Source: The Cancer Council Australia. National cancer prevention policy, 2007–2009. Available at www.cancer.org.au. National Screening Unit, New Zealand. Available at www.nsu.govt.nz.

Does drinking green tea decrease cancer risk?

EVIDENCE-BASED PRACTICE

Clinical question

For healthy adults (P), does green tea consumption (I) decrease the risk of cancer (O)?

Best available evidence

• Systematic review of case-control and cohort studies and randomised controlled trials

Conclusions

• Overall, green tea is unproven in preventing cancer and reducing mortality risk.

• Regular, moderate green tea consumption is safe.

Reference for evidence

Boehm K, Borrelli F, Ernst E, et al. Green tea (Camellia sinensis) for the prevention of cancer. Cochrane Database of Syst Rev. (3):2009. CD005004.

When educating the public about cancer, care should be taken to minimise the fear that surrounds the diagnosis. Teaching approaches that minimise anxiety and address the special needs of the learner or group are preferable. The goal of public education is to motivate people to recognise and modify behaviour patterns that may negatively affect their health, and to encourage awareness of and participation in health promoting behaviours. Although the general public can benefit from education, those at increased risk of cancer are the target population for educational cancer control efforts. To achieve the desired effect, nurses must recognise the challenge and proactively develop strategies to effectively teach cancer prevention and early detection principles.

Diagnosis of cancer

When a patient has a possible diagnosis of cancer, it is a stressful time for the patient and family. Patients may undergo several days to weeks of diagnostic studies. During this time fear of the unknown may be more stressful than the actual diagnosis of cancer.

While the patient is waiting for the results of the diagnostic studies, a health professional should be available to actively listen to the patient’s concerns and should be skilled in techniques that will engage the patient and family members or significant others in discussion about their cancer-related fears. It is important to recognise that the patient’s anxiety may arise from myths and misconceptions about cancer (e.g. cancer is a ‘death-sentence’, cancer treatment is worse than the illness). Correcting these misconceptions can help to minimise their anxiety. Nurses need to recognise their own discomfort when faced with discussions about cancer. It is important to avoid communication patterns that may hinder exploration of feelings and meaning, such as providing false reassurance that everything will be all right (e.g. ‘It’s probably nothing’), redirecting the discussion (e.g. ‘Let’s discuss that later’) or generalising (e.g. ‘Everyone feels this way’),¹³ and using overly technical language as a means of distancing from the patient.¹⁴ These self-protective strategies deny patients the opportunity to share the meaning of their experience, and impede the development of trusting relationships with healthcare providers.

During this time of high anxiety the patient may need repeated explanations about the diagnostic process. Explanations should include as much information as needed by the patient and family. The information should be given in clear, understandable terms and should be reinforced as necessary. Written information is helpful for reinforcement of verbal information. Tape recording visits for later reference is helpful for many patients, especially when a great deal of complex or new information is discussed.

A diagnostic plan for the person in whom cancer is suspected includes a health history, identification of risk factors, physical examination and specific diagnostic studies. (The specifics of the health history and the screening physical examination are presented in Ch 3.)

For many people, cancer is initially diagnosed following the findings of an abnormal screening test, whereas others are alerted to the presence of cancer due to a presenting symptom or cluster of symptoms (e.g. cough/haemoptysis, early satiety/weight loss). A thorough history and physical examination should be performed to fully describe the presenting symptom and its course (the history of the present illness). Other information about the patient’s medical condition should be obtained (past medical history), as well as information about allergies and current medication. Emphasis should be placed on risk factors for malignancy, such as family or personal history of cancer, exposure to or use of known carcinogens (e.g. cigarette smoking, exposure to occupational pollutants or chemicals, prior radiation exposure), diseases characterised by chronic inflammation (e.g. ulcerative colitis) and drug ingestion (e.g. hormone therapy, previous anticancer therapies). It is also important to assess factors that may warrant additional supportive care during therapy, including dietary habits, alcohol or recreational drug use, living situation, social support, and patterns and degree of coping with perceived stressors.

Diagnostic studies to be performed will depend on the suspected primary or metastatic site(s) of the cancer. (Specific procedures as they relate to each body system are discussed in the respective assessment chapters.) Examples of studies or procedures that may be included in the process of diagnosing cancer include the following:

BIOPSY

A biopsy is the removal of a tissue sample for pathological review. Various methods are used to obtain a biopsy depending on the location and size of the suspected tumour. Percutaneous biopsy is commonly performed for tissue that can be safely reached through the skin. Endoscopic biopsy may be used for lung or other intraluminal lesions (oesophagus, colon, bladder).

When a tumour is not easily accessible, a surgical procedure (laparotomy, thoracotomy, craniotomy) is often necessary to obtain a piece of the tumour tissue. Many radiographic techniques may be used in conjunction with the biopsy procedure (e.g. CT, MRI, ultrasound-guided biopsy, stereotactic biopsy, fluoroscopic-assisted biopsy) to improve tissue localisation and safety.

Various types and sizes of biopsy needles are available; they are selected according to the specific needs of the type of tissue to be sampled. Fine-needle aspiration (FNA) may be accomplished with a small-gauge aspiration needle that provides cells from the mass for cytological examination. Large-core biopsy cutting needles will deliver an actual piece of tissue (core) that can be analysed, with the advantage of preserving the histological architecture of the tissue specimen. Excisional biopsy involves the surgical removal of the entire lesion, lymph node, nodule or mass; therefore, it is therapeutic as well as diagnostic. If an excisional biopsy is not feasible, an incisional biopsy (partial excision) may be performed with a scalpel or dermal punch.

Multidisciplinary care

The goal of cancer treatment is cure, control or palliation (see Fig 15-8). Primary factors that determine the therapeutic approach are tumour histology and staging outcomes. Other important considerations in determining the treatment plan are the patient’s physiological status (e.g. presence of comorbid illnesses), psychological status and personal desires (e.g. active treatment versus palliation of symptoms). These factors influence the modalities chosen for treatment (i.e. surgery, radiation therapy, chemotherapy), how therapies are sequenced and the length of time the treatment is prescribed. A variety of evidence-based cancer treatment guidelines have been developed to guide the formulation of appropriate treatment recommendations for individual patients. Some examples include guidelines of the National Health and Medical Research Council, the Australian Cancer Network, the National Breast and Ovarian Cancer Centre and the New Zealand Guidelines Group (see the Resources on p 348). These guidelines have been developed for both clinicians and consumers. They provide valuable patient education and treatment decision-making resources.

Figure 15-8 Goals of cancer treatment.

When caring for the patient with cancer, the nurse needs to be aware of the goals of the treatment plan to appropriately communicate with, educate and support the patient. When cure is the goal, treatment is offered that is expected to have the greatest chance of disease eradication. Curative cancer therapy varies according to the particular cancer being treated and may involve local therapy (i.e. surgery or radiation) alone or in combination with periods of adjunctive systemic therapy (i.e. chemotherapy). For example, basal cell carcinoma of the skin is usually cured by surgical removal of the lesion or by several weeks of radiation therapy. Acute promyelocytic leukaemia in adults also has curative potential. In the treatment plan for acute leukaemias several chemotherapy drugs are given on a scheduled basis over many months to several years in sequential phases known as remission induction, remission consolidation and maintenance therapy. Head and neck cancers can be cured with a combination of surgery and pre- or postoperative radiation, with or without chemotherapy.

Risk of recurrence over time may vary according to the tumour type. Although there is no benchmark that assures ‘cure’ for most malignancies, in general it appears that the risk of recurrent disease is highest following treatment completion and gradually decreases the longer the patient remains disease-free following treatment. Cancers with a higher mitotic rate (e.g. testicular cancer) are less likely to recur later than cancers with a slower mitotic rate (e.g. postmenopausal breast cancer). Therefore, the timeframe to consider for ‘cured’ differs according to the tumour and its characteristics.

Control is the goal of the treatment plan for many cancers that cannot be completely eradicated but are responsive to anticancer therapies and, as with other chronic illnesses such as diabetes mellitus and heart failure, can be maintained for long periods of time with therapy. Examples include multiple myeloma, certain lung cancers and chronic lymphocytic leukaemia (see Ch 30). Patients may undergo an initial course of treatment followed by maintenance therapy for as long as the disease is responding or until adverse drug effects warrant discontinuation. Often patients are treated with a variety of regimens in a sequential pattern. Evidence of tumour resistance (such as disease progression) may warrant consideration of changing to an alternative therapy. Patients are followed closely for early signs and symptoms of disease recurrence or progression and the cumulative effects of therapy.

With the treatment goal of palliation, relief or control of symptoms and the maintenance of a satisfactory quality of life are the primary goals rather than cure or control of the disease process. It should be noted that palliation and disease control are not mutually exclusive. Examples of treatment in which palliation is the primary goal include using radiation therapy or chemotherapy to reduce tumour size and relieve the subsequent symptoms, such as the pain of bone metastasis.

The goals of cure, control and palliation are achieved through the use of four treatment modalities for cancer: surgery, chemotherapy, radiation therapy, and biological and targeted therapy. Each can be used alone or in any combination during initial treatment or as maintenance therapy, as well as in re-treatment if the disease does not respond or recurs after remission. For many cancers, two or more of the treatment modalities (known as ‘multimodality or combined modality therapy’) are used to achieve the goal of cure or control for a long period of time. Multimodality therapy has the benefit of being more effective (because it takes advantage of more than one mechanism of action), but this is often at the expense of some increased toxicity.

SURGICAL THERAPY

Surgery is the oldest form of local cancer treatment and in the early days it was the only effective method of cancer diagnosis and treatment. The treatment of choice for many years was to remove the cancer and as much of the surrounding normal tissue as possible. What this approach did not fully consider was the ability of malignant cells to travel from the original tumour site to other locations, making surgical cure possible only when the tumour was localised and relatively small. Today, with improved surgical techniques, expanded knowledge of tumour metastasis patterns and the availability of alternative therapies, surgery is employed to meet a variety of goals, as depicted in Figure 15-9, and the trend is towards less radical surgeries.

Figure 15-9 Role of surgery in the treatment of cancer.

Prevention

Surgical intervention can be used to eliminate or reduce the risk of cancer development in patients who have underlying conditions that increase their risk of developing cancer. For example, patients who have adenomatous familial polyposis may benefit from a total colectomy to prevent colorectal cancer (see Ch 42). Individuals who have genetic mutations for BRCA1 or BRCA2 and have a strong family history of early-onset breast cancer may consider the option of having a prophylactic mastectomy (see Ch 51). Prophylactic removal of non-vital organs has proven to be successful in reducing cancer incidence for selected malignancies. However, patients considering these approaches must weigh up the risks and benefits of such approaches.

Cure and control

To satisfy the goals of cancer cure or control, the object is to remove all or as much of the resectable tumour as possible while at the same time sparing normal tissue. Good prognostic indicators include small tumour size, tissue margins surrounding the site of resection that are free of disease, and the absence of node involvement and abnormal tumour marker values.

Examples of surgical procedures that are used for the cure or control of cancer include radical neck dissection, lumpectomy, mastectomy, pneumonectomy, orchiectomy, thyroidectomy, nephrectomy, hysterectomy and oophorectomy.

A debulking or cytoreductive procedure may be used if the tumour cannot be removed completely (e.g. it is attached to a vital organ). When this occurs, as much tumour as possible is removed and the patient is given chemotherapy and/or radiation therapy. This type of surgical procedure can make chemotherapy or radiation therapy more effective since the tumour mass is reduced prior to the initiation of treatment. Other times, there may be a need for the patient to receive neoadjuvant (treatment before surgery) chemotherapy and/or radiation therapy to enhance surgical outcomes.

Supportive and palliative care

When cure or control of cancer is no longer possible, the focus shifts to preserving quality of life at the highest possible level for the longest possible period of time. Supportive care and palliation of symptoms are the primary goals. Surgical procedures may be used to provide supportive care that maximises bodily function or facilitates cancer treatment. Examples of supportive surgical procedures include:

Quality of life is also affected by distressing symptoms (e.g. pain). Late effects of treatment or symptoms from metastatic cancer may necessitate surgical intervention. Examples of surgical procedures that are performed for the palliation of symptoms associated with cancer include:

• debulking of tumour or radiation therapy to relieve pain or pressure

• colostomy for the relief of a bowel obstruction (see Ch 42)

• laminectomy for the relief of a spinal cord compression (see Ch 60).

Rehabilitative care

Cancer surgery can produce a change in body image and function. It is often difficult for the patient to cope with these changes in conjunction with a diagnosis of cancer while attempting to maintain usual lifestyle patterns. As the treatment for certain cancers becomes more effective, the length of time the patient must live with an alteration created by surgery will be increased. To maintain quality of life, patients must be able to accept and cope with their altered body image and functional ability. Examples of rehabilitative surgical procedures include the creation of a bladder reservoir at the time of cystectomy, breast reconstruction after a mastectomy and the insertion of appliances to facilitate functionality (e.g. spinal or joint stabilising rods).

CHEMOTHERAPY

Chemotherapy (the use of chemicals as a systemic therapy for cancer) has been evolving over the past seven decades. In the 1940s chemotherapy nitrogen mustard, a chemical warfare agent used in World Wars I and II, was used in the treatment of lymphoma and acute leukaemia, and a folic acid antimetabolite (fluorouracil) was found to have anti-tumour activity. In the 1970s chemotherapy was established as an effective treatment modality for cancer. Chemotherapy is now a mainstay of cancer therapy and is used in the treatment of most solid tumours and haematological malignancies (e.g. leukaemias, lymphomas, myelomas and myelodysplastic syndromes). Chemotherapy has evolved to become a therapeutic option that can offer cure for certain cancers, control other cancers for long periods of time and, in some instances, offer palliative relief of symptoms when cure or control is no longer possible (see Fig 15-10).

Figure 15-10 Goals of chemotherapy.

The goal of chemotherapy is to eliminate or reduce the number of malignant cells present in the primary tumour and metastatic tumour site(s).¹⁶ Several factors determine the response of cancer cells to chemotherapy:

1. Mitotic rate of the tissue from which the tumour arises. The more rapid the mitotic rate, the greater the potential for response. Examples of tumours with rapid proliferative rates include acute leukaemia and small cell lung cancer.

2. Size of the tumour. The lower the tumour burden (i.e. smaller the number of cancer cells), the greater the potential for response.

3. Age of the tumour. The younger the tumour, the greater the response to chemotherapy. Newly developing tumours tend to have a greater percentage of proliferating cells.

4. Location of the tumour. Certain anatomical sites provide a protected environment from the effects of chemotherapy. For example, only a few drugs (nitrosoureas, bleomycin, temozolomide) cross the blood–brain barrier. New agents and techniques are being developed to cross this barrier more effectively.

5. Presence of resistant tumour cells. Mutation of cancer cells within the tumour mass can result in variant cells that are resistant to chemotherapy. Malignant cells unresponsive to chemotherapy can pass this resistance on to daughter cells, diminishing the response to further treatment over time.

Effect on cells

The effect of chemotherapy is at the cellular level. All cells (cancer cells and normal cells) enter the cell cycle for replication and proliferation (see Fig 15-1). The effects of the chemotherapeutic agents are described in relationship to the cell cycle. The two major categories of chemotherapeutic drugs are cell cycle non-specific and cell cycle phase-specific drugs. Cell cycle non-specific chemotherapeutic drugs have their effect on the cells during all phases of the cell cycle, including those in the process of cellular replication and proliferation and those in the resting phase (G₀). Cell cycle phase-specific chemotherapeutic drugs exert their most significant effects during specific phases of the cell cycle (i.e. when cells are in the process of cellular replication or proliferation during G₁, S₁, G₂ or M). Cell cycle phase-specific and cell cycle non-specific agents are often administered in combination with one another to maximise effectiveness by using agents that function by differing mechanisms and throughout the cell cycle.

When cancer first begins to develop, most of the cells are actively dividing. As the tumour increases in size, more cells become inactive and convert to a resting state (G₀). Because most chemotherapeutic agents are most effective against dividing cells, cells can escape death by staying in the G₀ phase. A major challenge in developing protocols is overcoming the effect of resistant resting and non-cycling cells.

Classification of chemotherapeutic drugs

Chemotherapeutic drugs are classified in general groups according to their molecular structure and mechanisms of action (see Table 15-7). Each drug in a particular classification has many similarities. However, there are major differences in how the drugs work and unique side effects associated with drugs in each class.

TABLE 15-7 Classification of chemotherapy drugs

DRUG THERAPY

Note: Many of these drugs are irritants or vesicants that require special attention during administration to avoid extravasation. It is important to know this information about a drug before administering it.

Preparation and administration of chemotherapy

It is very important to know the specific guidelines for administration of chemotherapeutic drugs. In addition, it is important to understand that drugs may pose an occupational hazard to healthcare professionals who do not follow safe handling guidelines. A person preparing, transporting or administering chemotherapy may absorb the drug through inhalation of particles when reconstituting a powder in an open ampoule and through skin contact if there is droplet exposure. There may also be some risk in handling the body fluids and excretions of patients receiving chemotherapy. Guidelines for the safe handling of chemotherapeutic agents have been developed in most states and territories of Australia (see the relevant government occupational health and safety authority in each state or territory), by the Department of Labour in New Zealand ¹⁷ and the US Oncology Nursing Society.¹⁸ These guidelines provide recommendations regarding appropriate control procedures for standard operating procedures; education and training; cytotoxic signs and labels; and personal protective equipment. Only those personnel specifically trained in chemotherapy handling techniques should be involved with the preparation and administration of antineoplastic agents. This training should cover occupational hazards of exposure to cytotoxic drugs and waste; work practices to be adopted when handling cytotoxic drugs and waste; correct selection, use, cleaning and disposal of personal protective equipment; correct storage and transport of cytotoxic drugs and related waste; and procedures to be adopted in the event of accident, injury or spill.

Methods of administration

Chemotherapy can be administered by multiple routes (see Table 15-8). The intravenous (IV) route is most common. Advances in drug formulation techniques are driving the re-emergence of oral antineoplastic agents. Major concerns associated with the IV administration of antineoplastic drugs include venous access difficulties, device- or catheter-related infection and extravasation (infiltration of drugs into tissues surrounding the infusion site), causing local tissue damage (see Fig 15-11).

TABLE 15-8 Methods of chemotherapy administration

DRUG THERAPY

Method	Examples
Oral	Cyclophosphamide, capecitabine, carmustine, temozolomide
Intramuscular	Bleomycin
Intravenous	Doxorubicin, vincristine, cisplatin, fluorouracil, paclitaxel
Intracavitary (pleural, peritoneal)	Radioisotopes, alkylating agents, methotrexate
Intrathecal	Methotrexate, cytarabine
Intraarterial	Dacarbazine, fluorouracil, methotrexate
Perfusion	Alkylating agents
Continuous infusion	Fluorouracil, methotrexate, cytarabine
Subcutaneous	Cytarabine
Topical	Fluorouracil cream

Figure 15-11 Extravasation injury from infiltration of chemotherapy drug.

Many chemotherapeutic drugs may be either irritants or vesicants. Irritants will damage the intima of the vein, causing phlebitis and sclerosis, and limit future peripheral venous access, but will not cause tissue damage if infiltrated. Vesicants, however, if inadvertently infiltrated into the skin, may cause severe local tissue breakdown and necrosis. It is extremely important to monitor for and promptly recognise symptoms associated with extravasation of a vesicant and to take immediate action if it occurs. The infusion should be turned off immediately and protocols for drug-specific extravasation procedures should be followed to minimise further tissue damage.¹⁹

Although pain is the cardinal symptom of extravasation, it has been known to occur without causing pain. Swelling, redness and the presence of vesicles on the skin are other signs of extravasation. After a few days, the tissue may begin to ulcerate and necrose. Vesicants may cause partial- or full-thickness loss of skin. Patients may need surgical intervention varying from debridement to skin grafting. Complications of extravasation include sepsis, scarring, contractures, joint pain and nerve loss.^18,²⁰

To minimise the associated physical discomforts, emotional distress and risks of infection and infiltration, IV chemotherapy can be administered by means of a central vascular access device (CVAD). CVADs are placed in large blood vessels and permit frequent, continuous or intermittent administration of chemotherapy, biological and targeted therapy, and other products, thus avoiding multiple venipunctures for vascular access. These devices are indicated in instances of limited vascular access, intensive chemotherapy, repetitive or continuous infusion of vesicant agents and projected long-term need for vascular access. (CVADs are discussed in Ch 16.)

Regional chemotherapy administration

Regional treatment with chemotherapy involves the delivery of the drug directly to the tumour site. The advantage of administering chemotherapy by this method is that higher concentrations of the drug can be delivered to the tumour with reduced systemic toxicity. Several regional delivery methods have been developed, including intraarterial, intraperitoneal, intrathecal or intraventricular and intravesical bladder chemotherapy.

Intraarterial chemotherapy

Intraarterial chemotherapy delivers the drug to the tumour via the arterial vessel supplying the tumour. This method has been used for the treatment of osteogenic sarcoma; cancers of the head and neck, bladder, brain and cervix; melanoma; primary liver cancer; and metastatic liver disease. One method of intraarterial drug delivery involves the surgical placement of a catheter that is subsequently connected to an external infusion pump or an implanted infusion pump for infusion of the chemotherapeutic agent. Generally, intraarterial chemotherapy results in reduced systemic toxicity. The type of toxicity experienced by the patient depends on the site of the tumour being treated. Complications include bleeding, embolism, pain, arterial injury, catheter migration or dislodgement, and occlusion.

Intraperitoneal chemotherapy

Intraperitoneal chemotherapy involves the delivery of chemotherapy to the peritoneal cavity for the treatment of peritoneal metastases from primary colorectal and ovarian cancers and malignant ascites. Temporary Silastic catheters (Tenckhoff, Hickman and Groshong) are percutaneously or surgically placed into the peritoneal cavity for short-term administration of chemotherapy. Alternatively, an implanted port can be used to administer chemotherapy intraperitoneally. Chemotherapy is generally infused into the peritoneum in 1–2 L of fluid and allowed to ‘dwell’ in the peritoneum for a period of 1–4 hours. Following the ‘dwell time’, the fluid is usually drained from the peritoneum. Complications of peritoneal chemotherapy include abdominal pain; catheter occlusion, dislodgement and migration; distension; ileus; intestinal perforation; and infection.

Intrathecal or intraventricular chemotherapy

Cancers that metastasise to the CNS—most commonly breast, lung and GI cancers, leukaemias and lymphomas—are difficult to treat because the blood–brain barrier often prevents distribution of chemotherapy to this area. One method that is used to treat metastasis to the CNS is intrathecal chemotherapy. This involves performing a lumbar puncture and injecting the chemotherapeutic agent into the subarachnoid space. However, this method has resulted in incomplete distribution of the drug in the CNS, particularly to the cisternal and ventricular areas.

To ensure more uniform distribution of chemotherapy to the cisternal and ventricular areas, an Ommaya reservoir is often inserted. An Ommaya reservoir is a Silastic, dome-shaped disc with an extension catheter that is surgically implanted through the cranium into a lateral ventricle. In addition to more consistent drug distribution, the Ommaya reservoir avoids the need for repeated, painful lumbar punctures. Intrathecal chemotherapy needs to be administered by a doctor trained to administer via this route. Complications of intrathecal or intraventricular chemotherapy include headache, nausea, vomiting, fever and nuchal rigidity.

Intravesical bladder chemotherapy

The patient with superficial transitional cell cancer of the bladder often has recurrent disease following traditional surgical therapy. Instillation of chemotherapy into the bladder promotes destruction of cancer cells and reduces the incidence of recurrent disease. Additional benefits of this therapy include reduced urinary and sexual dysfunction. The chemotherapeutic agent is instilled into the bladder via a urinary catheter and retained for 1–3 hours. Complications of this therapy include dysuria, urinary frequency, haematuria and bladder spasms.

Effects of chemotherapy on normal tissues

Chemotherapeutic agents cannot selectively distinguish between normal cells and cancer cells. Chemotherapy-induced side effects are the result of the destruction of normal cells, especially those that are rapidly proliferating, such as those in the bone marrow, the lining of the GI system and the integumentary system (skin, hair and nails; see Table 15-9). The effects of chemotherapy are caused by general cytotoxicity and organ-specific drug toxicities. The response of the body to the products of cellular destruction in the circulation may cause fatigue, anorexia and taste alterations.

TABLE 15-9 Cells with rapid rates of proliferation

Cells and generation time	Effect of cell destruction
Bone marrow stem cells, 6–24 h	Myelosuppression, infection, bleeding, anaemia
Neutrophils, 12 h	Leucopenia, infection
Epithelial cells lining the gastrointestinal tract, 12–24 h	Anorexia, mucositis (including stomatitis, oesophagitis), nausea and vomiting, diarrhoea
Cells of the hair follicle, 24 h	Alopecia
Ova or testes, 24–36 h	Reproductive dysfunction

The general and drug-specific adverse effects of these drugs are classified as acute, delayed or chronic. Acute toxicity occurs during and immediately after drug administration and includes anaphylactic and hypersensitivity reactions, extravasation or a flare reaction, anticipatory nausea and vomiting, and cardiac arrhythmias. Delayed effects are numerous and include delayed nausea and vomiting, mucositis, alopecia, skin rashes, bone marrow suppression, altered bowel function (diarrhoea or constipation) and a variety of cumulative neurotoxicities depending on the affected component of the nervous system (i.e. central or peripheral nervous system or cranial nerves). Chronic toxicities involve damage to organs such as the heart, liver, kidneys and lungs. Chronic toxicities can be either long-term effects that develop during or immediately following treatment and persist or late effects that are absent during treatment and manifest later. Some side effects fall into more than one category. For example, nausea and vomiting can be both acute and delayed.

Treatment plan

While single-drug chemotherapy can and sometimes is prescribed, combining agents in multidrug regimens has proven to be more effective in managing most cancers. Choosing agents with different mechanisms of action and varying toxicity profiles avoids tumour cell resistance and minimises the occurrence and severity of side effects. However, when chemotherapy agents are used in combination, patients can experience an increase in toxicities.

Drug regimens are selected based on the evidence supporting their use in specific cancers, and are sometimes customised to meet the needs of an individual patient. Chemotherapy is most effective when tumour burden is low, therapy is not interrupted and the patient receives the intended dose. The dose of each drug is carefully calculated according to the patient’s body surface area (i.e. calculation is based on the patient’s body weight and height).

RADIATION THERAPY

Radiation therapy is a local treatment modality for cancer. Along with surgery, it is one of the oldest methods of cancer treatment, having been first employed by Emil Grubbe (at the time a medical student) to treat an ulcerating breast cancer in 1896 (although the patient responded locally, she died later of metastatic disease).

The observation that radiation exposure caused tissue damage led scientists in the early 20th century to explore the use of radiation to treat tumours. The hypothesised association was that if radiation resulted in the destruction of the highly mitotic skin cells of workers, it could be used in a controlled way to prevent the continued growth of highly mitotic cancer cells. It was not until the 1960s that sophisticated equipment and treatment planning facilitated the delivery of adequate radiation doses to tumours and tolerable doses to normal tissues. Currently, approximately half of all patients receive radiation therapy at some point in the treatment of their disease.²¹

Effects of radiation

Radiation is the emission and distribution of energy through space or a material medium. Delivery of high-energy beams, when absorbed into tissue, produces ionisation of atomic particles. The local energy in ionising radiation and resultant generation of free radicals act to break the chemical bonds in DNA. Damage to cellular DNA may be either lethal or sublethal. Lethal damage causes sufficient chromosomal disruption that the cell is unable to replicate, or it may impair the protein synthesis functions that are necessary for survival. When sublethal DNA damage occurs, there is potential for repair in between radiation doses, or potential for accumulated damage to occur with repetitive doses, which ultimately leads to cell death. Cancer cells are more likely to be permanently damaged by cumulative doses of radiation because they are less capable of repairing sublethal DNA damage than healthy cells.

Different types of ionising radiation are used to treat cancer, including electromagnetic radiation (i.e. X-rays, gamma rays) and particulate radiation (alpha particles, electrons, neutrons, protons). The primary difference between X-rays and gamma rays is that gamma rays are emitted from a radioactive source through the process of constant decay. High-energy X-rays (photons) are generated by an electric machine, such as a linear accelerator. The main problem with emitted radiation (such as historic cobalt technology introduced in the 1960s) is that over time the source deteriorates, thus emitting less energy and requiring periodic replacement. Safety issues relating to housing the radioactive source are also a consideration. Technological advances have expanded and refined the sources and methods of delivering radiation therapy, thus offering more accurate and less invasive radiation treatment options.²² Most radiation centres in Australia and New Zealand currently use linear accelerator technology, and larger radiation facilities may offer a combination of treatment machines that permit expanded treatment options for patients at one treatment site.

Principles of radiobiology

As the radiation beam passes through the treatment field, the energy deposited is determined by the properties of the energy used and the absorptive properties of the matter through which the beam passes. Low-energy beams (such as electrons) expend energy quickly upon impact with matter. Therefore, they penetrate only a short distance. (They are clinically useful in treating superficial skin lesions.) High-energy beams (such as X-rays) have a greater depth of penetration, not attaining full intensity until they reach a certain depth. Therefore, they are suitable for delivering an optimal dose to internal targets while sparing the skin. The principles of radiotherapy dosing and fractionation are guided by cellular response to radiation, known as the four Rs of radiobiology (see Table 15-10).

TABLE 15-10 The four Rs of radiobiology

Technically, all cancer cells could be eradicated with radiation given high enough doses. However, to avoid serious toxicity and long-term complications of treatment, radiation to surrounding healthy tissue must be limited to the maximal tolerated dose for that specific tissue. Improvements in planning and delivery technology (such as intensity-modulated radiotherapy [IMRT]), have greatly improved the ability to deliver maximal doses to the target volume while sparing critical structures, such as the spinal cord, small bowel, carotid arteries, parotid glands, optic chiasm and other important structures, as much as possible.

Historically, the radiation dose was expressed in units called rads (radiation dosage absorbed). Current nomenclature is the gray (Gy) or centigray (cGy). A centigray is equivalent to 1 rad, and 100 centigray equals 1 gray (see Table 15-11).

TABLE 15-11 Measurement of radiation

Unit	Definition
Curie (Ci)	A measure of the number of atoms of a particular radioisotope that decays in 1 s
Roentgen (R)	A measure of the radiation required to produce a standard number of ions in air; a unit of exposure to radiation
Rad	Measurement of radiation dosage absorbed by the tissues
Rem	Measurement of the biological effectiveness of various forms of radiation on the human cell (1 rem = 1 rad)
Gray (Gy)	1 Gy = 100 rads; 1 centigray (cGy) = 1 rad

Once the total dose to be delivered is determined, that dose is divided into daily ‘fractions’ (generally 180–200 cGy). Treatment is typically delivered once a day Monday to Friday for a period of 2–8 weeks (depending on the desired total dose). This is considered standard fractionation. Other treatment schedules may be prescribed based on principles of radiobiological effect. High daily doses of radiation may be given with fewer fractions (hypofractionated), lower daily doses may be given over a longer period of time (hyperfractionated) or doses may be delivered twice daily (accelerated fractionation).

The amount of time that is required for the manifestation of radiation damage is determined by the mitotic rate of the tissue, with rapidly proliferating tissues being more sensitive. Rapidly dividing cells in the GI tract, oral mucosa and bone marrow will die quickly and exhibit early acute responses to radiation. Tissues with slowly proliferating cells, such as cartilage, bone and kidneys, manifest later responses to radiation. This differential rate of cellular death explains the timing of clinical manifestations related to radiation therapy. Certain cancers are more susceptible to the effects of radiation than others. Table 15-12 describes the relative radiosensitivity of a variety of tumours. In responsive tumours (such as lymphomas), even a large tumour burden will be affected by therapy. In less responsive tumours, a large tumour burden may result in a slower and perhaps incomplete response. Localised prostate cancer responds very slowly to radiation (over a period of several months). For some benign diseases (such as meningiomas), arrested growth (rather than disease regression) may be considered successful.

TABLE 15-12 Tumour radiosensitivity

Simulation

Simulation is a part of radiation treatment planning used to accurately localise the tumour and ensure set-up position reproducibility. During the simulation, the goals of the prescribed radiation plan are met by determining the orientation and size of radiation beams and the location of field-shaping blocks, and outlining the field on the patient’s skin. The patient is positioned on a simulator, which is a diagnostic X-ray machine that re-creates the actions of the linear accelerator. Immobilisation devices (e.g. casts, bite blocks, thermoplastic face masks) are typically used to help the patient maintain a stable position (see Fig 15-12). The target is defined using a variety of possible imaging techniques (e.g. X-rays, CT, MRI, PET scans), physical examination and surgical reports.²³ Under fluoroscopy the critical normal structures that will be included in the treatment field (or portal) are identified so that they can be protected. A film is taken to verify the field and marks are placed on the skin to delineate the ‘treatment port’; small tattoos may be placed to ensure the patient position is precisely reproduced on a daily basis.

Figure 15-12 Immobilisation device. A head holder and immobilisation mask may be used to ensure accurate positioning for daily treatment of head and neck cancer.

Courtesy of Jormain Cady, Virginia Mason Medical Center, Seattle.

Treatment

Radiation is used to treat a carefully defined area of the body to achieve local control of disease. As radiation only has an effect on tissues within the treatment field, it is not appropriate as an independent modality for patients with systemic disease. However, radiation may be used, independently or in combination with chemotherapy, to treat primary tumours, or for palliative control of metastatic lesions. Radiation can be delivered externally (teletherapy) or internally (brachytherapy). As with other cancer therapies, the goals of radiation therapy are cure, control or palliation. There are multiple settings in which radiation may be used, including:

• definitive or primary therapy: used as an independent treatment modality with curative intent (e.g. for cancers of the lung, prostate, bladder and head/neck; Hodgkin’s lymphoma)

• neoadjuvant therapy: given (with or without chemotherapy) preoperatively to minimise tumour burden and improve the likelihood of complete surgical resection, making a previously inoperable tumour (such as one adjacent to a critical structure) operable (e.g. lung, oesophageal or colorectal cancers)

• adjuvant therapy: administered following surgery or chemotherapy to improve local control of disease and reduce the risk of local disease recurrence (e.g. glioblastoma, head and neck cancers, cancers of the breast, lung, rectum, pancreas)

• prophylaxis: administered to high-risk areas to prevent future cancer development (such as prophylactic cranial irradiation to prevent brain metastasis secondary to small cell lung cancer)

• disease control: given to limit tumour growth to extend the symptom-free period as much as possible

• palliation: given to prevent or relieve distressing symptoms, such as pain (bone metastasis) or shortness of breath (obstructing bronchial tumour), or to preserve neurological function (brain metastasis or spinal cord compression).

External radiation

Teletherapy (external beam radiation) is the most common form of radiation treatment delivery. With this technique the patient is exposed to radiation from a megavoltage treatment machine. A linear accelerator, which generates ionising radiation from electricity and can produce multiple energies, is the most commonly used machine for delivering external beam radiation (see Fig 15-13). Gamma knife technology (used to deliver highly accurate stereotactic treatment to a localised treatment volume) uses a cobalt source. A cyclotron produces particulate energy, such as neutrons or protons. Proton therapy requires significant energy to generate, and there are only a small number of facilities equipped to provide this treatment.

Figure 15-13 Linear accelerator. Varian Clinac EX linear accelerator with multiple photon and electron energies available for use according to the treatment plan. This patient is positioned on a radiation treatment table for the treatment of head and neck cancer.

Courtesy of Jormain Cady, Virginia Mason Medical Center, Seattle.

A linear accelerator may be used to deliver different types of treatment techniques (or plans). A two-dimensional plan is the simplest type of therapy, designed using X-rays, bony landmarks and a simple beam arrangement. Three-dimensional conformal therapy plans treatment based on three-dimensional anatomy using CT and/or other imaging, with the goal of improved dose distribution around the target volume. Intensity-modulated radiotherapy (IMRT) is more labour-intensive to plan but has the advantage of tailoring beam intensity to optimise dose delivery to the target volume while minimising dose to critical structures. It is particularly well suited to treating irregularly shaped fields and fields adjacent to sensitive structures (such as head and neck cancers). The most recent evolution of treatment planning encompasses the element of time, or four-dimensional conformal therapy. Different available technologies incorporate varying imaging and localising methods to achieve the goal of controlling for physiological movement during therapy or anatomical changes (such as tumour shrinkage or weight loss) over the course of therapy, thereby further improving the accuracy of dose delivery to the intended target volume. Although it is unclear how much these technologies will affect survival benefit, reduced treatment toxicity has been demonstrated with IMRT treatment planning.

Internal radiation

Radiation can also be delivered as brachytherapy, which means ‘close’ or internal radiation treatment. It consists of the implantation or insertion of radioactive materials directly into the tumour (interstitial) or in close proximity adjacent to the tumour (intracavitary or intraluminal). This allows direct dose delivery to the target with minimal exposure to surrounding healthy tissues. (In external radiation the beam has to pass through external tissues to reach the internal source.) Brachytherapy is commonly used in combination with external radiation as a supplemental ‘boost’ treatment.

Sources of radiation for brachytherapy include temporary sealed sources, such as iridium-192 and caesium-137, and permanent sealed sources, such as iodine-125, gold-198 and palladium-103. These are supplied in the form of seeds or ribbons. With a temporary implant, the source may be placed into a special catheter or metal tube that has been inserted into the tumour area. It is left in place until the prescribed dose of radiation has been reached in the calculated number of hours.

Brachytherapy may be delivered as high dose rate (HDR) treatment (i.e. several doses administered at varying intervals over a few minutes each time) or low dose rate (LDR) treatment (i.e. continuous treatment over several hours or days). A remote ‘afterloading’ technique (i.e. the source is inserted after the applicator is in place) is designed to enhance doctor and patient safety and is used for HDR brachytherapy with iridium-192. These methods are commonly used for head and neck, lung, breast and gynaecological malignancies.

Permanent implants, such as prostate brachytherapy, involve the insertion of radioactive seeds directly into the tumour tissue, where they remain permanently. As interstitial seeds used for treatment emit low energies with limited tissue penetration, patients are not considered radioactive. However, some initial radiation precautions may be recommended as there is a small risk of seed dislodgement. Over time, the isotopes that are used decay and are no longer radioactive. The time frame for side effects induced by treatment can be predicted, based on the rate of decay of the specific isotope used.

Radiopharmaceutical therapy employs unsealed liquid radioactive sources that are administered orally as a drink, such as iodine-131 for thyroid cancer, or intravenously, as with yttrium-90 administered for refractory lymphomas or samarium-153 used to treat bone metastases.²³

Caring for the patient undergoing brachytherapy or receiving radiopharmaceuticals requires that all staff caring for the patient be aware that they are emitting radioactivity. Patients with temporary implants are radioactive only during the time the source is in place. In patients with permanent implants, because the sources have fairly short half-lives and are weak emitters, the radioactive exposure to the outside and others is well below recommended limits. These patients are not considered radioactive and may be discharged with precautions.

The principles of ALARA (As Low As Reasonably Achievable) and time, distance and shielding are vital to the safety of healthcare professionals when caring for patients with a source of internal radiation. Care should be organised to limit the amount of time spent in direct contact with the patient. To minimise anxiety and confusion, the patient should be made aware of the reason for time and distance limitations before the procedure. The radiation safety officer will indicate how much time at a specific distance can be spent with the patient. This is determined by the dose delivered by the implant. Because the source is non-penetrating, small differences in distance are critical. Only care that must be delivered near the source, such as checking placement of the implant, is performed in close proximity. Shielding should be used, if available. No care should be delivered without wearing a film badge. This badge indicates cumulative radiation exposure. The film badge should not be shared, should not be worn other than at work and should be returned according to the agency’s protocol.

NURSING MANAGEMENT: PATIENTS UNDERGOING CHEMOTHERAPY AND RADIATION THERAPY

Nurses have an important role to play in identifying, reporting and helping patients to deal with the side effects of radiation and chemotherapy. Teaching patients about their treatment regimen, supportive care options (e.g. antiemetics, antidiarrhoeals) and what to expect during the course of treatment help decrease fear and anxiety, encourage adherence and guide home self-management. However, before initiating education, the patient’s ability and desire to process information should be assessed. The nurse should customise teaching to meet the patient’s and family’s learning needs.

Nursing implementation

Common side effects of chemotherapy and radiation are presented in Table 15-13. Bone marrow suppression, fatigue, GI disturbances, integumentary and mucosal reactions, pulmonary and cardiovascular effects, and reproductive effects are discussed in this section.

TABLE 15-13 Nursing management of problems caused by chemotherapy and radiation therapy

BUN, blood urea nitrogen; ECG, electrocardiogram; GI, gastrointestinal; IL-1, interleukin 1; RBC, red blood cell; TNF, tumour necrosis factor; WBC, white blood cell.

Bone marrow suppression

Myelosuppression is one of the most common effects of chemotherapy and, to a lesser extent, it can also occur with radiation. Since bone marrow is responsible for producing critically important blood cells (red blood cells [RBCs], WBCs and platelets), treatment-induced reductions in blood cell production can result in life-threatening and distressing effects, including infection, haemorrhage and overwhelming fatigue. The major difference in manifestations between radiation and chemotherapy is that with radiation (a local therapy) only bone marrow within the treatment field will be affected, whereas chemotherapy (a systemic therapy) affects bone marrow function throughout the body. Therefore, effects are more profound with chemotherapy and when the two therapies are combined.

In general, the onset of bone marrow suppression is related to the life span of the type of blood cell. WBCs (especially neutrophils) are affected most acutely, within 1–2 weeks, platelets are affected in 2–3 weeks and RBCs, with a longer life span of 120 days, are affected at a later time. The severity of myelosuppression is dependent on the chemotherapy drugs used, dosages of drugs and the specific radiation treatment field. Radiation to large marrow-containing regions of the body produces the most clinically significant myelosuppression. In the adult, about 40% of active marrow is in the pelvis and 25% is in the thoracic and lumbar vertebrae.²³ Certain chemotherapy agents are more myelosuppressive than others and some drug regimens that include multiple myelosuppressive agents can result in significant effects.

Monitoring the full blood count is critical in patients receiving radiation and/or chemotherapy, particularly the neutrophil, platelet and RBC counts. It is typical for patients to experience the lowest blood counts (called the nadir) between 7 and 10 days after the initiation of therapy. However, the exact onset depends on the particular drug regimen and host factors.

Neutropenia is most common in patients receiving chemotherapy and can place them at significant risk of serious infection or sepsis. Significant neutropenia will prompt treatment delay or modification (i.e. lower dosages). The nurse should take every possible measure to prevent infections in these patients. (See NCP 30-3 on neutropenia.) Hand hygiene is the mainstay of patient protection, and patients, as well as their contacts (including hospital staff), should follow hand-washing guidelines. Other precautions to minimise risks from neutropenia are presented in Box 30-12. Temperature should be monitored routinely and any sign of infection should be treated promptly, as fever in the setting of neutropenia is a medical emergency. WBC growth factors (i.e. filgrastim, pegfilgrastim) are used to reduce the duration of chemotherapy-induced neutropenia and as a prophylactic measure to prevent neutropenia when highly myelosuppressive chemotherapy drugs are used.²⁴ (Neutropenia is discussed in Ch 30.)

Thrombocytopenia can result in spontaneous bleeding or major haemorrhage. The nurse should avoid invasive procedures and advise patients to avoid activities that place them at risk for injury or bleeding (including excessive straining). (See NCP 30-2 on thrombocytopenia.) Risk of serious bleeding is generally not apparent until the platelet count falls below 50,000/μL. Platelet transfusions may be necessary and are usually administered when the platelet counts fall below 20,000/μL.

Anaemia is common in patients undergoing either radiation or chemotherapy and generally has a later onset (about 3–4 months after treatment initiation). For patients with low haemoglobin levels (i.e. below 110 g/L), red cell growth factors (i.e. darbepoetin) may be administered if blood transfusion is not possible. In general, efforts are increasingly being made to avoid RBC transfusion. Haematopoietic growth factors are discussed later in this chapter.

Fatigue

Fatigue is the persistent subjective sense of tiredness associated with cancer and its treatment that interferes with usual day-to-day functioning. Fatigue is a nearly universal symptom affecting 70–100% of patients with cancer.²⁵ It is commonly reported by patients undergoing active treatment as the most distressing of treatment-related side effects, and may persist long after treatment has ended. The pathophysiological mechanisms of fatigue are unclear. One theory is that the accumulation of muscle metabolites, such as lactate, hydrogen ions and other end products from the destruction of cells, results in decreased muscle strength. Other explanations include cytokine production, changes in neuromuscular function, serotonin function and production, and an indirect association with anorexia, fever and infection typical in patients undergoing treatment. It is important to remember that reversible causes of fatigue, such as anaemia, hypothyroidism, depression, anxiety or infection, should be assessed and corrected if present.^26,²⁷ Medications that may contribute to fatigue should also be reviewed and adjusted if possible. Factors such as weight loss, depression, nausea and other symptoms can exacerbate the sensation of fatigue.

Nurses can help patients to recognise that fatigue is a common side effect of therapy and encourage energy-conserving strategies. Patients should also be helped to identify days or times during the day when they typically feel better to allow them to be more active during that time period. Resting before activity and having others assist with work or home management may be necessary. Ignoring the fatigue or overstressing the body when fatigue is tolerable may lead to an increase in symptoms. However, maintaining exercise and activity within tolerable limits is often helpful in managing fatigue. Walking programs are a way for most patients to keep active without overtaxing them. The ability to remain active helps to improve mood and avoids the debilitating cycle of fatigue–depression–fatigue that can occur in patients with cancer.

Maintaining good nutritional and hydration status and managing other symptoms (especially insomnia or altered sleep patterns, pain, depression and anxiety) also helps reduce fatigue. Published guidelines for the evaluation and management of cancer-related fatigue have been developed by the US National Comprehensive Cancer Network.²⁸

Gastrointestinal effects

The cells of the mucosal lining of the GI tract are highly proliferative, with surface cells replaced every 2–6 days. The intestinal mucosa is one of the most sensitive tissues to radiation and chemotherapy. The aetiology of GI reactions is related to a variety of mechanisms including: (1) the release of serotonin from the GI tract, which then stimulates the chemoreceptor trigger zone (CTZ) and the vomiting centre in the brain; and (2) cellular death and resulting damage to mucosal tissues and underlying structures in the GI lining responsible for digestion, secretion and absorption. Additionally, radiation to treatment fields that contain GI structures (i.e. abdominopelvic, lumbosacral and lower thoracic areas) and selected chemotherapy agents produce direct injury to GI epithelial cells. These injuries result in a variety of GI effects—nausea and vomiting, diarrhoea, mucositis and anorexia—all of which can significantly affect the patient’s hydration and nutritional status and sense of wellbeing.

Nausea and vomiting

Nausea and vomiting are common sequelae of chemotherapy, and in some instances radiation therapy. Vomiting may occur within 1 hour of chemotherapy administration or a few hours after radiation therapy to the chest or abdomen and may persist for 24 hours or more. Several antiemetic drugs are available. Metoclopramide, serotonin receptor antagonists (ondansetron, granisetron, dolasetron and tropistron) and dexamethasone have all been used to decrease nausea and vomiting caused by chemotherapy. Aprepitant is the first agent in a class of antiemetics known as neurokinin-1 receptor antagonists and is effective in preventing nausea and vomiting on the day of chemotherapy as well as for delayed symptoms. The three-drug combination of a serotonin receptor antagonist, dexamethasone and aprepitant is recommended before chemotherapy of high emetic risk.²⁹

Patients may also develop anticipatory nausea and vomiting if they experience poorly controlled nausea and vomiting following chemotherapy administration. In this phenomenon, encountering the cues even without receiving treatment may precipitate nausea and vomiting. Aggressive emetic control, including the use of prophylactic administration of antiemetics 1 hour before treatment, is recommended. The patient may find that eating a light meal of non-irritating food before treatment is also helpful.

Delayed nausea and vomiting can develop 24 hours and up to a week following treatment. Patients experiencing nausea and vomiting should be assessed for signs and symptoms of dehydration and metabolic alkalosis. Their fluid intake should be recorded to ensure that an adequate volume is being consumed and retained. Nausea and vomiting can be successfully managed with antiemetic regimens, dietary modification and other non-pharmacological interventions.

Diarrhoea

Diarrhoea is a reaction of the bowel mucosa to radiation and to certain antineoplastic agents. It is characterised by an increase in frequency or liquidity of stool. Pathophysiology of treatment-induced diarrhoea is multifaceted. The most common mechanisms are osmotic, secretory, hypermotility and exudative. The small bowel is extremely sensitive and does not tolerate significant radiation doses. With radiation, treating patients with a full bladder may be done to move the small bowel out of the treatment field. Both radiation and chemotherapy-induced diarrhoea are best managed with antidiarrhoeals, antimotility agents and antispasmodics. A diet low in fibre and residue before treatment with chemotherapy known to cause diarrhoea may be helpful. This includes limiting foods that are high in roughage (e.g. fresh fruits, vegetables, seeds, nuts). To prevent diarrhoea, other foods that may be avoided include fried or highly seasoned foods and foods that are gas-producing. Bowel mucosal injury from radiation may result in temporary lactose intolerance; therefore, avoiding milk products is helpful for some patients during and immediately after treatment. Depending on severity, hydration and electrolyte supplementation are also recommended. Lukewarm sitz baths may alleviate discomfort and cleanse the rectal area if significant rectal irritation has developed. The rectal area must be kept clean and dry to maintain skin integrity. Nurses need to visually inspect the perianal area for evidence of skin breakdown. Systemic analgesia may be warranted for the painful skin irritations that may develop. The nurse should note the number, volume, consistency and character of stools per day. Patients should be taught to maintain a diary or log to record episodes of diarrhoea and aggravating and alleviating factors.³⁰

Mucositis

Oral mucositis (irritation, inflammation and/or ulceration of the mucosa) is a common complication in almost all patients receiving radiation to the head and neck and in a significant number of patients receiving certain antineoplastic agents (especially fluorouracil). Similar to the bowel mucosa, the mucosal linings of the oral cavity, oropharynx and oesophagus are extremely sensitive to the effects of radiation and chemotherapy. Oral mucositis (or stomatitis) is a complex problem involving not only the epithelial lining but also other mucosal components, including the endothelial, extracellular matrix and connective tissues.

Certain factors can compound the problem. For example, head and neck irradiation can damage parotid gland function, resulting in decreased salivary flow and producing xerostomia (dry mouth). Dryness or thick saliva interferes with the salivary functions of assisting with cleansing teeth, moistening food and swallowing. Meticulous oral care during treatment and long-term after treatment reduces the risk of cavities caused by radiation, which may develop as a result of diminished saliva. Patients should continue their regular dental check-ups every 6 months and use fluoride supplements as recommended by their dentist. Saliva substitutes are available and may be offered to patients with xerostomia, although many patients find that drinking small amounts of water frequently has an equivalent effect. Amifostine (a cytoprotectant) may be used during radiation treatment if a significant radiation dose to the parotid glands is expected. However, there has been conflicting evidence about the role of amifostine in reducing radiation-related mucositis.³¹

Taste loss (dysgeusia) may occur during therapy and by the end of treatment patients often report that all food has lost its flavour. Ultimately, nutritional status may be compromised. Dysphagia (difficulty swallowing), which characterises oesophageal involvement, further impedes eating. Patients may report feeling that they have a ‘lump’ as they swallow and that foods ‘get stuck’. Odynophagia (painful swallowing) due to orogpharyngeal or oesophageal irritation and ulceration may require the use of analgesics before meals.

Oral assessment and meticulous intervention to keep the oral cavity moist, clean and free of debris are essential to prevent infection and to facilitate nutritional intake. Implementing standard oral care protocols that address prevention and management of mucositis facilitate routine assessment, patient/family education and intervention.³¹ The oral cavity, mucous membranes, characteristics of saliva and ability to swallow must be routinely assessed by a clinician. Assessment by a dentist before the initiation of treatment is also recommended. Patients should be taught to self-examine the oral cavity and how to perform oral care (proper brushing with a soft-bristle toothbrush, flossing and use of fluoride trays to prevent caries). Oral care should be performed at least before and after each meal and at bedtime. A saline solution of 1 teaspoon of salt in 1 L of water is an effective cleansing agent. One teaspoon of sodium bicarbonate may be added to the oral care solution to decrease odour, alleviate pain and dissolve mucin.

Alleviation of mucositis or pain in the throat can be achieved by systemic and/or topical analgesics and antibiotics if infection is documented. Frequent cleansing with saline and water and topical application of anaesthetic gels directly to the lesions are standard care.³²

Palifermin, a synthetic version of keratinocyte growth factor, is available to prevent and shorten the duration of mucositis if it develops. It is given intravenously and stimulates cells on the surface layer of the mouth to grow. This is thought to lead to faster replacement of these cells when killed by cancer treatment and is believed to speed up the healing process of mouth ulcers.³¹ Paliferm is currently recommended for mucositis prevention in patients with haematological malignancies undergoing high-dose chemotherapy and total body irradiation with autologous stem cell transplant.³¹ The safety and efficacy of palifermin for patients with non-haematological malignancies have not been established.

Soft, non-irritating, high-protein and high-kilojoule foods should be offered frequently throughout the day. Extremely hot or cold food and drinks should be avoided; so should tobacco and alcohol. The patient should be encouraged to take nutritional supplements as an adjunct to meals and fluid intake and should be weighed at least twice per week to monitor for weight loss. Families are an integral part of the healthcare team. As symptom severity increases, the family’s role in assisting the patient to eat becomes increasingly critical. If family members are not available, alternative support, such as volunteers and home aides, may be helpful.

Anorexia

Anorexia may develop as a general reaction to treatment. The mechanisms for anorexia are unclear but several theories exist. Macrophages release TNF and IL-1 in an attempt to fight the cancer. Both TNF and IL-1 have an appetite-suppressing (anorectic) effect. As tumours are destroyed by therapy, it is thought that increased levels of these factors may be released into the system and cross the blood–brain barrier, exerting an influence on the satiety centre. Large tumours produce more of these factors, thus resulting in the cachexia seen in advanced cancer. Other treatment-induced GI side effects can also interfere with appetite. Patients experiencing nausea and vomiting, bowel disturbances, mucositis and taste alterations typically have little desire for, and actual mechanical difficulty with, eating and drinking. Although it is highly individual, anorexia seems to peak at about 4 weeks of treatment and seems to resolve more quickly than fatigue when treatment ends. The nurse should monitor the patient with anorexia carefully during treatment to ensure that weight loss does not become excessive and offer dietary counselling. Small, frequent meals of high-protein, high-kilojoule foods are better tolerated than large meals. Nutritional supplements can be helpful as well. Enteral or parenteral nutrition may be indicated if the patient is severely malnourished or expected to have symptoms that interfere with nutrition for a protracted period or when the bowel is being rested. Medications, such as corticosteroids or progestins (e.g. Megestrol acetate), may also be of benefit to some patients.³³

Skin reactions

Like the bone marrow and the GI lining, the skin contains rapidly proliferating cells and therefore is affected by radiation and chemotherapy. With radiation, skin effects are local, occurring only in the treatment field. In contrast, there are a range of chemotherapy-related skin effects that occur throughout the integumentary system. Some examples are photosensitivity reactions with methotrexate and radiation recall dermatitis, which occurs months to years after radiation treatment or chemotherapy.

Radiation-induced skin changes can be acute or chronic depending on the area being radiated, the dosage and the technique. The skin-sparing property of modern radiation equipment limits the severity of these reactions. Erythema may develop 1–24 hours after a single treatment, but generally occurs progressively as the treatment dose accumulates. Erythema is an acute response followed by dry desquamation (see Fig 15-14). If the rate of cellular sloughing is faster than the ability of the new epidermal cells to replace dead cells, a wet desquamation occurs, with exposure of the dermis and weeping of serous fluid (see Fig 15-15). Skin reactions are particularly evident in areas of skin folds or where skin is subjected to pressure, such as behind the ears and in gluteal folds, perineum, breast, collar line and bony prominences.

Figure 15-14 Dry desquamation.

Figure 15-15 Wet desquamation.

Although skin care protocols vary between institutions, basic skin care principles apply. Prevention of infection and facilitation of wound healing are the therapeutic goals. Irradiated skin should be protected from temperature extremes, and heating pads, ice packs and hot-water bottles should not be used in the treatment field. The nurse should avoid using constricting garments, rubbing, harsh chemicals and deodorants as they may traumatise the skin. Dry reactions are uncomfortable and result in pruritus. Dry skin should be lubricated with a non-irritating lotion emollient (such as aloe vera) that contains no metal, alcohol, perfume or additives that can be irritating to the skin. Wet desquamation of tissues generally produces pain, drainage and increased infection risk. Skin care to manage wet desquamation includes keeping tissues clean with normal saline compresses and protected from further damage with moisture vapour-permeable dressings or Vaseline petroleum gauze. Because protocols vary widely, the instructions presented in Box 15-3 are only a guide; nurses must always adhere to their own institution’s radiation oncology protocols.

BOX 15-3 Radiation skin reactions

PATIENT & FAMILY TEACHING GUIDE

1. Gently cleanse the skin in the treatment field using a mild soap, tepid water, a soft cloth and a gentle patting motion. Rinse thoroughly and pat dry.

2. Apply non-medicated, non-perfumed, moisturising lotion or cream, such as aloe vera gel, to alleviate dry skin. This substance must be gently cleansed from the treatment field before each treatment and reapplied. (Note: Care differs from institution to institution.)

3. Rinse the area with saline solution. Expose the area to air as often as possible. If copious drainage is present, use of astringent compresses and non-adhesive absorbent dressings is warranted (they must be changed as soon as they become wet). Observe the area daily for signs of infection.

4. Avoid wearing tight-fitting clothing, such as brassieres and belts, over the treatment field.

5. Avoid wearing harsh fabrics, such as wool and corduroy. A lightweight cotton garment is best. If possible, expose the treatment field to air.

6. Use gentle detergents to wash clothing that will come in contact with the treatment field.

7. Avoid direct exposure to the sun. If the treatment field is in an area that is exposed to the sun, protective clothing, such as a wide-brimmed hat, should be worn during exposure to the sun and sunscreen lotion should be applied.

8. Avoid all sources of excessive heat (hot-water bottles, heating pads and sun lamps) on the treatment field.

9. Avoid exposing the treatment field to cold temperatures (ice bags or cold weather).

10. Avoid swimming in salt water or in chlorinated pools during the time of treatment.

11. Avoid the use of all medication, deodorants, perfumes, powders or cosmetics on the skin in the treatment field. Tape, dressings and adhesive bandages should also be avoided unless permitted by the radiation therapist. Avoid shaving the hair in the treatment field.

12. Sensitive skin must continue to be protected after the treatment is completed. The patient should do the following:

a. Avoid direct exposure to the sun. A sunscreen agent and protective clothing must be worn if the potential of exposure to the sun is present.

b. Use an electric razor if shaving is necessary in the treatment field.

Chemotherapy produces a wide array of cutaneous toxicities, ranging from mild erythema and hyperpigmentation to more distressing effects, such as acral erythema, palmar–plantar erythrodysaesthesia (PPE) and hand–foot syndrome (HFS), which is common with some of the targeted therapies. PPE can cause mild symptoms of redness and tingling of the palms of the hands and soles of the feet. PPE may also cause severe symptoms of painful wet desquamation, ulceration, blistering and pain. If severe symptoms occur, the chemotherapy drug should be withheld for 1–2 weeks to allow the skin to regenerate. Table 15-13 outlines more detailed descriptions of specific reactions and recommendations for management.

Alopecia (hair loss) is an easily recognisable effect of cancer therapy. It is frequently associated with varying degrees of emotional distress. Hair loss associated with radiation is local, whereas chemotherapy affects hair throughout the body. The degree and duration of hair loss experienced by patients undergoing radiation and chemotherapy depend on the type and dose of the chemotherapeutic agent, and the location of the radiation field and radiation dosage. Alopecia caused by the administration of chemotherapeutic agents is usually reversible, whereas radiation can produce temporary and partial hair loss or permanent hair loss depending on the location and dose of radiation. Sometimes the hair grows back while the patient is still receiving chemotherapeutic agents, but generally the hair does not grow back until 3–4 weeks after the drugs are discontinued. Often the new hair has a different colour and texture than the hair that was lost. Patients experience a range of emotions at the prospect of losing their hair and when hair loss actually occurs. These include anger, grief, embarrassment and fear. Hair loss is a constant reminder of their cancer and the challenges of treatment. For some, hair loss is one of the most stressful events experienced during the course of treatment. The ‘Look Good, Feel Better’ program offered by the Cancer Council Australia and the Cancer Society of New Zealand is an excellent support and resource for people experiencing not just hair loss but also body image changes in general.

Pulmonary effects

Both chemotherapy and radiation have the potential to produce pulmonary toxicity and tissue damage that is irreversible and progressive. Distinguishing between the complications of treatment and those related to disease is challenging, since the manifestations of therapy-induced toxicity to the lungs can mimic a broad array of problems. The type and severity of therapy-induced pulmonary effects is related to the actual radiation field (i.e. thoracic field) and volume treated, specific chemotherapeutic agents, dosages, past treatment and coexisting conditions. The effects of radiation on the lungs include both acute and late reactions. Immediate pulmonary effects of radiation can be alarming to patients because they may mimic symptoms that precipitated the cancer diagnosis. Cough and dyspnoea may increase during, and at completion of, therapy. The cough becomes more productive as alveoli that had been blocked are opened as the tumour responds to treatment, and due to increased production of respiratory secretions. As treatment continues, the cough can become dry as the mucosa begins to be altered by the radiation. Cough suppressants may be indicated at night.

Pneumonitis is a delayed acute inflammatory reaction that may potentially occur within 1–3 months following completion of thoracic radiation.³⁴ This reaction is often asymptomatic, although an increase in cough, fever and night sweats may occur. Treatment with bronchodilators, expectorants, bed rest and oxygen is preferable to treatment with corticosteroids. A minority of patients may develop pulmonary fibrosis (with or without prior pneumonitis), which is a late effect of therapy occurring 6 months to 2 years after treatment and may be chronic.

The most common pulmonary side effects associated with chemotherapy include pulmonary oedema (non-cardiogenic) related to capillary leak syndrome or fluid retention, hypersensitivity pneumonitis, interstitial fibrosis and pneumonitis produced by an inflammatory reaction or destruction of alveolar–capillary endothelium. Patients are managed according to the offending agent and the manifestations of toxicity.

Cardiovascular effects

Radiation to the thorax can damage the pericardium, myocardium, valves and coronary blood vessels. The pericardium is the most commonly involved, with pericardial effusion and pericarditis being the key problems. Although the incidence of radiation-induced heart disease is less common with improved accuracy of treatment planning technology, risk is higher in patients given high doses of radiation or if radiation therapy is concurrent with anthracyclines (e.g. doxorubicin, daunorubicin). Patients with pre-existing coronary artery disease are especially vulnerable.³⁴

Anthracyclines are the best studied of the anticancer drugs that cause cardiotoxicity. Acute cardiotoxicities may cause electrocardiogram (ECG) abnormalities, and late effects are left ventricular dysfunction and heart failure. Anthracycline toxicity can be decreased by changing administration from a rapid infusion to a continuous infusion. Cumulative anthracycline doses should be monitored and documented to ensure that recommended limits are not exceeded.

Fluorouracil can cause cardiac ischaemic syndrome. Monoclonal antibodies, when infused, commonly cause hypotension because of a massive release of cytokines. One type of monoclonal antibody, trastuzumab, which is used in the treatment of breast cancer, is cardiotoxic and may result in ventricular dysfunction and heart failure. Baseline and periodic echocardiograms should be considered to monitor left ventricular function during treatment. Trastuzumab-related cardiomyopathy is managed with angiotensin-converting enzyme inhibitors and β-adrenergic blockers (Ch 34 discusses heart failure).

Reproductive effects

Reproductive dysfunction secondary to radiation and chemotherapy varies according to the radiation treatment field and dosage and the particular chemotherapy agent and dose, as well as to host factors (e.g. age). Treatment can cause temporary or permanent gonadal failure. Reproductive effects occur most often when reproductive organs are included in the radiation treatment field and with alkylating agents.

The testes are highly sensitive to radiation and the testicles should be protected with a testicular shield whenever possible. Radiation doses of 15–30 cGy temporarily decrease the sperm count, with temporary aspermia developing at 35–230 cGy. The patient receiving 200–300 cGy may recover sperm production by 3 years following treatment, but in some cases permanent aspermia may result. The patient receiving 400–600 cGy either recovers in 2–5 years or not at all. Greater than 600 cGy exposure is associated with permanent sterility. Pre-treatment status may be a significant factor because a low sperm count and loss of motility are seen in individuals with testicular cancer and Hodgkin’s lymphoma before any therapy. Combined modality treatment or prior chemotherapy with alkylating agents enhances and prolongs the effects of radiation on the testes. When radiation is used alone with conventional doses and appropriate shielding, testicular recovery often occurs. Compromise of reproductive function in men may also result from erectile dysfunction following pelvic radiation due to related vascular and neurological effects.

The radiation dose necessary to induce ovarian failure changes with age. Permanent cessation of menses occurs at 500–1000 cGy in 95% of women less than 40 years of age and at 375 cGy in women over 40 years of age. Unlike the testes, there is no avenue for repair of ovarian function. The ovaries are shielded whenever possible. Other factors that influence reproductive or sexual functioning in women include reactions in the cervix and endometrium. These tissues withstand a high radiation dose with minimal sequelae, accounting for the ability to treat endometrial and cervical cancer with high external and brachytherapy doses. Acute reactions, such as tenderness, irritation and loss of lubrication, compromise sexual activity. Late effects of combined internal and external therapy include vaginal shortening related to fibrosis and loss of elasticity and lubrication.

The patient and partner require information about the expected effects of treatment relative to reproductive and sexual issues. Potential infertility can be a significant consequence for the individual and counselling may be indicated. However, in no case should the patient think that conception is not possible during treatment. Pre-treatment harvesting of sperm or ova may be considered. Specific suggestions to manage side effects that have an impact on sexual functioning include using a water-soluble vaginal lubricant and a vaginal dilator after pelvic irradiation. Nurses need to encourage discussion of issues related to sexuality, offer specific suggestions and make referrals for ongoing counselling when indicated.

Coping with therapy

Nurses have a key role in assisting patients to cope with the psycho-emotional issues associated with receiving cancer treatment. Anxiety is common among patients receiving anticancer therapy, including anxieties about various aspects of treatment administration (e.g. repeated venipuncture), dependency on others, potential side effects and poor outcomes. Repetitive clinic visits or hospitalisations, continuing medications and laboratory testing force patients to confront their cancer on a daily basis. Treatment-related uncertainties and fears are often most evident at the beginning of therapy. For those patients completing curative therapy, anxiety may surface again when therapy comes to an end (i.e. fear of recurrence, less available support). Telling patients that they will be followed up and that support is ongoing can be reassuring. Providing information and support can help to minimise the negative impact of anticancer therapy on quality of life. Patient teaching, symptom management and interventions designed to help patients self-manage their illness and normalise their experience (e.g. adjusting treatment schedules to permit patients to work when possible, referring patients to support groups) facilitate personal coping during and after cancer therapy and optimise lifestyle patterns to enhance quality of life. Arranging for patients to meet with individuals who have completed therapy successfully can offer hope and increase confidence. In addition, nurses can contact patients between follow-up appointments to assist with nutrition and emotional support and to advise about available resources, such as the Cancer Council Australia and the Cancer Society of New Zealand, self-help groups and, if appropriate, religious organisations and other community resources.

LATE EFFECTS OF RADIATION AND CHEMOTHERAPY

Cancer survivors are achieving long-term remission and increased survival rates with advancements in treatment modalities. However, these forms of therapy (especially radiation and chemotherapy) may produce long-term sequelae termed late effects that occur months to years after the cessation of therapy. Every body system can be affected to some extent by chemotherapy and radiation therapy. The effects of radiation on the body’s tissues are caused by cellular hypoplasia of stem cells and alterations in the fine vasculature and fibroconnective tissues. This may contribute to the risk of radiation necrosis, which is dose dependent. Alteration of the lymphatic channels (e.g. axillary lymph node dissection) may contribute to lymphoedema. In addition to the acute toxicities, chemotherapy can have long-term effects related to the loss of cells’ proliferative reserve capacity, including cataracts, arthralgias, endocrine alterations, renal insufficiency, hepatitis, osteoporosis, neurocognitive dysfunction and other effects, depending on the agents.³⁴ The additive effects of multi-agent chemotherapy before, during or after a course of radiotherapy can significantly increase the resulting physiological late effects.

The cancer survivor may also be at risk of leukaemias, angiosarcomas and other secondary malignancies resulting from therapy for the primary cancer. Approximately 8% of cancer survivors face a secondary malignancy, most commonly breast and colon cancer survivors.³⁵ Alkylating agents and high-dose radiation are the most frequently implicated therapies. However, the potential risk of developing a second malignancy does not contraindicate the use of cancer treatment. The overall risk of developing neoplastic complications is low, and the latency period may be long. Smoking may significantly increase the risk of secondary malignancies following some cancer treatments and therefore patients who smoke should be encouraged to stop smoking.³⁶

BIOLOGICAL AND TARGETED THERAPY

Biological and targeted therapy can be effective alone or in combination with surgery, radiation therapy and chemotherapy. Biological therapy, or biological response modifier therapy, consists of agents that modify the relationship between the host and the tumour by altering the biological response of the host to the tumour cells. Biological agents affect the host–tumour response in three ways: (1) they have direct anti-tumour effects; (2) they restore, augment or modulate host immune system mechanisms; and (3) they have other biological effects, such as interfering with the cancer cells’ ability to metastasise or differentiate (see Table 15-14). Targeted therapy interferes with cancer growth by targeting specific cellular receptors and pathways that are important in tumour growth. Targeted therapy works at sites that are on the cell surface, at the intracellular level or in the extracellular domain (see Table 15-14 and Fig 15-16). Targeted therapy is more selective for specific molecular targets than cytotoxic anticancer drugs and thus it is able to kill cancer cells without damaging normal cells.

TABLE 15-14 Biological and targeted therapy

DRUG THERAPY

CNS, central nervous system; DNA, deoxyribonucleic acid; GI, gastrointestinal; GIST, gastrointestinal stroma tumour; HER-2, human epidermal growth factor receptor 2; NK, natural killer

Figure 15-16 Sites of action of targeted therapy.

Targeted therapy includes epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors, BCR-ABL tyrosine kinase inhibitors, CD 20 monoclonal antibodies (MoAB), angiogenesis inhibitors and proteasome inhibitors. EGFR is a transmembrane molecule that works through activation of intracellular tyrosine kinase (TK). The receptor portion of EGFR, which is found on the outer surface of the cell membrane, is coupled with TK on the inner surface of the cell membrane. Binding of an agonist to EGFR activates TK, which inactivates signalling pathways that regulate cell proliferation and survival. Overexpression of EGFR is associated with unregulated growth and poor prognosis. Drugs that inhibit EGFR suppress cell proliferation and promote apoptosis (programmed cell death). EGFRs belong to the same receptor family as human epidermal growth factor receptor, the target for trastuzumab. HER-2 is overexpressed in certain cancers (especially breast cancers) and is associated with more aggressive disease and decreased survival. Trastuzumab is a monoclonal antibody that binds to HER-2 and inhibits the growth of breast cancer cells that overexpress the HER-2 protein. Trastuzumab is used in the treatment of metastatic breast cancers that overexpress HER-2.

Chronic myeloid leukaemia (CML) cells make an abnormal active enzyme called BCR-ABL tyrosine kinase. Drugs that inhibit this enzyme suppress proliferation of CML cells and promote apoptosis.

Angiogenesis inhibitors work by preventing the mechanisms and pathways necessary for the vascularisation of tumours. Bevacizumab, a recombinant human monoclonal antibody, combines with vascular endothelial growth factors (VEGF), a compound that stimulates blood vessel growth. When bevacizumab binds with VEGF, it prevents the binding of VEGF with its receptors on vascular endothelial cells. Thus it prevents VEGF from promoting new vessel formation. As a result, further tumour growth is inhibited.

Proteasomes are intracellular multi-enzyme complexes that degrade proteins. Proteasome inhibitors can cause these proteins to accumulate, thus leading to altered cell function. Normal cells are capable of recovering from proteasome inhibition but cancer cells undergo death when proteasomes are inhibited.

Side effects of biological and targeted therapy

The administration of one biological agent usually induces the endogenous release of other biological agents. The release and action of these biological agents result in systemic immune and inflammatory responses. The toxicities and side effects of biological agents are related to dose and schedule. Table 15-14 summarises the potential side effects associated with specific biological and targeted therapies.

Common side effects include constitutional flu-like symptoms, including headache, fever, chills, myalgias, fatigue, malaise, weakness, photosensitivity, anorexia and nausea. With interferon therapy, these flu-like symptoms almost invariably appear, but the severity of the symptoms generally decreases over time. Paracetamol administered every 4 hours, as prescribed, often reduces the severity of the flu-like syndrome. The patient is commonly premedicated with paracetamol in an attempt to prevent or decrease the intensity of these symptoms. In addition, large amounts of fluids help decrease the symptoms.

Tachycardia and orthostatic hypotension are also commonly reported. IL-2 and monoclonal antibodies can cause capillary leak syndrome, which can result in pulmonary oedema. Other toxic and side effects may involve the CNS, renal and hepatic systems and cardiovascular system. These effects are found particularly with interferons and IL-2.

A wide range of neurological deficits has been observed with interferon and IL-2 therapy. The nature and extent of these problems are not yet completely understood. However, these problems are understandably frightening to the patient and family, who must be taught to observe for neurological problems (e.g. confusion, memory loss, difficulty making decisions, insomnia), report their occurrence and institute appropriate safety and support measures.

MoABs (monoclonal antibodies) are administered by the infusion method. Patients may experience infusion-related symptoms, which can include fever, chills, urticaria, mucosal congestion, nausea, diarrhoea and myalgias. There is also a risk, although rare, of anaphylaxis associated with the administration of monoclonal antibodies. This potential exists because most monoclonal antibodies are produced by mouse lymphocytes and thus represent a foreign protein to the human body. The risk is significantly decreased with human MoABs. Onset of anaphylaxis can occur within 5 minutes of administration and can be a life-threatening event. If this occurs, administration of the monoclonal antibody should be stopped immediately, emergency assistance obtained and resuscitation measures implemented. (See Ch 66 for a discussion of nursing management of anaphylaxis.)

Skin rashes are common in patients receiving EGFR inhibitors and manifest generally as erythema and acneiform rashes that can cover up to 50% of the upper body. Antiangiogenics can produce life-threatening problems of arterial thrombi, haemorrhage, hypertension and proteinuria.³⁷ Other toxicities of monoclonal antibodies can include capillary leak syndrome, hepatotoxicity, bone marrow depression and CNS effects. Individuals who receive rituximab may have a reactivation of hepatitis. Patients who receive trastuzumab may also experience cardiac dysfunction, especially when it is administered in higher doses or in combination with anthracycline antibiotics, such as doxorubicin.

NURSING MANAGEMENT: BIOLOGICAL AND TARGETED THERAPY

Some problems experienced by the patient receiving biological and targeted therapy are different from those observed with more traditional forms of cancer therapy. These effects occur more acutely and are dose limited (i.e. effects resolve when the agent is discontinued). Capillary leak syndrome and pulmonary oedema are problems that require critical care nursing. Bone marrow depression occurring with biological therapy is generally more transient and less severe than that observed with chemotherapy. Fatigue associated with biological therapy can be so severe that it can constitute a dose-limiting toxicity. As these agents are increasingly combined with cytotoxic therapies, the spectrum of therapy-related effects expands.

Nursing interventions for flu-like syndrome include the administration of paracetamol before treatment and every 4 hours after treatment. IV pethidine has been used to control the severe chills associated with some biological agents. Other nursing measures include monitoring of vital signs and temperature, planning for periods of rest for the patient, assisting with activities of daily living and monitoring for adequate oral intake.

Haematopoietic growth factors

Haematopoietic growth factors are used to support cancer patients through the treatment of the disease (see Table 15-15). Colony-stimulating factors (CSFs) are a family of glycoproteins produced by various cells. CSFs stimulate the production, maturation, regulation and activation of cells of the haematological system. The name of the CSF is based on the specific cell line it affects (see Table 15-15).

TABLE 15-15 Haematopoietic growth factors used in cancer treatment

Erythopoiesis-stimulating agents (ESAs) should only be used when treating anaemia specifically caused by chemotherapy. Use of these agents has raised safety concerns because they can cause thromboembolic events and increase the risk for death and for serious cardiovascular events when administered to a patient with a haemoglobin level of greater than 120 g/L. Therefore, ESAs should be used only when blood transfusion is considered inappropriate, and the lowest dose should be used that will gradually increase haemoglobin to the lowest level sufficient to avoid the need for blood transfusion. In addition, the haemoglobin level should be monitored regularly.³⁸

Haematopoietic stem cell transplantation

Bone marrow transplantation (BMT) and peripheral stem cell transplantation (PSCT) are effective, lifesaving procedures for a number of malignant and non-malignant diseases (see Table 15-16). BMT and PSCT allow the safe use of very high doses of chemotherapy and/or radiation therapy to patients whose tumours have developed resistance or failed to respond to standard doses of chemotherapy and radiation. Although these procedures are lifesaving, patients may have long-term or delayed complications that can affect quality of life.³⁹

TABLE 15-16 Indications for haematopoietic stem cell transplantation

This therapeutic approach was typically referred to in prior years as BMT because the bone marrow was the original source of stem cells when the procedure was first developed. However, advances in harvesting and cryopreservation technologies have opened new pathways for the collection of stem cells from the peripheral blood. Consequently, the terminology is changing and it is now typical to refer to these procedures in general as haematopoietic stem cell transplantation (HSCT).³⁹ Whether the diagnosis is a malignant or non-malignant disease, the goal of HSCT is cure. Overall cure rates are still low but are steadily increasing. Even when cure is not achieved, transplant can result in a period of remission.

The approach is to eradicate tumour cells and/or clear the marrow of its components to make way for engraftment of the transplanted stem cells. This is accomplished by administering higher than usual dosages of chemotherapy with or without radiation therapy, which can produce life-threatening consequences associated with pancytopenia and other adverse effects. Infusing healthy stem cells after therapy has been completed ‘rescues’ the damaged bone marrow through the engraftment and subsequent normal proliferation and differentiation of the donated stem cells in the recipient. HSCT is an intensive procedure with many risks and some patients die from treatment-related complications or from relapse of the original disease. Because it is a highly toxic therapy, the patient must weigh the significant risks of treatment-related death or treatment failure (relapse) against the hope of cure.

TYPES OF HAEMATOPOIETIC STEM CELL TRANSPLANTS

HSCTs are categorised as allogeneic, syngeneic or autologous. The sources of stem cells include the bone marrow, peripheral circulating blood and umbilical cord blood.

In allogeneic transplantation stem cells are acquired from a donor who, through human leucocyte antigen (HLA) tissue typing, has been determined to be HLA-matched to the recipient. HLA typing involves testing WBCs to identify genetically inherited antigens that are common to both donor and recipient and that are important in the compatibility of transplanted tissue. (HLA tissue typing is discussed in Ch 13.) Often this is a family member but an unrelated donor may be found through a national or international bone marrow registry (e.g. the Australian or New Zealand Bone Marrow Donor Registries). Although there may be more risks and toxicities associated with an unrelated allogeneic transplant, an added benefit of this type of transplant is not only eradication of the tumour cells with high-dose therapy, but also the potential stimulation of the graft-versus-tumour effect, in which donor WBCs identify and attack malignant cells in the recipient. Common indications for allogeneic transplant are certain leukaemias, multiple myeloma and lymphoma.

Syngeneic transplantation is a type of allogeneic transplant that involves obtaining stem cells from one identical twin and infusing them into the other. Identical twins have identical HLA types and are a perfect match. Therefore, neither the graft-versus-host effect nor the graft-versus-tumour effect occurs.

In autologous transplantation patients receive their own stem cells back following myeloablative (bone-marrow destroying) chemotherapy (see Fig 15-17). The aim of this approach is purely ‘rescue’. It enables patients to receive intensive chemotherapy and/or radiation by supporting them with their previously harvested stem cells until their marrow is generating blood cells again on its own. Restoration usually takes 4–6 weeks depending on the particular conditioning regimen administered. Autologous transplants are typically used to treat haematological malignancies if there is no suitable donor or the patient cannot undergo allogeneic transplantation. The newer, non-myeloablative or reduced intensity transplant uses lower doses of radiation or chemotherapy that results in less toxicities and myelosuppression. HSCT continues to be investigated in the management of some solid tumours that are refractory to treatment.³⁹

Figure 15-17 Autologous stem cell transplant.

PROCEDURES

Harvest procedures

Haematopoietic stem cells are ‘harvested’ from a unique donor (for allogeneic transplantation) or from the recipient (for autologous transplantation) via two different methods. One type of procedure harvests stem cells residing in bone marrow (as the process was originally developed). The procedure is performed in the operating room using general or spinal anaesthesia. Multiple bone marrow aspirations (usually from the iliac crest but sometimes from the sternum) are carried out to obtain a specific quantity of stem cells (i.e. the number needed to ensure engraftment). The entire bone marrow harvest procedure takes about 1–2 hours and the patient can be discharged following recovery. Post-harvest, the donor may experience pain at the collection site that may last up to 7 days and can be treated with mild analgesics. The donor’s body will replenish the bone marrow removed in a few weeks.

In the other type of procedure, peripheral stem cell transplants are obtained from the peripheral blood in an outpatient procedure. It is done using cell separator equipment, which automatically separates the stem cells from the blood circulating through the machine and returns the remaining blood components to the donor. The process averages about 2–4 hours but can sometimes be longer depending on donor factors and the quality of the venous access. Often it takes more than one procedure to obtain enough stem cells. Because there are fewer stem cells in the blood than in the bone marrow, ‘mobilisation’ of stem cells from the bone marrow into the peripheral blood can be accomplished using chemotherapy and/or haematopoietic growth factors. Common growth factors that are used are granulocyte–macrophage (GM)-CSF and granulocyte (G)-CSF (see Table 15-15), but chemotherapeutic agents, typically cyclophosphamide, can also be used if there is a need to reduce tumour burden. When patients are given growth factors for mobilisation, stem cells are harvested following 4–5 days of growth factor injections.

Plerixafor is a drug given subcutaneously that, when used in combination with G-CSF, boosts the number of stem cells released from the bone marrow into the bloodstream. Plerixafor is intended to be used in combination with G-CSF for treatment of multiple myeloma or non-Hodgkin’s lymphomas.

Harvested marrow is processed to strain out bone fragments (this is not necessary with peripheral collections). The marrow or peripherally collected stem cells are then bagged with preservative for cryopreservation and storage until needed or for more immediate administration. Since they come from the patient, autologous stem cells are sometimes treated (purged) to remove undetected cancer cells. Many different pharmacological, immunological, physical and chemical agents have been used for this purpose.

Umbilical cord blood is also rich in haematopoietic stem cells and successful allogeneic transplants have been performed using this source. Cord blood can be HLA-typed and cryopreserved. A disadvantage of cord blood is the possibility of insufficient numbers of stem cells to permit transplant to adults. Considerable research is currently ongoing to define the optimal application of this technology.⁴⁰

Preparative regimens and stem cell infusions

In malignant diseases, patients receive myeloablative dosages of chemotherapy with or without adjunctive radiation to treat underlying disease. Total body radiation can be used for immunosuppression or to treat the disease. These preparative therapies are known as the ‘conditioning regimen’.

The timing of stem cell harvest and reinfusion is critical, particularly with autologous transplantation. To ensure the collection of optimally functioning stem cells in adequate numbers, conditioning is commenced only after stem cells have already been harvested. They are thawed and reinfused only after chemotherapy has been eliminated from the body (i.e. usually at about 24–48 hours) to avoid damage to newly infused cells.

Stem cell infusions are administered intravenously and can be injected via the slow bolus method or infused much like a blood transfusion. The infused stem cells reconstitute the bone marrow elements, ‘rescuing’ the recipient’s haematopoietic system. Usually 2–4 weeks are required for the transplanted marrow to start producing haematopoietic blood cells. During this pancytopenic period it is critical for the patient to be protected from exposure to infectious agents and supported with electrolyte supplements, nutrition and blood component transfusions (as needed) to maintain adequate levels of circulating RBCs and platelets.

Complications

Bacterial, viral and fungal infections are common following HSCT. Prophylactic antibiotic therapy may reduce their incidence. A potentially serious complication of allogeneic transplant is graft-versus-host disease. This occurs when the T lymphocytes from the donated marrow (graft) recognise the recipient (host) as foreign and begin to attack certain organs such as the skin, liver and GI tract. (Graft-versus-host disease is discussed in Ch 13.) The occurrence and severity of post-transplant complications are also dependent on the drugs comprising the patient’s particular conditioning regimen (some are more toxic than others) and the stem cell source. Because stem cells in the peripheral blood are more mature than those harvested from the marrow, the haematological recovery period in PSCT is shorter, and fewer, less severe complications are seen.⁴¹

Gene therapy

Gene therapy is an experimental therapy that involves introducing genetic material into a person’s cells to fight disease. Researchers are studying several ways to treat cancer using gene therapy. Some approaches target healthy cells to enhance their ability to fight cancer. Other approaches target cancer cells to destroy them or prevent their growth. In one approach, researchers replace missing or altered genes with healthy genes. Because some missing or altered genes (e.g. p53) may lead to cancer, substituting ‘working’ copies of these genes may keep cancer from developing. Researchers are also studying ways to improve a patient’s immune response to cancer. In this approach, gene therapy is used to stimulate the body’s natural ability to attack cancer cells. Other research is focused on the use of gene therapy to prevent cancer cells from developing new blood vessels (angiogenesis). Gene therapy is not used as general therapy but as part of ongoing research investigations to assess its efficacy. (Gene therapy is discussed in Ch 13.)

Complications resulting from cancer

The patient may develop complications related to the continual growth of the malignancy into normal tissue or to the side effects of treatment.

NUTRITIONAL PROBLEMS

Malnutrition

The patient with cancer often experiences protein and kilojoule malnutrition characterised by fat and muscle depletion. (Assessment of the degree of malnutrition is discussed in Ch 39.) Foods suggested for increasing the protein intake to facilitate repair and regeneration of cells are presented in Table 15-17. High-kilojoule foods that provide energy and minimise weight loss are presented in Table 15-18. A sample high-kilojoule, high-protein diet is presented in Table 39-10.

TABLE 15-17 High-protein foods

DRUG THERAPY

TABLE 15-18 High-kilojoule foods

NUTRITIONAL THERAPY

Patients with cancer will probably need a nutritional supplement as soon as a 5% weight loss is noted or if they have the potential for protein and kilojoule malnutrition. Albumin and prealbumin levels should be monitored. Once a 4.5-kg weight loss occurs in a person of normal weight, it may be difficult to maintain an adequate nutritional status. The patient should be taught to use nutritional supplements in place of milk when cooking or baking. Foods to which nutritional supplements can be added easily include scrambled eggs, pudding, custard, mashed potatoes, cereal and cream sauces. Packages of instant breakfast can be used as indicated or sprinkled on cereals, desserts and casseroles.

If the malnutrition cannot be treated with dietary intake, it may be necessary to use enteral or parenteral nutrition as an adjunct nutritional measure. (Enteral and parenteral nutrition are discussed in Ch 39.)

Altered taste sensation

Patients with cancer often complain about a bitter taste in their mouths. It is theorised that cancer cells release substances that resemble amino acids and stimulate the bitter taste buds. The patient may also experience an alteration in the sweet taste sensation, as well as in the sour and salty taste sensations. Meat may also taste bitter to the patient. The physiological basis of these varied taste alterations is unknown. Patients with altered taste problems should avoid foods they dislike. Frequently, patients feel compelled to eat certain foods because those foods are believed to be beneficial. They can experiment with spices and other seasoning agents in an attempt to mask the taste alterations that are occurring. Lemon juice, onion, mint, basil and fruit juice marinades may improve the taste of certain meats and fish. Bacon bits, onion and pieces of ham may enhance the taste of vegetables.

INFECTION

Infection is a primary cause of death in patients with cancer. The usual sites of infection include the lungs, genitourinary system, mouth, rectum, peritoneal cavity and blood (septicaemia). Infection occurs as a result of the ulceration and necrosis caused by the tumour, the compression of vital organs by the tumour and neutropenia caused by the disease process or the treatment of cancer. Outpatients with a risk of neutropenia should be instructed to call when they have a temperature of 38ºC or greater. Assessment most often includes signs and symptoms of fever, determination of possible aetiology and full blood count.

Many patients are neutropenic when an infection develops. In these individuals, infection may cause significant morbidity and may be rapidly fatal if not treated promptly. The classic manifestations of infection are not often present in a patient with neutropenia and a depressed immune system. (Neutropenia is discussed in Ch 30.)

ONCOLOGICAL EMERGENCIES

Oncological emergencies are life-threatening emergencies that can occur as a result of cancer or cancer treatment. These emergencies can be obstructive, metabolic or infiltrative.

Obstructive emergencies

Obstructive emergencies are primarily caused by tumour obstruction of an organ or blood vessel. Obstructive emergencies include superior vena cava syndrome, spinal cord compression syndrome, third space syndrome and intestinal obstruction.

Superior vena cava syndrome

Superior vena cava syndrome results from obstruction of the superior vena cava by a tumour or thrombosis. The clinical manifestations include facial oedema, periorbital oedema, distension of veins of the head, neck and chest (see Fig 15-18), headache and seizures. A mediastinal mass is often visible on chest X-ray. The most common causes are lung cancer, non-Hodgkin’s lymphoma and metastatic breast cancer. Superior vena cava syndrome is considered a serious medical problem. The presence of a central venous catheter and previous radiation therapy to the mediastinum increases the risk for the development of superior vena cava syndrome.⁴²

Figure 15-18 Superior vena caval obstruction in bronchial carcinoma. Note the swelling of the face and neck and the development of collateral circulation in the veins.

Source: Forbes CD, Jackson WF. Color atlas and text of clinical medicine. 3rd edn. London: Mosby; 2003.

Superior vena cancer syndrome is considered a serious medical problem. Management usually involves radiation therapy to the site of obstruction. However, chemotherapy may be administered for tumours more sensitive to this form of therapy.

Spinal cord compression

Spinal cord compression is a neurological emergency caused by the presence of a malignant tumour in the epidural space of the spinal cord. The most common primary tumours that produce this problem are breast, lung, prostate, GI, melanoma and renal tumours.⁴² Lymphomas also pose a risk if diseased lymph tissue invades the epidural space. The manifestations are back pain that is intense, localised and persistent, accompanied by vertebral tenderness and aggravated by the Valsalva manoeuvre; motor weakness and dysfunction; sensory paraesthesia and loss; and autonomic dysfunction. One of the clinical symptoms that reflects autonomic dysfunction is a reported change in bowel or bladder function. Radiation therapy in conjunction with prompt initiation of corticosteroids is generally associated with some initial improvement. Surgical decompressive laminectomy is used less commonly. It may be considered for patients with tumours that are relatively radioresistant or when the tumour is in a previously irradiated area. Activity limitations and pain management are important nursing interventions.

Third space syndrome

Third space syndrome involves a shifting of fluid from the vascular space to the interstitial space, which primarily occurs secondary to extensive surgical procedures, biological therapy or septic shock. Initially patients exhibit signs of hypovolaemia, including hypotension, tachycardia, low central venous pressure and decreased urine output. Treatment includes fluid, electrolyte and plasma protein replacement. During recovery hypervolaemia can occur, resulting in hypertension, elevated central venous pressure, weight gain and shortness of breath. Treatment generally involves reduction in fluid administration and fluid balance monitoring.

Intestinal obstruction

Chapter 42 presents a complete discussion of intestinal obstruction.

Metabolic emergencies

Metabolic emergencies are caused by the production of ectopic hormones directly from the tumour or secondary to metabolic alterations caused by the presence of the tumour or cancer treatment. Ectopic hormones arise from tissues that do not normally produce these hormones. Cancer cells return to a more embryological form, thus allowing the stored potential of the cells to become evident. Metabolic emergencies include syndrome of inappropriate antidiuretic hormone (SIADH), hypercalcaemia, tumour lysis syndrome, septic shock and disseminated intravascular coagulation.

Syndrome of inappropriate antidiuretic hormone

SIADH results from abnormal or sustained production of antidiuretic hormone (ADH) with resultant water retention and hyponatraemia (see Ch 49). SIADH occurs most frequently in carcinoma of the lung (especially small cell lung cancer) but can also occur in cancers of the pancreas, duodenum, brain, oesophagus, colon, ovary, prostate, bronchus and nasopharynx; leukaemia; mesothelioma; reticulum cell sarcoma; Hodgkin’s lymphoma; and thymoma. Cancer cells in these tumours are actually able to manufacture, store and release ADH. The chemotherapeutic agents vincristine and cyclophosphamide also stimulate the release of ADH from the pituitary or tumour cells. Symptoms of SIADH include weight gain, weakness, anorexia, nausea, vomiting, personality changes, seizures and coma. Treatment of SIADH includes treating the underlying malignancy and measures to correct the sodium–water imbalance, including fluid restriction and, in severe cases, IV administration of 3% sodium chloride solution. The sodium level should be monitored because correcting SIADH rapidly may result in seizures or death.⁴³

Hypercalcaemia

Hypercalcaemia can occur in the presence of cancer that involves metastatic disease of the bone or multiple myeloma, or when a parathyroid hormone-like substance is secreted by cancer cells in the absence of bony metastasis. Hypercalcaemia resulting from malignancies that have metastasised occurs most frequently in patients with lung, breast, kidney, colon, ovarian or thyroid cancer. Hypercalcaemia resulting from secretion of parathyroid hormone-like substance occurs most frequently in squamous cell carcinoma of the lung; head and neck, cervical and oesophageal cancer; lymphomas; and leukaemia. Immobility and dehydration can contribute to or exacerbate hypercalcaemia.

The primary manifestations of hypercalcaemia include apathy, depression, fatigue, muscle weakness, electrocardiogram changes, polyuria and nocturia, anorexia, nausea and vomiting. Serum levels of calcium in excess of 3 mmol/L will often produce symptoms, and significant calcium elevations can be life-threatening. Serum calcium levels are affected by a low albumin level. A low albumin will give a false-normal calcium level. Therefore, the calcium level needs to be adjusted for serum albumin levels or an ionised calcium level needs to be checked.⁴³ Chronic hypercalcaemia can result in nephrocalcinosis and irreversible renal failure. The long-term treatment of hypercalcaemia is aimed at the primary disease. Acute hypercalcaemia is treated by hydration (3 L/day), diuretic (particularly loop diuretics) administration and a bisphosphonate (a drug that inhibits the action of osteoclasts). Infusion of the bisphosphonate zoledronic acid or pamidronate is the treatment of choice. These drugs are also used to prevent bone complications in patients with bone metastasis.

Tumour lysis syndrome

Acute tumour lysis syndrome (TLS) is a metabolic complication characterised by rapid release of intracellular components in response to chemotherapy. It occurs less commonly with radiation therapy. TLS is often associated with tumours that have high growth rates and are sensitive to the effects of chemotherapy. Massive cellular destruction, associated with aggressive chemotherapy for rapidly growing tumours, releases a host of intracellular components into the bloodstream, including potassium, phosphate, and DNA and RNA components (which are metabolised to uric acid by the liver). A rise in the serum phosphate level drives serum calcium levels down, with resultant hypocalcaemia. Metabolic abnormalities and concentrated uric acid (which crystallises in the distal tubules of the kidneys) quickly lead to acute renal failure if this is not identified and treated early.

The four hallmark signs of TLS are hyperuricaemia, hyperphosphataemia, hyperkalaemia and hypocalcaemia. Early symptoms include weakness, muscle cramps, diarrhoea, nausea and vomiting.⁴³ TLS usually occurs within the first 24–48 hours after the initiation of chemotherapy and may persist for approximately 5–7 days. The primary goal of TLS management is preventing renal failure and severe electrolyte imbalances. The primary treatment includes increasing urine production using hydration therapy and decreasing uric acid concentrations using allopurinol.⁴⁴

Septic shock and disseminated intravascular coagulation

Septic shock is discussed in Chapter 66, and disseminated intravascular coagulation is discussed in Chapter 30.

Infiltrative emergencies

Infiltrative emergencies occur when malignant tumours infiltrate major organs or secondary to cancer therapy. The most common infiltrative emergencies are cardiac tamponade and carotid artery rupture.

Cardiac tamponade

Cardiac tamponade results from fluid accumulation in the pericardial sac, constriction of the pericardium by tumour or pericarditis secondary to radiation therapy to the chest. Manifestations include a heavy feeling over the chest, shortness of breath, tachycardia, cough, dysphagia, hiccups, hoarseness, nausea, vomiting, excessive perspiration, decreased level of consciousness, pulsus paradoxus, distant or muted heart sounds and extreme anxiety. Emergency management is aimed at reducing fluid around the heart and includes surgical establishment of a pericardial window or an indwelling pericardial catheter. Supportive therapy includes administration of oxygen therapy, intravenous hydration and vasopressor therapy.

Carotid artery rupture

Rupture of the carotid artery occurs most frequently in patients with cancer of the head and neck secondary to invasion of the arterial wall by tumour or erosion following surgery or radiation therapy. Bleeding can manifest as minor oozing or spurting of blood in the case of a ‘blow-out’ of the artery. In the presence of a blow-out, pressure should be applied to the site with a finger. Intravenous fluid and blood products are administered in an attempt to stabilise the patient for surgery. Surgical management involves ligation of the carotid artery above and below the rupture site and reduction of local tumour.

Management of cancer pain

Moderate-to-severe pain occurs in approximately 50% of patients who are receiving active treatment for their cancer and in 80–90% of patients with advanced cancer. It is important to note that these statistics have not changed in the past 30 years (see Ch 8 for detailed discussion of pain). Undertreatment of cancer pain is common and causes needless suffering, hampers quality of life and increases the burden on family carers.⁴⁵

The National Comprehensive Cancer Network has clinical practice guidelines that describe the management of cancer pain.⁴⁶ Inadequate pain assessment is the single greatest barrier to effective pain management. Data such as vital signs and patient behaviours are not reliable indicators of pain, especially longstanding, chronic pain. It is important to distinguish between persistent pain and breakthrough pain, and thus a comprehensive pain assessment should include a detailed history to determine the presence of persistent pain and breakthrough pain. Pain management plans need to be developed to address both components of pain if they are present.⁴⁷

As part of the plan, patients should be taught how to keep a pain management diary. Ongoing assessment of cancer pain is needed to determine the effectiveness of the treatment plan. Data need to be obtained and documented initially and at regular intervals on the location and intensity of the pain, what it feels like and how it is relieved. Patterns of change should also be assessed. The patient report should always be believed and accepted as the primary source of assessment data. Table 15-19 presents assessment questions that may facilitate this data collection.

TABLE 15-19 Pain assessment in cancer patients

Drug therapy, including non-steroidal anti-inflammatory drugs, opioids and adjuvant pain medications, should be used. Opioids are normally prescribed for the treatment of moderate-to-severe cancer pain. Analgesic medications (e.g. morphine, fentanyl) should be given on a regular schedule (around the clock), with additional doses available as needed for breakthrough pain. In general, oral administration of the medication is preferred, but other routes (e.g. transdermal) are also available. It is important to remember that with opioid drugs such as morphine, the appropriate dose is whatever is necessary to control the pain with the least side effects. Fear of addiction is not justified as it rarely, if ever, occurs when given for pain relief, but it is an issue that must be addressed as part of patient teaching relevant to pain control, since it is a significant barrier to appropriate pain management for both the patient and the nurse (see Ch 8).

Patient education should clarify myths and misconceptions and reassure patients and family carers that cancer pain can be relieved effectively. Furthermore, addiction and tolerance are not problems associated with effective cancer pain management.⁴⁷ Non-drug interventions, including relaxation therapy and imagery, can be effectively used to manage pain.

Psychological support

Psychological support of the patient is an important aspect of cancer care. The patient with cancer may experience a variety of psychosocial concerns, including fears of dependency, loss of control, familial or financial burden, and fear of death. Distress may be experienced at many points throughout the cancer continuum including at diagnosis, during or after treatment, and in association with long-term follow-up visits. Adaptation and coping with a cancer diagnosis may be influenced by a variety of factors including demographic factors, prior coping skills and strategies, social support, and religious and spiritual beliefs.⁴⁸ Nurses are in a key position to assess the patient’s and family’s responses and support positive coping strategies.

The following factors may influence how the patient will cope with the diagnosis of cancer:

1. Ability to cope with stressful events in the past (e.g. loss of job, major disappointment). By simply asking how the patient has coped with previous stressful events, the nurse can gain an understanding of the patient’s coping patterns, the effectiveness of the usual coping patterns and the usual coping time framework. Furthermore, prior history of a significant traumatic event (or posttraumatic stress disorder) may predict greater difficulty adapting to a diagnosis for some patients.

2. Availability of significant others. The patient who has effective support systems tends to cope more effectively than the patient who does not have a meaningful, available support system.

3. Ability to express feelings and concerns. The patient who is able to express feelings and needs and who seeks and asks for help appears to cope more effectively than the patient who internalises feelings and needs.

4. Age at the time of diagnosis. Age determines coping strategies to a great degree. For example, a young mother with cancer will have concerns that differ from those of a 70-year-old woman with cancer.

5. Extent of disease. Cure or control of the disease is usually easier to cope with than the reality of terminal illness.

6. Disruption of body image. Disruption of body image (e.g. due to radical neck dissection, alopecia, mastectomy) may intensify the psychological impact of cancer.

7. Presence of symptoms. Symptoms such as fatigue, nausea, diarrhoea and pain may intensify the psychological impact of cancer.

8. Past experience with cancer. Negative experiences with cancer (personal or in others) are likely to influence perceptions about the current situation.

9. Attitude associated with the cancer. A patient who feels in control and has a positive attitude about cancer and cancer treatment is better able to cope with the diagnosis and treatment of cancer than the patient who feels hopeless, helpless and out of control.

10. Access to social support systems and services. Limited availability of specialist cancer services diminishes as geographical isolation increases, and access to professional and psychological services may be more difficult for those who live in more isolated rural and remote areas.

To facilitate the development of a hopeful attitude about cancer and to support the patient and family during the various stages of the process of cancer, the nurse should do the following:

1. Be available and continue to be available, especially during difficult times.

2. Exhibit a caring attitude.

3. Listen actively to fears and concerns.

4. Provide relief from distressing symptoms.

5. Provide essential information regarding cancer and cancer care.

6. Maintain a relationship based on trust and confidence; be open, honest and caring in the approach.

7. Use touch to exhibit caring. A squeeze of the hand or a hug may at times be more effective than words.

8. Assist the patient in setting realistic, reachable short-term and long-term goals.

9. Assist the patient in maintaining usual lifestyle patterns.

10. Maintain hope, which is the key to effective cancer care. Hope varies, depending on the patient’s status—hope that the symptoms are not serious, hope that the treatment is curative, hope for independence, hope for relief of pain, hope for a longer life or hope for a peaceful death. Hope provides control over what is occurring and is the basis of a positive attitude towards cancer and cancer care.

Organisations and journals available as resources for the nurse are listed in the Resources on p 348. In many states and cities, local units of the Cancer Council Australia or the Cancer Society of New Zealand provide a wide variety of services.

Cancer survivorship

At the end of 2004 (the latest available figures) there were an estimated 654,777 Australians who had a history of cancer in the past 23 years.⁴⁹ In New Zealand, between 1994 and 2007, the cumulative relative survival ratio for all adult cancers was 0.607 after 5 years of follow-up and 0.570 after 10 years of follow-up.⁵⁰ Given progressive advances in early detection and treatment, further increases in the prevalence of cancer survivors are expected.⁵¹

Along with the rapid increase in cancer survivors is coming greater awareness of the long-term health and quality-of-life burden that a cancer diagnosis imposes. Cancer survivors experience a variety of long-term and late effects following treatment. The impact of cancer and its treatment confers greater risk of non-cancer-related death and comorbidities (e.g. heart disease, diabetes, metabolic syndrome, endocrine dysfunction, osteoporosis) among cancer survivors than found among the general population. Furthermore, cancer survivors may continue to experience symptoms or functional impairment related to treatment for years following treatment.

Gerontological considerations: cancer

Cancer is often a disease of ageing, with most cancers occurring in people over the age of 65. Of those diagnosed with cancer in Australia in 2007, 56.7% were aged over 65. Cancer mortality is also exceedingly high in older people, with 73.3% of all cancer deaths in Australia in 2007 occurring in those over the age of 65.⁵² This is especially important since life span is lengthening and the over-65 population is growing—it is expected to double from 13% of the Australian population in 2004 to 26–28% by 2051, and from 12% of the New Zealand population in 2005 to more than 25% in 2030.

Clinical manifestations of cancer in older adults may be mistakenly attributed to age-related changes and ignored by the person.⁵³ Older adults are particularly vulnerable to the complications of both cancer and cancer therapy. This is due to their decline in physiological functioning, social and emotional resources, and cognitive function. The functional status of an older adult should be taken into consideration when selecting a treatment plan. Age alone is not a good predictor of tolerance or response to treatment. Advances in the treatment of cancer are making cancer therapies beneficial to an increasing number of older adults, including patients with suboptimal health. Some important questions to consider when an older person is diagnosed with cancer include: Will the treatment provide more benefits than harm? Will the patient be able to tolerate the treatment safely? What are the patient’s preferences and wishes?

The impact of a cancer diagnosis can affect many aspects of a person’s life, with cancer survivors commonly reporting financial, vocational, marital and emotional concerns, even long after treatment is over. The psychosocial effects experienced after cancer treatment can play a profound role in a patient’s life after cancer, with issues related to living in uncertainty being frequently encountered.

It is essential for nurses to understand the meaning of the cancer experience for each individual in order to better assist survivors.⁵⁴ Some patients may wish to return to their normal lives as soon as possible; such behaviour may result in them not attending scheduled follow-up appointments. Other survivors may become cancer advocates or become active members of a cancer support group. Still others may allow their lives to revolve around the cancer and may even become resistant to giving up the illness role. The Australian Cancer Survivorship Centre has recently been established to assist the development of services and promote research, education and discussion within the health system to increase knowledge about cancer survivorship (see the Resources on p 348).

Nurses can help cancer survivors by doing the following:

1. providing all cancer patients with a treatment summary and care plan outlining treatment exposures, the risk of late effects, preventative care recommendations and a follow-up surveillance plan after completion of treatment

2. educating other healthcare providers about the needs of cancer survivors, including long-term effects of cancer and cancer treatments

3. teaching cancer survivors to look for and report late effects of radiation therapy and chemotherapy and to report ongoing or intrusive symptoms resulting from treatment

4. promoting healthy behaviours regarding prevention (such as good nutrition, exercise, smoking cessation and avoidance, maintaining proper weight, reducing cardiac risk, bone health) and early detection (such as routine health screenings—e.g. breast, cholesterol, diabetes, osteoporosis—as recommended)

5. encouraging cancer survivors to have regular follow-up examinations with an identified general practitioner

6. assessing for psycho-emotional, financial or vocational problems related to cancer and assisting patients in getting appropriate help if necessary.

Information disclosure

CLINICAL PRACTICE