Nutrition and Cancer E-Book

Clare Shaw

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 811

Veröffentlichungsjahr: 2010

Beschreibung

Nutrition plays a crucial role in supporting patients receiving treatment for cancer. Carefully considered nutritional options can help to manage patients with weight loss and cachexia, support the patient’s ability to recover from surgery and cope with treatments such as chemotherapy and radiotherapy. Patients living with and beyond cancer can also benefit from advice on optimal nutrition and lifestyle changes.

Edited by Dr Clare Shaw, Consultant Dietitian at The Royal Marsden NHS Foundation Trust, Nutrition and Cancer takes an unrivalled look at this prevalent disease, offering the reader:

• An insight into the nutritional challenges faced for patients with cancer
• A practical guide to nutrition and dietetic practice in cancer care
• A detailed look at nutritional options for different diagnostic groups
• Contributions from a wide range of cancer specialists

An excellent resource for dietitians, clinical nutritionists, doctors, nurses and other health professionals working with cancer patients, this book is also a fascinating reference for students and researchers with an interest in the area.

Leseprobe

Contents

Cover

Half Title Page

Title Page

Copyright

Contributors

Preface

Chapter 1: Cancer in the twenty-first century

Introduction

What is cancer and what causes it?

Development and spread of cancer

What is the global burden of cancer?

Whom does cancer affect?

Historical perspective on cancer treatment

Cancer survivorship – living with and beyond cancer

Nutrition and cancer

Chapter 2: Cancer and nutritional status

Introduction

Nutritional status and outcome in cancer patients

Cancer cachexia

Pathogenesis of anorexia and reduced energy intake

Pathogenesis of wasting

Cancer cachexia: a neurological disease?

Summary

Chapter 3: Treatment of cancer

Introduction

Treatment intent

Treatment setting

Treatment modalities

Conclusion

Chapter 4: Effect of malnutrition on cancer patients

Introduction

Prevalence of malnutrition amongst cancer patients

Effect of malnutrition on outcome

Mortality

Type of cancer

Nutritional status as a prognostic indicator

Morbidity

Quality of life

Chapter 5: Nutrition screening

Introduction

Scored Patient-Generated Subjective Global Assessment

Malnutrition Universal Screening Tool

Mini Nutritional Assessment

Nutritional Risk Screening

Malnutrition Screening Tool

Conclusion

Summary

Chapter 6: Nutritional requirements of patients with cancer

Introduction

Energy

Methods used to estimate energy requirements

Disease-specific requirements

Staging and tumour burden

Treatment

Response to treatment

Tumour recurrence

Inflammatory response and cachexia

Protein

Micronutrients

What should we do in clinical practice?

Summary

Chapter 7: The psychosocial influences of food choices made by cancer patients

Introduction

Food and cancer

Influences of food choices

Other dietary approaches patients choose to take and the reasons why

Sourcing information

Summary

Chapter 8: Nutritional support for the cancer patient

Introduction

Food provision in a health care setting

Symptom management

Oral nutritional supplements

Artificial nutrition support

Summary

Chapter 9: Late effects of cancer treatment in adult patients

Cancer is a chronic disease

What is survivorship?

Who should the dietitian aim to help?

The stocktaking interview at the end of the treatment

The metabolic syndrome

Management of the metabolic syndrome

Malnutrition in the cancer survivor

Summary

Chapter 10: Nutrition and palliative care

Introduction

The role of nutrition in palliative care

Psychological aspects of food intake

Nutrition support in palliative care

Management of nutritional problems

Artificial nutrition support in palliative care

Summary

Chapter 11: Head and neck cancer

Introduction

The impact of malnutrition

Treatment in head and neck cancer

Nutritional intervention and outcomes

Immunonutrition

Functional implications following surgery

Nutrition effects in radiotherapy and chemoradiotherapy

Nutritional management

Nutritional screening

Nutritional assessment

Nutritional requirements

Oral nutrition support

Enteral nutrition support

Nutrition monitoring and rehabilitation

Summary

Chapter 12: Nutrition in upper gastrointestinal cancer

Introduction

Epidemiology and aetiology

The upper gastrointestinal anatomy

Clinical presentation

Staging

Treatment pathways and role of nutrition

Advanced disease

Summary

Chapter 13: Cancers of the lower gastrointestinal tract

Introduction

Nutritional management

Symptom management in palliative care

Summary

Chapter 14: Gynaecological cancer

Introduction

Ovarian cancer

Endometrial cancer

Cervical cancer

Vulval and vaginal cancers

Nutritional issues

Nutritional implications of treatment

Medical problems

Nutrition and survivorship

Summary

Chapter 15: Haemato-oncology

Introduction

Disease characteristics and nutritional implications at diagnosis

Nutritional implications during induction and intensification treatment

Stem cell transplantation (consolidation phase)

Nutrition support post-transplantation

Long-term implications following transplantation

Summary

Chapter 16: Paediatric oncology

Introduction

Types of childhood cancers

Aetiology of malnutrition in children with cancer

Identification of nutritional risk

Nutritional support

Chapter 17: Nutrition and breast cancer

Introduction

The role of diet in breast cancer aetiology and survival

Gestational nutrition and subsequent birth weight

Breastfeeding

Body fatness, body composition and weight management

Alcohol

Dietary fat

Fruits and vegetables (including beans and pulses)

Dairy foods

Meat and meat products

Specific nutrient associations and nutritional supplements

Contaminants in foods

Physical activity

Benefits of physical activity to breast cancer survivors

Nutritional problems during breast cancer treatment

Summary

Chapter 18: Nutritional management in prostate cancer

Introduction

Dietary factors that may reduce the risk of prostate cancer

Factors that may increase risk of prostate cancer

Dietary interventions and prostate cancer progression

Obesity/weight management

Nutritional issues during treatment for prostate cancer

Nutrition-related side effects of medications used to treat prostate cancer

Malnutrition in prostate cancer

Palliative care in prostate cancer

Summary

Chapter 19: Lung cancer

Introduction

Diet and development of lung cancer

Nutritional status at presentation

Treatment of non-small cell lung cancer

Treatment of small cell lung cancer

Treatment of mesothelioma

Palliative treatments

Symptom management

Summary

Index

Nutrition and Cancer

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Library of Congress Cataloging-in-Publication Data

Nutrition and cancer / edited by Clare Shaw. p. ; cm. Includes bibliographical references and index. ISBN 978-1-4051-9042-8 (pbk. : alk. paper) 1. Cancer–Nutritional aspects. I. Shaw, Clare, 1963- [DNLM: 1. Neoplasms–diet therapy. 2. Nutrition Therapy–methods. 3. Nutritional Physiological Phenomena. QZ 266 N9757 2011] RC268.45 .N873011 616.99′40654–dc22 2010018328

A catalogue record for this book is available from the British Library.

This book is published in the following electronic formats: ePDF 9781444329292; ePub: 9781444329308

Contributors

Jervoise AndreyevThe Royal Marsden NHS Foundation Trust, London, UK

Gayle BlackThe Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK

Saira ChowdhuryDepartment of Nutrition and Dietetics, Guy's and St. Thomas' Hospital NHS Foundation Trust, London, UK

Mhairi DonaldSussex Cancer Centre, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK

Natalie DoyleThe Royal Marsden NHS Foundation Trust, London, UK

Lucy EldridgeBarts and the London NHS Trust, London, UK

Filippo Rossi FanelliSapienza University of Rome, Rome, Italy

Louise HenryThe Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK

Orla HynesDepartment of Nutrition and Dietetics, Guy's and St. Thomas' Hospital NHS Foundation Trust, London, UK

Alessandro LavianoSapienza University of Rome, Rome, Italy

Sian LewisVelindre Hospital, Cardiff, Wales, UK

Kathryn ParrClatterbridge Centre for Oncology NHS Foundation Trust, Wirral, UK

Barbara ParryWinchester and Andover Breast Unit, Royal Hampshire County Hospital, Winchester, UK

Sanjay PopatThe Royal Marsden NHS Foundation Trust, London, UK

Jane PowerBetsi Cadwaladr University Health Board and Wrexham Maelor Hospital, Wrexham, Wales, UK

Isabella PreziosaSapienza University of Rome, Rome, Italy

Clare ShawThe Royal Marsden NHS Foundation Trust, London, UK

Bella TalwarHead and Neck Cancer Services, University College London Hospitals NHS Trust, London, UK

Evelyn WardThe Leeds Children's Hospital, The Leeds General Infirmary, Leeds, UK

C. Elizabeth WeekesGuy's and St Thomas' NHS Foundation Trust, London, UK

Cherry VickeryNorth Wales Cancer Treatment Centre, Betsi Cadwaladr University Health Board (Central), Wales, UK

Preface

Good nutrition is essential for good health. However, maintaining a good nutritional status and adequate nutritional intake during illness is often difficult. Weight loss, reduced intake of food and fluid may be early presenting symptoms of disease, particularly cancer. These changes may proceed to profoundly influence body composition, functional ability and quality of life. After a diagnosis of cancer, the focus is on successfully treating the cancer and importantly managing symptoms that patients may experience. Treatment modalities such as surgery, chemotherapy, radiotherapy and novel treatments such as targeted therapies are often used in combination or sequentially. Increasingly, these treatments are successful, and there are now rising numbers of people living with and beyond cancer.

When cancer is diagnosed, the patient embarks on investigations and a treatment pathway. Often, the issues relating to weight loss and nutritional risk are poorly addressed at this time. This is despite the fact that high levels of malnutrition in cancer patients have been documented for many years. Treatment modalities may cause a further deterioration in nutritional status which ultimately impacts on functional status, ability to tolerate treatment, quality of life and potentially survival. Not all cancer diagnoses and treatments will have the same effect on nutritional status, so individualised screening, assessment and appropriate advice and support are essential to address individual problems.

Whilst it is known that poor nutritional status can impact on an individual's ability to undergo cancer treatment, there is a paucity of nutrition intervention studies to demonstrate the best method of nutritional support, when more intensive nutritional support should be commenced, which clinical outcomes can be influenced and to what extent. Nutritional issues may contribute to health both during treatment and throughout the person's life. Some patients may have no long-term nutritional problems, but for others their appetite, ability to eat, digest and absorb food may be altered irreversibly. Some may struggle with changes in body weight or function, whilst others consider how their future diet can influence their health and survival.

This book aims to explore many of the nutritional issues that occur after a diagnosis of cancer. Although there is increasing evidence of the role of diet as a causative factor in the development of cancer, this aspect of diet is addressed in a number of excellent publications elsewhere.

The first part of this book addresses a number of generic aspects of nutrition that apply across different diagnostic groups. It looks at the physiological changes that may occur in cancer and the impact these may have on clinical outcomes. It outlines current cancer treatments which ultimately influence nutritional management as screening, assessment and the provision of nutrition support must be tailored to patients' needs during the treatment pathway. Nutritional problems do not finish at the end of treatment. Increasingly, it is becoming clear that problems may arise weeks, months or years after treatment has finished. Patients should be made aware that follow-up after treatment will focus not only on disease-free survival but also on potential side effects that can impact on quality of life. These are outlined in the chapter on late effects of treatment. Nutrition may continue to be important for patients for whom a cure is not possible and should be included in holistic assessment and care.

The second part of the book looks in more detail at particular diagnoses that have specific nutritional needs. Knowledge of the potential nutritional problems that may occur in the short and long term enables these aspects of care to be monitored and appropriate interventions to be planned. Increasingly, new treatments are being introduced, particularly multimodality treatments that may have a greater impact on nutritional status. A more detailed knowledge of these enables better planning, monitoring and ultimately better patient outcomes. Survivorship issues, in particular diagnoses, focus on the need for long-term healthy eating and lifestyle advice to potentially impact on recurrence of cancer and to reduce the chance of comorbidities such as heart disease, diabetes and obesity.

Research on nutrition for the cancer patient is sadly lacking. Whilst the implications of reduced performance status and poor nutritional status on patient outcomes are documented, there is still a lack of conclusive research data on the potential effect of improvement in nutritional status and clinical outcomes such as morbidity and mortality. Where data exist it is often very specific, clearly defined and in particular diagnostic groups. In the absence of such data, the health care professional may need to turn to general nutrition recommendations and position papers produced by expert groups such as ESPEN and ASPEN. This book aims to be patient focused and not specific to the provision of health care in either a hospital or community care.

Authors who have contributed to this book have brought together research evidence, generic nutrition recommendations and a wealth of clinical expertise from their area of work to help guide the reader to understand the nutritional problems patients may experience, methods of providing optimal support, where research evidence exists and where it does not. It is anticipated that the reader may not read the book as a whole but may identify sections relevant to their patient group or particular nutritional problem. Ultimately, it is hoped that nutrition will become a more integral part of the cancer patient's care from diagnosis to end of life, wherever that care may be provided.

Clare Shaw

Chapter 1

Cancer in the twenty-first century

Natalie Doyle and Clare Shaw

Introduction

Cancer was recognised as a disease many centuries ago, being mentioned by the ancient Egyptians in 1500 BC. Much later, Hippocrates used the Greek words to describe a crab, carcinos and carcinoma, to describe tumours. The Greek word ‘karkinoma’, meaning a crab, was used because of the likeness of blood vessels extending out of a tumour to a crab's body and legs. It is known from early Egyptian papyrus that attempts were made to burn or cauterise tumours but that this was always to no avail.

Much has changed since ancient times. Cancer is now part of everyday vocabulary around the world, and although cancer remains the leading cause of death, much has changed with respect to its diagnosis and treatment. Today, it is recognised that about one-third of all cancers are preventable, and improvements in detection and treatment have meant that many people survive the cancer and treatment. Survival rates around the World, however, vary greatly (Coleman et al., 2008). Most of the wide global range in cancer survival is attributable to differences in access to diagnostic and treatment services.

What is cancer and what causes it?

Cancer is not a single disease but rather a group of diseases characterised by uncontrolled cellular growth. There are over 200 different types of cancer arising from different cells of the body. In normal circumstances of cell and tissue division, differentiation and cell death are carefully regulated processes. Cancer can arise when a single cell has lost control of the normal balance of cell proliferation and cell death and appropriate cell different-iation.

Usual cell division involves the exact replication of the DNA helix. For this to take place accurately, a number of mechanisms are in place, and these are influenced by chemicals from within the cell itself, from different cells or by hormones produced by distant tissues and transported in the bloodstream. These influence cell division by binding to receptors on the cell surface and transmitting signals to the cell to stop or start the process of division. Binding with cell receptors involves the process of phosphorylation or dephosphorylation, which is necessary to transmit the appropriate signal within the cell.

Hundreds of proteins, or genes, are involved in the processes within the cell that involve the exact replication of the DNA helix. Transcription factors are the proteins involved in the regulation of gene expression and carry the signals from the cell surface to the nucleus of the cell and therefore the DNA.

Genes involved in cell division can be divided into four main types, and it is thought that tumours have a fault or mutation in one or more copies of these genes (see Table 1.1).

Table 1.1 Different cancer-causing genes

Type of genesActionOncogenesInitiate cell division, when faulty increases the rate of transformation from a normal cell to a cancer cell.Tumour-suppressor genesPrevent excessive growth of a cell either by control of cell proliferation or by control of DNA repair rate.DNA repair genesWork in different ways to repair damaged DNA, for example, to correct mismatched bases, copying errors, errors that distort structure of DNA.Apoptosis genesCells are programmed to reproduce a certain number of times and then they die. There are genes within the cell that control the process. There is much interest in these genes as they may help the understanding of how cells start to self-destruct.

Knowledge of the underlying genetic causes of cancer has increased rapidly particularly within the past 30 years and has resulted in improvements in the prevention, detection and treatment of cancer. Significant progress has been made in the identification of genes responsible for both sporadic and familial cancers such as BRCA1, BRCA2 (breast, ovarian, colon and prostate cancer) and APC (familial adenomatous polyposis for colon cancer). It is also now accepted that as well as genetic mutations, epigenetic changes and the interactions of genes with lifestyle factors, such as smoking, diet, body weight and exercise, affect the development of cancer. This knowledge brings with it the challenge of how to develop measures to prevent cancers forming. In some familial cancers, this may be through screening, chemoprevention, prophylactic surgery and lifestyle changes.

The environmental factors for cancer development also vary greatly around the world. Increasingly, it is recognised that it is this interaction between genetics and the environment that plays a role in the development of cancer.

The known lifestyle, infectious agents or genetic abnormalities that can cause cancer are outlined in Table 1.2. The causes of cancer are multifactorial, and in any individual different factors will either contribute or protect against the development of cancer.

Table 1.2 Factors contributing to the development of cancer

CarcinogensSubstances such as asbestos and tobacco smoke are known carcinogens although not all those exposed will necessarily develop cancer.AgeThree non-mutually exclusive factors may explain the association of ageing and cancer: (1) the lengthy process of carcinogenesis, (2) molecular changes to tissue with age and (3) age-related environmental changes favouring the growth of cancer cells.Genetic make-upA proportion of cancers occur in individuals who are genetically predisposed to develop these cancers. This is about 5–10% of common cancers. The most common abnormality is the BRCA1 and BRCA2 genes that increase the risk of breast and ovarian cancer in women and prostate cancer in men.The immune systemCancer is more common in people who have a suppressed immune system which may be due to drugs, for example after organ transplantation, disease affecting the immune system such as HIV or AIDS or in rare medical conditions where the immune system is affected. These conditions tend to increase the rate of cancers caused by viruses such as cervical cancers or in the development of lymphomas.Body weight, diet and physical activityIncreased body weight, diet and lack of physical activity are thought to contribute to approximately one-third of all cancers worldwide. A thorough and comprehensive review of the evidence has been undertaken by the World Cancer Research Fund and enabled dietary recommendations relating to food intake, body weight and physical activity that are aimed to reduce the risk of cancer (World Cancer Research Fund, 2007). Generally, higher rates of cancer are observed in countries where the diet is lower in fruits, vegetables and plant-based foods and higher in animal products such as meat. The consumption of alcohol, salty foods and mouldy foods also contributes to an increased risk of cancer.EnvironmentEnvironmental hazards include exposure to tobacco smoke, radiation, work-related carcinogens such as asbestos and exposure to the sun. It is difficult to quantify the actual contribution of all these elements to cancer risk.VirusesSome cancers can be attributed to viral infections, and it is thought that these may represent approximately 15% of all cancers. Cervical cancer, Kaposi's sarcoma and hepatocellular cancer are all caused by viruses. It is thought that the action is by stimulation of cellular proliferation that is not inhibited by normal cellular or immune control mechanisms.Bacterial infectionSome bacterial infections cause cancer; for example, Helicobacter pylori causes approximately 60% of stomach cancers in developed countries. It works by invading the stomach lining and causing chronic gastritis.Doll and Peto (1981), World Cancer Research Fund (2007) and Cancer Research UK (2010a).

Development and spread of cancer

Cells, whether they are normal or cancerous, grow and interact with adjacent cells and tissues through a complex network of control signalling, which involves communication via both compounds within the membrane of the cell and extracellular growth factors and cytokines. These bind to receptors on the membrane of the cell and influence cell proliferation and differentiation. In cancer, these processes may be altered to produce an unregulated growth of abnormal cells.

As cancer cells divide and grow, they occupy space in the surrounding normal tissue. This is known as local invasion and can result in the cancer-infiltrating local tissue, blood vessels and the lymph system. When the cancer cells become detached from the primary tumour and enter the bloodstream or the lymphatics, they can become lodged in other tissues in the body. This is a complex process as the cells must penetrate blood vessels or lymphatics to spread throughout the body. Eventually, the cancer cells must develop a new blood supply to grow into a secondary or metastatic cancer.

It is likely that some of the cells that spread are killed by the body's immune system but others may lodge in tissues separate from the primary site of the cancer, causing secondary tumours or metastasis. Often this initial spread will not be detectable by current methods of scanning and is deemed as micrometastases. The pattern of spread is particular to different primary diagnoses but may include spread to essential organs such as the lungs, liver, brain and bones. For some diseases, this spread may have already occurred and therefore may be already present at the initial diagnoses, whilst for others they live with the uncertainty of whether the cancer will recur as metastases. For some types of cancer, this intervening period between treatment of the initial primary cancer and detection of metastases may be a number of years, indicating that the cells may remain dormant or very slow growing during this period.

The aim of the treatment of cancer is not only to eradicate the initial site of cancer growth but also to treat or prevent the spread of cancer cells to other tissues and organs in the body (see Chapter 3 on treatment of cancer). This requires both the detection of such disease and appropriate methods of destroying these cancer cells whilst maintaining the integrity and function of the remaining tissues and organs.

What is the global burden of cancer?

Cancer is an important cause of ill health worldwide. In 2008, an estimated 12.4 million people were diagnosed with cancer. The most common cancers, primarily breast, lung, stomach, bowel or prostate cancer, accounted for 50% of diagnoses. The large populations in Asia mean that they account for a large number of the total global cancer burden and actually represent 45% of all those diagnosed with the most common cancers listed. The contribution of cancer as the cause of death varies around the world (see Figure 1.1). This figure is influenced by the age demographics of the population and access to health care. Generally, survival is positively associated with gross domestic product and the amount of investment in health care. For example, for colorectal cancer, 5-year survival for patients ranges from around 60% in North America, Japan, Australia and France down to 40% in Algeria, Brazil, Czech Republic, Estonia, Poland, Slovenia and Wales (Coleman et al., 2008). Rates also vary within a country with those having access to health insurance showing higher rates of survival.

Figure 1.1 Percentage of all deaths due to cancer in the different regions of the world. (Reproduced with kind permission of Cancer Research UK, 2010b.)

There are 6.7 million reported deaths from cancer annually; again half of these deaths are in Asia, making up 12% of deaths worldwide. This is more than HIV/AIDS, malaria and tuberculosis combined. It is estimated that there are 24.6 million people alive who have been diagnosed with cancer in the last 5 years; half of these people live in Europe or North America. Survival figures for different types of cancer vary greatly (see Figure 1.2). Advances in treatment have seen survival rates for many cancers increase, and in the United Kingdom over 50% of cancer patients will be alive 5 years after diagnosis.

Figure 1.2 Relative 5-year survival estimates based on survival probabilities observed during 2000–2001, by sex and site, England and Wales. (Reproduced with kind permission of Cancer Research UK, 2002.)

Whom does cancer affect?

Cancer can affect anyone of any age. Childhood cancer (below the age of 15) affects about 1500 children a year in the United Kingdom, with a risk factor of 1 in 500. The cancers seen commonly in adults in developed countries are rarely seen in children, and the common childhood cancers are equally rare in adults.

It is important to note that the population of the world is ageing; this is significant because cancer is predominantly a disease of the elderly. Principally, as a result of the post-war baby boom, 10% of the world's population is currently 60 years or older, varying from 20% in the developed world to 8% in the less developed areas. By 2050, the overall percentage will rise to 22%, 33% in the developed world and 19% elsewhere. Consequently, there will be an increase in the number of cancer diagnoses. The many and varied complications of old age are well documented. Hypertension, heart conditions, arthritis and gastrointestinal problems are the most common comorbid illnesses in the elderly population who have cancer, and by the age of 75 a typical patient will have four comorbidities, which also require assessment and apposite treatment (Hurria, 2008). By the age of 85, frailty increases with a decline in vision and hearing, which can make people more prone to injury and functional dependence (Balducci & Extermann, 2000). This will undoubtedly contribute to the assigning of performance status, which will in turn affect the treatment options available.

Historical perspective on cancer treatment

The history of cancer diagnosis and treatment options is long and varied but allows us to understand the complex global situation of today.

Several thousand years BC, the Chinese and the Egyptians both made descriptions of tumours and the therapies used to treat them, ranging from surgery to five forms of therapeutic care including diet. In 460 BC, Hippocrates, the father of medicine, was born and texts on the treatment of tumours have been subsequently attributed to him. By AD 129, the world saw the birth of Galen, the first person to suggest that breast cancer arose from melancholia.

However, it was not until 1829 that Joseph Recalmier, a French gynaecologist, first used the term ‘metastasis’ to describe the spread of cancer and 1867 before this mechanism was investigated by Wilhelm Gottfried Waldeyer-Hartz, a German anatomist. In 1830, the first book containing illustrations of cancer cells as seen under a microscope was published by English surgeon Everard Home, and by 1851 the first hospital in Britain devoted to cancer was opened by William Marsden. In 1895, antibody treatment for cancer was first described by Hericourt and Richet, with several patients receiving an individual antiserum. Despite treatment not resulting in cure, they showed significant improvements in their symptoms. This line of investigation was abandoned in 1929, reappearing in 1975, when Kohler and Milstein's work on monoclonal antibodies was published. This work continues to evolve in the twenty-first century.

Another significant milestone in the diagnosis of cancer was also made in 1895 when Wilhelm Konrad Rontgen discovered X-rays able to visualise bones and soft tissues; within a year of this discovery, there were reports of damage to human tissue caused by the X-rays. By 1898, Marie and Pierre Curie had isolated the radioactive elements of polonium and radium, and by 1904 it was confirmed that radium rays destroyed diseased cells. The use of radiation treatment for cancer remains one of the most significant treatment developments.

In 1902, the Imperial Cancer Research Fund was founded in the United Kingdom, followed in 1907 by the American Association for Cancer Research and in 1909 by the Institute Curie in Paris. International cancer statistics were first published in 1915, and in 1919 James Ewing established oncology as a medical speciality in the United States. These treatment-focused initiatives were complemented in 1911 by the founding of the UK National Society for Cancer Relief by Douglas Macmillan following his father's death from cancer. This experience highlighted to him the importance of the holistic needs of people affected by cancer. During this time individuals working with specific tumours also made significant discoveries, for example the association of aniline used in the dye industry and cancer of the bladder was demonstrated by Lueunberger in 1912 and the eponymous James Ewing described an endothelial tumour of the shaft of long bones in 1920.

The specific classification of tumours began in 1920 when an US pathologist classified tumours into four groups on the basis of differentiation of cells, and in 1944 the TNM (tumour, node, metastasis) classification was proposed. The 1930s saw the combining of radiotherapy and surgery as an effective treatment modality in certain tumours and the passing of the Cancer Act by the British government to aid the early diagnosis and treatment of the disease. At the same time, reports appeared in the literature about how nutritional status may influence the outcome of patients being treated in hospitals. Studley (1936) reported that patients undergoing surgery had a poorer outcome if they had lost weight prior to surgery. However, there is little in the literature about whether nutrition was addressed as part of the treatment or care of the cancer patient (Studley, 1936).

Around this time, advances in treatment were being made with the discovery of the therapeutic effects of radiation. The next notable landmark in systemic anticancer treatment was the announcement in 1946 of the successful use of nitrogen mustard in the treatment of some lymphomas and leukaemia resulting from observations on the blood counts of troops gassed in World War I.

The post-war era brought the founding of the United Nations and the World Health Organization. By 1950, Doll and Hill had demonstrated an indisputable link between cigarette smoking and lung cancer, and in 1959 work was first published on the role of hereditary factors in breast cancer. Laboratory work also looking at the growth of breast cancer indicated that diet may have a role to play influencing the growth of mammary cancer cells in mice (Silverstone & Tannenbaum, 1950).

During the 1960s and 1970s, major advances were made in the use of chemotherapy in addition to surgery in the treatment of cancer, resulting in an increase in the number of drugs developed. During this time, the developments in intravenous therapy enabled the administration of many more drugs, blood products and electrolyte solutions, thereby allowing the more effective management of critically ill patients (Dougherty & Lamb, 2008). These years also saw the therapeutic advancement of bone marrow transplantation, and by 1971 a cure for childhood leukaemia had been found using a combination of radiotherapy and chemotherapy. With the aim of making the conquest of cancer, a national crusade, the National Cancer Act, was passed in the United States in 1971, with an initial budget of US$500 million. In 1973, another milestone in diagnostics had been reached with the simultaneous trans-Atlantic discovery of computerised axial tomography (CT scanning).

However, advances in the treatment of cancer were not universal, and in 1975 a report from the WHO noted that deaths from breast cancer had not decreased since 1900. This acted as a strong advocate for the use of combination therapies, demonstrating that surgery alone was not sufficient to successfully treat cancer.

By 1975, the cancer-suppressor P53 gene had been isolated, and the 1980s brought the publication of landmark papers to support the effects of lifestyle on cancer causation. In ‘The Causes of Cancer’ (1981), Sir Richard Doll suggested that 70% of cancers were connected to diet, and in 1992 the evidence was presented establishing the relationship between ageing and development of cancer (Doll & Peto, 1981). Throughout these developments, there continued to be advances in the support of patients during their treatment. The 1980s proclaimed the development of fine-bore feeding tubes and almost simultaneously percutaneous endoscopic gastrostomy to allow delivery of the vital adequate nutrition needed by people during cancer treatment.

The 1980s also saw the role of oncogenes and tumour-suppressor genes in cancer isolated and the 1990s the identification of two breast cancer genes, BRCA1 and BRCA2; by 1999 the human papilloma virus was shown to be present in 99.7% of all cases of cervical cancer.

The twentieth century has witnessed the development of targeted cancer therapies in both radiotherapy and chemotherapy as a result of the discovery of the role of oncogenes. There has also been an increased use of systemic therapy to combat metastatic disease, resulting in a reduction in the amount of radical surgery carried out and an increase in the use of techniques such as laparoscopic and robotic surgery. The century has also seen the further development of biological and hormone treatments and their use as a preventive measure in, for example, prostate cancer.

The future of systemic cancer treatments is increasingly tailored towards the individual utilising the significant progress made in three main areas of research: (1) the inhibition of the angiogenesis factor, to destroy the vital blood supply to a tumour; (2) the interruption of single transduction, the signalling mechanism to the nucleus of a cell; and (3) the introduction of genes into cancer cells for treatment purposes (see Chapter 3).

Increasingly, cancer is now identified as a preventable disease, and whilst much emphasis has been placed on finding a cure, the focus for the twenty-first century is on strategies that prevent, cure and care with respect to cancer (World Health Organization, 2007). Effective approaches to prevention have been demonstrated around the world, including in less developed countries such as Brazil where tobacco control measures have had an impact on the rates of lung cancer. Other countries are tackling other lifestyle issues such as diet, obesity, physical exercise and alcohol consumption, which will impact on not only cancer but also other chronic diseases.

The global burden of cancer also focuses on access to screening, early detection of cancer, and access to treatment. Some countries are receiving advice on acquiring health devices and technologies that will enable them to offer screening and treatment more effectively to their population (World Health Organization, 2007). There is a particular burden on low- and middle-income countries where the cost of treating cancer, particularly the use of expensive chemotherapy, may prevent access to appropriate treatment. This may also be the case for drugs that palliate symptoms, particularly the use of morphine for pain control.

Cancer survivorship – living with and beyond cancer

A cancer survivor is anyone who has received a cancer diagnosis during his or her life. In the UK, for example there are approximately 2 million cancer survivors; 13% or 1 in 8 of the population over the age of 65 are cancer survivors (Maddams et al., 2009). It is also estimated that 15 years post-diagnosis 40% of people still receive some form of cancer-related care (Corner, 2008). These figures will vary worldwide, where other factors constitute a threat to life.

The concept of surviving cancer is complex; the experience will be unique to the individual but have universal aspects, change over time and be life changing. There will be positive and negative aspects to the experience, and the person will live with an element of uncertainty thereafter. The consequences of receiving a cancer diagnosis and living with and beyond it can be physical, psychological, social or spiritual (Doyle, 2008).

Cancer is now classified as a chronic life-threatening illness and in the developed world where more people are living longer but not necessarily healthier lives. A new attitude to disease management is needed to reflect this, particularly as previously described, cancer is a complex disease. A cancer diagnosis often leads to what Bury describes as ‘biographical disruption’ where a person is forced to reassess their life (Bury, 1982). Recently, writing autobiographical accounts of the cancer experience has become increasingly prevalent as has the use of daily blogs and tweets, giving the public immediate access to the daily activities and thoughts of people affected by cancer (Picardie, 1998; Armstrong, 2001). These accounts allow for cancer and its meanings to feature in the public psyche, more than ever before, creating a culture where cancer touches everyone's lives. Little et al. comment on the state of limbo people find themselves in between health and wellness, depicting a state of liminality (Little et al., 2000). It is important to note that a cancer diagnosis carries a particular message to the world, and although this is beginning to change, that message remains one of inevitable fatality (Tritter & Calnan, 2002).

Up until now, it has been relatively easy for people to abdicate responsibility for health concerns to health care professionals by the very nature of health service structure and ethos – the doctor knows best. The changing social, financial and political climate that dominates the advent of the twenty-first century means that individuals will need to start to accept personal responsibility for aspects of their health. Wherever possible, the use of chronic disease management on an individual, population and system level and supported self-management techniques needs to be employed to promote empowerment and independence (Forbes & While, 2009). The basic principles of self-management are basic problem-solving skills, decision-making, the finding and utilisation of resources, developing partnerships with health care providers and taking action (Lorig & Holman, 2003). Health literacy levels will vary worldwide, and until people affected by a disease such as cancer understand its causes and consequences, little progress will be made towards creating the empowered survivor (Nutbeam, 2008). The cancer survivor has many needs, but there must also be a cultural shift in society towards the care and support for people affected by cancer with a greater focus on recovery, health and well-being. The United Kingdom is working on a National Cancer Survivorship Initiative, which looks at improving the care pathway for survivors (Department of Health, 2010).

A diagnosis of cancer is known to affect more than just the individual concerned; this heightening of awareness of health issues can and should be capitalised on for the benefit of public health. The ‘teachable moment’ as described by Demark-Wahnefried presents an ideal way of introducing important public health initiatives such as smoking cessation, the importance of exercise and healthy eating advice such as reducing fat intake, limiting intake of red meat and consuming at least five portions of fruits and vegetables daily (Demark-Wahnefried et al., 2005). However, the uptake of these lifestyle messages is variable; for example studies suggest that only 25–42% of survivors consume at least five portions of fruits and vegetables daily, indicating that such behavioural interventions are not embraced by all. Health promotion guidance is provided by only 20% of oncologists, and further work needs to evaluate how this advice applies to particular diagnostic groups or whether it is suitable for all (see Chapter 9 on late effects of cancer treatment).

Increasingly, it is recognised that patients may require support services and rehabilitation in relation to their cancer, at any point along their care pathway. Often these needs, which may include nutrition, are overlooked, and patients are left without the appropriate assessment and intervention. In the United Kingdom, a national project has been undertaken to produce rehabilitation guidelines which have linked the evidence base to therapy interventions in different cancer diagnoses (NHS Cancer Programme for England, 2007). Nutrition and dietetics features in all the rehabilitation pathways and provides an excellent basis for highlighting patients’ need and planning service delivery to those undergoing treatment, post-treatment and for those surviving after a cancer diagnosis.

Nutrition and cancer

Nutrition has been demonstrated to have a key role and influence in many aspects of the development of cancer not only through the direct role of food components and nutrients but also through its influence on body composition, hormones and growth factors. The influence of diet in the causation of cancer is discussed in detail elsewhere in the excellent review by the World Cancer Research Fund (World Cancer Research Fund, 2007).

Once cancer has developed in an individual then a variety of nutritional problems may develop. The interaction of metabolic and nutritional changes may influence body composition, performance status, psychological state and ability to withstand cancer treatment. Treatment in the malnourished patient may pose challenges as it is associated with increased morbidity and mortality. These changes can have a profound impact on the quality of life of the cancer patient and their carers.

Nutrition is therefore crucial in the support of cancer patients undergoing intensive treatment, in the lifestyle changes that cancer survivors may make and in the management of some of the side effects of cancer treatment. For those patients who cannot hope for a cure, food and nutrition may continue to be an important part of ensuring their quality of life, and for all patients, food may remain central to the social aspects of being with family and friends.

This book aims to examine the role of food and nutrition for the cancer patient and the complex interaction of nutrition, the metabolic changes that occur in cancer, nutritional requirements and the provision of appropriate nutritional support for the cancer patient. The provision of dietary advice and nutritional support for the cancer patient must be timely and consider the potential benefits and burden to the patient. It should be in a way that supports the patient to the best effect, taking into account their cancer, treatment, lifestyle and prognosis and be with maximal benefit and minimal risk. Evidence-based practice is the cornerstone of planning nutritional interventions, but in the absence of evidence, good practice guidance and patient's experience contribute to our knowledge of the best methods of support.

As the chance of survival after a diagnosis of cancer increases then it is likely that the nutritional problems that present will also increase and change. The search for the optimal diet for cancer survivors must continue and needs to consider any dietary changes that may influence the chance of recurrence or the development of new primary tumours. It must also consider the potential effect on other chronic diseases such as heart disease and stroke. Increasingly, there will be the presentation of chronic side effects of treatment that influence dietary intake, for example chronic gastrointestinal symptoms or dysphagia caused by radiotherapy. These symptoms have profound physical and psychological consequences for the patient and should be recognised early and managed appropriately. Good nutrition is essential for all and should be considered at all stages of the development and management of cancer.

References

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Bury, M. (1982) Chronic illness as a biographical disruption. Sociology of Health and Illness 4(2), 167–182.

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Chapter 2

Cancer and nutritional status

Alessandro Laviano, Isabella Preziosa and Filippo Rossi Fanelli

Introduction

Progressive nutritional depletion is frequently found in cancer patients. Reduced energy intake and increased wasting are the factors determining the different phenotypes of this syndrome, whose main feature is a varying combination of reduced food intake, weight loss and changes in body composition. The clinical relevance of the progressive nutritional depletion of cancer patients is underlined by its high prevalence and its impact on patients’ morbidity and mortality. However, only recently, the clinical relevance of the better understanding of the molecular mechanisms leading to weight loss in cancer patients has been recognised. Different catabolic pathways have been identified and characterised, providing potential targets for the development of effective therapeutic strategies to prevent or counteract nutritional depletion.

Nutritional status and outcome in cancer patients

Epidemiology

Nutritional depletion is frequently found in cancer patients. The prevalence of patients reporting weight loss may amply vary according to the stage of the disease and the site of origin of the tumour. Indeed, patients with gastrointestinal cancers and/or with advanced diseases show the highest prevalence of weight loss (Meguid & Laviano, 1996).

Impact of nutritional status on outcome

The negative impact of nutritional depletion on cancer patients’ outcome has been recognised since the early 1980s (DeWys et al., 1980). Medical therapy significantly improved during the past 30 years, and the efficacy of antitumour therapies has greatly improved. Therefore, one would be inclined to believe that the impact of nutritional status on patients’ morbidity and mortality has dramatically declined. Actually, robust clinical evidence shows that depletion of nutritional status remains a negative prognostic factor for treatment-associated toxicity and survival for cancer patients, either when undergoing surgery (Tewari et al., 2007) or receiving chemotherapy (Meyerhardt et al., 2004). During the past decade, the progressive rise of the prevalence of obesity increased the number of obese cancer patients. Interestingly, obesity seems to confer protection against treatment-associated toxicity, but remains a negative prognostic factor for cancer patients, particularly for those patients with a body mass index more than 35 kg/m2 (Dignam et al., 2006).

Impact of nutritional status on quality of life

Quality of life is an important endpoint in the management of cancer patients. As an example, many cancer patients would not choose chemotherapy for a likely survival benefit of few months, but would if it improved quality of life (Sculpher et al., 2004). Nutritional status may profoundly influence patients’ quality of life. It has been calculated that weight loss and nutritional intake contribute to quality-of-life function scores by 30 and 20%, respectively (Ravasco et al., 2004). Several mechanisms may explain how nutritional status influences quality of life (Marin Caro et al., 2007). Weight-losing cancer patients have increased post-operative complication rate, higher chances to develop fatigue, and reduced tolerance/response to chemo- and radiotherapy. These clinical consequences of weight loss contribute to reduce the autonomy of cancer patients, thereby impinging on patients’ quality of life. The possibility to improve quality of life by improving nutritional status remains a debated issue. However, recent evidence suggests that nutritional intervention is likely to yield positive effects on quality of life when it is started early in the clinical course of the disease (Huhmann & Cunningham, 2005). Therefore, the timely nutritional intervention, aimed at addressing the specific needs of each patient, has greater chances to result in significant clinical benefits.

Cancer cachexia

Clinical features

Although it may be very simple to recognise at first sight a nutritionally depleted cancer patients, a general consensus does not exist on the term better describing this syndrome. Cancer-associated weight loss cannot be simply defined as malnutrition. Malnutrition usually refers to the nutritional depletion associated with uncomplicated starvation, which promptly responds to nutritional supplementation. Also, starvation triggers a number of biological mechanisms, which minimise energy needs by reducing energy expenditure, and preserve muscle mass at the expense of fat mass. In cancer patients, and more generally in the presence of acute or chronic diseases, these protective pathways are not operating, which accelerates nutritional depletion and progressive loss of muscle and fat mass. Also, cancer-induced weight loss is minimally responsive to standard nutritional support, particularly in the advanced stages of the disease.

Nutritional depletion in cancer patients is characterised by the development of a number of different symptoms, the most important being anorexia (i.e. the loss of desire to eat), reduced food intake, weight loss, fatigue, muscle wasting, fat mass loss and impaired immune function. Highlighting the clinical relevance of the individual genetic profile, patients with similar cancers may present all, some or even none of the previously mentioned symptoms. Cancer-associated nutritional depletion is usually defined as anorexia–cachexia syndrome, the term which acknowledges the two most prominent symptoms determining weight loss, that is, anorexia and wasting (cachexia – bad conditions, from Greek words). ‘Cachexia’ is a term which is also frequently used per se, to highlight the metabolic changes rather than the behavioural alteration (i.e. anorexia), whose effects on energy balance cannot completely account for the observed weight loss. However, data suggest that the molecular mechanisms responsible for wasting and anorexia may share a number of common pathways (Laviano et al., 2008). Therefore, it may appear more pathogenesis-based the use of the term ‘cachexia’ to indicate the complex clinical syndrome, in which the specific contributions of changes in eating behaviour, energy expenditure or intermediary metabolism largely vary from patients to patients.

Diagnosis

Although a universally accepted definition of cachexia does not exist yet, a number of proposals have been suggested. In particular, cancer cachexia has been related to increased inflammatory response (as defined by increased C-reactive protein levels), reduced energy intake (<1500 kcal/day) and weight loss (>10% vs usual body weight) (Fearon et al., 2006). Although this definition allows it to identify cancer patients at the risk of poorer outcome, on the other hand, patients meeting this three-factor definition of cancer cachexia are likely in an advanced stage of nutritional depletion, which may limit the benefit of nutritional intervention. In an alternative approach to define cancer cachexia, it has been proposed that cachexia is diagnosed based on weight loss and poor responsiveness to standard nutrition support (Bozzetti & Mariani, 2009). Recently, cachexia has been defined as a complex metabolic syndrome associated to an underlying illness, and characterised by loss of weight and muscle mass with or without the loss of fat mass (Evans et al., 2008). Consequently, the diagnostic criteria for cachexia in adults are weight loss of at least 5% in 12 months or less in the presence of underlying cancer, plus three of the following criteria: decreased muscle strength, fatigue, anorexia, low fat-free mass index and abnormal biochemistry (i.e. increased inflammatory markers, anaemia, low serum albumin) (Evans et al., 2008)

As discussed later in this chapter, recent data show that the complex constellation of behavioural and metabolic alterations observed in weight-losing cancer patients may recognise common pathogenic mechanisms. Therefore, cachexia could also be defined as a multifactorial syndrome characterised by weight loss due to underlying disease, contributory factors being anorexia and metabolic alterations (i.e. increased inflammatory status, increased muscle proteolysis, impaired carbohydrate, lipid and protein metabolism). The advantage of this definition lays in being consistent with the clinical practice, in which cancer patients’ weight loss could result from anorexia, wasting or both.

The major limitation of the search for a universally accepted definition of cachexia is its focus on patients who are already cachectic, and therefore with limited chances to benefit from nutritional intervention. There is now general agreement that cancer cachexia is a continuum, ranging from biochemical alterations with minimal or any weight loss, to severe nutritional depletion (Fearon, 2008). Therefore, it would be important to develop diagnostic tools to identify those patients who will become cachectic. Indeed, treating all new cancer patients to address those who will develop cachexia is not feasible. Currently, an established marker of ‘pre-cachexia’ has not been identified, but a number of tools have been proposed. Anorexia is often the presenting symptom of cancer and may precede the development of weight loss. A number of questionnaires have been devised to assess the presence of anorexia (NCCTG questionnaire, FAACT questionnaire), but their compilation may be time-consuming and not well accepted by cancer patients. A list of symptoms likely related to the neurochemical derangements responsible for cancer anorexia have been proposed (i.e. meat aversion, changes of taste/smell, nausea/vomiting and early satiety), and the presence of at least one of them allows to consider the patient as anorexic. Also, the use of a visual analogue scale may be useful in screening anorexic patients, although its use appears more suitable for the follow-up of cancer anorexia than for its diagnosis. Recently, the mere subjective assessment of reduced appetite has been shown to represent a negative prognostic factor in a large population of hospitalised patients, being more reliable than weight loss (Hiesmayr et al., 2009). These results suggest that anorexia could be used as an early marker for cachexia, at least in those cancer patients who develop it.

Biochemical alterations may well represent markers of ‘pre-cachexia’. Tumour growth is frequently associated to the development of insulin resistance, and therefore impaired oral glucose tolerance test may serve to identify patients at higher risk of wasting. Increased expression and activity of proteolytic systems involved in muscle wasting have been demonstrated in cancer patients, even in the early stages of the disease and in the absence of significant weight loss (Bossola et al., 2003). The complexity of the analytical methods used to quantify their expression and activity currently prevents their routine utilisation as early markers. As previously mentioned, the clinical features of cachexia are influenced by individual genetic profile. Recent studies have shown that specific polymorphisms of key genes, including those of the cytokines interleukin-6 (IL-6), IL-10, tumour necrosis factor-α (TNF-α) among other candidate genes, are related to the development of cachexia (Deans et al., 2009). Therefore, it is likely that in the next future the characterisation of the polymorphisms of a few genes may disclose those patients at higher risk of developing cachexia, thereby prompting an early nutritional intervention.

Pathogenesis of anorexia and reduced energy intake

The symptoms and signs mainly characterising cancer cachexia are anorexia and metabolic derangements leading to wasting. In this section, the pathogenesis of anorexia in cancer patients is discussed in detail.

Regulation of food intake

Under physiological conditions, the homeostasis of food intake is controlled by complex and redundant mechanisms (Ellacott & Cone, 2006). Neural, metabolic and humoral signals from peripheral tissues inform the brain whether energy stores are being repleted or depleted. The hypothalamus receives and integrates peripheral signals. Within the hypothalamus, the infundibular nucleus in humans (i.e. the arcuate nucleus in rodents) is considered to act as an important sensor of alterations in energy stores to control appetite and body weight. Involved in this role are two distinct subsets of neurons.

The first population of neurons express pro-opiomelanocortin (POMC). POMC is an inert polypeptide precursor which is cleaved into the biologically active melanocortins, that is, α-, β-, γ-melanocyte-stimulating hormones (MSH). The biological effects of melanocortins are mediated through a family of five melanocortin receptors, termed MC1R to MC5R. Among them, MC4R is a crucial molecular component of the homoeostatic circuit that regulates energy balance by mediating anorectic and catabolic responses.

The second subset of neurons expresses the potent orexigenic peptides neuropeptide Y (NPY) and agouti-related protein (AgRP). Interestingly, AgRP is the endogenous antagonist of MC4Rs, thereby antagonising the anorexigenic effects of melanocortins. This evidence underlines the reciprocal functional relationship between the two subsets of hypothalamic neurons. The POMC and NPY/AgRP neurons project to related hypothalamic nuclei, and these downstream second-order neurons expressing melanocortin receptors are included in the hypothalamic melanocortin system.

The melanocortin system plays a crucial role in the homeostasis of energy metabolism. In the presence of excess energy, POMC neurons are activated and trigger the release of melanocortins, which activate MC4R, thereby leading to suppressed food intake and increased energy expenditure. Simultaneously, the activity of arcuate AgRP/NPY system is suppressed, which would otherwise antagonise the effects of melanocortins on MC4R. In contrast, in times of energy depletion, the activity of anorexigenic POMC neurons is decreased but the activity of orexigenic NPY/AgRP neurons is increased.

Peripheral factors and cancer anorexia

Under physiological conditions, the hypothalamus integrates a number of peripheral inputs and modulates eating behaviour accordingly. These signals arise from peripheral tissues, mainly from the gastrointestinal tract, and are conveyed to the hypothalamus (Wren & Bloom, 2007). The biological functions of these signals are different and time-specific. Consequently, peripheral signals are usually classified as short-term, medium-term and long-term signals.