NUTRITION AND CANCERdownload.e-bookshelf.de/download/0000/5998/35/L-G... · Nutrition plays a crucial role in supporting patients receiving treatment for cancer. Carefully considered

NUTRITION AND CANCEREDITED BY CLARE SHAW

NUTRITION AND CANCEREDITED BY CLARE SHAW

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.

Cover design by David Ollerhead

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Nutrition and Cancer

i



ii



Nutrition and Cancer

Edited by

Clare Shaw, PhD, RD

A John Wiley & Sons, Ltd., Publication

iii



This edition first published 2011C© 2011 Blackwell Publishing Ltd

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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

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Contents

Contributors xiPreface xiii

1 Cancer in the twenty-first century 1Natalie Doyle and Clare Shaw

Introduction 1What is cancer and what causes it? 1Development and spread of cancer 2What is the global burden of cancer? 4Whom does cancer affect? 5Historical perspective on cancer treatment 6Cancer survivorship – living with and beyond cancer 9Nutrition and cancer 10References 11

2 Cancer and nutritional status 13Alessandro Laviano, Isabella Preziosa and Filippo Rossi Fanelli

Introduction 13Nutritional status and outcome in cancer patients 13Cancer cachexia 14Pathogenesis of anorexia and reduced energy intake 16Pathogenesis of wasting 20Cancer cachexia: a neurological disease? 23Summary 24References 24

3 Treatment of cancer 27Sanjay Popat

Introduction 27Treatment intent 27Treatment setting 28Treatment modalities 28Conclusion 43References 44



vi Contents

4 Effect of malnutrition on cancer patients 45Louise Henry

Introduction 45Prevalence of malnutrition amongst cancer patients 46Effect of malnutrition on outcome 61Mortality 68Type of cancer 69Nutritional status as a prognostic indicator 69Morbidity 70Quality of life 71References 75

5 Nutrition screening 83Sian Lewis

Introduction 83Scored Patient-Generated Subjective Global Assessment 85Malnutrition Universal Screening Tool 89Mini Nutritional Assessment 90Nutritional Risk Screening 91Malnutrition Screening Tool 91Conclusion 93Summary 93References 94

6 Nutritional requirements of patients with cancer 97C. Elizabeth Weekes

Introduction 97Energy 98Methods used to estimate energy requirements 100Disease-specific requirements 102Staging and tumour burden 105Treatment 105Response to treatment 107Tumour recurrence 107Inflammatory response and cachexia 107Protein 108Micronutrients 111What should we do in clinical practice? 112Summary 114References 115



Contents vii

7 The psychosocial influences of food choices made by cancer patients 121Lucy Eldridge

Introduction 121Food and cancer 121Influences to food choices 122Other dietary approaches patients choose to take and the reasons why 125Sourcing information 126Summary 127References 128

8 Nutritional support for the cancer patient 130Clare Shaw and Jane Power

Introduction 130Food provision in a health care setting 130Symptom management 136Oral nutritional supplements 141Artificial nutrition support 142Summary 153References 154

9 Late effects of cancer treatment in adult patients 158Jervoise Andreyev

Cancer is a chronic disease 158What is survivorship? 160Who should the dietitian aim to help? 160The stocktaking interview at the end of the treatment 161The metabolic syndrome 163Management of the metabolic syndrome 164Malnutrition in the cancer survivor 164Summary 170References 170

10 Nutrition and palliative care 173Clare Shaw

Introduction 173The role of nutrition in palliative care 175Psychological aspects of food intake 177Nutrition support in palliative care 179Management of nutritional problems 180Artificial nutrition support in palliative care 182Summary 185References 185



viii Contents

11 Head and neck cancer 188Bella Talwar

Introduction 188The impact of malnutrition 189Treatment in head and neck cancer 189Nutritional intervention and outcomes 192Immunonutrition 195Functional implications following surgery 196Nutrition effects in radiotherapy and chemoradiotherapy 201Nutritional management 204Nutritional screening 204Nutritional assessment 206Nutritional requirements 207Oral nutrition support 208Enteral nutrition support 209Nutrition monitoring and rehabilitation 212Summary 214References 215

12 Nutrition in upper gastrointestinal cancer 221Saira Chowdhury and Orla Hynes

Introduction 221Epidemiology and aetiology 221The upper gastrointestinal anatomy 223Clinical presentation 224Staging 226Treatment pathways and role of nutrition 227Advanced disease 242Summary 244References 245

13 Cancers of the lower gastrointestinal tract 255Jane Power

Introduction 255Nutritional management 261Symptom management in palliative care 267Summary 267References 267

14 Gynaecological cancer 270Mhairi Donald

Introduction 270Ovarian cancer 270Endometrial cancer 272



Contents ix

Cervical cancer 272Vulval and vaginal cancers 273Nutritional issues 273Nutritional implications of treatment 274Medical problems 279Nutrition and survivorship 283Summary 283References 283

15 Haemato-oncology 287Gayle Black

Introduction 287Disease characteristics and nutritional implications at diagnosis 287Nutritional implications during induction and intensification treatment 289Stem cell transplantation (consolidation phase) 289Nutrition support post-transplantation 299Long-term implications following transplantation 304Summary 305References 305

16 Paediatric oncology 311Evelyn Ward

Introduction 311Types of childhood cancers 312Aetiology of malnutrition in children with cancer 315Identification of nutritional risk 317Nutritional support 318References 329

17 Nutrition and breast cancer 334Barbara Parry

Introduction 334The role of diet in breast cancer aetiology and survival 336Gestational nutrition and subsequent birth weight 336Breastfeeding 341Body fatness, body composition and weight management 342Alcohol 343Dietary fat 345Fruits and vegetables (including beans and pulses) 347Dairy foods 351Meat and meat products 352Specific nutrient associations and nutritional supplements 353Contaminants in foods 353Physical activity 354



x Contents

Benefits of physical activity to breast cancer survivors 355Nutritional problems during breast cancer treatment 356Summary 358References 358

18 Nutritional management in prostate cancer 363Kathryn Parr

Introduction 363Dietary factors that may reduce the risk of prostate cancer 364Factors that may increase risk of prostate cancer 367Dietary interventions and prostate cancer progression 368Obesity/weight management 371Nutritional issues during treatment for prostate cancer 371Nutrition-related side effects of medications used to treat prostate cancer 372Malnutrition in prostate cancer 373Palliative care in prostate cancer 373Summary 373References 375

19 Lung cancer 379Cherry Vickery

Introduction 379Diet and development of lung cancer 380Nutritional status at presentation 381Treatment of non-small cell lung cancer 382Treatment of small cell lung cancer 383Treatment of mesothelioma 384Palliative treatments 384Symptom management 386Summary 388References 388

Index 391



Contributors

Jervoise AndreyevThe Royal Marsden NHS FoundationTrust, London, UK

Gayle BlackThe Royal Marsden NHS FoundationTrust, Sutton, Surrey, UK

Saira ChowdhuryDepartment of Nutrition and Dietetics,Guy’s and St. Thomas’ Hospital NHSFoundation Trust, London, UK

Mhairi DonaldSussex Cancer Centre, Brighton andSussex University Hospitals NHS Trust,Brighton, UK

Natalie DoyleThe Royal Marsden NHS FoundationTrust, London, UK

Lucy EldridgeBarts and the London NHS Trust, London,UK

Filippo Rossi FanelliSapienza University of Rome, Rome, Italy

Louise HenryThe Royal Marsden NHS FoundationTrust, Sutton, Surrey, UK

Orla HynesDepartment of Nutrition and Dietetics,Guy’s and St. Thomas’ Hospital NHSFoundation Trust, London, UK

Alessandro LavianoSapienza University of Rome, Rome, Italy

Sian LewisVelindre Hospital, Cardiff, Wales, UK

Kathryn ParrClatterbridge Centre for Oncology NHSFoundation Trust, Wirral, UK

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

Sanjay PopatThe Royal Marsden NHS FoundationTrust, London, UK

Jane PowerBetsi Cadwaladr University Health Boardand Wrexham Maelor Hospital, Wrexham,Wales, UK

Isabella PreziosaSapienza University of Rome, Rome, Italy



xii Contributors

Clare ShawThe Royal Marsden NHS FoundationTrust, London, UK

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

Evelyn WardThe Leeds Children’s Hospital, The LeedsGeneral Infirmary, Leeds, UK

C. Elizabeth WeekesGuy’s and St Thomas’ NHS FoundationTrust, 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 statusand adequate nutritional intake during illness is often difficult. Weight loss, reduced intakeof food and fluid may be early presenting symptoms of disease, particularly cancer. Thesechanges may proceed to profoundly influence body composition, functional ability andquality of life. After a diagnosis of cancer, the focus is on successfully treating the cancerand importantly managing symptoms that patients may experience. Treatment modali-ties such as surgery, chemotherapy, radiotherapy and novel treatments such as targetedtherapies are often used in combination or sequentially. Increasingly, these treatments aresuccessful, and there are now rising numbers of people living with and beyond cancer.

When cancer is diagnosed, the patient embarks on investigations and a treatmentpathway. Often, the issues relating to weight loss and nutritional risk are poorly addressedat this time. This is despite the fact that high levels of malnutrition in cancer patients havebeen documented for many years. Treatment modalities may cause a further deteriorationin nutritional status which ultimately impacts on functional status, ability to toleratetreatment, quality of life and potentially survival. Not all cancer diagnoses and treatmentswill have the same effect on nutritional status, so individualised screening, assessmentand 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 toundergo cancer treatment, there is a paucity of nutrition intervention studies to demonstratethe best method of nutritional support, when more intensive nutritional support should becommenced, which clinical outcomes can be influenced and to what extent. Nutritionalissues 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 strugglewith changes in body weight or function, whilst others consider how their future diet caninfluence their health and survival.

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

The first part of this book addresses a number of generic aspects of nutrition that applyacross different diagnostic groups. It looks at the physiological changes that may occurin cancer and the impact these may have on clinical outcomes. It outlines current cancertreatments which ultimately influence nutritional management as screening, assessment



xiv Preface

and the provision of nutrition support must be tailored to patients’ needs during thetreatment 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 hasfinished. Patients should be made aware that follow-up after treatment will focus not onlyon disease-free survival but also on potential side effects that can impact on quality oflife. These are outlined in the chapter on late effects of treatment. Nutrition may continueto be important for patients for whom a cure is not possible and should be included inholistic assessment and care.

The second part of the book looks in more detail at particular diagnoses that havespecific nutritional needs. Knowledge of the potential nutritional problems that may occurin the short and long term enables these aspects of care to be monitored and appropriateinterventions to be planned. Increasingly, new treatments are being introduced, particularlymultimodality treatments that may have a greater impact on nutritional status. A moredetailed knowledge of these enables better planning, monitoring and ultimately betterpatient 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 andto reduce the chance of comorbidities such as heart disease, diabetes and obesity.

Research on nutrition for the cancer patient is sadly lacking. Whilst the implicationsof reduced performance status and poor nutritional status on patient outcomes are docu-mented, there is still a lack of conclusive research data on the potential effect of improve-ment in nutritional status and clinical outcomes such as morbidity and mortality. Wheredata exist it is often very specific, clearly defined and in particular diagnostic groups. Inthe absence of such data, the health care professional may need to turn to general nutritionrecommendations and position papers produced by expert groups such as ESPEN andASPEN. This book aims to be patient focused and not specific to the provision of healthcare 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 areaof work to help guide the reader to understand the nutritional problems patients mayexperience, methods of providing optimal support, where research evidence exists andwhere it does not. It is anticipated that the reader may not read the book as a wholebut 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’scare from diagnosis to end of life, wherever that care may be provided.

Clare Shaw

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Chapter 1

Cancer in the twenty-first centuryNatalie Doyle and Clare Shaw

Introduction

Cancer was recognised as a disease many centuries ago, being mentioned by the ancientEgyptians 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 acrab, was used because of the likeness of blood vessels extending out of a tumour to acrab’s body and legs. It is known from early Egyptian papyrus that attempts were madeto burn or cauterise tumours but that this was always to no avail.

Much has changed since ancient times. Cancer is now part of everyday vocabularyaround the world, and although cancer remains the leading cause of death, much haschanged with respect to its diagnosis and treatment. Today, it is recognised that aboutone-third of all cancers are preventable, and improvements in detection and treatmenthave meant that many people survive the cancer and treatment. Survival rates around theWorld, however, vary greatly (Coleman et al., 2008). Most of the wide global range incancer 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 uncontrolledcellular growth. There are over 200 different types of cancer arising from different cellsof the body. In normal circumstances of cell and tissue division, differentiation and celldeath are carefully regulated processes. Cancer can arise when a single cell has lost controlof 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 placeaccurately, a number of mechanisms are in place, and these are influenced by chemicalsfrom within the cell itself, from different cells or by hormones produced by distant tissuesand transported in the bloodstream. These influence cell division by binding to receptorson the cell surface and transmitting signals to the cell to stop or start the process of division.

Nutrition and Cancer, First Edition, edited by Clare ShawC© 2011 Blackwell Publishing Ltd

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2 Nutrition and Cancer

Table 1.1 Different cancer-causing genes

Type of genes Action

Oncogenes Initiate cell division, when faulty increases the rate oftransformation from a normal cell to a cancer cell.

Tumour-suppressorgenes

Prevent excessive growth of a cell either by control of cellproliferation or by control of DNA repair rate.

DNA repair genes Work in different ways to repair damaged DNA, for example,to correct mismatched bases, copying errors, errors thatdistort structure of DNA.

Apoptosis genes Cells are programmed to reproduce a certain number of timesand then they die. There are genes within the cell that controlthe process. There is much interest in these genes as theymay help the understanding of how cells start to self-destruct.

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 involvethe exact replication of the DNA helix. Transcription factors are the proteins involved inthe regulation of gene expression and carry the signals from the cell surface to the nucleusof the cell and therefore the DNA.

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

Knowledge of the underlying genetic causes of cancer has increased rapidly particularlywithin the past 30 years and has resulted in improvements in the prevention, detectionand treatment of cancer. Significant progress has been made in the identification of genesresponsible for both sporadic and familial cancers such as BRCA1, BRCA2 (breast,ovarian, colon and prostate cancer) and APC (familial adenomatous polyposis for coloncancer). It is also now accepted that as well as genetic mutations, epigenetic changes andthe interactions of genes with lifestyle factors, such as smoking, diet, body weight andexercise, affect the development of cancer. This knowledge brings with it the challenge ofhow to develop measures to prevent cancers forming. In some familial cancers, this maybe 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 environmentthat plays a role in the development of cancer.

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

Development and spread of cancer

Cells, whether they are normal or cancerous, grow and interact with adjacent cells andtissues through a complex network of control signalling, which involves communication

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Cancer in the twenty-first century 3

Table 1.2 Factors contributing to the development of cancer

Carcinogens Substances such as asbestos and tobacco smoke are knowncarcinogens although not all those exposed will necessarily developcancer.

Age Three non-mutually exclusive factors may explain the association ofageing and cancer: (1) the lengthy process of carcinogenesis, (2)molecular changes to tissue with age and (3) age-related environmentalchanges favouring the growth of cancer cells.

Geneticmake-up

A proportion of cancers occur in individuals who are geneticallypredisposed to develop these cancers. This is about 5–10% of commoncancers. The most common abnormality is the BRCA1 and BRCA2genes that increase the risk of breast and ovarian cancer in women andprostate cancer in men.

The immunesystem

Cancer is more common in people who have a suppressed immunesystem which may be due to drugs, for example after organtransplantation, disease affecting the immune system such as HIV orAIDS or in rare medical conditions where the immune system is affected.These conditions tend to increase the rate of cancers caused by virusessuch as cervical cancers or in the development of lymphomas.

Body weight,diet andphysicalactivity

Increased body weight, diet and lack of physical activity are thought tocontribute to approximately one-third of all cancers worldwide. Athorough and comprehensive review of the evidence has beenundertaken by the World Cancer Research Fund and enabled dietaryrecommendations relating to food intake, body weight and physicalactivity that are aimed to reduce the risk of cancer (World CancerResearch Fund, 2007). Generally, higher rates of cancer are observedin countries where the diet is lower in fruits, vegetables and plant-basedfoods and higher in animal products such as meat. The consumption ofalcohol, salty foods and mouldy foods also contributes to an increasedrisk of cancer.

Environment Environmental hazards include exposure to tobacco smoke, radiation,work-related carcinogens such as asbestos and exposure to the sun. Itis difficult to quantify the actual contribution of all these elements tocancer risk.

Viruses Some cancers can be attributed to viral infections, and it is thought thatthese 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 thatis not inhibited by normal cellular or immune control mechanisms.

Bacterialinfection

Some bacterial infections cause cancer; for example, Helicobacter pyloricauses 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).

via both compounds within the membrane of the cell and extracellular growth factorsand cytokines. These bind to receptors on the membrane of the cell and influence cellproliferation and differentiation. In cancer, these processes may be altered to produce anunregulated 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

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vessels and the lymph system. When the cancer cells become detached from the primarytumour and enter the bloodstream or the lymphatics, they can become lodged in othertissues in the body. This is a complex process as the cells must penetrate blood vesselsor lymphatics to spread throughout the body. Eventually, the cancer cells must develop anew 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 butothers may lodge in tissues separate from the primary site of the cancer, causing secondarytumours or metastasis. Often this initial spread will not be detectable by current methodsof scanning and is deemed as micrometastases. The pattern of spread is particular todifferent 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 andtherefore may be already present at the initial diagnoses, whilst for others they live withthe 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 ofmetastases may be a number of years, indicating that the cells may remain dormant orvery slow growing during this period.

The aim of the treatment of cancer is not only to eradicate the initial site of cancergrowth but also to treat or prevent the spread of cancer cells to other tissues and organs inthe body (see Chapter 3 on treatment of cancer). This requires both the detection of suchdisease and appropriate methods of destroying these cancer cells whilst maintaining theintegrity 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 millionpeople were diagnosed with cancer. The most common cancers, primarily breast, lung,stomach, bowel or prostate cancer, accounted for 50% of diagnoses. The large populationsin Asia mean that they account for a large number of the total global cancer burden andactually represent 45% of all those diagnosed with the most common cancers listed. Thecontribution of cancer as the cause of death varies around the world (see Figure 1.1). Thisfigure 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 ofinvestment in health care. For example, for colorectal cancer, 5-year survival for patientsranges from around 60% in North America, Japan, Australia and France down to 40%in Algeria, Brazil, Czech Republic, Estonia, Poland, Slovenia and Wales (Coleman etal., 2008). Rates also vary within a country with those having access to health insuranceshowing higher rates of survival.

There are 6.7 million reported deaths from cancer annually; again half of these deathsare in Asia, making up 12% of deaths worldwide. This is more than HIV/AIDS, malariaand tuberculosis combined. It is estimated that there are 24.6 million people alive whohave been diagnosed with cancer in the last 5 years; half of these people live in Europeor North America. Survival figures for different types of cancer vary greatly (see Figure1.2). Advances in treatment have seen survival rates for many cancers increase, and in theUnited Kingdom over 50% of cancer patients will be alive 5 years after diagnosis.

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Africa4%

Asia

12%

Europe

19%

Latin America andthe Carribbean

13%

Northern America

23%

Oceania

21%

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.)

Whom does cancer affect?

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

It is important to note that the population of the world is ageing; this is significantbecause cancer is predominantly a disease of the elderly. Principally, as a result of thepost-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 manyand varied complications of old age are well documented. Hypertension, heart conditions,arthritis and gastrointestinal problems are the most common comorbid illnesses in theelderly population who have cancer, and by the age of 75 a typical patient will have fourcomorbidities, which also require assessment and apposite treatment (Hurria, 2008). Bythe age of 85, frailty increases with a decline in vision and hearing, which can makepeople more prone to injury and functional dependence (Balducci & Extermann, 2000).This will undoubtedly contribute to the assigning of performance status, which will inturn affect the treatment options available.

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2%6%8%

13%15%

22%34%36%

43%45%

48%52%

61%68%

76%79%

83%90%

3%6%7%

12%13%

24%38%

45%45%46%

51%61%

67%71%

78%84%

95%

PancreasLung

OesophagusStomach

BrainMultiple myeloma

OvaryLeukaemia

KidneyColon

Rectum NHL

BladderCervix UterusBreast

Hodgkin's lymphomaMelanomaPancreas

LungOesophagus

StomachBrain

Multiple myelomaLeukaemia

KidneyRectum

ColonNHL

ProstateLarynx

BladderMelanoma

Hodgkin's lymphomaTestis

Men

Wom

en

Five-year relative survival

10–50% survival:29% of cases

diagnosed

More than 50%survival:

38% of casesdiagnosed

Less than 10% survival:24% of cases diagnosed

More than 50%survival:

50% of casesdiagnosed

10–50% survival:27% of cases diagnosed

Less than 10% survival:15% of cases diagnosed

Figure 1.2 Relative 5-year survival estimates based on survival probabilities observed during2000–2001, by sex and site, England and Wales. (Reproduced with kind permission of CancerResearch UK, 2002.)

Historical perspective on cancer treatment

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

Several thousand years bc, the Chinese and the Egyptians both made descriptions oftumours and the therapies used to treat them, ranging from surgery to five forms oftherapeutic care including diet. In 460 bc, Hippocrates, the father of medicine, was bornand texts on the treatment of tumours have been subsequently attributed to him. By ad129, the world saw the birth of Galen, the first person to suggest that breast cancer arosefrom melancholia.

However, it was not until 1829 that Joseph Recalmier, a French gynaecologist, first usedthe term ‘metastasis’ to describe the spread of cancer and 1867 before this mechanismwas investigated by Wilhelm Gottfried Waldeyer-Hartz, a German anatomist. In 1830,

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the first book containing illustrations of cancer cells as seen under a microscope waspublished by English surgeon Everard Home, and by 1851 the first hospital in Britaindevoted to cancer was opened by William Marsden. In 1895, antibody treatment for cancerwas first described by Hericourt and Richet, with several patients receiving an individualantiserum. Despite treatment not resulting in cure, they showed significant improvementsin 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 workcontinues to evolve in the twenty-first century.

Another significant milestone in the diagnosis of cancer was also made in 1895 whenWilhelm 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 bythe X-rays. By 1898, Marie and Pierre Curie had isolated the radioactive elements ofpolonium and radium, and by 1904 it was confirmed that radium rays destroyed diseasedcells. The use of radiation treatment for cancer remains one of the most significanttreatment 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 theInstitute Curie in Paris. International cancer statistics were first published in 1915, andin 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 theUK National Society for Cancer Relief by Douglas Macmillan following his father’s deathfrom cancer. This experience highlighted to him the importance of the holistic needs ofpeople affected by cancer. During this time individuals working with specific tumoursalso made significant discoveries, for example the association of aniline used in the dyeindustry and cancer of the bladder was demonstrated by Lueunberger in 1912 and theeponymous James Ewing described an endothelial tumour of the shaft of long bones in1920.

The specific classification of tumours began in 1920 when an US pathologist classifiedtumours 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 combiningof radiotherapy and surgery as an effective treatment modality in certain tumours andthe passing of the Cancer Act by the British government to aid the early diagnosis andtreatment of the disease. At the same time, reports appeared in the literature about hownutritional 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 lostweight prior to surgery. However, there is little in the literature about whether nutritionwas 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 thetherapeutic effects of radiation. The next notable landmark in systemic anticancer treat-ment was the announcement in 1946 of the successful use of nitrogen mustard in thetreatment of some lymphomas and leukaemia resulting from observations on the bloodcounts of troops gassed in World War I.

The post-war era brought the founding of the United Nations and the World HealthOrganization. By 1950, Doll and Hill had demonstrated an indisputable link betweencigarette smoking and lung cancer, and in 1959 work was first published on the role of

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hereditary factors in breast cancer. Laboratory work also looking at the growth of breastcancer indicated that diet may have a role to play influencing the growth of mammarycancer cells in mice (Silverstone & Tannenbaum, 1950).

During the 1960s and 1970s, major advances were made in the use of chemotherapyin addition to surgery in the treatment of cancer, resulting in an increase in the number ofdrugs developed. During this time, the developments in intravenous therapy enabled theadministration of many more drugs, blood products and electrolyte solutions, thereby al-lowing the more effective management of critically ill patients (Dougherty & Lamb, 2008).These years also saw the therapeutic advancement of bone marrow transplantation, and by1971 a cure for childhood leukaemia had been found using a combination of radiotherapyand 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 budgetof US$500 million. In 1973, another milestone in diagnostics had been reached with thesimultaneous trans-Atlantic discovery of computerised axial tomography (CT scanning).

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

By 1975, the cancer-suppressor P53 gene had been isolated, and the 1980s broughtthe 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 wereconnected to diet, and in 1992 the evidence was presented establishing the relationshipbetween ageing and development of cancer (Doll & Peto, 1981). Throughout these devel-opments, 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 simul-taneously percutaneous endoscopic gastrostomy to allow delivery of the vital adequatenutrition needed by people during cancer treatment.

The 1980s also saw the role of oncogenes and tumour-suppressor genes in cancerisolated 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 ofcervical cancer.

The twentieth century has witnessed the development of targeted cancer therapies inboth 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 theuse of techniques such as laparoscopic and robotic surgery. The century has also seen thefurther development of biological and hormone treatments and their use as a preventivemeasure in, for example, prostate cancer.

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

Increasingly, cancer is now identified as a preventable disease, and whilst much empha-sis has been placed on finding a cure, the focus for the twenty-first century is on strategies

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that prevent, cure and care with respect to cancer (World Health Organization, 2007).Effective approaches to prevention have been demonstrated around the world, includingin less developed countries such as Brazil where tobacco control measures have had animpact on the rates of lung cancer. Other countries are tackling other lifestyle issues suchas diet, obesity, physical exercise and alcohol consumption, which will impact on not onlycancer but also other chronic diseases.

The global burden of cancer also focuses on access to screening, early detection ofcancer, and access to treatment. Some countries are receiving advice on acquiring healthdevices and technologies that will enable them to offer screening and treatment moreeffectively to their population (World Health Organization, 2007). There is a particularburden on low- and middle-income countries where the cost of treating cancer, particularlythe use of expensive chemotherapy, may prevent access to appropriate treatment. This mayalso be the case for drugs that palliate symptoms, particularly the use of morphine forpain 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 1in 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 formof cancer-related care (Corner, 2008). These figures will vary worldwide, where otherfactors constitute a threat to life.

The concept of surviving cancer is complex; the experience will be unique to theindividual but have universal aspects, change over time and be life changing. There willbe positive and negative aspects to the experience, and the person will live with an elementof uncertainty thereafter. The consequences of receiving a cancer diagnosis and living withand 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 worldwhere more people are living longer but not necessarily healthier lives. A new attitude todisease management is needed to reflect this, particularly as previously described, cancer isa complex disease. A cancer diagnosis often leads to what Bury describes as ‘biographicaldisruption’ where a person is forced to reassess their life (Bury, 1982). Recently, writingautobiographical accounts of the cancer experience has become increasingly prevalent ashas the use of daily blogs and tweets, giving the public immediate access to the dailyactivities 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, morethan 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 cancerdiagnosis carries a particular message to the world, and although this is beginning tochange, that message remains one of inevitable fatality (Tritter & Calnan, 2002).

Up until now, it has been relatively easy for people to abdicate responsibility for healthconcerns to health care professionals by the very nature of health service structure and

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ethos – the doctor knows best. The changing social, financial and political climate thatdominates the advent of the twenty-first century means that individuals will need tostart to accept personal responsibility for aspects of their health. Wherever possible, theuse of chronic disease management on an individual, population and system level andsupported self-management techniques needs to be employed to promote empowermentand independence (Forbes & While, 2009). The basic principles of self-management arebasic 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 diseasesuch as cancer understand its causes and consequences, little progress will be madetowards creating the empowered survivor (Nutbeam, 2008). The cancer survivor hasmany needs, but there must also be a cultural shift in society towards the care and supportfor people affected by cancer with a greater focus on recovery, health and well-being. TheUnited Kingdom is working on a National Cancer Survivorship Initiative, which looks atimproving the care pathway for survivors (Department of Health, 2010).

A diagnosis of cancer is known to affect more than just the individual concerned; thisheightening of awareness of health issues can and should be capitalised on for the benefitof public health. The ‘teachable moment’ as described by Demark-Wahnefried presentsan 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, limitingintake 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 isvariable; for example studies suggest that only 25–42% of survivors consume at least fiveportions of fruits and vegetables daily, indicating that such behavioural interventions arenot 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 groupsor 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 rehabilita-tion 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 appropriateassessment and intervention. In the United Kingdom, a national project has been under-taken to produce rehabilitation guidelines which have linked the evidence base to therapyinterventions in different cancer diagnoses (NHS Cancer Programme for England, 2007).Nutrition and dietetics features in all the rehabilitation pathways and provides an excellentbasis for highlighting patients’ need and planning service delivery to those undergoingtreatment, 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 thedevelopment of cancer not only through the direct role of food components and nutrientsbut also through its influence on body composition, hormones and growth factors. Theinfluence of diet in the causation of cancer is discussed in detail elsewhere in the excellentreview by the World Cancer Research Fund (World Cancer Research Fund, 2007).

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

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

This book aims to examine the role of food and nutrition for the cancer patient and thecomplex interaction of nutrition, the metabolic changes that occur in cancer, nutritionalrequirements and the provision of appropriate nutritional support for the cancer patient.The provision of dietary advice and nutritional support for the cancer patient must betimely and consider the potential benefits and burden to the patient. It should be in a waythat 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-basedpractice is the cornerstone of planning nutritional interventions, but in the absence ofevidence, good practice guidance and patient’s experience contribute to our knowledgeof the best methods of support.

As the chance of survival after a diagnosis of cancer increases then it is likely that thenutritional problems that present will also increase and change. The search for the optimaldiet for cancer survivors must continue and needs to consider any dietary changes thatmay influence the chance of recurrence or the development of new primary tumours. Itmust also consider the potential effect on other chronic diseases such as heart diseaseand stroke. Increasingly, there will be the presentation of chronic side effects of treatmentthat influence dietary intake, for example chronic gastrointestinal symptoms or dyspha-gia caused by radiotherapy. These symptoms have profound physical and psychologicalconsequences 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 developmentand management of cancer.

References

Armstrong, L. (2001) It’s Not About the Bike: My Journey Back to Life. London: Yellow JerseyPress.

Balducci, L. and Extermann, M. (2000) Management of cancer in the older person: a practicalapproach. Oncologist 5(3), 224–237.

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

Cancer Research UK (2002) Relative five-year survival estimates based on survival probabilitiesobserved during 2000–2001, by sex and site, England and Wales. Available at: http://info.cancerresearchuk.org/cancerstats/survival/latestrates/index.htm (accessed 21 January 2010).

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Cancer Research UK. (2010a) Causes of cancer. Available at: http://info.cancerresearchuk.org/cancerstats/causes/index.htm (accessed 15 January 2010).

Cancer Research UK. (2010b) Percentage of all deaths due to cancer in the different regions ofthe world. Available at: http://info.cancerresearchuk.org/cancerstats/world/mortality/index.htm(accessed 25 January 2010).

Coleman, M.P., Quaresma, M., Berrino, F., et al. (2008) Cancer survival in five continents: aworldwide population-based study (CONCORD). The Lancet Oncology 9(8), 730–756.

Corner, J. (2008) Addressing the needs of cancer survivors: issues and challenges. PharmoeconomicsOutcomes Research 8(5), 443–451.

Demark-Wahnefried, W., Aziz, N.M., Rowland, J.H., et al. (2005) Riding the crest of the teachablemoment: promoting long-term health after the diagnosis of cancer. Journal of Clinical Oncology23(24), 5814–5830.

Department of Health, Macmillan Cancer Support and Improvement, N. (2010) TheNational Cancer Survivorship Initiative vision. Available at: http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH 111230 (accessed27 January 2010).

Doll, R. and Peto, R. (1981) The causes of cancer: quantitative estimates of avoidable risks of cancerin the United States today. Journal of the National Cancer Institute 66(6), 1191–1308.

Dougherty, L. and Lamb, J. (2008) Intravenous Therapy in Nursing Practice. Oxford: BlackwellPublishing Ltd.

Doyle, N. (2008) Cancer survivorship: evolutionary concept analysis. Journal of Advanced Nursing62(4), 499–509.

Forbes, A. and While, A. (2009) The nursing contribution to chronic disease management: adiscussion paper. International Journal of Nursing Studies 46(1), 119–130.

Hurria, A. (2008) Assessment of the older adult with cancer. The Journal of Supportive Oncology6(2), 80–81.

Little, M., Sayers, E.J., Paul, K., et al. (2000) On surviving cancer. Journal of the Royal Society ofMedicine 93(10), 501–503.

Lorig, K.R. and Holman, H. (2003) Self-management education: history, definition, outcomes, andmechanisms. Annals of Behavioral Medicine 26(1), 1–7.

Maddams, J., Brewster, D., Gavin, A., et al. (2009) Cancer prevalence in the United Kingdom:estimates for 2008. British Journal of Cancer 101(3), 541–547.

NHS Cancer Programme for England (2007) Raising the bar for rehabilitation service provisionin cancer and palliative care. Available at: http://www.cancer.nhs.uk/rehabilitation/index.htm(accessed 21 January 2010).

Nutbeam, D. (2008) The evolving concept of health literacy. Social Science and Medicine 67(12),2072–2078.

Picardie, R. (1998) Before I Say Goodbye. London: Penguin.Silverstone, H. and Tannenbaum, A. (1950) The effect of the proportion of dietary fat on the rate of

formation of mammary carcinoma in mice. Cancer Research 10, 448–453.Studley, H.O. (1936) Percentage of weight loss. A basic indicator of surgical risk in patients with

chronic peptic ulcer. Journal of the American Medical Association 106(6), 458–460.Tritter, J.Q. and Calnan, M. (2002) Cancer as a chronic illness? Reconsidering categorisation and

exploring experience. European Journal of Cancer 11, 161–165.World Cancer Research Fund (2007) Food, Nutrition, Physical Activity and the Prevention of

Cancer: A Global Perspective. Washington DC.World Health Organization. (2007) The World Health Organization’s fight against cancer.

Strategies that prevent, cure and care. Available at: http://www.who.int/cancer/publicat/WHOCancerBrochure2007.FINALweb.pdf (accessed 22 January 2010).

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Chapter 2

Cancer and nutritional statusAlessandro Laviano, Isabella Preziosa andFilippo Rossi Fanelli

Introduction

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

Nutritional status and outcome in cancer patients

Epidemiology

Nutritional depletion is frequently found in cancer patients. The prevalence of patientsreporting weight loss may amply vary according to the stage of the disease and the site oforigin of the tumour. Indeed, patients with gastrointestinal cancers and/or with advanceddiseases 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 recog-nised since the early 1980s (DeWys et al., 1980). Medical therapy significantly improvedduring 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 onpatients’ morbidity and mortality has dramatically declined. Actually, robust clinical ev-idence shows that depletion of nutritional status remains a negative prognostic factor

Nutrition and Cancer, First Edition, edited by Clare ShawC© 2011 Blackwell Publishing Ltd

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for treatment-associated toxicity and survival for cancer patients, either when undergo-ing 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 thenumber of obese cancer patients. Interestingly, obesity seems to confer protection againsttreatment-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 anexample, many cancer patients would not choose chemotherapy for a likely survival benefitof few months, but would if it improved quality of life (Sculpher et al., 2004). Nutritionalstatus may profoundly influence patients’ quality of life. It has been calculated that weightloss 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 statusinfluences quality of life (Marin Caro et al., 2007). Weight-losing cancer patients haveincreased post-operative complication rate, higher chances to develop fatigue, and reducedtolerance/response to chemo- and radiotherapy. These clinical consequences of weightloss 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 statusremains a debated issue. However, recent evidence suggests that nutritional interventionis likely to yield positive effects on quality of life when it is started early in the clinicalcourse of the disease (Huhmann & Cunningham, 2005). Therefore, the timely nutritionalintervention, aimed at addressing the specific needs of each patient, has greater chancesto result in significant clinical benefits.

Cancer cachexia

Clinical features

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

Nutritional depletion in cancer patients is characterised by the development of a num-ber of different symptoms, the most important being anorexia (i.e. the loss of desire to

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