ESMO HANDBOOK OF

www.esmo.org

NUTRITION AND CANCER

ESMO HANDBOOK OF
NUTRITION AND CANCER
Edited by Aminah Jatoi, Stein Kaasa and Michiel Strijbos 2N D ED I TI O N

The second edition of the ESMO Handbook of Nutrition and Cancer

brings together dozens of experts from around the world to update
clinically important topics on the interface between nutrition and
cancer. Chapters cover the basic concepts of nutrition to the health
economics of nutrition, with numerous pertinent topics in between.
The tremendous effort that went into this fully revised edition is
intended to provide clinicians with the latest knowledge as they
provide state-of-the-art nutritional education to patients with cancer,
to those at risk for cancer, or to those with a history of cancer.

2ND EDITION
ESMO Press
ESMO HANDBOOK OF
ESMO Handbook Series
ISBN 978-88-944465-6-2

NUTRITION AND CANCER

ISBN 978-88-944465-6-2

9 788894 446562 Edited by Aminah Jatoi, Stein Kaasa and Michiel Strijbos 2N D ED I TI O N
[ S A M P LE B A R C O D E ]

ESMO Handbook Series

European Society for Medical Oncology
Via Ginevra 4, 6900 Lugano, Switzerland www.esmo.org ESMO Handbook Series

ESMO_handbook_nutrition.indd 1 05/06/2023 10:19

 ESMO HANDBOOK OF
NUTRITION AND CANCER

Second edition
 ESMO HANDBOOK OF
NUTRITION AND CANCER

Second edition

Edited by

Aminah Jatoi
Department of Oncology, Mayo Clinic, Rochester, MN, USA

Stein Kaasa
Oncology and Palliative Medicine, University of Oslo, Oslo;
Department of Oncology, Oslo University Hospital, Oslo;
European Palliative Care Research Centre (PRC), Oslo University
Hospital and Oslo University, Oslo, Norway

Michiel Strijbos
Department of Medical Oncology, GZA Hospitals Sint-Augustinus,
Wilrijk, Belgium

ESMO Press
Second edition published in 2023 by ESMO Press.
First edition published in 2011.

© 2023 European Society for Medical Oncology

All rights reserved. No part of this book may be reprinted, reproduced, transmitted, or utilised
in any form by any electronic, mechanical, or other means, now known or hereafter invented,
including photocopying, microfilming, and recording, or in any information storage or retrieval
system, without written permission of the publisher or in accordance with the provisions of the
Copyright, Designs, and Patents Act 1988 or under the terms of any license permitting limited
copying issued by the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA
01923, USA (www.copyright.com/ or telephone 978-750-8400). Product or corporate names
may be trademarks or registered trademarks, and are used only for identification and explanation
without intent to infringe.

This book contains information obtained from authentic and highly regarded sources. Reprinted
material is quoted with permission and sources are indicated. A wide variety of references are
listed. Reasonable efforts have been made to publish reliable data and information, but the authors
and publisher cannot assume responsibility for the validity of all materials or for the consequence
of their use.

Although every effort has been made to ensure that drug doses, treatments, and other information
are presented accurately in this publication, the ultimate responsibility rests with the prescribing
physician. Neither the publisher nor the authors can be held responsible for errors or for any
consequences arising from the use of information contained herein. For detailed prescribing
information on the use of any product or procedure discussed herein, please consult the
prescribing information or instructional material issued by the manufacturer.

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

ISBN: 978-88-944465-6-2

For orders, corporate sales, foreign rights and reprint permissions, please contact:
ESMO Head Office
Licensing and Publications Sales Department
Via Ginevra 4
6900 Lugano
Switzerland
Tel: +41 (0)91 973 19 00
Email: [email protected]
www.esmo.org
Contents

Editors ix
Contributors xii
Reviewers xv
Abbreviations xvii
Acknowledgements xx
Preface xxi

1 Introduction 1
2 Basic Concepts of Nutrition 3
Energy and Protein Balance 3
Appetite and Its Control 4
Metabolism of Macro- and Micronutrients 4
Body Composition Assessment 7
Diagnosis of Malnutrition 9
Influence of Undernutrition on Physiological Functioning 11
Physiological Function and Deficiency States of Trace Elements
and Vitamins 12
Obesity in Cancer Patients 13
Goals of Nutritional Therapy 14
Nutritional Requirements of Adults 14
Diet and Dietary Patterns 15
Further Reading 16
3 Role of Nutrition in Cancer Prevention 18
Basic Concepts of Nutrition 18
Body Fatness 18
Physical Activity 19

v
 Plant Food 20
Red Meat 21
Processed Meat 21
Alcohol 22
Dietary Supplements 23
Other Food Groups Associated With Cancer 23
Conclusion 23
Further Reading 23
4 Psychosocial and Cultural Aspects of Nutrition 26
Clinical Guidelines 27
What Psychosocial Issues Related to Nutrition Do
Cancer Patients Face? 27
How Can Healthcare Professionals Help? 29
Culturally Sensitive Communication to Help the Patient Cope
with Eating Problems 30
Coping with Eating-related Distress 31
What About the Family? 32
Conclusion 34
Further Reading 34
5 Nutritional Counselling and Intervention 37
Individualised Nutritional Counselling 37
Goals of Individualised Nutrition in Cancer 39
What Does the Evidence Show About the Benefits of
Individualised Nutritional Counselling? 41
Conclusion 42
Key Messages 43
Further Reading 43
6 Cancer and the Nutritional Status 46
Evaluation of the Nutritional Status of a Patient with Cancer 46
Cancer Anorexia and Cachexia: Causes and Treatment Options 49
Conclusion 51
Further Reading 51

vi Contents
7 Cancer Treatment and Nutrition 53
Nutritional Support During Cancer Treatment 54
Impact of Food on Anticancer Drugs (e.g. Interactions Between
Anticancer Drugs and Nutritional or Herbal Supplements) 59
Monitoring of Nutritional Support During Cancer Treatment 61
Use/Indications of Parenteral and Enteral Nutrition During
Cancer Treatment 63
Further Reading 67
8 Nutritional Support for the Advanced Cancer Patient 69
Nutritional Support During Best Supportive Care 69
Clinical Situations for Nutritional Support 70
Reasons to Consider Initiation, Withholding and/or
Withdrawing Artificial Nutrition and Hydration in
Patients Who Are Imminently Dying 72
General Principles of Nutritional Support 73
The Role of Ketones 74
Further Reading 75
9 Nutrition in the Older Patient with Cancer 78
Step 1: Recognise the Risk Factors of Cachexia in
Older Adults with Cancer 80
Step 2: Perform Nutritional Screening and Assessment in
Older Adults with Cancer 83
Step 3: Manage Nutritional Impairments in Older Adults
with Cancer 84
Conclusion 85
Further Reading 85
10 Energy Balance, Nutrition, Cancer Incidence
and Survivorship 88
Energy Balance and Cancer Risk 88
Energy Balance in Cancer Survivorship 90
Mechanisms 92
Further Reading 95

Contents vii
11 Navigating Nutritional Decision-Making 97
An Association Should Not Imply Causation:
Understanding Studies with Different Designs 97
Secondary Outcomes Should Not Guide Definitive Clinical
Recommendations 100
Missing Data Can Mislead 102
Further Reading 103
12 Implementation Science to Advance Nutritional Care
in Cancer 105
Why Do We See These Evidence-Practice Gaps in
Nutritional Care in Cancer? 106
The Rationale for Using an Implementation Science Strategy to
Improve Adherence to Evidence-Based Nutrition Guidelines? 107
How to Implement Nutritional Care as Part of Cancer Care,
the Practical Perspective 110
Conclusion 112
Further Reading 112
13 Health Economics in Oncology Nutrition Research 115
Defining Health Economics 116
Measuring Economic Outcomes – Potential Approaches 117
Cost-Benefit Analysis 117
Health Economics in Nutrition Research 120
Further Reading 121
Index 124

viii Contents
Editors

Aminah Jatoi
Department of Oncology, Mayo Clinic, Rochester, MN, USA

Aminah Jatoi, MD is the Betty J. Foust, MD and Parents’ Professor of

Oncology at the Mayo Clinic in Rochester, Minnesota, USA. A practising
oncologist, she cares for patients with gastrointestinal and gynaecologi-
cal malignancies. Her research interests focus largely on palliative and
supportive care strategies for patients with cancer with a special interest
in geriatric oncology.
She has authored or co-authored over 400 publications, and her research
has been funded by the United States’ National Institutes of Health as
well as by various foundations. With dual training in both medical oncol-
ogy and human nutrition, understanding nutritional issues in patients
with cancer has remained a particularly salient aspect of Dr Jatoi’s career
interests.

Declaration of Interest:
Dr Jatoi reports institutional funding for advisory board membership
from Novartis and Meter Health and an institutional research grant from
AstraZeneca for an investigator-initiated research study.

ix
 Stein Kaasa
Oncology and Palliative Medicine, University of Oslo, Oslo;
Department of Oncology, Oslo University Hospital, Oslo; European
Palliative Care Research Centre (PRC), Oslo University Hospital and
Oslo University, Oslo, Norway

Stein Kaasa is an MD with specialisation in medical oncology, radiotherapy

and palliative medicine. In 1993 he was appointed the first Professor in Pal-
liative Medicine in Scandinavia and was one of the founders of the Palliative
Care Unit in Trondheim, Norway and is currently leader of the PRC.
He has been the National Cancer Director in Norway, President of the
European Association for Palliative Care (EAPC) and leader of the
EAPC Research Network, where he is currently the coordinator of the
MyPath Project. He worked extensively to get palliative care and patient-
centred care research on the agenda, both nationally and internationally.
Currently he is Head of the Department of Oncology at Oslo University
Hospital, Norway and Professor of Oncology and Palliative Medicine at
the University of Oslo, Norway.
Professor Kaasa has published 546 articles and book chapters with an
H index of 100. He is a member of the European Society for Medical
Oncology (ESMO) Designated Centres Working Group.

Declaration of Interest:
Professor Kaasa reports institutional funding for advisory board membership
from Helsinn Healthcare, webinar lectures from Pfizer Norway and Nutricia
Norway, a writing engagement from Nutricia Norway, invited speaker fees
from MEDIDEO and Fresenius Kabi Deutschland, research grants from The
Norwegian Cancer Society and the South-Eastern Norway Regional Health
Authority for his work as coordinating principal investigator from Helse-
forsk, and from Nutricia Research for his work on the PROTES Project. He
reports personal royalties from the Oxford Textbook of Palliative Medicine.

x Editors
 Michiel Strijbos
Department of Medical Oncology, GZA Hospitals Sint-Augustinus,
Wilrijk, Belgium

Dr Michiel Strijbos is a Consultant Medical Oncologist at the Sint-

Augustinus Hospital in Wilrijk, Belgium. He trained at Leuven University
in Belgium and the Erasmus University in Rotterdam, Netherlands, where
he graduated in 2004, and obtained his PhD in Tumour Immunology in
2009.
He is an investigator in clinical trials in genitourinary cancers and has a
specific interest in health technology. Dr Strijbos has been a member of
the ESMO Young Oncologists Committee and Chair of the ESMO Practis-
ing Oncologists Working Group. He is currently a member of the ESMO
Educational Publications Working Group.
Dr Strijbos is the author of several papers published in indexed peer-
reviewed international journals and has been an invited speaker at several
national and international oncology meetings.

Declaration of Interest:
Dr Strijbos reports personal speaker fees from Ipsen, Janssen, Bayer and
MSD, personal advisory board fees from MSD, Bayer and Roche and a
travel grant from Bayer. He holds stocks in Need Inc. and is employed
part-time by Need Inc.

Editors xi
Contributors

Arends J. Universitätsklinikum Freiburg, Freiburg, Germany

Baracos V.E. Department of Oncology, University of Alberta,
Edmonton, AB, Canada
Boeykens K. Nutrition Support Team, Vitaz Hospital, Sint-Niklaas,
Belgium
Bozzetti F. Faculty of Medicine, University of Milan, Milan, Italy
Caccialanza R. Clinical Nutrition and Dietetics Unit, Fondazione
IRCCS Policlinico San Matteo, Pavia, Italy
Chasen M. Palliative and Supportive Care, William Osler Health
System, Brampton, ON; McMaster University, Hamilton, ON, Canada
Dajani O. Oncology and Palliative Medicine, University of Oslo, Oslo;
Department of Oncology, Oslo University Hospital, Oslo; European
Palliative Care Research Centre (PRC), Oslo University Hospital and
Oslo University, Oslo, Norway
Fallon M.T. Institute of Genetics and Cancer, University of Edinburgh,
Edinburgh; Edinburgh Cancer Centre, NHS Lothian, Edinburgh, UK
Hjermstad M.J. Oncology and Palliative Medicine, University of Oslo,
Oslo; Department of Oncology, Oslo University Hospital, Oslo; European
Palliative Care Research Centre (PRC), Oslo University Hospital and
Oslo University, Oslo, Norway
Hopkinson J.B. School of Healthcare Sciences, College of Biomedical
and Life Sciences, Cardiff University, Cardiff, UK
Jatoi A. Department of Oncology, Mayo Clinic, Rochester, MN, USA

xii
Kaasa S. Oncology and Palliative Medicine, University of Oslo, Oslo;
Department of Oncology, Oslo University Hospital, Oslo; European
Palliative Care Research Centre (PRC), Oslo University Hospital and
Oslo University, Oslo, Norway
Laird B.J.A. Institute of Genetics and Cancer, University of Edinburgh,
Edinburgh; Edinburgh Cancer Centre, NHS Lothian, Edinburgh;
St Columba’s Hospice Care, Edinburgh, UK
Laviano A. Department of Translational and Precision Medicine,
Sapienza University, Rome, Italy
Lee M. Division of Clinical Trials and Biostatistics, Mayo Clinic,
Rochester, MN, USA
Le-Rademacher J.G. Division of Clinical Trials and Biostatistics,
Mayo Clinic, Rochester, MN; Department of Oncology, Mayo Clinic,
Rochester, MN, USA
Ligibel J.A. Dana-Farber Cancer Institute, Harvard Medical School,
Boston, MA, USA
Mislang A.R.A. Department of Medical Oncology, Flinders Centre for
Innovation in Cancer, Flinders Medical Centre, Bedford Park, Adelaide,
SA; College of Medicine and Public Health, Flinders University, Bedford
Park, Adelaide, SA, Australia
Morgan G. Skåne University Hospital, Department of Medical and
Radiation Oncology, Lund, Sweden
Mukherjee M.S. Caring Futures Institute, College of Nursing and Health
Sciences, Flinders University, Bedford Park, Adelaide, SA, Australia
Ravasco P. Universidade Católica Portuguesa, Faculty of Medicine and
Centre for Interdisciplinary Research in Health (CCIS-UCP), Lisbon;
Egas Moniz School of Health and Science, Centre for Interdisciplinary
Research Egas Moniz, Almada, Portugal
Schuetz P. Medical University Department, Division of General Internal
and Emergency Medicine, Medical Faculty of the University of Basel,
Kantonsspital Aarau, Aarau, Switzerland

Contributors xiii
Stanga Z. Division of Diabetes, Endocrinology, Nutritional Medicine
and Metabolism, University of Bern and Bern University Hospital, Bern,
Switzerland
Strasser F. Cantonal Hospital St. Gallen and Cancer Fatigue
Clinic, Onkologie Schaffhausen, Schaffhausen; Cantonal Hospital
Münsterlingen, Münsterlingen; Center Radiotherapy Rüti, Rüti,
Switzerland
To T.H.M. Research Centre for Palliative Care, Death and Dying,
College of Nursing and Health Sciences, Flinders University, Bedford
Park, Adelaide, SA; Southern Adelaide Palliative Service, Flinders
Medical Centre, Bedford Park, Adelaide, SA; College of Medicine
and Public Health, Flinders University, Bedford Park, Adelaide, SA,
Australia
Yi D. Cicely Saunders Institute of Palliative Care, Policy &
Rehabilitation, King's College London, London, UK

xiv Contributors
Reviewers

The editors and authors wish to thank the following reviewers.

Sara A. Arscott, Osher Center for Integrative Health, Department of

Family Medicine and Community Health, University of Wisconsin -
Madison, WI, USA
Vickie E. Baracos, Department of Oncology, University of Alberta,
Edmonton, AB, Canada
Martin Chasen, Palliative and Supportive Care, William Osler Health
System, Brampton, ON; McMaster University, Hamilton, ON, Canada
Karin Jordan, Department of Hematology, Oncology and Palliative
Care, Klinikum Ernst von Bergmann Potsdam, Potsdam; Department
of Medicine V, Hematology, Oncology and Rheumatology, University of
Heidelberg, Heidelberg, Germany
Alessandro Laviano, Department of Translational and Precision
Medicine, Sapienza University, Rome, Italy
Charles Loprinzi, Mayo Clinic, Rochester, MN, USA
Lisa Moloney, Academy of Nutrition and Dietetics, Chicago, IL, USA
Manpreet Mundi, Division of Endocrinology, Diabetes, Metabolism
and Nutrition, Mayo Clinic, Rochester, MN, USA
Maurizio Muscaritoli, Sapienza University of Rome, Department of
Translational and Precision Medicine, Rome, Italy
Elena Paillaud, Department of Geriatrics, European Georges Pompidou
Hospital, Paris Cancer Institute CARPEM, Assistance-Publique
Hôpitaux de Paris, Paris; Paris Est Créteil University, Inserm U995,
IMRB Créteil, France

xv
Philippe Paillet, Paris Est Créteil University, Inserm U995, IMRB
Créteil; APHP, Department of Geriatrics, European Georges Pompidou
Hospital, Unité de coordination en Onco-gériatrie Paris-Ouest, Paris,
France
Olav Erich Yri, European Palliative Care Research Centre (PRC),
Department of Oncology, Oslo University Hospital; Institute of Clinical
Medicine, University of Oslo, Oslo, Norway

xvi Reviewers
Abbreviations

AEE Activity-induced energy expenditure

AN Artificial nutrition
ASCO American Society of Clinical Oncology
ATP Adenosine triphosphate
BCAA Branched-chain amino acid
BIA Bioimpedance analysis
BMI Body mass index
BW Body weight
CBA Cost-benefit analysis
CC Calf circumference
CEA Cost-effectiveness analysis
CHEERS Consolidated Health Economic Evaluation Reporting
Standards
CI Confidence interval
CT Computed tomography
CUA Cost-utility analysis
DASH Dietary Approaches to Stopping Hypertension
DEE Diet-induced energy expenditure
DEXA Dual-energy X-ray absorptiometry
DHA Docosahexaenoic acid
DRM Disease-related malnutrition
ECOG Eastern Cooperative Oncology Group
EMA European Medicines Agency
EMR Electronic medical record
EN Enteral nutrition
EORTC QLQ-30 European Organisation for Research and Treatment
of Cancer Quality of Life Questionnaire-30
EPA Eicosapentaenoic acid
EQ-5D EuroQol 5 Dimension
ERAS Enhanced recovery after surgery
ESMO European Society for Medical Oncology

xvii
ESPEN European Society for Clinical Nutrition and Metabolism
EVOO Extra virgin olive oil
FDA Food and Drug Administration
GA Geriatric assessment
GDF-15 Growth/differentiation factor-15
GI Gastrointestinal
GLIM Global Leadership Initiative on Malnutrition
HMB Beta-hydroxy-beta-methylbutyrate
HR Hazard ratio
i.v. Intravenous
IARC International Agency for Research on Cancer
IGF-1 Insulin-like growth factor 1
i-PARIHS Integrated Promoting Action on Research
Implementation in Health Services
IPOS Integrated Palliative care Outcome Scale
Look AHEAD Action for Health in Diabetes trial
MASCC Multinational Association of Supportive Care in Cancer
MNA Mini Nutritional Assessment
MRI Magnetic resonance imaging
NCCN National Comprehensive Cancer Network
NHS National Health Service
NRS-2002 Nutritional Risk Screening 2002
NSAID Non-steroidal anti-inflammatory drug
ONS Oral nutritional supplement
PEG Percutaneous endoscopic gastrostomy
PET Positron emission tomography
PG-SGA Patient-Generated Subjective Global Assessment
PhA Phase angle
PICC Peripherally inserted central catheter
PN Parenteral nutrition
POS-E Palliative care Outcome Scale for Economic evaluations
PRO Problem, resources, outcome
PROM Patient-reported outcome measure
PUFA Polyunsaturated fatty acid
QALY Quality-adjusted life year
QoL Quality of life
RCT Randomised controlled trial
REE Resting energy expenditure

xviii Abbreviations
RR Risk ratio
SCM Supportive Care Measure
SF-36 36-Item Short Form Health Survey
TEE Total energy expenditure
WCRF World Cancer Research Fund
WHO World Health Organization

Abbreviations xix
Acknowledgements

We would like to express our heartfelt appreciation to the staff of

ESMO for their tremendous support and assistance during the creation
of this book. Their expertise and guidance in the field of oncology were
essential to the book’s success. Their advice and feedback helped us
refine every chapter.

We would like to extend our sincere thanks to Aude Galli, Nicki Peters
and Claire Bramley for their unwavering assistance throughout the
journey. It is with deep gratitude that we acknowledge their remarkable
contribution. Thank you.

Dr Michiel Strijbos, on behalf of all the Editors

xx
Preface

Patients diagnosed with cancer are often overwhelmed. The diagnosis

itself, the risk factors (or their absence) that might have led to the
cancer diagnosis, the essential further testing and establishment of
a cancer stage, the prognosis, the logistics of cancer therapy and the
management of therapy-induced side effects and cancer-induced
symptoms – all contribute to the overwhelming nature of cancer.

Throughout this complex journey and perhaps with the goal of acquiring
some degree of control in their daily lives, patients frequently pose
the following question to their healthcare providers: “What should I
be eating?” The ESMO Handbook of Nutrition and Cancer (Second
edition) is intended to help healthcare providers respond to this
misleadingly simple – but ever so complex – question with accurate and
pragmatic information from experts in the field. Providing succinct peer-
reviewed chapters on a variety of pertinent topics, this handbook serves
as a resource designed to help oncologists help patients, as these patients
contend with what may be some of the most challenging circumstances
of their lives.

Dr Aminah Jatoi, on behalf of all the Editors

xxi
Introduction
A. Jatoi1
1
S. Kaasa2
Department of Oncology, Mayo Clinic, Rochester, MN, USA
1

Oncology and Palliative Medicine, University of Oslo, Oslo; Department of

2

Oncology, Oslo University Hospital, Oslo; European Palliative Care Research

Centre (PRC), Oslo University Hospital and Oslo University, Oslo, Norway

An old English proverb reads, “Don’t dig your grave with your own knife
and fork.” If only it were that simple and if only clinicians were able
to resort to one simple imperative when rendering nutritional advice to
patients with cancer, to those with a history of cancer, and to individu-
als at risk for this disease! Had it been that simple, the editors of the
European Society for Medical Oncology (ESMO) Handbook of Nutrition
and Cancer and the staff at ESMO would have finished their task of
finalising this second edition way ahead of schedule!
Instead, for this second edition of the ESMO Handbook of Nutrition and
Cancer, dozens of experts well-versed in the interface between nutri-
tion and cancer came together from around the globe to write, critique,
edit, deliberate and update a variety of chapter-based topics that span
all the way from the basic concepts of nutrition to the health econom-
ics of nutrition, all within the context of cancer. The topics covered in
this handbook are grounded in basic, translational and clinical science.
One topic focuses on cancer prevention. Others describe how to clini-
cally assess patients with cancer for nutritional decline; how to review
the prognostic significance of biomarkers (such as cross-sectional mus-
cle area as measured on computed tomography scans), which serve to
flag nutritional compromise; and how to manage patients who might
benefit from nutritional counselling, caloric repletion, pharmacological
interventions and supportive and palliative care. Recognising that can-
cer therapy itself can wreak havoc on nutritional parameters, we have

1
included a specific chapter dedicated to nutrition during cancer treat-
ment. And in keeping with shifting worldwide demographics that point
to a growing number of older patients with cancer in some countries
and to an increasing number of patients who are surviving after a can-
cer diagnosis, these two populations are covered in their own respective
chapters. Two new chapters – one on implementation science and the
other on managing divergent recommendations from different informa-
tion sources – now serve to address these important areas that are gaining
further attention in medicine.
A product of tremendous effort on the part of many, the second edition
of the ESMO Handbook of Nutrition and Cancer brings invaluable state-
of-the-art management approaches, which go far beyond the accoutre-
ments referenced in the old English proverb above and provide concrete,
evidence-based recommendations. We sincerely hope that this handbook
will help clinicians as they, in turn, work to help patients with cancer and
their families.

2 Jatoi and Kaasa

Basic Concepts of Nutrition
A. Laviano1
2
R. Caccialanza2
Department of Translational and Precision Medicine,
1

Sapienza University, Rome, Italy

Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico
2

San Matteo, Pavia, Italy

Energy and Protein Balance

Living organisms require energy to grow, differentiate and procreate.
Animals oxidise diet-derived macronutrients, i.e. carbohydrates, lipids
and proteins, to produce energy and thus support their metabolic and ana-
bolic needs. The universal energy ‘currency’ is adenosine triphosphate
(ATP), which is synthesised in the presence of an excess of energy and
degraded when energy is promptly needed. The turnover of ATP is very
high, reaching 1.3 mmol/kg/sec, which leads to the complete exhaus-
tion of the total body pool of ATP within one minute. Consequently,
a constant supply of energy is needed, even during sleep and rest. As
food intake is not a continuous process, between meals the organism has
to utilise energy substrates from its reserves. Under normal (non-stress)
situations, ingested carbohydrates, fat and protein are partly stored as
glycogen and lipid. Accumulation of protein can occur only in a quan-
titatively limited manner, as may happen during the growth of an indi-
vidual, the building of muscle, or recovery after illness associated with
loss of proteins – especially muscle. During energy production, carbohy-
drates, protein, fat or alcohol are combusted, consuming oxygen, while
carbon dioxide, water and heat are produced. Therefore, measurement
of energy expenditure can be calculated from heat production – referred
to as ‘direct calorimetry’. However, more often, energy expenditure is
calculated from oxygen consumption and/or carbon dioxide production
– referred to as ‘indirect calorimetry’.

3
Appetite and Its Control
Patients with cancer often report changes in their appetite and a reduced
food intake. The analysis of the pathophysiology of food intake control
explains the possible role of pharmacological agents to improve energy
and protein intake. Food intake is governed by the coordinated recur-
rence of hunger, appetite, satiation and satiety. The hypothalamus inte-
grates neural, metabolic and hormonal signals originating from periph-
eral tissues, and transduces these inputs into neuronal responses and,
via second-order neuronal signalling pathways, into behavioural and
metabolic responses. The hypothalamic melanocortin neurons mediate
anorectic responses, whereas neurons expressing neuropeptide Y trigger
the onset of appetite. Influencing the activity of these neuronal networks,
a number of factors, including pro-inflammatory cytokines, neurotrans-
mitters and peptides (i.e. GDF-15 [growth/differentiation factor-15], lep-
tin), activate the anorexigenic pathway and mediate wasting.

Metabolism of Macro- and Micronutrients

Carbohydrates
Carbohydrates represent the largest part (40%–70%) of the total energy
intake (recommendation: 45%–65%). Dietary carbohydrates are digested
to hexoses (mainly glucose), which are absorbed in the portal circula-
tion. Glucose is the universal source of energy for all cells, either via full
oxidisation in the Krebs cycle or by glycolysis. Glucose metabolism is
regulated by insulin. On the other hand, catabolic hormones (e.g. gluca-
gon, adrenaline and cortisol) decrease glucose uptake in muscle and
adipose tissue, and stimulate hepatic glucose production from lactate,
glycerol and amino acids via gluconeogenesis.

Lipids
Lipids represent the most energy-dense component of energy intake.
They constitute approximately 25%–50% of ingested energy (recom-
mendation: 20%–35%). The majority is ingested as triglycerides (90%),
while the remainder are phospholipids and cholesterol. After ingestion,
lipids are emulsified to small droplets (primary micelles) that are hydrolysed

4 Laviano and Caccialanza

to free fatty acids, monoacylglycerol, cholesterol and phospholip-
ids, which form secondary micelles, which are in turn hydrolysed and
absorbed by enterocytes. Inside enterocytes, long-chain fatty acids are
synthesised into chylomicrons which are released in the lymphatic sys-
tem to the systemic blood circulation. The major proportion of chy-
lomicron triglycerides is hydrolysed, and fatty acids are either stored
in adipose tissue or oxidised as energy substrate. Lipids are not mere
energy sources, since they may play a significant role in influencing
human metabolism. The potential modulating effects of omega-3 poly-
unsaturated fatty acids (PUFAs) on inflammatory response suggest that
they may contribute to shaping a favourable metabolic environment in
patients with cancer. Large epidemiological studies and limited interven-
tional trials appear to demonstrate that omega-3 PUFA intake, as either
a dietary component or supplement, may preserve nutritional status,
improve quality of life and possibly influence mortality. However, more
robust clinical trials are needed before omega-3 PUFA supplementation
can be routinely recommended.

Proteins and Amino Acids

Proteins represent 15%–20% of energy intake in a typical diet. The usual
need for an adult is 0.8–1.2 g/kg of body weight (BW) /day. Ingested
proteins are hydrolysed in the intestine to amino acids and oligopeptides,
which are then further hydrolysed in enterocytes. Amino acids are the
building blocks of body proteins. Their oxidisation to produce energy
during fasting is associated with loss of muscle mass. During severe
stress, the primary currency is glucose and hence, via the process of glu-
coneogenesis, body proteins are utilised in severe stress or inflammatory
situations or during severe malnutrition.
Unlike carbohydrates and fat, proteins are not stored unless in association
with the nitrogen accretion of body building or during repair and growth.
This is apparent in the case of muscle mass, which is fully dependent on
protein intake and physical activity. Bed rest usually leads to negative
nitrogen balance in spite of sufficient protein and energy intakes. This is
important especially in patients who lost weight due to malignant disease
and its treatment. Since muscle contraction is a potent inducer of anabolism,

Basic Concepts of Nutrition 5

regaining of muscle in these patients, which is a relatively slow process,
can be enhanced by preventing immobility and favouring mild to moder-
ate physical activity when possible.
Nine essential amino acids cannot be synthesised in humans and are manda-
tory in the diet or during artificial nutrition. These are histidine, isoleucine,
leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine.
As already discussed for lipids, a number of amino acids influence human
metabolism in a way that could be exploited for patients with cancer.
Leucine and its derivative HMB (beta-hydroxy-beta-methylbutyrate)
have been shown to enhance muscle anabolism, even during catabolic
conditions. Arginine is required for immune response and its provision
within the tumour microenvironment increases antitumour activity of
lymphocytes. Translation of this evidence into clinical practice is still
limited due to the lack of robust clinical trials.

Fibres
Given the increased interest on the role of intestinal microbiota in
enhancing the efficacy of anticancer therapies, the intake of fibre has
gained considerable attention. As an example, daily intake of at least 20 g
of fibre appears to enhance the efficacy of immunotherapy in melanoma
patients.

Water and Electrolytes

Recommended intake of water ranges between 20 and 40 mL/kg BW/
day (not counting for losses). Acute stress and inflammation are associ-
ated with water and sodium retention and loss of potassium, magnesium
and phosphate. More importantly, dehydration is associated with sarco-
penia and increased risk of all-cause mortality. Recovery is accompanied
by water and sodium mobilisation and diuresis (loss of oedema) and by
increased need of potassium, magnesium and phosphate to replenish
intracellular loss. A similar situation is apparent during refeeding after
long-term starvation. Decreased levels of plasma phosphate, potassium
and magnesium lead to muscle paralysis, cardiac arrhythmias, water
retention and even sudden death, the so-called ‘refeeding syndrome’.

6 Laviano and Caccialanza

Body Composition Assessment
Human metabolism aims to preserve body cell mass and body composition.
Body composition can be assessed using various techniques, the sensitivity
and specificity of which differ significantly. Measurement or estimation of
adipose and muscle tissues play a relevant role in predicting the outcome
of patients with cancer. Robust clinical evidence demonstrates that early
quantitative and qualitative changes in muscle and adipose tissues predict
chemotherapy-associated toxicity, the risk of low relative dose intensity of
chemotherapy, the degradation rate of immune checkpoint inhibitors and,
ultimately, progression-free and overall survival. Consequently, the early
assessment of nutritional status, including body composition when feasi-
ble, is now recommended by international guidelines (European Society
for Clinical Nutrition and Metabolism [ESPEN] and European Society for
Medical Oncology [ESMO]) on the management of patients with cancer.
Considering the contributory, yet relevant, role of body composition
changes in informing the clinical decisions on the long-term manage-
ment of patients with cancer, it is self-evident that muscle mass and adi-
pose tissue should be measured rather than estimated. The gold standard
for the measurement of body composition changes in patients with can-
cer, as well as in other diseases, is the analysis of tissue density using a
computed tomography (CT) scan at the level of the third lumbar verte-
bra. This technique allows a precise measurement not only of quantita-
tive changes, i.e. sarcopenia, but of qualitative changes as well, including
fat infiltration within muscle mass, i.e. myosteatosis.
CT scan analysis is facilitated by using software which automatically
calculates the tissue attenuation as expressed by Hounsfield units and
derives the quantity of muscle and adipose tissues. Nevertheless, CT-
based body composition assessment remains poorly implemented in
clinical practice. To overcome at least some of the barriers, more levels
along the spine have been proposed, without major success. Also, the
use of other imaging techniques, including dual-energy X-ray absorpti-
ometry (DEXA), magnetic resonance imaging (MRI) and ultrasound of
quadriceps muscle, have been proposed but their feasibility and reliabil-
ity remain questionable at the time of publication.

Basic Concepts of Nutrition 7

So far, no biochemical biomarker of nutritional status and body com-
position has been proposed and robustly validated. Therefore, in daily
clinical practice, body composition is estimated rather than measured.
Anthropometry (measurement of circumferences and skinfolds) has
been shown to be affected by large inter- and intra-observer variability
and is not routinely implemented. In contrast, a very easily performed
yet robust predictor of muscle mass in patients with cancer is calf cir-
cumference (CC), which has been demonstrated to predict mortality.
Bioimpedance analysis (BIA), which derives fat mass and fat-free mass
from hydration status using validated formulae, is used routinely. This
gives reasonable data for patients who are in a stable condition; however,
caution is necessary for subjects who are acutely ill and have hydration
problems (ascites, hydrothorax, etc.). In recent years, phase angle (PhA),
a raw BIA variable, has received much attention because studies have
suggested its potential as an index of body cell mass and cellular integ-
rity. In particular, a low PhA is associated with malnutrition and poor
outcome in patients with cancer.
Measuring/estimating nutritional status and body composition allows to
estimate energy stores, which are presented in Table 1.
Table 1 Normal Body Energy Stores in Well-nourished, Non-obese Individuals.
Adapted from: Garrow JS. Energy stores in man, their composition and measurement. Proc Nutr Soc 1982;
41:175–181.
Fuel type kg kcal
Fat (1 kg fat = 1.1 kg adipose tissue) 15 141 000
Protein (1 kg protein = 4 kg muscle tissue) 12 40 000
Glycogen (liver) 0.2 400
Glycogen (muscle) 0.5 800
Glucose (blood) 0.02 80

Given that exact measurement of body compartments is difficult, the key

is to regularly measure changes in body compartments, either to prompt
nutritional therapy or to monitor its efficacy. When this is not feasible,
regular measurement of BW and calculation of changes in BW and body
mass index (BMI) are also clinically relevant and useful. In summary,
healthcare professionals should take advantage of imaging prescribed for

8 Laviano and Caccialanza

any clinical indications to also check and monitor the body composition
changes of their patients. Nutritional status can also be estimated by using
BIA, CC, etc. When body composition cannot be measured nor estimated,
non-volitional weight loss is a good proxy of deteriorating nutritional sta-
tus. Interestingly, combining BMI with non-volitional weight loss (%) in
the previous months predicts survival in patients with cancer.

Diagnosis of Malnutrition
Nutritional Screening
Nutritional screening needs to be simple, rapid and easily performed on
hospital admission or at each oncological visit. This procedure serves
as a baseline and dictates appropriate nutritional intervention. Several
screening tools exist, based on actual BW, recent weight loss and recent
food intake. Nutritional screening should be a mandatory and regular
part of the medical care of cancer patients, given the increased risk of
disease- and therapy-related undernutrition. The ESPEN guidelines rec-
ommend the use of specific screening tools according to the clinical set-
ting. However, the key is using any tool which has been validated in the
specific clinical setting. It is important to differentiate nutritional screen-
ing from nutritional assessment beyond the competencies needed to per-
form them. In fact, nutritional assessment is key to select the group of
patients within a larger population which may suffer from malnutrition.
By performing nutritional assessment, not only is the perception of a risk
translated into a definite diagnosis of malnutrition, more importantly it
highlights the body compartment mostly affected as well as the factors
determining malnutrition.

Nutritional Assessment
Nutritional assessment is a more detailed evaluation of nutritional sta-
tus, aimed at diagnosing the presence of malnutrition and at informing
the provision of nutritional support. Nutritional assessment is clinically
indicated in cancer patients because of their higher risk for malnutrition.
Given the complexity of nutritional assessment, which may prevent its
implementation in daily clinical routine, an easily applicable protocol

Basic Concepts of Nutrition 9

for the diagnosis of malnutrition, involving widely available criteria,
has been recently proposed by an international panel of experts from
European, North American, Latin American and Asian clinical nutrition
societies. The so-called Global Leadership Initiative on Malnutrition
(GLIM) criteria recommend that patients at nutritional risk, based on a
validated screening tool, are assessed for the presence of aetiological and
phenotypic criteria (Table 2).

Table 2 GLIM Criteria.

Adapted from: Cederholm T, Jensen GL, Correia MITD, et al; GLIM Core Leadership Committee; GLIM
Working Group. GLIM criteria for the diagnosis of malnutrition – a consensus report from the global
clinical nutrition community. Clin Nutr 2019; 38:1–9.

Phenotypic criteria Non-volitional weight loss1

Low BMI2
Reduced muscle mass3
Aetiological criteria Reduced food intake or assimilation4
Disease burden/inflammatory condition5
1
>5% within the past 6 months, or >10% beyond 6 months.
2
<20 if <70 years, or <22 if >70 years; Asia: <18.5 if <70 years, or <20 if >70 years.
3
Reduced by validated body composition measuring techniques (i.e. DEXA, BIA, CT, MRI; when not available, physical
examination or standard anthropometric measures such as mid-arm muscle or calf circumferences may be used).
4
≤50% of ERs >1 week, or any reduction for >2 weeks, or any chronic GI condition that adversely impacts food assimilation
or absorption.
5
Acute disease/injury or chronic disease-related (C-reactive protein may be used as a supportive laboratory measure).
Abbreviations: BIA, bioimpedance analysis; BMI, body mass index; CT, computed tomography; DEXA, dual-energy X-ray
absorptiometry; ER, energy requirement; GI, gastrointestinal; GLIM, Global Leadership Initiative on Malnutrition; MRI,
magnetic resonance imaging.

Patients with at least one aetiological and one phenotypic criterion can
be diagnosed with malnutrition. It is acknowledged that the proposed
framework may minimise the metabolic and functional complexity of
nutritional status. However, it is important to remember that the assess-
ment of the nutritional domains involved in preserving nutritional sta-
tus, and thus health, remains necessary after having posed a diagnosis
of malnutrition. This analysis guides the provision of a qualitatively and
quantitatively appropriate nutritional intervention and allows for moni-
toring and fine tuning of its efficacy.
The domains of nutritional assessment can be divided into:
n Measurement of nutrient balance (nutrition balance, intake and output)

10 Laviano and Caccialanza

n Measurement of body composition (BMI, anthropometry, BIA, imaging)


n Measurement of inflammatory activity (C-reactive protein, neutro-

phil-to-lymphocyte ratio, leukocyte count)

n Measurement of function (muscle function [dynamometry], respira-

tory function, immune function)

For all methods of nutritional assessment, measurements must be

repeated at various time intervals according to clinical status and needs,
because it is the directional change that guides therapy. Each test has its
unique advantages and limitations. However, their interpretation must
take into consideration the underlying disease, the ongoing therapy and
the overall clinical picture. In summary, patients should be empowered
and responsible for monitoring their BW every 2-3 weeks, and immedi-
ately report non-volitional weight loss >5% of their usual BW. It is also
advisable that changes in their functional ability be reported even in the
absence of significant weight loss.

Influence of Undernutrition on Physiological

Functioning
Undernutrition and negative energy balance have substantial effects on
energy stores and organ function. The rapidity of energy store loss and
change in organ function depend on the degree of energy and protein
deficiency as well as on clinical conditions during starvation. These are
dependent on food intake as well as on the presence of stress factors
including trauma, blood loss, inflammation or other conditions.

Simple Starvation
In simple starvation, the substrate–hormone profile is not disturbed by
acute stress or inflammation. It is characterised by hormonal adapta-
tion, decreased resting energy expenditure (REE) and also by reduction
of physical activity. Energy need is furnished mainly by fat tissue and
ketone bodies, whereas the protein compartment is relatively preserved.
This enables long-term survival during famine periods (60–70 days in
normal-weight subjects).

Basic Concepts of Nutrition 11

Stress Starvation
Acute and chronic diseases, including cancer, lead to systemic inflam-
mation. This is associated with a greater need for glucose as a substrate
to mount the immune response and sustain the recovery phase. On the
other hand, systemic inflammation is associated with insulin resistance,
leading to hyperglycaemia and the development of anorexia and reduced
food intake. From a mechanistic point of view, systemic inflammation
appears to promote self-recovery based on endogenous stores and meta-
bolic switch. In particular, muscles are degraded to amino acids, which
in turn are converted via gluconeogenesis to glucose for use by inflam-
matory tissue and cells of the immune system. An increase in fatty acid
turnover occurs, with decreased production of ketone bodies, insulin
resistance and fat accumulation in various organs. Phenotypically, stress
starvation is characterised by rapid loss of muscle, reduction of adipose
tissue and decrease of muscle function. This constellation of symp-
toms and clinical signs is defined as ‘disease-related malnutrition with
inflammation’ (i.e. cachexia), to differentiate it from simple starvation.
As survival is dependent mainly on the degree of the protein loss, and
the amount of lean body mass is determined by genetics and physical
stature, the period of starvation in these conditions is significantly lower
(usually 14-21 days, depending on inflammatory activity).
It is therefore apparent that nutritional therapy in cancer patients with
malnutrition should always consider its two major causative factors:
reduced food intake or impaired digestion and absorption by the gut
mucosa, and metabolic changes induced by inflammation. Of great
importance is the evidence that the nutritional and metabolic status of
a patient with cancer may well change over their long clinical journey,
requiring mostly replenishment of calorie and protein gaps at some time
points, while in contrast modulation of inflammation and metabolic
changes may represent the key intervention at other time points.

Physiological Function and Deficiency States of

Trace Elements and Vitamins
Although a limited daily intake of micronutrients is required, trace

12 Laviano and Caccialanza

elements (essential inorganic micronutrients) and vitamins (essential
organic micronutrients) play a critical role in health and disease. Their
role can be classified as follows: cofactors in metabolism, coenzymes in
metabolism, control functions, structural components, antioxidants.
Recommendations for the daily intake of micronutrients have been
developed. These are based on the intakes associated with health. There-
fore, they are adequate for planning food strategy for a population, but
are less useful for the individual. During disease, the concentrations of
many trace elements decrease, and this has been associated with reduced
oxidative defence, impaired immune response and deranged metabolism.
However, clinical trials testing the effects of trace element supplementa-
tion during acute and chronic illness have not yielded consistently posi-
tive results, and their use in patients with cancer should be cautiously
considered, particularly during anticancer treatments.

Obesity in Cancer Patients

Malnutrition is a broad term, which defines pathological deviations from
optimal nutritional status. Consequently, overnutrition, i.e. obesity, is
included under the umbrella of malnutrition syndromes. There is still
debate on whether obesity, beyond predisposing to certain types of can-
cer, may also protect from rapid wasting and therefore extend survival of
patients with cancer. Much of the debate is based on the variable body
composition of obese patients.
The majority of patients with cancer in Europe and North America are
either overweight or obese, based on their BMI. However, body com-
position studies consistently show that obese patients may well present
sarcopenia (i.e. sarcopaenic obesity). In patients with cancer, sarcopae-
nic obesity has been shown to be associated with poor clinical outcomes.
Body composition analysis is therefore recommended in obese patients
with cancer, to reveal hidden nutritional deficits and inform a tailored
nutritional intervention promoting supervised weight loss/stability, con-
sisting of mostly adipose tissue loss and preservation of muscle mass.

Basic Concepts of Nutrition 13

Goals of Nutritional Therapy
Nutritional therapy is based on a stepwise approach to the unmet sub-
strate needs of patients. Based on the patient’s potential to meet at least
part of their requirements via the oral route, on the existence of a func-
tioning gut, and on the feasibility to have access to the gastrointestinal
tract or to the circulatory system, nutritional therapy includes counsel-
ling, supplementation with food or oral nutritional supplements, enteral
nutrition and finally parenteral nutrition, either peripherally or centrally
infused. Given the current technology, it can be said that all patients can
be fed, and therefore not feeding a patient remains a clinical decision.
The goal of nutritional therapy in cancer patients is to prevent and treat
undernutrition, which in turn impacts on physiological functioning, i.e.
muscle function, cardiovascular function, respiratory function, gastroin-
testinal function, immune function, cognitive function and thermoregu-
lation.
Qualitatively and quantitatively appropriate nutritional intake is key
to better toleration of the catabolic effects of the growing tumour and
anticancer therapies. Evidence shows that nutritional therapy during
any catabolic crisis (surgery, chemotherapy, radiotherapy, etc.) not only
improves short-term outcomes, but better prepares the patient for the
next catabolic crisis. Therefore, omitting to adequately feed a patient
with cancer not only reduces their chances of tolerating aggressive thera-
pies, but limits the benefit from the following therapeutic steps during
the long clinical journey.

Nutritional Requirements of Adults

A critical factor in maintaining health or alternatively in recover-
ing quickly from disease is ensuring that adequate energy and protein
requirements are met. In a healthy adult with stable weight, physical
and cognitive performance depend on the tight balance between energy
expenditure and energy intake.
Different components define total energy expenditure (TEE), and in
particular: REE, the energy needed to preserve basic vital functions,

14 Laviano and Caccialanza

diet-induced energy expenditure (DEE), the energy spent to digest and
absorb nutrients, and activity-induced energy expenditure (AEE), the
energy spent on physical activity. The determinants of TEE may vary
widely according to each individual’s lifestyle, age, sex and body compo-
sition. In clinical practice, the contribution of acute and chronic diseases
to increase REE (i.e. hypermetabolism) should always be considered.
To calculate daily energy requirements, daily energy expenditure should
be assessed. REE can be measured by indirect calorimetry. However,
in clinical practice, REE is more frequently estimated by equations. An
easy and practical approach to estimate REE consists of multiplying the
BW and the daily energy requirements of BW. This ranges from 20 to
35 kcal/kg BW/day. These formulae do not consider body composition,
and may under- or overestimate disease-induced hypermetabolism in the
presence of severe malnutrition and obesity. In this regard, international
guidelines suggest measuring REE rather than estimating it. Given the
variability of REE along the clinical journey of a patient with cancer,
regular measurement of REE may prevent the complications associated
with over- and under-feeding.

Diet and Dietary Patterns

The journey of cancer patients is characterised by a progressive nutri-
tional and functional decline, accelerated by catabolic crisis (i.e. surgery,
chemotherapy, radiotherapy, etc.). Effective nutritional therapy should
inform patients on the recommended long-term lifestyle changes associ-
ated with longer survival and better quality of life, and implement spe-
cific and tailored interventions during the catabolic crisis.
Given the role of diet in influencing the risk for cancer, it has been
postulated that diet may also have a specific role in reducing the pro-
gression of cancer. A number of ‘anticancer’ diets have been proposed
(e.g. vegetarian, vegan, ketogenic, basic, etc.), none of which has been
validated by robust clinical or epidemiological data. In contrast, a Med-
iterranean-style diet, which includes fruit, vegetables and whole cereals,
and favours plant protein over animal protein, appears to extend survival
when implemented in conjunction with other lifestyle habits.

Basic Concepts of Nutrition 15

Caloric restriction is associated with reduced risk of cancer. Whether
short-term and supervised caloric restriction also benefits cancer patients
receiving anticancer therapies remains to be tested in clinical trials.
Preliminary reports addressing the link between circadian rhythms and
food intake have drawn considerable interest. If efficacy is demonstrated
by clinical trials, limiting the feeding time to less than 12 hours synchro-
nous with the light/dark cycle may represent an additional opportunity to
enhance the efficacy of anticancer therapies.

Further Reading
Arends J, Bachmann P, Baracos V, et al. ESPEN guidelines on nutrition in cancer
patients. Clin Nutr 2017; 36:11–48.
Arends J, Strasser F, Gonella S, et al; ESMO Guidelines Committee. Cancer
cachexia in adult patients: ESMO Clinical Practice Guidelines. ESMO Open
2021; 6:100092.
Bahat G. Measuring calf circumference: a practical tool to predict skeletal mus-
cle mass via adjustment with BMI. Am J Clin Nutr 2021; 113:1398–1399.
Bargetzi L, Bargetzi M, Laviano A, et al. Inflammation reduces the effect of
nutritional therapy on clinical outcomes in cancer patients. Ann Oncol 2021;
32:1451–1452.
Bargetzi L, Brack C, Herrmann J, et al. Nutritional support during the hospital
stay reduces mortality in patients with different types of cancers: secondary
analysis of a prospective randomized trial. Ann Oncol 2021; 32:1025–1033.
Goncalves MD, Maddocks ODK. Engineered diets to improve cancer outcomes.
Curr Opin Biotechnol 2021; 70:29–35
Laviano A, Inui A, Marks DL, et al. Neural control of the anorexia-cachexia
syndrome. Am J Physiol Endocrinol Metab 2008; 295:E1000–E1008.
Manoogian ENC, Panda S. Circadian rhythms, time-restricted feeding, and
healthy aging. Ageing Res Rev 2017; 39:59–67.

Declaration of Interest:
Professor Laviano has declared personal advisory board fees from DSM, Nestlé
Health Science, Nutricia and Fresenius Kabi; and personal speaker remuneration
from Abbott, Baxter, B. Braun, Nestlé Health Science, Nutricia and Fresenius
Kabi. He has declared institutional research funding for his work as local principal
investigator from Fresenius Kabi.

16 Laviano and Caccialanza

Dr Caccialanza has declared personal advisory board fees from Baxter, Eli Lilly
and Nestlé Health Science; invited speaker fees from Akern, Baxter, Eli Lilly, Ital-
farmaco and Nestlé Health Science; and expert testimony fees from B. Braun, Fre-
senius Kabi and Nutricia. He has declared institutional research grants from Nestlé
Health Science and Nutricia. He is the Secretary of the Survivorship Care and
Nutritional Support Working Group for the Alliance Against Cancer.

Basic Concepts of Nutrition 17

Role of Nutrition
in Cancer Prevention 3
G. Morgan
Skåne University Hospital, Department of Medical and Radiation Oncology,
Lund, Sweden

Nutrition is important for survival. Food affects not only human develop-
ment, but also the development of diseases, and cancer is not an excep-
tion. This chapter will cover a variety of topics related to nutrition that
affect the ability to reduce the risk of developing certain types of cancers.

Basic Concepts of Nutrition

Nutrients are essential for life and keep the body in balance by maintain-
ing and replenishing cells. A balanced diet is made up of the five food
groups: fruits, vegetables, cereals, proteins and dairy products. These
contain six major classes of nutrients: carbohydrates, fats, minerals, pro-
teins, vitamins and water. These nutrients are the key building blocks
and their daily intake is required for human development. In cancer care,
nutrients play a critical role, helping to fight disease more effectively, in
healing, in recuperation and even in prevention.

Body Fatness
Obesity or excess body fat is a major risk factor for cancer. According to
research from the American Cancer Society, in the United States excess
body weight is thought to be responsible for ~11% of cancers in women,
~5% of cancers in men and ~7% of all cancer deaths (Rock et al, 2020).
Evidence suggests that increased cancer risk may be associated with
increased body weight and a body mass index (BMI) outside the healthy
range. Some studies have shown that being obese or overweight during
childhood and in young adulthood could be a stronger risk factor than

18
weight gain in later life. Research is ongoing to try to better understand
this link and how it affects and increases cancer risk (Stone et al, 2018).
Although the mechanisms are not yet known, the role of inflammation
has been suggested, since it may influence the cells’ ability to live longer,
or encourage blood-vessel growth, which may even aid cancer cells to
metastasise. Maintaining a stable, healthy weight may reduce the levels
of hormones such as insulin, androgens and oestrogens, which are also
related to cancer risk. Significant benefits are associated with weight loss
in overweight/obese persons: decreasing their risk of heart disease and
diabetes, increasing mobility and, in some cases, reducing pain. Hence,
obesity and excess body fat negatively affect general health and can also
increase the risk of developing cancer.

Physical Activity
There are possible links between cancer risk and a person’s level of phys-
ical activity. These activities can vary from walking, running, swimming
or cycling to doing household chores.
Observational studies, where subjects report their physical activity and
are followed for cancer diagnosis, have yet to prove the relationship, but
point out the possible link (McTiernan et al, 2019). It has been proposed
that physical activity may be protective against the occurrence of some
cancers by lowering the level of sex hormones, preventing high levels
of insulin, reducing inflammation, altering metabolism or improving the
function of the immune system. However, it is not just an active lifestyle
that has the potential to reduce cancer risk, but conversely, a sedentary
lifestyle has been shown to be a risk factor for developing chronic health
conditions and an early death.
To achieve substantial health benefits, 150-300 minutes of moderate
intensity aerobic activity or 75-100 minutes of vigorous aerobic activity
per week are recommended (Yang, 2019). For a more complete workout,
this can be coupled with strength and balance training.
For cancer survivors, not only is it safe to engage in exercise, but it is rec-
ommended. There is evidence that moderate-intensity aerobic exercise or
resistance training after cancer treatment has the potential to reduce stress,

Role of Nutrition in Cancer Prevention 19

depression, anxiety and fatigue, which patients may experience as a result of
their cancer diagnosis. Some studies in breast cancer survivors have shown
that those who were physically active had a 42% lower risk of death from
any cause and a 40% lower risk of dying of breast cancer than those who
were inactive; studies in colorectal cancer and prostate cancer have shown
similar effects (Spei et al, 2019). Although research is still ongoing, physi-
cians can strongly promote exercising and avoiding a sedentary lifestyle.

Plant Food
There is increasing evidence that a vegetarian diet is associated with a
decreased risk of cancer. Certain studies have demonstrated that people
who consume little or no red meat have a lower risk of developing colo-
rectal cancer. Some of these studies have also shown that there is a lower
risk of postmenopausal breast cancer in women who follow a vegetarian
diet. It is unclear whether it is the plant-based diet or the absence of meat
that reduces the risk of cancer. However, it cannot be denied that a diet
rich in fruits, cereals, vegetables and legumes is part of a healthy lifestyle
and has been linked with potential lower cancer rates.
One possible correlation between plant-based diets and lower cancer
rates is the exposure to phytochemicals, which have an anti-inflamma-
tory effect and protect cells from damage, and may thereby have a role in
cancer prevention. It has been observed that cruciferous vegetables have
a positive influence on cancer prevention. Higher levels of fibre con-
sumption may also be beneficial. Studies have found that young women
who had a diet rich in fibre were 25% less likely to be diagnosed with
cancer later in life (Farvid et al, 2016). Another study showed that a daily
intake of 10 g of fibre could decrease the risk of colon cancer by 10%
(Aune et al, 2011). A possible explanation is the lower caloric intake, as
people who eat a plant-based diet often consume fewer calories, in turn
helping to maintain a stable weight.
It is important to note that people who do not eat meat should make sure
they are getting their daily allowances of vitamin B12, zinc, calcium
and omega-3 fatty acids, which are normally found in meat and other
animal foods.

20 Morgan
Red Meat
The link between red meat and cancer is well established. A study found
that a daily intake of 100 g of red meat increases the risk of colorectal
polyps by 2% (Aykan, 2015). Another study showed that a weekly intake
of 700 g of red meat increases the risk of bowel cancer. Although red
meat has long been a staple of many Western diets, increased red meat
consumption has been proportionally linked to higher mortality risk, pos-
sibly due to the promotion of cardiometabolic disturbances. When cooked
at high temperatures, red meat produces compounds, some of which
may be carcinogenic when consumed. For this reason, the World Health
Organization (WHO) has classified red meat as a Group 2A carcino-
gen. This does not mean that red meat must be avoided completely, but
rather consumed in moderation. The recommended quantity is 1 serving
(90-100 g raw or 65 g cooked) of lean red meat per day or 2 servings
3-4 times per week, with a total of 350-500 g of cooked red meat a week.

Processed Meat
There is strong evidence that processed meat causes cancer; so strong
that ham, bacon, salami and Frankfurt sausages are classified as Group 1
carcinogens by the WHO. Studies are very clear about the association,
with some findings showing that consuming processed meat increases
the risk of colorectal polyps by 29%, increasing the risk for stomach and
bowel cancer (Santarelli et al, 2008). The risk of developing bowel cancer
increases 1.18 times for every 50 g of processed meat consumed per day.
The nitrates present in processed meats generate N-nitroso compounds
in the gut, and these compounds are known to damage the bowel lining,
potentially leading to cancer. The chemicals in processed meat contrib-
ute to their carcinogenic potential. Exposure to these chemicals increases
inflammation in the tissues and leads to an increased risk of developing
cancers. For these reasons, there is no recommended serving for pro-
cessed meat, but rather these should all be excluded from the diet to
reduce the risk of cancer.

Role of Nutrition in Cancer Prevention 21

Alcohol
Alcohol has been directly linked to at least seven types of cancer: mouth
and upper throat, larynx, oesophagus, breast, liver and bowel cancer.
There is a correlation between the amount of alcohol consumed and the
increased risk of developing cancer, and there is no threshold. In the
European Union, ~80 000 people died from alcohol-attributable cancer
in 2016, equivalent to 1.9 million years of life lost due to disability or
premature mortality. Looking at worldwide incidence, it is estimated that
alcohol is the cause of ~3 million deaths each year, of which >400 000
are from cancer (Rehm et al, 2021).
A study published in The Lancet Oncology (Rumgay et al, 2021) found
that in 2020, 4% of the world's newly diagnosed cases of oesophageal,
mouth, larynx, colon, rectum, liver and breast cancers were attributed to
alcohol intake: a total of 741 300 people. In this study, 75% of all alco-
hol-related cancers occurred in men. In women, there were 172 600
alcohol-related cancers, of which 98 300 were breast cancers. The study
highlighted that the more people drank, the higher their risk of alcohol-
related cancer was, with the greatest risk being for those consuming
2-6 drinks a day (28-84 g of pure alcohol). However, even those with a
‘moderate’ consumption (≤2 drinks per day) made up 14% (103 000) of
alcohol-related cancer cases. Although there is no way to prevent cancer
totally, risk reduction can be achieved by reducing alcohol intake. When
combined with alcohol consumption, being overweight, poor oral hygiene
and poor diet are additional factors which increase the risk of cancer, but
perhaps the most damaging combination is that of drinking and smoking.
Binge drinking (>4 drinks in a short period, for men ≥5 drinks) may
increase the risk for certain cancers compared with those who do not
binge drink. Even if a person’s alcohol consumption is light to moderate
most of the time, any health benefits associated with that disappear with
regular binge drinking. Examples of such potential benefits are reduced
risk of developing or dying from heart disease and possibly decreased
risk of ischaemic stroke. There is no exception to the alcohol rule, and
this includes red wine which has been suggested as having an ability to
prevent cancer, despite no clear evidence to prove this.

22 Morgan
Arguably, the most important factor in increasing cancer risk seems to
be the amount of alcohol consumed over time. Although the reality is
that most people will sometimes enjoy a serving of alcohol, what can be
recommended is doing so in moderation.

Dietary Supplements
Although the role of dietary supplements in cancer prevention is uncer-
tain and at times confusing, there is no proven evidence that any availa-
ble dietary supplement can help in preventing cancer. To ensure a healthy
supply of vitamins and minerals, the best recommendation is a well-
balanced diet.

Other Food Groups Associated With Cancer

Making the right choices regarding what you eat could have a great
impact on your risk of developing cancer. The cancer most associated
with a poor diet is colorectal cancer, and these poor diets have a common
pattern: they are low in dairy, vegetables, fruits and whole cereals, and
high in sugary beverages and processed meat.

Conclusion
Nutrition and exercise can play a central role in the risk of developing can-
cer. Although there is a big impact from one's own genetics, the choices we
make in what we consume impact our body and it is up to us to determine
if this will be a positive impact or a negative one.

Further Reading
American Cancer Society. Cancer Prevention & Early Detection Facts & Figures
2019-2020. Atlanta: American Cancer Society; 2019.
Aune D, Chan DS, Lau R, et al. Dietary fibre, whole grains, and risk of colorectal
cancer: systematic review and dose-response meta-analysis of prospective
studies. BMJ 2011; 343:d6617.
Aykan NF. Red meat and colorectal cancer. Oncol Rev 2015; 9:288.

Role of Nutrition in Cancer Prevention 23

Connor J. Alcohol consumption as a cause of cancer. Addiction 2017;
112:222–228.
Farvid MS, Eliassen AH, Cho E, et al. Dietary fiber intake in young adults and
breast cancer risk. Pediatrics 2016; 137:e20151226.
Gilsing AMJ, Schouten LJ, Goldbohm RA, et al. Vegetarianism, low meat con-
sumption and the risk of colorectal cancer in a population based cohort study.
Sci Rep 2015; 5:13484.
McTiernan A, Friedenreich CM, Katzmarzyk PT, et al; 2018 Physical Activity
Guidelines Advisory Committee. Physical activity in cancer prevention and
survival: a systematic review. Med Sci Sports Exerc 2019; 51:1252–1261.
Murillo G, Mehta RG. Cruciferous vegetables and cancer prevention. Nutr Can-
cer 2001; 41:17–28.
Pelucchi C, Gallus S, Garavello W, et al. Cancer risk associated with alcohol
and tobacco use: focus on upper aero-digestive tract and liver. Alcohol Res
Health 2006; 29:193–198.
Plant power: using diet to lower cancer risk - Mayo Clinic. https://www.may-
oclinichealthsystem.org/hometown-health/speaking-of-health/plant-power-
to-lower-cancer-risk (23 May 2023, date last accessed).
Physical Activity and Cancer Fact Sheet – National Cancer Institute. https://
www.cancer.gov/about-cancer/causesprevention/risk/obesity/physicalactiv-
ity-fact-sheet (24 May 2023, date last accessed).
Ranjan A, Ramachandran S, Gupta N, et al. Role of phytochemicals in cancer
prevention. Int J Mol Sci 2019; 20:4981.
Rehm J, Shield KD. Alcohol use and cancer in the European Union. Eur Addict
Res 2021; 27:1–8.
Rock CL, Thomson C, Gansler T, et al. American Cancer Society guideline for
diet and physical activity for cancer prevention. CA Cancer J Clin 2020;
70:245–271.
Rumgay H, Shield K, Charvat H, et al. Global burden of cancer in 2020 attribut-
able to alcohol consumption: a population-based study. Lancet Oncol 2021;
22:1071–1080.
Santarelli RL, Pierre F, Corpet DE. Processed meat and colorectal cancer:
a review of epidemiologic and experimental evidence. Nutr Cancer 2008;
60:131–144.
Spei ME, Samoli E, Bravi F, et al. Physical activity in breast cancer survivors:
a systematic review and meta-analysis on overall and breast cancer survival.
Breast 2019; 44:144–152.
Stone TW, McPherson M, Gail Darlington L. Obesity and cancer: existing and
new hypotheses for a causal connection. EBioMedicine 2018; 30:14–28.

24 Morgan
Watling CZ, Schmidt JA, Dunneram Y, et al. Risk of cancer in regular and
low meat-eaters, fish-eaters, and vegetarians: a prospective analysis of UK
Biobank participants. BMC Med 2022; 20:73.
World Cancer Research Fund/American Institute for Cancer Research. Diet,
Nutrition, Physical Activity, and Cancer: A Global Perspective. Continuous
Update Project Expert Report 2018. http://www.dietandcancerreport.org/
(24 May 2023, date last accessed).
Yang YJ. An overview of current physical activity recommendations in primary
care. Korean J Fam Med 2019; 40:135–142.
Zheng W, Lee SA. Well-done meat intake, heterocyclic amine exposure, and can-
cer risk. Nutr Cancer 2009; 61:437–446.

Declaration of Interest:
Dr Morgan reports personal advisory board fees from Pfizer, Roche, Sanofi and
Lilly; and invited speaker fees from Novartis and AstraZeneca.

Role of Nutrition in Cancer Prevention 25

Psychosocial and Cultural
Aspects of Nutrition 4
J.B. Hopkinson1
F. Strasser2
School of Healthcare Sciences, College of Biomedical and Life Sciences,
1

Cardiff University, Cardiff, UK

Cantonal Hospital St. Gallen and Cancer Fatigue Clinic, Onkologie
2

Schaffhausen, Schaffhausen; Cantonal Hospital Münsterlingen,

Münsterlingen; Center Radiotherapy Rüti, Rüti, Switzerland

This chapter is about providing culturally sensitive psychosocial support

for eating well when living with or at risk of cancer cachexia.
“In our family, we always laugh at the portions … because we’ve always
eaten a lot. Always big healthy portions of meat, vegetables, you know,
nice, homemade food. But Dad now hardly eats a saucerful … it’s going
to make you ill by not eating, if you’re not getting the proper vitamins
and nutrients that your body needs. And this is the problem. And it’s
trying to think, for my Mum and everyone else, what he can eat … Just
seeing him losing weight … you feel helpless … it’s very distressing.”
(Jo, daughter of a patient with oesophageal cancer)
Anorexia, early satiety and other changes in eating are symptoms of cancer
cachexia syndrome that can occur at any point across the cancer journey.
These symptoms have a negative emotional and social impact on both
patients and their family members, thus disrupting everyday life. They are
associated with impaired physical function, reduced tolerance to antican-
cer treatment and reduced survival and have an adverse effect on quality
of life. The psychosocial consequences of cancer cachexia include: conflict
over food in families, accusations of healthcare professional neglect and
distress, such as the helplessness expressed above by Jo.

26
Clinical Guidelines
The emotional and social effects of changing eating habits impact on
nutrition in cancer patients. These effects are influenced by culture: the
patient’s values, beliefs and behavioural norms. The European Society
for Medical Oncology (ESMO) guideline for the management of can-
cer cachexia in adult patients recommends multimodal intervention to
include nutritional and psychosocial support. This management should
include assessment of secondary causes of impaired nutritional intake,
which can include cultural influence, and the management of related psy-
chosocial distress. It should be integrated with oncology treatment, as
multimodal intervention is likely of benefit across all stages of cachexia
and before cancer is refractory. Supportive care is relevant throughout
the continuum of the cancer experience, from diagnosis through treat-
ment to post-treatment care, and should be available in all cancer treat-
ment centres (as defined by the Multinational Association of Supportive
Care in Cancer [MASCC]).
But what psychosocial issues should be managed and how? Our response
to this question is based mainly on research with patients who have late-
stage cancer. However, findings from our recent research with patients
who have stage II-III colorectal cancer are consistent with this, suggest-
ing that our recommendations translate to patients earlier in the disease
trajectory.

What Psychosocial Issues Related to Nutrition

Do Cancer Patients Face?
Factors Affecting the Patient’s Oral Intake
Information about diet, food and nutrition is easily accessible, for exam-
ple via the internet and social media. As a consequence, cancer patients
can experience information overload or confusion and generic informa-
tion can be difficult to apply in personal circumstances. Dominant dis-
course is about healthy eating to reduce the risk of all-cause disease.
When overwhelmed by information or confused about what to do, this
messaging can mislead patients, for example, patients who should take a
high-energy, high-protein diet because they are malnourished.

Psychosocial and Cultural Aspects of Nutrition 27

Taking comfort through eating may also influence decisions about what
to eat. Following a cancer diagnosis and during anticancer treatment,
maintaining ‘normal’ eating habits can provide comfort. Eating what
you have always eaten and following family mealtime routines can be
reassuring for all involved. In contrast, poor appetite and involuntary
weight loss are typically interpreted as indications of declining health
and approaching death. Maintaining pre-illness dietary habits is reas-
suring but can distract from considering nutritional intake and risk of
malnutrition following a cancer diagnosis and through treatment.

Factors Affecting the Role of the Family Carer

A growing number of cancer patients receive treatment and care in their
own home. Family carers of people with cancer thus have an increasingly
important role to play. Their role includes helping with the management
of symptoms, treatment side effects and nutritional risk. Some carers
describe their role as changing from a partner to a nurse.
The attitudes and beliefs of the family carer can influence the support
provided for eating problems and nutritional risk in the patient. Like
patients, they can find information about food, eating and cancer both
conflicting and overwhelming. Like patients, they can be wrong to
believe that healthy eating advocated to reduce the risk of disease is also
a way to arrest cancer or even to cure it. Unlike patients, they often have
no first-hand experience of cancer-induced eating difficulties and find
them difficult to understand. Moreover, in some communities, the under-
standing of cancer and its progression is poor. Thus, cancer-induced sick-
ness behaviours, such as food refusal, food aversions and poor appetite,
can be wrongly attributed to a lack of will on the part of the patient –
the family can believe the patient is not trying hard enough to eat.

Key Factors Affecting Eating-related Distress and Quality of Life

Differences between family members in understanding what causes eat-
ing problems in cancer patients can lead to disagreements in the home
and even lead to force-feeding when the patient resists offers of food.
Prior relationships between family members can also affect how disa-
greement is managed and whether it escalates to conflict. The known

28 Hopkinson and Strasser

association between mood and appetite suggests that addressing psycho-
social issues may both improve the emotional health of the patient and
help to optimise their nutritional intake.
Body image can be an eating-related source of distress identified using a
distress thermometer, such as the National Comprehensive Cancer Net-
work (NCCN) Distress Thermometer. Change in body image because
of cancer and its treatments is associated with anxiety and depression.
Psychosocial interventions can educate to aid understanding and emo-
tional adjustment, mitigating body image concerns and benefitting rela-
tionships and nutritional status.
Despite the impact of eating-related problems on quality of life, many
patients do not seek help for symptoms such as anorexia, nausea and sore
mouth. Psychosocial obstacles to seeking help include:
i) belief that the clinician’s role is around treatment rather than eating
difficulties,
ii) belief that nothing can be done,
iii) reluctance to follow nutritional advice and
iv) perceived social benefits of weight loss, particularly for those who are
overweight.
Healthcare professionals can also be reluctant to initiate discussion about
involuntary weight and eating problems, lacking confidence that they
know what to do or fearing they may cause distress. This may be particu-
larly so when cultural difference leads to conflict between patient values
and health-professional values and practices.

How Can Healthcare Professionals Help?

When psychosocial factors compromise nutrition in weight-losing can-
cer patients, the interventions described below have the potential to miti-
gate distress and improve nutritional intake. Amano et al (J Palliat Care
2020) validated an assessment tool to aid the identification of cachexia-
related distress. The scale has three dimensions: coping with eating prob-
lems, coping with eating-related distress, and distress arising from fam-
ily conflict.

Psychosocial and Cultural Aspects of Nutrition 29

Behavioural change techniques can be used within each of the three
dimensions of cachexia-related distress. The techniques include normal-
ising and encouraging appropriate goal setting. They can provide the
framework for personalised education about cancer cachexia and nutri-
tion that facilitates adherence to clinical advice. They can also support
coping strategies to aid adaptation and alleviate distress in patients and
their family members.

Culturally Sensitive Communication to Help the

Patient Cope with Eating Problems
Using Indirect Methods of Communication
Offering advice on sensitive topics is difficult, as it involves communicat-
ing information in a context of competing values that can create barriers
to trust and respect. Weight loss can be a sensitive topic. Weight loss may
also not be apparent, particularly in patients who are obese. Thus oppor-
tunities to encourage patients to attend to their nutrition can be missed.
Storytelling can be a constructive approach that is less confrontational
than presenting factual information. Moreover, many people remem-
ber information in stories that they would otherwise forget. A story can
be tailored to share information in a culturally sensitive way by using
examples from the patient’s own community. Although we all tell stories
in our everyday lives, therapeutic storytelling is a skill learned through
practice. The PRO approach is one approach to therapeutic storytelling.
The PRO story presents a problem (P), offers alternative resources (R) to
deal with it and ends with an outcome (O) desired by the characters in the
story. For example, information about an appropriate diet for someone
with a poor appetite and weight loss that challenges beliefs such as ‘eat-
ing organic food cures cancer’ can be communicated in a story. PRO sto-
ries can be developed from clinical experience, combining experiential
learning from work with more than one patient. The story might begin:
“I meet a lot of people who worry that they are not eating enough organic
food. What you’ve just told me brings to mind another family I met …”

30 Hopkinson and Strasser

Information and Education to Dispel Myths and Misunderstandings
Discussing weight loss and eating concerns may reveal gaps in knowl-
edge. The general public (and many healthcare professionals) have a
poor understanding of cancer cachexia. People assume that, as in health,
there is a balance between eating and weight: eating more leads to weight
gain and eating less results in weight loss. The disturbance of this bal-
ance in primary cancer cachexia is not understood. The ‘factory talk’
can help patients with cancer cachexia understand their situation: “To
build wooden furniture, both a wood supply (tree trunks) and a factory is
needed.” In cachexia, the factory (internal body processes) to transform
nutrients into muscle is dysfunctional.
There is expert consensus that providing information about appropriate
diet is an important part of managing the emotional aspects of cachexia.
A belief in benefits, a ‘feel-good’ factor, influences whether patients
engage with and adhere to nutritional advice. Understanding how nutri-
tion can contribute to treatment outcomes and emotional wellbeing is
likely to be important for this feel-good factor.
Cultural humility may be needed to learn about the patient’s values,
beliefs and behaviours relating to food and eating that should be taken
into account when offering advice. Enquiring about concerns can be a
way of opening up the possibility of providing information and educa-
tion. Asking the person with cachexia: “What did you eat yesterday?”,
followed by: “Is this the same as before your cancer diagnosis?” can
prompt talk that reveals misunderstandings or provides an opportunity
to support self-management of nutritional risk. An example would be to
identify preferred foods that are nutritionally dense, such as chocolate.

Coping with Eating-related Distress

Managing Disagreement
Teaching patients and their family members about the common causes
and symptoms of cancer cachexia can help to address concerns and dis-
tress caused by misunderstandings. Presenting different perspectives on
the same problem can also be helpful. This might be done using a PRO
story that presents different ways patients can manage a problem such

Psychosocial and Cultural Aspects of Nutrition 31

as unwanted advice on what to eat. It can also be achieved by invit-
ing different perspectives, such as by asking the patient and each family
member to say what concerns them about eating problems. This can be
surprising for all involved and can start a discussion leading to agree-
ment on how to manage problems. Signposting to evidence-based patient
resources about nutrition, eating and cancer can also be a way of present-
ing alternative perspectives and raising awareness of culturally appropri-
ate solutions, such as when it is acceptable to break a religious fast.
Sometimes it is important to disrupt lack of concern, for example if it
accompanies inappropriate self-management of undernutrition. For
patients who are experiencing involuntary weight loss, it may be impor-
tant to encourage adaptation of usual food and fluid intake to mitigate
nutritional risk.

What About the Family?

Patient and family-member experiences of eating-related distress can be
intertwined, which is why communication should be with carers as well
as patients. Family traditions influence cooking methods, mealtimes,
ingredients and beliefs about the relationship between food and health.
Family carers typically want to help the patient; they can feel respon-
sible for nutritional care and may take charge of what the patient eats.
Some try to coax, encourage or even force the patient to eat. While many
patients recognise these behaviours as well-intentioned, their effects can
be the opposite of that intended. Patients can find the pressure to eat
inhibits their appetite: “If I’m forced to eat, I don’t eat.” Family pressure
is usually motivated by anxiety and/or false beliefs, such as the belief
that liquid food supplements provide less nutritional value than a proper
meal. See Box 1 for a list of some of the other widely held ‘common
sense’ beliefs that can inform family members’ feeding behaviour and
that may need to be challenged.
Talking with families about the patient’s eating habits and weight loss
can be a sensitive topic of conversation because of the feelings it evokes.
For clinicians, an appropriate question to open a conversation is: “Are
you concerned about what (patient’s name) is eating?”, followed by:

32 Hopkinson and Strasser

“Can you tell me about your concerns?” See Box 2 for other questions
that can facilitate a conversation about weight loss and changing eat-
ing habits with a patient and their family. Providing information about
cancer cachexia can mitigate eating and weight-related distress in fam-
ily members. Furthermore, family members can help motivate patients
to achieve nutritional goals. Where possible, nutritional care in cancer
should have a family component.
Box 1 Mistaken ‘common sense’ beliefs that can inform the behaviour of family members.

n Solid foods have greater nutritional value than liquids

n Hot foods have greater nutritional value than cold foods
n People eat more when sharing a meal compared to when eating alone
n Eating between meals is always a bad habit
n Eating cakes and puddings is always harmful to health
n Not trying to eat is being awkward (or emotionally weak)
n The patient is starving to death, so should be force fed
n Food feeds the cancer, so it is best not to eat
n Fruit and vegetables can cure cancer
n It is always healthy to lose weight

Box 2 Questions that can facilitate discussion about weight loss and eating concerns.

Can you tell me about:

n any change in (patient’s) weight?
n any change in the food (patient) eats?
n what (patient) ate yesterday (amount, timing, context)?

Why do you think:

n (patient) has lost weight?
n (patient) is having difficulty eating?
n (patient) is not interested in food?

How concerned do you feel about:

n the change in (patient’s) weight?
n (patient) not eating certain foods?

n (patient) eating small portions?

Psychosocial and Cultural Aspects of Nutrition 33

Since involuntary weight loss and declining function almost always raise
concerns about dying, these concerns merit acknowledgment. Support to
prepare for end-of-life can be helpful for patients and family members.

Conclusion
Culturally sensitive psychosocial support for optimal oral nutritional
intake when living with cachexia can:
n Enhance the quality of life of patients and family carers by helping

them to cope with the emotional and social impact of disease-related

malnutrition.
n Empower patients and family carers to be partners in cancer treat-

ment through engagement in nutritional care.

Further Reading
Amano K, Hopkinson J, Baracos V. Psychological symptoms of illness and emo-
tional distress in advanced cancer cachexia. Curr Opin Clin Nutr Metab Care
2022; 25:167–172.
Amano K, Morita T, Miyashita M. Potential measurement properties of a question-
naire for eating-related distress among advanced cancer patients with cachexia:
preliminary findings of reliability and validity analysis. J Palliat Care 2022;
37:107–112.
Amano K, Morita T, Miura T, et al. Development and validation of questionnaires for
eating-related distress among advanced cancer patients and families. J Cachexia
Sarcopenia Muscle 2023; 14:310–325.
Arends J, Strasser F, Gonella S, et al; ESMO Guidelines Committee. Cancer
cachexia in adult patients: ESMO Clinical Practice Guidelines. ESMO Open
2021; 6:100092.
Behavioural Change Project 2020. Available at: https://theoryandtechniquetool.
humanbehaviourchange.org/tool (24 May 2023, date last accessed).
Burns GW. 101 Healing Stories: Using Metaphors in Therapy. New York: John
Wiley & Sons, 2001.
Chopra D, De La Garza R II. Depressive, anxiety, and distress symptoms among
cancer patients who endorse appearance problems. Palliat Support Care 2019;
17:328–332.
Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia:
an international consensus. Lancet Oncol 2011; 12:489–495.

34 Hopkinson and Strasser

Hall CC, Skipworth RJE, Blackwood H, et al. A randomised, feasibility trial of an
exercise and nutrition-based rehabilitation programme (ENeRgy) versus standard
care in people with cancer. J Cachexia Sarcopenia Muscle 2021; 12:2034–2044.
Hopkinson JB. Psychosocial impact of cancer cachexia. J Cachexia Sarcopenia
Muscle 2014; 5:89–94.
Hopkinson JB. The nursing contribution to nutritional care in cancer cachexia.
Proc Nutr Soc 2015; 74:413–418.
Hopkinson JB, Kazmi C, Wheelwright S, et al. Diet and weight management by peo-
ple with non-metastatic colorectal cancer during chemotherapy: mixed methods
research. Colorectal Cancer 2020; 9:2.
Hopkinson JB. Food connections: a qualitative exploratory study of weight- and
eating-related distress in families affected by advanced cancer. Eur J Oncol Nurs
2016; 20:87–96.
Hopkinson JB. The psychosocial components of multimodal interventions offered
to people with cancer cachexia: a scoping review. Asia Pac J Oncol Nurs 2021;
8:450–461.
Hopkinson JB, Fenlon DR, Foster CL. Outcomes of a nurse-delivered psychosocial
intervention for weight- and eating-related distress in family carers of patients
with advanced cancer. Int J Palliat Nurs 2013; 19:118–123.
Hopkinson JB, Richardson A. A mixed-methods qualitative research study to develop
a complex intervention for weight loss and anorexia in advanced cancer: the
Family Approach to Weight and Eating (FAWE). Palliat Med 2015; 29:164–176.
Multinational Association of Supportive Care in Cancer (MASCC). What is support-
ive care? Available at: https://mascc.org/what-is-supportive-care/ (24 May 2023,
date last accessed).
Muscaritoli M, Arends J, Bachmann P, et al. ESPEN practical guideline: clinical
nutrition in cancer. Clin Nutr 2021; 40:2898–2913.
Ream E, Richardson A, Lucas G, et al. Understanding the support needs of family
members of people undergoing chemotherapy: a longitudinal qualitative study.
Eur J Oncol Nurs 2021; 50:101861.
Roeland EJ, Bohlke K, Baracos VE, et al. Management of cancer cachexia: ASCO
guideline. J Clin Oncol 2020; 38:2438–2453.
Strasser F, Binswanger J, Cerny T, Kesselring A. Fighting a losing battle: eating-
related distress of men with advanced cancer and their female partners. A mixed-
methods study. Palliat Med 2007; 21:129–137.
Wen FH, Chou WC, Hsieh CH, et al. Conjoint cognitive and emotional death-prepar-
edness states and their changes within cancer patients' last 6 months. Psychoon-
cology 2021; 30:691–698.

Psychosocial and Cultural Aspects of Nutrition 35

Wheelwright S, Darlington AS, Hopkinson JB, et al. A systematic review and the-
matic synthesis of quality of life in the informal carers of cancer patients with
cachexia. Palliat Med 2016; 30:149–160.
Wheelwright SJ, Hopkinson JB, Darlington A-S, et al; EORTC Quality of Life
Group. Development of the EORTC QLQ-CAX24, a questionnaire for cancer
patients with cachexia. J Pain Symptom Manage 2017; 53:232–242.

Declaration of Interest:
Professor Hopkinson has declared no conflicts of interest.
Professor Strasser has declared personal expert testimony fees from Helsinn; per-
sonal advisory board fees from Pfizer; and speaker remuneration from Sharing
Progress in Cancer Care, Oncology Nursing Switzerland, Gastrointestinal Tumor
Center and PharmaKey.

36 Hopkinson and Strasser

Nutritional Counselling
and Intervention 5
P. Ravasco
Universidade Católica Portuguesa, Faculty of Medicine and
Centre for Interdisciplinary Research in Health (CCIS-UCP), Lisbon;
Egas Moniz School of Health and Science, Centre for Interdisciplinary
Research Egas Moniz, Almada, Portugal

Individualised Nutritional Counselling

In clinical practice, oral nutrition is the priority in patients with cancer
who can tolerate intensive nutritional counselling; this is not the case
for patients at the end of life or with established cachexia. The aim of
nutritional support is to ensure adequate intake of energy and nutrients
by enabling the patient to eat normal food, enjoy eating and participate in
meals with others as a component of their social life. Thus, oral nutrition
is the preferred route since it is a significant part of the patient’s daily
routine and contributes to the patient’s autonomy. On most occasions,
eating is a source of pleasure and a privileged time to spend with family
and friends. The acknowledgement that the prescribed diet is individu-
alised and adequate for their needs empowers the patient with dimen-
sions of control, contributing to their psychological wellbeing. All these
factors may contribute to improving the patient’s quality of life (QoL)
and modulate acute and late treatment morbidities. Hence, dietary coun-
selling must be based on a comprehensive assessment of the patient’s
situation and an evaluation of reasonable, available treatment options,
resulting in a personalised approach.
An adequate food intake is recognised by the patient, as well as by their
family and caregivers, as essential to maintaining daily activities, energy
levels, functional capacity and the success of their cancer journey. Also,
clinicians must acknowledge the patient’s treatment objectives and plans,

37
and that the role of nutrition cannot drive treatment decisions. In patients
undergoing anticancer therapy, ensuring an adequate energy and nutrient
intake should be pursued vigorously.
Individualised dietary counselling must be based on a thorough assessment
of various nutritional and clinical parameters evaluated during any nutri-
tional consultation, using structured, specific and validated questionnaires.
These include the 24-hour recall and/or the 72-hour registry (2 weekdays
and 1 weekend day) of all meals and foods that have been consumed, as
well as a food frequency questionnaire that provides data on food habits
and patterns relative to the previous 12 months.
Also, the clinical nutritionist/dietician must evaluate the patient’s dietary
preferences, habits and/or intolerances or food aversions and record the
daily meal distribution. The patient’s psychological status, autonomy,
cooperation and need for the help or support of others in the act of eating
are fundamental dimensions that always precede any dietary counsel-
ling. A detailed symptom assessment is mandatory (Table 1).
After recording and interpreting these dimensions, the patient’s nutri-
tional requirements are calculated according to 25-30 kcal/kg body weight
(BW)/day and 1.2-1.5 g protein/kg BW/day (considered to represent basic
macronutrient requirements in patients with cancer), and a nutritionally
adequate individualised diet is prescribed, containing the patient's pre-
ferred foods and respecting their habits. A full explanation to the patient/
caregiver is the only way to ensure that the patient understands the pre-
scription; therefore, effective communication skills are required to achieve
maximum compliance. Informing the patient, their family and caregivers
on the importance of the diet and its content (the types and amounts of
food needed) is a fundamental step for the implementation of any dietary
plan. A detailed dietary plan is constructed in accordance with the patient's
opinions and must contain the number of meals, a timetable including the
intervals between meals, and a list of the foods and their quantity, with
alternative equivalent choices. A copy of this plan is then given to the
patient as a nutritional guide for their daily dietary intake.

38 Ravasco
Table 1 Causes of Cancer-related Malnutrition.
n Deterioration in taste, smell and appetite, as a consequence of the disease and/or therapy
n Altered food preferences/avoidance/aversion
n Anorexia
n Dysphagia, odynophagia
n Partial/total gastrointestinal obstruction or dysfunction
n Early satiety, nausea and vomiting
n Soreness, xerostomia, sticky saliva, painful throat, trismus
n Oral lesions and oesophagitis
n Radiotherapy-/chemotherapy-induced mucositis
n Acute or chronic radiation enteritis during and after radiotherapy
n Depression, anxiety
n Pain

Goals of Individualised Nutrition in Cancer

The goals of individualised nutritional counselling differ between
patients with early malignancy and curative treatment options and those
in end-of-life situations. The content of this section refers to the first
cohort of cancer patients. Major goals include: to arrange the patient’s
nutritional intake to ensure it meets their individual requirements in terms
of energy and macro- and micronutrients, and to modulate symptoms by
reducing the foods that may worsen them and/or increase foods that may
reduce their severity. In many cases, concomitant pharmacological ther-
apy for management of symptoms may be required. Dietary counselling
involves the prescription of therapeutic diets using regular foods, which
may be further modified to provide for individual requirements. If the
patient is unable to meet their nutritional requirements via regular foods,
oral nutritional supplements (ONSs) may be prescribed, the composi-
tion of which is based on the dietary deficits detected in the individual
and from their detailed intake questionnaire. To achieve the highest level
of compliance, the patient's usual dietary pattern should be maintained
as much as possible. The type and quantity of food and the frequency
of eating depend upon the patient, the disease and the therapeutic goal.
The monitoring of patient compliance with recommendations and
Nutritional Counselling and Intervention 39
weekly/bi-weekly consultations with a clinical nutritionist are consid-
ered essential to follow-up after nutritional counselling. Integration of
dietary counselling with the regular treatment visit schedule is manda-
tory for timely adaptations.
Any nutritional intervention needs to take into account other factors,
for example, digestive and absorptive capacity, the need to alleviate or
arrest symptoms, psychological factors, and disease stage and progres-
sion. Therapeutic diets are regularly adjusted to the patient’s reported
diet, thereby recognising personal eating patterns and preferences, which
form the basis for individualised dietary counselling. Prescribed diets
include information on the type, amount and frequency of eating, and
specify the caloric/protein level to attain, together with any restrictions
and limited or increased individual dietary components.
The clinical nutritionist/dietician in charge of the individualised dietary
counselling should always follow an evidence-based decision-making
plan (Figure 1).

Patient’s GI tract Counselling ± supplements

is functional?
YES

Evaluate intake How much?

and prescribe Which nutrients?

NO
Insufficient vs Sufficient
<75% needs ≥90% needs

Duration
+
Monitoring
nutritional status From 75%-90%
requires tight monitoring

PARENTERAL Artificial nutrition ENTERAL

Figure 1 Nutritional support decision-making process for cancer patients with

early-stage disease.
Abbreviation: GI, gastrointestinal.

40 Ravasco
Cancer patients who cannot eat adequate amounts of food should receive
nutritional support as an essential component of best supportive care,
to improve food intake, nutritional status, BW and QoL. Nutritional
support in patients able to eat should be based on dietary counselling,
guidance on choosing high-energy, high-protein foods, enriching foods
(e.g. by adding fat/oils, protein powder) and use of ONSs. If this proves
inadequate, tube feeding should be offered if the lower gastrointestinal
(GI) tract is working; otherwise, parenteral nutrition is the method of
choice. Separate routes of feeding may be combined for optimal effect.

What Does the Evidence Show About the Benefits

of Individualised Nutritional Counselling?
Nutrition is a major issue in oncology, and nutritional decline may ensue
from both the disease course and its treatment(s). This carries a negative
prognosis. Symptomatic manifestations of antineoplastic treatments and
their nutritional consequences have long been recognised, and the role of
adjuvant oral nutritional counselling on patient outcomes has been dem-
onstrated. Research focusing on outcomes, for example, hard evidence
on the effectiveness of adjuvant nutrition, is essential to prove the value
of any nutritional intervention. Research should be action-orientated, so
that interventions leading to positive outcomes can be determined, and
ineffective practices phased out or discarded.
In cancer patients under active treatment, despite the expected and expe-
rienced acute detrimental effects of treatments, individualised nutritional
intervention, education and monitoring, as well as timely management of
symptoms, improve nutritional and non-nutritional outcomes. Early indi-
vidualised nutritional counselling contributes to reduced treatment toxic-
ity and improved nutritional intake and status, as well as QoL. Such ben-
efits in nutritional outcomes concur with what has been proposed as the
causal pathway, i.e. optimising nutritional intake may be the most effec-
tive method for treating disease-related malnutrition. There is evidence
in a range of health conditions to support the hypothesis that providing
appropriate nutritional therapy leads to improved BW and fat free-mass,
and that this generally reflects an improvement in protein-energy status.

Nutritional Counselling and Intervention 41

Intensive individualised nutritional counselling has become the stand-
ard recommendation in the European Society for Clinical Nutrition and
Metabolism (ESPEN) guidelines, later also recommended in the Euro-
pean Society for Medical Oncology (ESMO) guidelines.
Studies have also shown that the nutritional content of the patient’s diet
with appropriate manipulation, and not just protein and calorie sup-
plementation, is important to improve GI function and other sympto-
matic manifestations during treatment and in the medium term. Treat-
ment toxicity and incidence/severity of symptoms are lower in patients
who receive dietary counselling and education, and their recovery in the
medium term tends to be faster. Dietary modifications may alter bowel
functions, such as motility, enzyme secretion and nutrient absorption;
likewise, nutrition modulates the GI flora, whose ecology is central to the
pathogenesis of radiotherapy injury severity.
Nutrition is also a key determinant of QoL in cancer patients. Individu-
alised dietary counselling, in association with an adequate dietary intake
and nutritional status, contributes to improved QoL function scores in
patients able to eat and in patients fit enough to comply with an indi-
vidualised nutritional plan. It is unlikely that nutritional interventions
will achieve the same level of improvement in the QoL of patients with
advanced cancer and established anorexia-cachexia syndrome.

Conclusion
Nutrition is an effective complement to antineoplastic treatments. Early
nutritional intervention is paramount to prevent nutritional and physio-
logical deficits. It can modulate weight loss and morbidity, and maintain
an adequate nutritional status, performance status and QoL. It has the
potential to stabilise or improve the patient’s clinical status and augment
the potential for favourable response to therapy, recovery and progno-
sis. With the advent of more effective cancer therapies leading to an
increased number of long-term survivors, greater emphasis is urgently
required to provide the best care during treatment to improve the clini-
cal course of patients. Early intervention and sensible partnerships with
patients are the keys to success.

42 Ravasco
Key Messages
n Early identification of patients on antineoplastic therapy who are at


risk of becoming or are already malnourished is critical for optimis-

ing treatment success and defining the urgency of nutritional inter-
vention.
n Malnourished patients are at increased risk of being unable to tolerate

the most effective ‘level’ and ‘duration’ of treatment, with significant

implications for both short- (during treatment) and long-term outcomes.
n In cancer patients, food intake may be compromised by several factors

including nutrition impact symptoms (e.g. nausea, vomiting, anorexia,

dysphagia). If, after alleviating these symptoms, food intake is still
inadequate, nutrition-based interventions should be initiated.
n In patients with inadequate food intake and/or who are receiving

anticancer therapy, nutritional interventions should be escalated, as

required. In other situations, low-risk interventions (e.g. counselling
and ONSs) are preferred.
n To maintain nutritional status, patients should ingest at least 25-30

kcal/kg BW/day and 1.2-1.5 g protein/kg BW/day.

n Dietary counselling should be the first choice of nutritional support

offered to improve oral intake and possibly weight gain in cachectic or

at-risk patients who are able to eat. Dietary counselling should empha-
sise protein intake, an increased number of meals per day, include
recommendations to modulate symptoms that impact nutritional intake
and offer ONSs when necessary. An appropriately trained professional
should guide this advice.
n ONSs can be supplied as part of dietary counselling to improve

energy and protein intake.

Further Reading
Arends J, Bachmann P, Baracos V, et al. ESPEN guidelines on nutrition in cancer
patients. Clin Nutr 2017; 36:11–48.
Bargetzi L, Brack C, Herrmann J, et al. Nutritional support during the hospital stay
reduces mortality in patients with different types of cancers: secondary analysis
of a prospective randomized trial. Ann Oncol 2021; 32:1025–1033

Nutritional Counselling and Intervention 43

Cardenas D, Toulson Davisson Correia MI, Ochoa JB, et al. Clinical nutrition and
human rights. An international position paper. Clin Nutr 2021; 40:4029–4036.
Cereda E, Cappello S, Colombo S, et al. Nutritional counseling with or without
systematic use of oral nutritional supplements in head and neck cancer patients
undergoing radiotherapy. Radiother Oncol 2018; 126:81–88.
de van der Schueren MAE, Laviano A, Blanchard H, et al. Systematic review and
meta-analysis of the evidence for oral nutritional intervention on nutritional and
clinical outcomes during chemo(radio)therapy: current evidence and guidance
for design of future trials. Ann Oncol 2018; 29:1141–1153.
Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia:
an international consensus. Lancet Oncol 2011;12: 489–495.
Garg S, Yoo J, Winquist E. Nutritional support for head and neck cancer patients
receiving radiotherapy: a systematic review. Support Care Cancer 2010;
18:667–677.
Langius JA, Zandbergen MC, Eerenstein SE, et al. Effect of nutritional interven-
tions on nutritional status, quality of life and mortality in patients with head
and neck cancer receiving (chemo)radiotherapy: a systematic review. Clin Nutr
2013;32:671–678.
Laviano A, Calder PC, Schols AMWJ, et al. Safety and tolerability of targeted medi-
cal nutrition for cachexia in non-small-cell lung cancer: a randomized, double-
blind, controlled pilot trial. Nutr Cancer 2020; 72:439–450.
Lee JLC, Leong LP, Lim SL. Nutrition intervention approaches to reduce malnu-
trition in oncology patients: a systematic review. Support Care Cancer 2016;
24:469–480.
Muscaritoli M, Arends J, Bachmann P, et al. ESPEN practical guideline: clinical
nutrition in cancer. Clin Nutr 2021; 40:2898–2913.
Omlin A, Blum D, Wierecky J, et al. Nutrition impact symptoms in advanced cancer
patients: frequency and specific interventions, a case-control study. J Cachexia
Sarcopenia Muscle 2013; 4:55–61.
Orell H, Schwab U, Saarilahti K, et al. Nutritional counseling for head and neck
cancer patients undergoing (chemo) radiotherapy – a prospective randomized
trial. Front Nutr 2019; 6:22.
Qiu Y, You J, Wang K, et al. Effect of whole-course nutrition management on patients
with esophageal cancer undergoing concurrent chemoradiotherapy: a rand-
omized control trial. Nutrition 2020; 69:110558.
Rauh S, Antonuzzo A, Bossi P, et al. Nutrition in patients with cancer: a new area for
medical oncologists? A practising oncologist’s interdisciplinary position paper.
ESMO Open 2018; 3:e000345.

44 Ravasco
Ravasco P, Monteiro-Grillo I, Camilo M. Individualized nutrition intervention is of
major benefit to colorectal cancer patients: long-term follow-up of a randomized
controlled trial of nutritional therapy. Am J Clin Nut 2012; 96:1346–1353.
Ravasco P, Monteiro-Grillo I, Marques Vidal P, Ermelinda Camilo M. Dietary
counseling improves patient outcomes: a prospective randomized controlled
trial in colorectal cancer patients undergoing radiotherapy. J Clin Oncol 2005;
23:1431–1438.
Roeland EJ, Bohlke K, Baracos VE, et al. Management of cancer cachexia: ASCO
Guideline. J Clin Oncol 2020; 38:2438–2453.
Tan S, Meng Q, Jiang Y, et al. Impact of oral nutritional supplements in post-dis-
charge patients at nutritional risk following colorectal cancer surgery: a rand-
omized clinical trial. Clin Nutr 2021; 40:47–53.
Yalcin S, Gumus M, Oksuzoglu B, et al. Nutritional aspect of cancer care in medical
oncology patients. Clin Ther 2019; 41:2382–2396.

Declaration of Interest:
Dr Ravasco has declared no conflicts of interest.

Nutritional Counselling and Intervention 45

Cancer and the
Nutritional Status 6
V.E. Baracos
Department of Oncology, University of Alberta, Edmonton, AB, Canada

Evaluation of the Nutritional Status of a Patient

with Cancer
The wasting syndrome that accompanies malignant disease can be termed
‘cancer-associated malnutrition’. This condition is primarily defined on
a pathophysiological basis to consist of nutritional deficit in the presence
of disease-related metabolic alterations. The cardinal diagnostic crite-
rion for cancer-associated malnutrition is weight loss. Weight loss has
already occurred at time of malignant diagnosis for many patients, con-
tinues over the course of cancer evolution and is particularly prominent
in advanced/metastatic disease. Cumulative losses can be considerable,
culminating in emaciation. In light of the progressive nature of weight
loss, it is essential to record height and weight at presentation, and take
a weight history from the patient or medical records (e.g. What was their
weight 6 months ago? Their usual body weight prior to illness?). The
severity of weight loss should be graded (Figure 1).
Grading allows the clinician to assess the degree to which the patient
is already depleted and the presence of active weight loss. The topmost
cancers associated with weight loss and malnutrition are pancreatic,
hepatic, gastric, oesophageal and lung cancer; in the case of incurable
cancers, all patients are at elevated risk of malnutrition. Future risks of
weight loss should be considered; these may vary according to the antici-
pated treatment plan. Aggressive treatment, for example, radiotherapy
with concurrent chemotherapy, is often associated with acute weight
loss of >10%. For radiotherapy, the site of treatment may have impor-
tant nutritional consequences, for example radiation to the oral cavity,

46
 BMI (kg/m2)
28 25 22 20

0 0 1 1 3
2.5
Weight Loss (%)
1 2 2 2 3
6
2 3 3 3 4
11
3 3 3 4 4
15
3 4 4 4 4

Figure 1 Classification of cancer-associated weight loss. This tool captures the

intensity of weight loss, as well as the overall depletion of the body mass index (BMI),
as defined by their association with mortality. Severity of weight loss is classified from
Grade 0 (high BMI, no weight loss) through Grade 4 (large weight loss, low BMI).
From: Martin L, Senesse P, Gioulbasanis I, et al. Diagnostic criteria for the classification of cancer-
associated weight loss. J Clin Oncol 2015; 33:90–99.

laryngeal, pharyngeal and oesophageal regions: the resulting pain and

mucositis impair dietary intake. Early assessment of weight-loss grade
provides a benchmark against which future weights are compared, as
well as a tool to prioritise patients for further investigation. At a time of
endemic obesity and obesity-associated cancer, weight loss is nonethe-
less associated with poor clinical outcomes in obese patients with can-
cers of advanced stage.
A deficit of skeletal muscle mass is a diagnostic criterion for cancer-
associated malnutrition. Loss of muscle may appear early and before the
occurrence of a clinically apparent weight loss. Patients may have deficits
in muscle mass at presentation and further losses of muscle over time,
during treatment and disease progression. Muscle depletion is strongly
associated with mortality, complications of cancer surgery and toxicity of
systemic therapies. Computed tomography images used to follow cancer
progression may be used to derive very precise radiological measures of

Cancer and the Nutritional Status 47

muscle mass/loss; however, these are not yet routine and are just emerg-
ing into clinical workflows. For many patients, muscle deficit goes unde-
tected. It should be noted that malnutrition screening tools (e.g. Mal-
nutrition Screening Tool, Malnutrition Universal Screening Tool, Mini
Nutritional Assessment [MNA]) cannot be relied upon to detect reduced
muscle mass. Muscle depletion is estimated to occur in one out of four
obese patients with advanced-stage disease; however, clinical manage-
ment protocols for sarcopaenic obese patients require development.
Reduced food intake and abnormal metabolism are the primary drivers
of weight loss. The proportional contribution of these factors is vari-
able among individuals. The severity of food intake impairment may be
assessed with validated clinical tools: MNA, the Patient-Generated Sub-
jective Global Assessment (PG-SGA) or the Ingesta 10-point numerical
scale. These tools are validated for patient reporting and are anchored to
the patient’s knowledge of food intake that is normal for them, versus
moderately or severely reduced food intake. Patients with reduced food
intake should be referred for in-depth nutritional assessment and nutri-
tion care. It is well established that symptoms experienced by patients
constrain food intake; these are the ‘nutrition impact symptoms’ (e.g. lack
of appetite, nausea, vomiting, constipation, diarrhoea, pain, fatigue, dry
mouth, dysphagia, mouth sores, shortness of breath, chewing difficulty).
A validated 17-item nutrition impact tool for evaluation of food intake
impairment is available: the Head and Neck Patient Symptom Checklist.
The abnormal metabolism underlying wasting remains the most chal-
lenging aspect of cancer-associated malnutrition, and is particularly
prominent in patients with advanced/unresectable cancers. Tumour mass
and intrinsic metabolic activity may comprise a quantitatively impor-
tant drain of nutrients, mainly in the case of widely disseminated meta-
static disease. A variety of molecules derived from the tumour or result-
ing from tumour interactions with the host immune system can mediate
wasting at the tissue level in both skeletal muscle and adipose tissue, as
well as act on the central nervous system to accelerate wasting by gener-
ating sensory changes, anorexia, adrenal activation and fatigue. Inflam-
matory activity is strongly associated with weight loss, and inflammation
reduces the benefit of nutritional therapy in hospitalised cancer patients.

48 Baracos
Inflammation in this context may be assessed by the blood levels of the
acute phase reactants C-reactive protein and albumin, or by raised neutro-
phil-lymphocyte ratios. For most inflammatory and catabolic effector
molecules, there is currently no means of modifying their production or
action, but these are considered potential therapeutic targets for the treat-
ment of cancer-associated weight loss. Last, cytotoxic and targeted can-
cer therapies have been implicated as direct drivers of muscle and fat
catabolism at the tissue level; however, protocols for prevention or treat-
ment of these off-target effects are not yet available.

Cancer Anorexia and Cachexia: Causes and

Treatment Options
Evidence-based guidelines are a primary resource for the management
of cancer-associated malnutrition/wasting. These include guidelines for
clinical nutrition in oncology (e.g. European Society for Clinical Nutri-
tion and Metabolism [ESPEN] guidelines) and management of cancer
cachexia (e.g. the European Society for Medical Oncology [ESMO],
American Society of Clinical Oncology [ASCO]). Evidence remains
insufficient to strongly endorse any pharmacological agent to improve
clinical outcomes. There are currently no approved medications for can-
cer cachexia by either the European Medicines Agency (EMA) or the US
Food and Drug Administration (FDA). However, anamorelin, an appetite-
stimulating agent targeting ghrelin receptors, received regulatory approval
in Japan in 2021 for the treatment of patients with advanced/unresectable
lung and gastrointestinal cancers. If concordant with the goals of care,
clinicians may offer a short-term trial of a progesterone analogue or a cor-
ticosteroid to patients with advanced cancer experiencing loss of appetite.

Pain and Symptom Management at the Forefront

Medical management of pain and other symptoms may be important for
the management of cancer-associated malnutrition. Potentially revers-
ible causes of weight loss and reduced food intake need to be identified.
Symptoms such as pain, nausea, vomiting, dry mouth (after anticancer
treatments), dental problems, dysphagia, intestinal motility disorders,
oesophageal obstruction, malabsorption, infection, psychological distress,

Cancer and the Nutritional Status 49

endocrine and metabolic disorders may be amenable to medical man-
agement. For example, common side effects of cytotoxic chemotherapy
include anorexia, nausea and vomiting, and radiotherapy to the head and
neck may give life-long oral problems. These effects can be substantial.
Successful management of nausea may result in immediate restoration
of appetite in proportion to the antiemetic effect. Evidence-based guide-
lines are available for nausea/vomiting (e.g. the Multinational Associa-
tion of Supportive Care in Cancer [MASCC], ESMO, ASCO guidelines).
Psychosocial factors can also act as barriers to food intake, for example
mood disorders, food insecurity, lack of social support for assistance
with meal preparation and poor dietary habits. These issues should be
treated accordingly.

Specialist Consultation and Support

Specialist consultation is an important recourse for specific aspects
of management. Inadequate dietary intake is endemic in patients with
advanced cancer. Referral to specialist pain and symptom/supportive
care teams, if available, may help reduce barriers to oral intake. When
nutritional deficit is identified, referral to a nutrition expert (i.e. regis-
tered dietician) is advised for assessment and counselling, with the goal
of providing patients and caregivers with practical and safe advice for
feeding; education regarding high-protein, high-calorie, nutrient-dense
food; and advice against fad diets and other unproven or extreme diets.
Dietary counselling, with or without oral nutritional supplements, may
increase body weight, and individualised nutritional support during hos-
pital stay may reduce mortality in patients with different types of can-
cers. Gastroenterologist input may be required for specific issues such as
stent, malignant bowel obstruction and artificial nutrition (gastrostomy,
parenteral feeding). Enteral tube feeding and parenteral nutrition are not
recommended for routine use in patients with advanced/unresectable
cancers; however, parenteral nutrition may be offered to patients with
early-stage disease as well as selected patients with conditions such as a
reversible bowel obstruction, short bowel syndrome or other issues con-
tributing to malabsorption. Further information on enteral and parenteral
nutrition can be found in Chapter 8.

50 Baracos
Conclusion
Cancer-associated malnutrition is a highly complex and, as of yet, not
fully understood condition. A framework for a therapeutic platform
begins with thorough assessment of the patient, including a history of
and ongoing monitoring of the cumulative severity of weight loss and
assessment of dietary intake and nutrition impact symptoms. Treatment
decisions rely on identification of potential elements of wasting that
are present, including tumour- and treatment-related effects, symptoms
and psychosocial factors. While evidence is limited, clinicians do have
avenues to mitigate malnutrition through evidence-based clinical prac-
tice guidelines, optimising pain and symptom management, and have
recourse to refer their patients for specialist nutritional support and mul-
tidisciplinary supportive care/symptom management.

Further Reading
Aapro M, Caprariu Z, Chilingirov P, et al. Assessing the impact of antiemetic
guideline compliance on prevention of chemotherapy-induced nausea and
vomiting: results of the nausea/emesis registry in oncology (NERO). Eur J
Cancer 2022; 166:126–133.
Arends J, Strasser F, Gonella S, et al; ESMO Guidelines Committee. Cancer
cachexia in adult patients: ESMO Clinical Practice Guidelines. ESMO Open
2021; 6:100092.
Baracos VE, Arribas L. Sarcopenic obesity: hidden muscle wasting and its
impact for survival and complications of cancer therapy. Ann Oncol 2018;
29(suppl_2):ii1–ii9.
Baracos VE, Martin L, Korc M, et al. Cancer-associated cachexia. Nat Rev Dis
Primers 2018; 4:17105.
Bargetzi L, Bargetzi M, Laviano A, et al. Inflammation reduces the effect of
nutritional therapy on clinical outcomes in cancer patients. Ann Oncol 2021;
32:1451–1452.
Bargetzi L, Brack C, Herrmann J, et al. Nutritional support during the hospital
stay reduces mortality in patients with different types of cancers: secondary
analysis of a prospective randomized trial. Ann Oncol 2021; 32:1025–1033.
Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer
cachexia: an international consensus. Lancet Oncol 2011; 12:489–495.

Cancer and the Nutritional Status 51

Jensen GL, Mirtallo J, Compher C, et al; International Consensus Guideline Com-
mittee. Adult starvation and disease-related malnutrition: a proposal for etiology-
based diagnosis in the clinical practice setting from the International Consen-
sus Guideline Committee. JPEN J Parenter Enteral Nutr 2010; 34:156–169.
Kubrak C, Olson K, Baracos VE. The head and neck symptom checklist©: an
instrument to evaluate nutrition impact symptoms effect on energy intake and
weight loss. Support Care Cancer 2013; 21:3127–3136.
Martin L, Gioulbasanis I, Senesse P, Baracos VE. Cancer-associated malnutrition
and CT-defined sarcopenia and myosteatosis are endemic in overweight and
obese patients. JPEN J Parenter Enteral Nutr 2020; 44:227–238.
Martin L, Muscaritoli M, Bourdel-Marchasson I, et al. Diagnostic criteria for can-
cer cachexia: reduced food intake and inflammation predict weight loss and
survival in an international, multi-cohort analysis. J Cachexia Sarcopenia Mus-
cle 2021; 12:1189–1202.
Martin L, Senesse P, Gioulbasanis I, et al. Diagnostic criteria for the classification
of cancer-associated weight loss. J Clin Oncol 2015; 33:90–99.
Muscaritoli M, Arends J, Bachmann P, et al. ESPEN practical guideline: clinical
nutrition in cancer. Clin Nutr 2021; 40:2898–2913.
Navari RM, Pywell CM, Le-Rademacher JG, et al. Olanzapine for the treatment of
advanced cancer-related chronic nausea and/or vomiting: a randomized pilot
trial. JAMA Oncol 2020; 6:895–899.
Roeland EJ, Bohlke K, Baracos VE, et al. Management of cancer cachexia: ASCO
guideline. J Clin Oncol 2020; 38:2438–2453.
Temel JS, Abernethy AP, Currow DC, et al. Anamorelin in patients with non-small-
cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from
two randomised, double-blind, phase 3 trials. Lancet Oncol 2016; 17:519–531.
Wakabayashi H, Arai H, Inui A. The regulatory approval of anamorelin for treat-
ment of cachexia in patients with non-small cell lung cancer, gastric can-
cer, pancreatic cancer, and colorectal cancer in Japan: facts and numbers.
J Cachexia Sarcopenia Muscle 2021; 12:14–16.

Declaration of Interest:
Professor Baracos has received advisory board honoraria as an ad-hoc advisor
from Pfizer and Nestlé; and institutional research funding for her work as
Coordinating Principal Investigator from Baxter Healthcare (2019-2021).

52 Baracos
Cancer Treatment
and Nutrition 7
Z. Stanga1
P. Schuetz2
Division of Diabetes, Endocrinology, Nutritional Medicine and Metabolism,
1

University of Bern and Bern University Hospital, Bern, Switzerland

Medical University Department, Division of General Internal and Emergency
2

Medicine, Medical Faculty of the University of Basel, Kantonsspital Aarau,

Aarau, Switzerland

Numerous factors contribute to high malnutrition risk in patients with

cancer including tumour-derived effectors release, causing loss of appe-
tite and anorexia, and side effects of cancer treatment, again interfer-
ing with appetite and normal food intake. Disease-related malnutrition
(DRM) or therapy-related malnutrition is a frequent problem in these
patients and negatively influences clinical outcome. To prevent adverse
consequences related to DRM, the ESPEN (European Society for Clini-
cal Nutrition and Metabolism) recommends identifying malnourished
patients with cancer through early screening followed by nutritional
assessment, nutritional care planning and nutritional support. Different
screening tools are recommended, including the Nutritional Risk Screen-
ing 2002 (NRS-2002) and the Patient-Generated Subjective Global
Assessment (PG-SGA). The majority of patients with cancer suffer from
systemic inflammation, which influences and stimulates the production
of acute phase proteins – altering protein turnover and reducing mus-
cle mass. This condition leads to impaired glucose tolerance and often
to insulin resistance. Resulting symptoms are anorexia, weight loss,
fatigue, weakness and reduced wellbeing.
Under these metabolic circumstances, adequate nutritional treatment
plays an important role within multimodal cancer care. As DRM is linked

53
to worse prognosis and is difficult to reverse, nutritional therapy should
ideally be initiated at an early stage beginning with cancer diagnosis,
when the purpose of care is maintaining or improving nutritional status.
The principal goals of nutritional therapy include preventing and treating
DRM, reversing weight loss, and maintaining/improving strength and
quality of life. Moreover, an adequate individual nutritional intervention
may minimise nutritional complaints related to cancer treatment toxicity
and thus, enhance energy and protein intake.

Nutritional Support During Cancer Treatment

Weight loss and muscle wasting are core factors that define DRM in
patients with cancer and have been demonstrated to be a major cause of
morbidity as well as robustly predicting complications and mortality. An
impaired nutritional state during cancer treatment has been associated
with a number of clinical consequences and a range of poor outcomes,
including impaired functional status, more emergency hospital visits,
increased in-hospital morbidity, increased length of hospital stay, more
cancer treatment interruptions, compromised treatment efficacy, reduced
quality of life and reduced survival. Currently, as shown in a USA popu-
lation study from Tu et al (2022), a relevant proportion of patients with
cancer is overweight (body mass index [BMI] 25-29.9 kg/m2: 35.8%)
or even obese (BMI ≥30 kg/m2: 30.7%) at diagnosis. In this population,
there is a lot of evidence supporting the safety of exercise and dietary
interventions in the adjuvant and post-treatment settings; however, the
optimal practice to reduce weight gain during cancer treatment and to
achieve weight loss after treatment, across various early-stage cancers,
has yet to be explored. In our opinion, these patients should be prescribed
a high-protein intake with a slightly reduced energy intake.
Weight loss and muscle protein depletion are typical features of DRM.
If this condition is compounded by chronic inflammation, then we talk
about the cancer cachexia syndrome, which may range from mild meta-
bolic disorders to devastating effects on nutritional status. Its clinical
manifestations are stratified in three stages:

54 Stanga and Schuetz

n Pre-cachexia:


n Weight loss ≤5%, anorexia, increased inflammatory response and

metabolic disturbances
n Cachexia:


n Weight loss >5%, OR

n BMI <20 kg/m2 and weight loss >2%, OR

n Sarcopenia and weight loss >2%

n Often reduced food intake and systemic inflammation

n Refractory cachexia:

n Severe weight loss and wasting, characterised by a negative protein

and energy balance driven by a variable combination of reduced

food intake and abnormal metabolism
n Cancer disease both pro-catabolic and not responsive to anticancer

treatment
n Low performance score

n Expected survival <3 months

Direct and inexpensive measurement of muscle mass is still not avail-

able, but muscle function assessment provides important insights into
muscle wasting in cancer.
Various authors have focused on nutritional risk as a cause of delay and
even failure in the scheduled administration of anticancer treatment.
DRM may be responsible for increased toxicity of anticancer drugs and
for several complications following the treatment. It may cause changes
in drug absorption, metabolism and ultimately elimination, as already
reported for some drugs in the literature. Therefore, maintaining ade-
quate energy intake during therapy is mandatory, and requires consider-
able commitment and motivation in most patients.
An important part of the nutritional care programme is individualised
nutritional support to reach protein and energy goals, based on nutritional
state, general conditions, patient tolerance, tumour site, stage of disease,
treatment and related side effects. Management by dieticians is available
in most cancer centres and hospitals. Tailored approaches are important to
set realistic and achievable goals (Figure 1). Macronutrient requirements
depend on the pathological condition of the patient, with energy intake

Cancer Treatment and Nutrition 55

 Nutrition risk screening within 24-48 hours after hospital admission in all cancer patients

If increased risk for malnutrition 🡒 individual assessment of the patient

Disease-related malnutrition present? Indication for nutritional therapy?
If yes 🡒 establish a strategy for the achievement of individual nutritional targets

Nutrition targets

Calorie Protein Micronutrient Specific

requirements requirements requirements targets
25-35 kcal/kg BW or 1.2-1.5 g/kg BW/day Mineral preparations, Disease-specific
Harris-Benedict with (0.8 in renal failure other micronutrients adaptations
adjusted BW without dialysis) according to
laboratory results

Nutritional strategy to reach the nutrition targets

Level I: + Vitamins and minerals according to 100% RDA

Oral nutrition (recommended daily allowance)

Adaption Oral nutrition

(+) Between meals (+) Enrichment (+)
preferences supplements

YES Reassessment every 24-48 hours: ≥75% of energy and protein requirement?
NO and achievement is not foreseeable
Escalation Level II after 5 days
Level II: Oral nutrition (see above), no vitamins per os necessary,
(+)
Enteral nutrition if enteral nutrition ≥1500 kcal

YES Reassessment every 24-48 hours: ≥75% of energy and protein requirement?
NO and achievement is not foreseeable
Escalation Level III after 5 days
Level III:
(+) Enteral and/or oral nutrition (see above)
Parenteral nutrition

Strive for concomitant minimal oral/enteral nutrition

(avoidance of villous atrophy)

Figure 1 Nutritional support algorithm.

Adapted from: Bounoure L, Gomes F, Stanga Z, et al. Detection and treatment of medical inpatients
with or at-risk of malnutrition: suggested procedures based on validated guidelines. Nutrition 2016;
32:790–798.
Abbreviation: BW, body weight.

56 Stanga and Schuetz

varying between 25 and 35 kcal/kg body weight (BW)/day, depending
on the patient's performance status and physical activity. The optimal daily
protein intake should be between 1.2 and 1.5 g/kg BW to adjust for higher
protein breakdown during acute disease and systemic inflammation, with
lower targets for patients with acute renal failure (0.8 g/kg BW/day). To
reach these goals and minimise weight loss as well as facilitate repair
and regeneration of damaged tissues, dieticians should formulate an indi-
vidualised nutrition plan for consideration by treating physicians, such as
high-energy and high-protein diets providing adequate macro- and micro-
nutrients. A therapeutic plan should be centred on oral nutrition in mal-
nourished patients with cancer who are able to eat. This includes dietary
advice, nutritional counselling and psycho-oncological support that may be
needed to help and encourage patients to comply with their nutritional sup-
port requirements. If oral intake drops below 75% of daily energy require-
ments, the measures should include a patient-adapted intervention plan,
starting with easy but essential measures such as the creation of a daily
meal schedule (quantity, quality and presentation of menu), food adjust-
ment according to patient preferences, food fortification (e.g. by adding
protein or maltodextrin powder), introduction of small and frequent snacks
between meals, and providing patients with oral sip drinks and oral nutri-
tional supplements (ONSs). Favourite foods should be offered to tempt
the appetite. The modification of food texture may be required to facilitate
chewing and swallowing. Dry mouth and changes in taste perception may
increase the effort required for optimal intake. The goal of oral intake is to
achieve more than 75% of the daily energy requirements. As demonstrated
in the EFFORT study published in 2019, further increase in nutritional
support by enteral (EN) or parenteral nutrition (PN) in suitable patients
was recommended if at least 75% of energy and protein targets could not
be reached due to chronic insufficient dietary intake and/or uncontrollable
malabsorption. If food intake has been decreased severely for a prolonged
period, it is recommended to increase (oral, enteral or parenteral) nutri-
tion slowly over several days and to take additional precautions to prevent
refeeding syndrome. Adequate nutritional support should be supplemented
by maintenance or an increased level of physical activity to support muscle
mass, physical function and metabolic pattern.

Cancer Treatment and Nutrition 57

Pharmaconutrients and Pharmacological Agents
Various substances can be used to stimulate the appetite of anorectic
cancer patients during oncological treatment, but they are often associ-
ated with side effects and the evidence for an overall benefit of these
treatments is weak. For a restricted time, corticosteroids, androgenic
steroids or progestins may be utilised. There is not sufficient clinical data
to support use of cannabinoids to improve taste disorders and anorexia
in patients with cancer. Efforts to improve weight and lean body mass in
catabolic cancer patients with supplementation of branched amino acids
or metabolites, as well as the use of non-steroidal anti-inflammatory
drugs (NSAIDs), are still a matter of debate due to insufficient clinical
data, and are not recommended as routine practice.
In the presence of inflammation, dietary supplementation with spe-
cific nutrients (i.e. omega-3 fatty acids, eicosapentaenoic acid [EPA]
and docosahexaenoic acid [DHA]) may provide beneficial effects
by modulating several aspects of the inflammatory response. The evi-
dence demonstrating that the intake of omega-3 fatty acids from fish oil or
from purer preparations of EPA/DHA results in enhanced efficacy of
anticancer treatment, chemotherapy in particular, and increased clinical
benefit on nutrition-related endpoints, is still insufficient (contradictory
data in several systematic reviews). For individual administration, >2 g
EPA/DHA/day may be used on a trial basis for a prolonged period
of time (>8 weeks) for patients with advanced cancer.
Over the last decades, progress has led to reduced morbidity and mortality
after cancer surgery. Even with such efforts, perioperative complications
are frequent in oncology patients. Thus, minimising the risk of potential
complications in the preoperative phase is mandatory. There is substan-
tial evidence that a deteriorated preoperative nutritional status adversely
affects outcome in terms of increased complications and reduced quality
of life, which in turn have cost implications for the healthcare system.
Impaired nutritional status before major surgery is related to increased
incidence of nosocomial infections, longer length of stay (i.e. intensive
care unit) and, frequently, readmission to hospital and higher mortality.
DRM may also influence multiple organ dysfunctions, functional recov-
ery, wound healing and the incidence of postoperative surgical wound

58 Stanga and Schuetz

infections. The stress of surgery or trauma additionally increases protein
and energy requirements by creating a hypermetabolic, catabolic state.
As a result, identifying and treating DRM with appropriate nutritional
support in patients with cancer prior to the operation is critical to achieve
favourable patient outcomes. For patients undergoing either curative
or palliative surgery, the ESPEN guidelines recommend management
within an enhanced recovery after surgery (ERAS) programme. With
special regard to patients with cancer with an obvious severe nutritional
risk, those undergoing major cancer surgery of the neck (laryngectomy,
pharyngectomy) or abdomen (oesophagectomy, gastrectomy and pan-
creatoduodenectomy) benefit from the use of immune-modulating oral/
enteral formulae, namely enriched with arginine, omega-3 fatty acids
and nucleotides, with or without glutamine.

Impact of Food on Anticancer Drugs

(e.g. Interactions Between Anticancer Drugs
and Nutritional or Herbal Supplements)
There is a paucity of clinical data in the literature regarding this issue.
Use of herbal supplements and vitamins in patients receiving chemother-
apy is common: McCune et al reported in 2004 a frequency of 78%, with
27% of the study participants being at risk of a detrimental chemother-
apy-herbal and/or -vitamin interaction. Food interactions with anticancer
drugs are often difficult to assess, given the polypharmacy that exists in
oncology patients and the frequent inability to distinguish which factor
is responsible for a specific toxicity. Food can interact with anticancer
medicines through reduction of the bioavailability and/or by induction
or inhibition of the metabolism of the administered drug (Table 1), often
due to their metabolism by the cytochrome P450 system. There are some
publications reporting that the most used herbal supplements among
patients with cancer are echinacea, Ginkgo biloba, garlic, green and
black tea, shark cartilage, grape seed extract and milk thistle. The most
popular micronutrients are calcium, multivitamins, antioxidants,
vitamin C and vitamin E.

Cancer Treatment and Nutrition 59

Table 1 Potential Drug-Food Interactions and/or Important Side Effects Which Can
Interfere with Metabolism.
Drug name Potential interactions and/or side effects
L-asparaginase Can cause azotaemia accompanied by an increase in calcium and phosphorus
excretion due to increased protein degradation
This therapy is frequently associated with impairment of pancreatic function
that may be a result of decreased insulin synthesis, causing hyperglycaemia
Bexarotene Grapefruit may increase the drug’s effect
Carboplatin Decreased serum electrolytes, specifically magnesium and potassium
Docetaxel Milk thistle: decreased AUC
Garlic: no significant modification to increased AUC
Cannabis, echinacea: no significant modification of AUC
Estramustine The bioavailability and peak serum concentrations of the drug are decreased
following concomitant milk or food ingestion
Etoposide, VP-16 Grapefruit: decreased drug absorption
Garlic: decreased AUC
Everolimus Curcumin + piperine: decreased AUC
Imatinib St John’s wort: decreased AUC
Irinotecan, CPT-11 St John’s wort: inductive effect
Cannabis: no significant modification of AUC
Milk thistle: no significant modification to decreased AUC
Methotrexate Alcohol may cause liver damage
Plicamycin Supplements of calcium and vitamin D may decrease the drug’s effect
Procarbazine Alcohol may cause headache, trouble breathing, flushed skin, sickness, nausea
and vomiting. Avoid tyramine-containing foods. Maintain tyramine-free diet for
14 days after treatment ceases
Sunitinib Grapefruit: increased AUC
Tamoxifen Curcumin: decreased AUC
Soy: no significant modification of AUC
Temozolomide Food may slow or reduce the drug’s effect
Busulfan, fluorouracil, Food intake delays the absorption of the drug (effect on rate)
methotrexate, topotecan
Altretamine, capecitabine, Food intake decreases the absorption of the drug (effect on extent)
chlorambucil, estramustine,
gefitinib, melphalan,
thioguanine
Erlotinib, tretinoin Food intake increases the absorption of the drug (effect on extent and/or rate)
Abbreviation: AUC, area under the concentration-time curve.

60 Stanga and Schuetz

Sudden and unexplained changes in the clinical response of a patient to
prescribed chemotherapy could be the result of a food-drug interaction.
Physicians should be aware of this possibility and initiate discussions
with their patients about the consequences of ingesting nutritional sup-
plements. Further studies evaluating how herbs or vitamins may alter the
pharmacokinetics and pharmacodynamics of anticancer and supportive
care medications are needed.

Monitoring of Nutritional Support During

Cancer Treatment
First-line monitoring strategies should include routine, accurate, practi-
cal and non-time-consuming nutritional screening, which should be per-
formed at diagnosis and before and during anticancer treatment. In patients
at nutritional risk, assessment of nutritional status and metabolic parameters
as well as monitoring of nutrition therapy and outcomes are of central
importance. Therefore, it is recommended to monitor the following
parameters before and during treatment:
n Primary tumour site affected and presence of metastases

n Pre-existing medical conditions

n Type and frequency of treatments, potential side effects, influence of

malignancy on the ingestion, digestion and absorption of nutrients as

well as nutrition impact symptoms (Table 2)
n Quality of current food intake and appetite. To demonstrate a reduc-

tion in normal food intake, a simple 24-48-hour recall or completion

of Box 2 (food intake) of the PG-SGA is usually sufficient to calcu-
late actual protein and energy intake
n Physical performance may be graded using the World Health Organi-

zation/Eastern Cooperative Oncology Group (WHO/ECOG) scale

(0 = normal performance, 4 = bed-bound) or the Karnofsky Perfor-
mance Scale (0-100)
n Quality of life should be measured with a standardised questionnaire,

i.e. European Organisation for Research and Treatment of Cancer

Quality of Life Questionnaire 30 (EORTC QLQ-C30)

Cancer Treatment and Nutrition 61

Table 2 Nutritionally Relevant Adverse Effects of Oncological Treatment.
Drugs frequently associated with severe nausea and Drugs frequently associated with mucositis
vomiting Oral mucositis is a common complication of
Chemotherapy-induced nausea and vomiting is a chemotherapy, which may begin 5-10 days after the
debilitating side effect of cancer treatment, affecting initiation of chemotherapy and lasts 7-14 days
up to 40% of patients
Carmustine, BCNU Actinomycin D
Carboplatin Bleomycin
Cisplatin Dactinomycin
Cyclophosphamide Doxorubicin
Dacarbazine, DTIC Fluorouracil (FU), 5-FU
Docetaxel Etoposide
Doxorubicin Irinotecan plus FU/leucovorin (IFL)
Epirubicin Melphalan
Etoposide Methotrexate
Lomustine Vinblastine
Mustine hydrochloride, mechlorethamine
hydrochloride USP
Streptozocin
Nutritional complications associated with radiotherapy
Head and neck Odynophagia, xerostomia, mucositis, anorexia,
dysosmia, hypogeusia
Thorax Dysphagia
Abdomen and pelvis Anorexia, nausea, vomiting, diarrhoea, enteritis, colitis

n Height, weight and weight changes over time



n Dehydration or excessive fluid loads (hydration status)

n Assessment of muscle and fat mass reserves can be performed by

anthropometry, bio-impedance analysis (BIA) or with more sophis-

ticated analysis such as cross-sectional imaging (computed tomo-
graphy [CT] or magnetic resonance imaging [MRI]) or dual-energy
X-ray absorptiometry (DEXA)
n Quantitate physical performance such as walking tests or measurements

of muscle strength with a handheld dynamometer are easy to perform

62 Stanga and Schuetz

n Laboratory tests such as serum albumin and prealbumin can be used


as a pretreatment prognostic factor in patients with cancer, with low

levels being associated with poor outcome. The extent of systemic
inflammation, recognised as a precursor of cachexia, may be estimated
by measuring serum C-reactive protein and albumin. The laboratory
results must be interpreted carefully, as cancer and/or its treatment
often results in pathological values independent of nutritional status
n Calculate the daily energy, protein and micronutrient requirements,

and draw up the nutritional support concept (action plan)

Use/Indications of Parenteral and Enteral

Nutrition During Cancer Treatment
Before the decision is made to implement non-volitional feeding, the care-
giver must be fully informed about the patient’s overall circumstances
(underlying disease, disease development, prognosis, general and per-
formance status, social situation, ethical aspects, patient’s wishes, etc.).
The functioning and capacity of the gastrointestinal tract, the underlying
disease and patient tolerance must be assessed to determine the appropri-
ate method of administration.

Enteral Nutrition
EN is considered when oral intake is insufficient to meet the nutritional
needs of the patient, but gut function is preserved. Feeding solutions
should be introduced to the gastrointestinal tract where absorption is
possible. Modified feeds (e.g. peptide-based formulae) may be used to
overcome gastrointestinal incapacity. The insertion of an enteral access
is an interdisciplinary decision. The treating medical team, the general
practitioner, the patient and the patient’s family must be involved in the
evaluation. Patients with swallowing difficulties or mucositis can usually
use nasogastric (duration <3 weeks) or gastrostomy (>3 weeks) tubes
to overcome nutritional obstacles. Feeding tubes are beneficial in facili-
tating adequate nutrition and hydration during cancer treatment. Percu-
taneous endoscopic gastrostomy (PEG) has rapidly become a standard
procedure for nutritional purposes – for example, in patients with severe

Cancer Treatment and Nutrition 63

mucositis – to prevent weight loss and interruption of radiotherapy. Per-
cutaneous tubes are preferred over nasogastric tubes in patients with
head and neck cancer. Prophylactic PEG placement at treatment initia-
tion, prior to development of mucositis and weight loss, is recommended
more and more often. Although PEG insertion is considered relatively
safe and has a low rate of significant associated complications, it is not
a completely benign procedure. Frequent complications associated with
PEG are local site infections, tube blockage and migration or dislodge-
ment. Serious complications, such as peritonitis, fistula development or
abscess, are relatively rare.
Major complications of enteral tube feeding are diarrhoea and abdominal
cramps, secondary to the high osmotic load. Tube feeding may be con-
traindicated in situations of severe gastrointestinal dysfunction or bleed-
ing, intractable vomiting or diarrhoea. Use of and indications for EN in
patients with cancer are listed in Table 3.

Parenteral Nutrition
For selected patients, parenteral delivery of nutrition is the only prac-
ticable way to guarantee receipt of daily energy requirements (short-
term PN: 2-3 weeks). Long-term (home) PN (duration >3 weeks) should
be applied through a tunnelled central venous catheter (e.g. Hickman®
device), implanted port systems (e.g. Port-a-Cath®) or a peripherally
inserted central catheter (PICC), and may be recommended, for instance,
in hypophagic/(sub)obstructed patients (e.g. peritoneal carcinomatosis)
if their performance status is acceptable and they are expected to die
from DRM prior to the tumour dissemination. A careful and in-depth
risk-benefit analysis should be performed to justify use of PN in patients
with cancer, because of the high potential for life-threatening complica-
tions, such as catheter-related and metabolic problems. Use of and indi-
cations for PN in patients with cancer are listed in Table 4.
The most frequent, and for all involved stressful, problem with eating
and drinking is the decision whether and by what means progressive
malnutrition with important weight loss and functional decline should
be counteracted in end-of-life situations. As soon as nutrition is ensured
by technical aids (non-volitional feeding), the question arises whether

64 Stanga and Schuetz

Table 3 Use of/Indications for EN in Patients with Cancer According to the ESPEN
Guidelines.
During curative or palliative anticancer drug treatment
n It is advisable to ensure an adequate nutritional intake and to maintain physical activity

n In general, start (supplemental) EN if malnutrition already exists or if it is anticipated that the patient will be

unable to eat for >7 days

n Start EN if inadequate food intake (<75% of estimated energy expenditure for >10 days) is anticipated

n In patients losing weight due to insufficient oral food intake despite counselling and ONSs, EN should be

provided to improve or maintain nutritional status

n Use tube feeding if an obstructing head and neck or oesophageal cancer interferes with swallowing or if

severe local mucositis is expected

n In general, use standard formulae. In weight-losing cancer patients with insulin resistance, it is

recommended to increase the ratio of energy from fat to energy from carbohydrates
n There are insufficient consistent clinical data to recommend glutamine supplementation during

conventional cytotoxic or targeted therapy

n Routine EN during chemotherapy has no effect on tumour response to chemotherapy or on

chemotherapy-associated undesirable effects, and therefore is not considered useful

n EN should be preferred in patients with cancer because it is more cost-effective than PN and results in

fewer complications
During radiotherapy
n It is recommended that during radiotherapy – with special attention to radiotherapy of the head and

neck, thorax and GI tract – an adequate nutritional intake should be ensured primarily by individualised
nutritional counselling and/or with use of ONSs, in order to avoid nutritional deterioration, maintain intake
and avoid radiotherapy interruptions
n It is recommended to screen for and manage dysphagia and to encourage and educate patients on how

to maintain their swallowing function during EN

n EN using nasogastric or percutaneous tubes is recommended in radiation-induced severe mucositis or

obstructive tumours of the head and neck or thorax

n Because of radiation-induced oral and oesophageal mucositis, a PEG may be preferred

n Routine EN is not indicated during radiotherapy

n There are insufficient consistent clinical data to recommend glutamine to prevent radiation-induced

enteritis/diarrhoea, stomatitis, oesophagitis or skin toxicity

n There are insufficient consistent clinical data to recommend probiotics to reduce radiation-induced diarrhoea

During high-dose chemotherapy and haematopoietic stem cell transplantation

n During intensive chemotherapy and after stem cell transplantation, it is recommended to maintain

physical activity and to ensure an adequate nutritional intake. This may require EN and/or PN
n If oral nutrition is inadequate, EN is preferable to PN unless there is severe mucositis, intractable vomiting,

ileus, severe malabsorption, protracted diarrhoea or symptomatic GI graft-versus-host disease

n The routine use of EN during stem cell transplantation is not recommended

n If oral intake is decreased, PN may be preferred to EN in certain situations (i.e. increased risk of

haemorrhage and infections associated with enteral tube placement in immunocompromised and
thrombocytopaenic patients)
n There are insufficient consistent clinical data to recommend a low-bacterial diet for patients more than

30 days after allogeneic transplantation

n There are insufficient consistent clinical data to recommend glutamine to improve clinical outcome in

patients undergoing high-dose chemotherapy and haematopoietic stem cell transplantation

Cancer Treatment and Nutrition 65

Table 3 Use of/Indications for EN in Patients with Cancer According to the ESPEN
Guidelines. (Continued)
Methods of administration
n Continuous: administered at a constant steady rate based on 20-22 hours/day, allowing for interruptions

in delivery. Patients may initially benefit from a continuous infusion to establish tolerance to EN and later
transition to an intermittent or bolus infusion
n Cyclic: administered at a constantly increased rate over 8-12 hours, often overnight. This feeding method

should be considered for patients who are active during the day and desire free time ‘off the pump’
n Intermittent or bolus: the volume of desired feeding is divided over several feedings per day. Feedings are

usually given over a 30-60-minute period. Intermittent or bolus feeding can be administered by gravity dip
or syringe bolus for those patients with gastric feeding tubes (bolus feeding occurs 3-4 times per day)
Abbreviations: EN, enteral nutrition; ESPEN, European Society for Clinical Nutrition and Metabolism; GI, gastrointestinal;
ONS, oral nutritional supplement; PEG, percutaneous endoscopic gastrostomy; PN, parenteral nutrition.

Table 4 Use of/Indications for PN in Patients with Cancer According to the ESPEN Guidelines.
During curative or palliative anticancer drug treatment
n In a patient undergoing curative anticancer drug treatment, where oral and/or enteral food intake is

inadequate (<75% of estimated daily energy requirements is anticipated for >10 days), it is recommended
to evaluate supplemental PN
n The majority of patients requiring PN for only a short period do not need a special formulation

n A higher percentage of the lipid component (e.g. 50% of non-protein energy) may be beneficial for those

patients with frank cachexia needing prolonged PN

n PN is ineffective and probably harmful in non-aphagic patients in whom there is no gastrointestinal reason

for intestinal failure

During chemo-/radiotherapy
n PN is not generally recommended during radiotherapy, only if adequate oral and/or enteral nutrition is not

possible, e.g. in severe radiation enteritis or severe malabsorption, because it is usually better tolerated and
more efficient in preventing nutritional deterioration
n Long-term PN is often indicated in patients with sub-acute/chronic radiation enteropathy

n PN is recommended in patients with severe mucositis or severe radiation enteritis

n The routine use of PN during chemotherapy, radiotherapy or combined therapy is not recommended

During high-dose chemotherapy and haematopoietic stem cell transplantation

n In haematopoietic stem cell transplantation, PN should be reserved for those patients with severe mucositis,

ileus or intractable vomiting

n No clear recommendation can be made as to the time of introduction of PN in those patients. Its withdrawal

should be considered when patients are able to tolerate approximately 75% of their requirements enterally
Methods of administration
n In patients with transient and partial gastrointestinal failure, peripheral PN can be administered as a

complement to enteral or oral nutrition

n Analogous to EN, PN can be administered in a continuous (over 20-22 hours/day) or a cyclic mode

(over 8-12 hours, often overnight). Cyclic administration is recommended in patients with home PN
n Solutions not exceeding 850 mOsm/L (osmolarity) can be infused for a short period peripherally via peripheral

cannula or midline
n The use of infusion pumps is recommended, but is not practised in all countries

Abbreviations: EN, enteral nutrition; ESPEN, European Society for Clinical Nutrition and Metabolism; PN, parenteral nutrition.

66 Stanga and Schuetz

nutrition remains a fundamental right or has rather become a negotia-
ble therapeutic measure. This is where ethical and ideological attitudes
towards life and the personal experiences of all involved come together.
The extent of, and decisions for, nutritional support must be individu-
alised and should change according to the course of disease. The nutri-
tional interventions should be chosen with the aim of maintaining well-
being/quality of life and controlling symptoms. Nutritional measures in
the end-of-life phase should be kept to a minimum and evaluated on a
case-by-case basis with the medical care team, patients and relatives.

Further Reading
Arends J, Bachmann P, Baracos V, et al. ESPEN guidelines on nutrition in cancer
patients. Clin Nutr 2017; 36:11–48.
Arends J, Baracos V, Bertz H, et al. ESPEN expert group recommendations for
action against cancer-related malnutrition. Clin Nutr 2017; 36:1187–1196.
Arends J, Bodoky G, Bozzetti F, et al. ESPEN guidelines on enteral nutrition:
non-surgical oncology. Clin Nutr 2006; 25:245–259.
Arends J, Strasser F, Gonella S, et al. Cancer cachexia in adult patients: ESMO
Clinical Practice Guidelines. ESMO Open 2021; 6:100092.
Bargetzi L, Brack C, Herrmann J, et al. Nutritional support during the hospital
stay reduces mortality in patients with different types of cancers: secondary
analysis of a prospective randomized trial. Ann Oncol 2021; 32:1025–1033.
Bozzetti F, Arends J, Lundholm K, et al. ESPEN guidelines on parenteral nutri-
tion: non-surgical oncology. Clin Nutr 2009; 28:445–454.
Bozzetti F, Stanga Z. Does nutrition for cancer patients feed the tumour? A clini-
cal perspective. Crit Rev Oncol Hematol 2020; 153:103061.
Capitão C, Coutinho D, Neves PM, et al. Protein intake and muscle mass main-
tenance in patients with cancer types with high prevalence of sarcopenia: a
systematic review. Support Care Cancer 2022; 30:3007–3015.
Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer
cachexia: an international consensus. Lancet Oncol 2011; 12:489–495.
Ford KL, Arends J, Atherton PJ, et al. The importance of protein sources to sup-
port muscle anabolism in cancer: an expert group opinion. Clin Nutr 2022;
41:192–201.
Gomes F, Schuetz P, Bounoure L, et al. ESPEN guidelines on nutritional support
for polymorbid internal medicine patients. Clin Nutr 2018; 37:336–353.
Jager-Wittenaar H, Ottery FD. Assessing nutritional status in cancer: role of
the Patient-Generated Subjective Global Assessment. Curr Opin Clin Nutr
Metab Care 2017; 20:322–329.

Cancer Treatment and Nutrition 67

LeVasseur N, Cheng W, Mazzarello S, et al. Optimising weight-loss interven-
tions in cancer patients – a systematic review and network meta-analysis.
PLoS One 2021; 16:e0245794.
Ljungqvist O, Scott M, Fearon KC. Enhanced recovery after surgery: a review.
JAMA Surg 2017; 152:292–298.
Kondrup J, Rasmussen HH, Hamberg O, Stanga Z. Nutritional risk screening
(NRS 2002): a new method based on an analysis of controlled clinical trials.
Clin Nutr 2003; 22:321–336.
McCune JS, Hatfield AJ, Blackburn AA, et al. Potential of chemotherapy-herb
interactions in adult cancer patients. Support Care Cancer 2004; 12:454–462.
Muscaritoli M, Arends J, Bachmann P, et al. ESPEN practical guideline: clinical
nutrition in cancer. Clin Nutr 2021; 40:2898–2913.
Ravasco P. Nutrition in cancer patients. J Clin Med 2019; 8:1211.
Reber E, Schönenberger KA, Vasiloglou MF, Stanga Z. Nutritional risk screen-
ing in cancer patients: the first step toward better clinical outcome. Front
Nutr 2021; 8:603936.
Schuetz P, Fehr R, Baechli V, et al. Individualised nutritional support in medi-
cal inpatients at nutritional risk: a randomised clinical trial. Lancet 2019;
393:2312–2321.
Schuetz P, Seres D, Lobo DN, et al. Management of disease-related malnutrition
for patients being treated in hospital. Lancet 2021; 398:1927–1938.
Tu H, McQuade JL, Davies MA, et al. Body mass index and survival after cancer
diagnosis: a pan-cancer cohort study of 114 430 patients with cancer. Innova-
tion (Camb) 2022; 3:100344.

Declaration of Interest:
Professor Stanga has received institutional research grants from Nestlé Health
Science and Abbott Nutrition; and institutional education grants from B Braun
and Fresenius Kabi.
Professor Schuetz has received institutional funding for his work as an invited
speaker from Nestlé Health Science and Abbott Nutrition; and institutional
research grants from Nestlé Health Science and Abbott Nutrition.

68 Stanga and Schuetz

Nutritional Support for the
Advanced Cancer Patient 8
F. Bozzetti1
M. Chasen2
K. Boeykens3
Faculty of Medicine, University of Milan, Milan, Italy
1

2
Palliative and Supportive Care, William Osler Health System,
Brampton, ON; McMaster University, Hamilton, ON, Canada
3
Nutrition Support Team, Vitaz Hospital, Sint-Niklaas, Belgium

Nutritional Support During Best Supportive Care

The use of enteral (EN) or parenteral (PN) nutrition to feed patients
with advanced cancer was introduced in clinical practice following the
seminal paper from DeWys et al in 1980, which showed that weight loss
was an independent negative prognostic factor on survival length. Subse-
quent large studies have also shown that the lower the body mass index
(BMI), the lower the weight loss required to be associated with mortality.
Both weight loss and poor food intake are independently associated with
mortality. Weight loss has consistently been shown to be significantly
associated with shorter failure-free and overall survival and decreased
response, quality of life and performance status. More recently, several
studies on body compartments have demonstrated that the depletion of
muscle mass plays a major role in the outcome of these patients. The
malnutrition–mortality association does not directly imply that there is
a cause–effect relationship between these indications and malnutrition,
because patients with more advanced cancer more often exhibit severe
weight loss, anorexia and systemic inflammation. However, there are
studies reporting that patients with incurable cancer survive longer than
one would expect with complete macronutrient starvation if they are

69
supported through PN. The experience of patients with malignant bowel
obstruction receiving or not receiving PN is consistent with this thinking.

Clinical Situations for Nutritional Support

Overall, nutritional support of the advanced cancer patient may be used
in two broad clinical conditions:
I. To enable patients to receive life-prolonging anticancer therapies;
II. To improve the nutritional status of patients with incurable cancer
who are expected to die from starvation and nutritional deterioration
rather than from cancer progression.
In the real world, these two conditions can sometimes overlap because in
some incurable cancers, further oncological treatments can be attempted,
and some patients are supported during intensive oncological therapy
even if clinicians are indeed quite sceptical about the possibility of
achieving a significant result.
Regardless of the indication, the type of nutritional treatment depends on
the functionality of the gastrointestinal (GI) tract and the need for either
total nutritional support or only supplementation.

I. Patients Who Are Malnourished, Anorectic and Are Candidates for

Anticancer Therapies Or
II. Patients Who Are Expected to Face Severe GI Toxicity
Usually, these patients have a functioning GI tract and may benefit from
oral nutritional supplements (ONSs), sometimes combined with antiano-
rectic agents (e.g. megestrol acetate, anamorelin). ONSs are not a sub-
stitute for a complete meal, but can be integrated with suboptimal oral
feeding. Since these patients frequently experience symptoms of early
satiety, ONSs should be taken in-between meals so as not to compromise
the food intake at lunch or dinner. Liquid formulae with high caloric
density (2 kcal/mL) may sometimes be preferable; it is recommended
to use formulae with different tastes to maintain good compliance. The
use of omega-3- or protein-enriched formulations has been successful in
restoring the fat-free mass and improving the quality of life of patients in

70 Bozzetti et al.
comparative trials and in some subgroups of patients within randomised
controlled trials (RCTs). However, as of today these cannot be considered
standard treatment procedures. Recently, a few RCTs have demonstrated
that ONSs administered for some weeks may improve tolerance to chemo-
therapy and radiotherapy and improve long-term outcome. In patients
with head and neck cancer, the oral route is often not practicable; a
nasogastric feeding tube or a gastrostomy are valid alternatives. The
choice between the two modalities as either prophylactic or ‘on demand’
is still controversial.

III. Patients With Incurable Cancer

This issue is sometimes controversial also because the term ‘advanced
cancer patient’ may apply to different types of patients. Regarding the
indication for nutritional support, the term ‘malignant (sub)obstruc-
tion’ is used when referring to patients who have exhausted all available
oncological therapies, are severely malnourished, and starving because
of anorexia or a condition of chronic gut dysfunction. These patients
are ‘oncologically’ but not ‘biologically’ terminal. They are not cachec-
tic and could succumb to nutritional deterioration rather than tumour
progression. It is noteworthy that in a recent multinational survey of
experience and attitudes towards commencing home PN for patients
with advanced cancer, the combination of malnutrition and cachexia
accounted for the most common reason for the use of home PN in this
patient cohort. There may be a rationale for feeding these patients intra-
venously if it can be reasonably estimated that their survival will be
longer than 3 months, due to the tumour spread. Consolidated experience
has shown that healthy people on a hunger strike die within 2 months,
while patients with malignant small bowel obstruction survive 1 month
without PN and 3 months or more with PN. There are several prognos-
tic factors for predicting survival in such patients on home PN and, in
2015, a prognostic nomogram including performance status, type of pri-
mary, tumour spread and Glasgow Prognostic Score was built to identify
patients who are likely to survive less than 1 month compared to those
surviving more than 9 months (Figure 1).

Nutritional Support for the Advanced Cancer Patient 71

 0 10 20 30 40 50 60 70 80 90 100
Points
N.A. 2
Glasgow Prognostic Score
0 Yes 1
Metastases if Site = Ovary Yes
No
if Site = GI Yes
No
if Site = Other
No N.A.
Karnofsky Performance Status
> 50 ≤50
Total points
0 20 40 60 80 100 120 140 160 180 200 220 240 260 280
Median survival time
9 8 7 6 5 4 3 2
3-month survival probability
0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1
6-month survival probability
0.6 0.55 0.5 0.45 0.4 0.35 0.3 0.25 0.2 0.15 0.1 0.05

Figure 1 Cox modelling-based nomogram for predicting 3-, 6-month and median
OS in cancer patients receiving home parenteral nutrition.
From: Bozzetti F, Cotogni P, Lo Vullo S, et al. Development and validation of a nomogram to predict
survival in incurable cachectic cancer patients on home parenteral nutrition. Ann Oncol 2015;26:
2335-2340.
Abbreviations: GI, gastrointestinal; N.A. not available; OS, overall survival.

Reasons to Consider Initiation, Withholding and/

or Withdrawing Artificial Nutrition and Hydration
in Patients Who Are Imminently Dying
Artificial nutrition (AN) and hydration should be considered separately
for two reasons: first, it is possible to hydrate a patient without nourish-
ment, as AN provides both macronutrients and water and, second, the
patient populations fit for AN and those fit for hydration are different.
AN in hospital and at home has no role in the imminently dying patient
but can be considered when the patient has an expected survival of less
than 2 months due to starvation but not due to cachexia. If this is the
case and there is the possibility of home PN, the oncologist could pro-
pose this to the patient. The main goal of PN is to provide all the neces-
sary care at home with the presumption that if palliation of symptoms is
effective in hospital, receiving intravenous (i.v.) nutrition at home should
further improve the quality of life of the patient. From the start of the
programme, the clinician must explain to the patient and their family
what achievable treatment goals can be expected and the myriad of fac-
tors besides the nutritional status that affect quality of life. Plans should

72 Bozzetti et al.
be made to decrease the energy content or stop the PN when disease
progression and/or a deterioration in the quality of life of the patient is
seen. Oncologists should not force the use of home PN on patients with
a presumably favourable outcome because of the weakness of the avail-
able predictive outcomes; however, they should not deny this approach
to highly motivated patients.
Regarding hydration of imminently dying patients, there is a paucity of
investigations on this subject, and the few RCTs that have studied the
effect of i.v. solutions were not specific for rehydration. Isotonic bal-
anced solutions containing dextrose may prevent feelings of thirst and
confusion, but it is important to avoid fluid overload in patients with res-
piratory failure. The infusion of iso-osmolar fluids can be administered
subcutaneously (hypodermoclysis), sparing venous infusion which may
be problematic in these situations.

General Principles of Nutritional Support

The oncologist should be aware that even the best nutritional support can
only prevent or blunt further nutritional deterioration and cannot fully
reverse a status of cachexia. Cachexia cannot be equated to simple star-
vation because it is caused not only by poor intake of nutrients, but also
a deranged metabolism driven by systemic inflammation. This does not
mean that malnourished patients with high inflammatory markers should
not receive AN, because all the physiological functions of the body’s
organs still require appropriate substrates.
The traditional nutritional approach follows a rule that prefers use of the
oral route as the initial step and the i.v. route as the final approach, hence
following the old dictum ‘if the gut works, use it’. Whereas this is true
in most cases, several patients with advanced cancer have a working gut,
but the presence of anorexia, nausea, dysgeusia and/or early satiation can
preclude efficient use of the oral route.
Experience has shown that ONSs are particularly useful when symptoms
of cachexia are minimal. They are prescribed preventatively to antican-
cer treatments associated with GI toxicity or for patients recovering after

Nutritional Support for the Advanced Cancer Patient 73

treatment. They cannot fully meet the nutritional needs of patients who
may require ≥30 kcal/kg body weight (BW)/day and 1.2-1.5 g amino
acid/kg BW/day; however, even minor amounts can prove clinically
beneficial. If patients are totally starving and their GI tract is not work-
ing or accessible, the only alternative is PN. Some pros and cons of EN
and PN are reported in Table 1. Whatever the choice of feeding route, it
is noteworthy that patients with advanced cancer metabolise fat better
than healthy people, hence the regimen should be fat-enriched. Regard-
ing amino acid content, it is important to give protein rich in essential
amino acids, especially branched-chain amino acids (BCAAs) or leu-
cine, which have a special anabolic function.
Table 1 Pros and Cons of Enteral and Parenteral Nutrition.

Enteral nutrition Parenteral nutrition

Pros Cons Pros Cons
Simpler Requires a functioning Higher compliance with More demanding
gut the desired quality/
quantity of nutrients
Low cost May require a gastric Better modulation of the More expensive
tube substrates
Safer A critical volume is Regimen may be adjusted Potentially more
obligatory to meet all without withdrawing the dangerous as regards
requirements administration metabolic/infective
complications
Metabolically better in Adverse effects may lead Compliance is generally
the long-term to discontinuation good

The value of exercise in addition to the nutritional support should be

emphasised and encouraged in order to promote muscle strength and
improve the daily functionality of patients.

The Role of Ketones

It is known that about 50% of human tumours have a glycolytic phenotype
and their growth could be impaired in conditions of caloric restriction.
This is associated with high levels of ketones in the body, which cancer
cells cannot metabolise because of a deficient mitochondrial function.

74 Bozzetti et al.
However, a safer way to realise hyperketonaemic glucose deprivation to
the tumour is the use of a eucaloric ketogenic diet in which fats account
for about 70%-75%, protein 20%-25% and carbohydrates 5%-10% of
total energy intake. There are many scattered reports on the feasibility
and metabolic efficacy of this approach, which should be reserved only
to patients with high fluorodeoxyglucose uptake on a positron emission
tomography (PET) scan. The major problem is the palatability of these
diets, which decreases long-term patient compliance, while such a regi-
men by vein appears to be well accepted. In consideration of the good
metabolic utilisation of fat by cancer patients and the introduction of
ketone-enriched diets or supplements to the market, this approach will
be developed in the near future.

Further Reading
Andreyev HJ, Norman AR, Oates J, Cunningham D. Why do patients with
weight loss have a worse outcome when undergoing chemotherapy for gas-
trointestinal malignancies? Eur J Cancer 1998; 34:503–509.
Bargetzi L, Brack C, Herrmann J, et al. Nutritional support during the hospital
stay reduces mortality in patients with different types of cancers: secondary
analysis of a prospective randomized trial. Ann Oncol 2021; 32:1025–1033.
Bhargava R, Chasen M, Elten M, MacDonald N. The effect of ginger (Zingiber
officinale Roscoe) in patients with advanced cancer. Support Care Cancer
2020; 28:3279–3286.
Boeykens K, Duysburgh I. Prevention and management of major complications
in percutaneous endoscopic gastrostomy. BMJ Open Gastroenterol 2021;
8:e000628.
Bozzetti F. The role of parenteral nutrition in patients with malignant bowel
obstruction. Support Care Cancer 2019; 27:4393–4399.
Bozzetti F, Caccialanza R, Cotogni P, et al. SINPE Position Paper on the use of
home parenteral nutrition in cancer patients. Co-published in Nutrition 2022;
95:111578 and Support Care Cancer 2022; 30:2909–2914.
Bozzetti F, Mariani L, Lo Vullo S, et al; SCRINIO Working Group. The nutri-
tional risk in oncology: a study of 1,453 cancer outpatients. Support Care
Cancer 2012; 20:1919–1928.
Bozzetti F, Stanga Z. Does nutrition for cancer patients feed the tumour? A clini-
cal perspective. Crit Rev Oncol Hematol 2020; 153:103061.

Nutritional Support for the Advanced Cancer Patient 75

Cereda E, Turri A, Klersy C, et al. Whey protein isolate supplementation
improves body composition, muscle strength, and treatment tolerance in
malnourished advanced cancer patients undergoing chemotherapy. Cancer
Med 2019; 8:6923–6932.
Chasen M, Bhargava R, MacDonald N. Rehabilitation for patients with advanced
cancer. CMAJ 2014; 186:1071–1075.
de van der Schueren MAE, Laviano A, Blanchard H, et al. Systematic review and
meta-analysis of the evidence for oral nutritional intervention on nutritional
and clinical outcomes during chemo(radio)therapy: current evidence and
guidance for design of future trials. Ann Oncol 2018; 29:1141–1153.
Dewys WD, Begg C, Lavin PT, et al. Prognostic effect of weight loss prior to
chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am
J Med 1980; 69:491–497.
Martin L, Muscaritoli M, Bourdel-Marchasson I, et al. Diagnostic criteria for
cancer cachexia: reduced food intake and inflammation predict weight loss
and survival in an international, multi-cohort analysis. J Cachexia Sarcopenia
Muscle 2021; 12:1189–1202.
Martin L, Senesse P, Gioulbasanis I, et al. Diagnostic criteria for the classifica-
tion of cancer-associated weight loss. J Clin Oncol 2015; 33:90–99.
Naghibi M, Skinner C, Burden ST, et al. A multi-national survey of experience
and attitudes towards commencing home parenteral nutrition for patients
with advanced cancer. Clin Nutr ESPEN 2022; 47:246–251.
Payne C, Larkin PJ, McIlfatrick S, et al. Exercise and nutrition interventions in
advanced lung cancer: a systematic review. Curr Oncol 2013; 20:e321–e337.
Pereira J, Chasen MR. Early palliative care: taking ownership and creating the
conditions. Curr Oncol 2016; 23:367–370.
Pironi L, Boeykens K, Bozzetti F, et al. ESPEN guideline on home parenteral
nutrition. Clin Nutr 2020; 39:1645–1666.
Prado CM, Laviano A, Gillis C, et al. Examining guidelines and new evidence
in oncology nutrition: a position paper on gaps and opportunities in mul-
timodal approaches to improve patient care. Support Care Cancer 2022;
30:3073–3083.
Wolfe RR, Miller SL, Miller KB. Optimal protein intake in the elderly. Clin Nutr
2008; 27:675–684.

Acknowledgements
The authors give thanks to Donny Li from McMaster University, Canada
for his input and administration of this chapter.

76 Bozzetti et al.
Declaration of Interest:
Professor Bozzetti has declared no conflicts of interest.
Dr Chasen reports personal advisory board fees from Abbott for his participation
in a round-table discussion.
Mr Boeykens has declared no conflicts of interest.

Nutritional Support for the Advanced Cancer Patient 77

Nutrition in the Older Patient
with Cancer 9
M.S. Mukherjee1
T.H.M. To2,3,5
A.R.A. Mislang4,5
Caring Futures Institute, College of Nursing and Health Sciences, Flinders
1

University, Bedford Park, Adelaide, SA, Australia

Research Centre for Palliative Care, Death and Dying, College of Nursing and
2

Health Sciences, Flinders University, Bedford Park, Adelaide, SA, Australia

Southern Adelaide Palliative Service, Flinders Medical Centre, Bedford Park,
3

Adelaide, SA, Australia

Department of Medical Oncology, Flinders Centre for Innovation in Cancer,
4

Flinders Medical Centre, Bedford Park, Adelaide, SA, Australia

College of Medicine and Public Health, Flinders University, Bedford Park,
5

Adelaide, SA, Australia

More than 50% of the patients with cancer are aged 70 years or older.
The management of older adults with cancer is complex due to the pres-
ence of competing comorbidities, polypharmacy, cognitive dysfunction,
functional impairments and frailty – all contributing to and/or causing
nutritional deficits. Older adults have additional nutritional needs com-
pared with younger adults, due to age-related physiological changes.
Pre-existing deficiencies may be compounded by the presence of comor-
bidities, including cancer and its treatment.
Malnutrition is defined as a suboptimal intake of nutrients and/or a
state where an increased nutritional requirement is not met, resulting
in poorer outcomes. Malnutrition can be diagnosed by the presence of
at least one phenotypic criterion (non-volitional weight loss, low body
mass index [BMI], reduced muscle mass) and at least one aetiologic
criterion (reduced food intake and/or absorption, increased inflammation).

78
In older adults with cancer, the prevalence of malnutrition ranges from
3% to 83% depending on the nutrition screening tools used, and cancer
site and stage. The risk of mortality from malnutrition is two-fold and
is associated with lower quality of life, longer hospital stays and more
frequent readmissions. While malnutrition in adults with cancer is fre-
quently mentioned in the literature, ‘cancer cachexia’ is increasingly the
preferred term. Cachexia is defined as a multifactorial syndrome involv-
ing complex, pathological metabolic changes, systemic inflammation,
continuous loss of fat and muscle mass, fatigue and anorexia due to acti-
vation of catabolic pathways. This acknowledges the complexity of the
factors involved in muscle wasting and the metabolic changes due to
cancer-associated catabolic and inflammatory pathways, which may not
simply be reversed by the provision of nutritional support, unlike mal-
nutrition. Notably, weight loss or BMI alone are not sufficient to diag-
nose cachexia, as gain in adipose tissue can offset loss in skeletal mus-
cle. Evans et al’s (2008) criteria for diagnosing cancer cachexia include
weight loss in the presence of any of three of the following: anorexia,
fatigue, decreased muscle mass and strength, decline in free fat mass and
inflammation/anaemia/low serum albumin. All patients with cachexia
have malnutrition but not vice versa. Sarcopenia, on the other hand, can
be a physiological process exacerbated by the increase in metabolic and
inflammatory states from cancer, and is diagnosed primarily by loss of
muscle strength or function. It has been associated with poor outcomes
such as falls, fractures, physical disability and mortality. In this chapter,
we will use cachexia to encompass the nutritional impairments seen in
older adults with cancer.
The prevalence of cachexia in older adults with cancer is 52%-62%, and
sarcopenia is present in up to 57%. Both cachexia and sarcopenia are pro-
gressive, debilitating disorders of muscle deficiency that negatively affect
functional performance, leading to ‘frailty’, a state of reduced physi-
ological reserve characterised by a marked vulnerability to adverse health
events. In older adults with cancer, frailty is associated with lower treat-
ment tolerance, greater risk of treatment-related toxicity, post-surgical
complications and mortality. Often, this leads to premature cessation of
treatment and shorter survival.

Nutrition in the Older Patient with Cancer 79

In this chapter, we highlight the increased risk of nutritional impairments
in older adults with cancer, and provide a stepwise approach for screen-
ing, assessment and management of their nutritional needs, to improve
outcomes. Table 1 summarises these steps and offers examples of inter-
ventions that can be adapted by clinicians caring for older adults with
cancer, depending on available resources.

Step 1: Recognise the Risk Factors of Cachexia in

Older Adults with Cancer
Several factors increase the risk of cachexia in older adults with can-
cer. Often, the symptoms commence prior to the diagnosis of cancer.
Although the nutritional risk factors mentioned below are not specific to
older adults with cancer, older adults are at an increased risk for nutri-
tional impairment, due to higher pre-existing rates of malnutrition in the
general population, the prevalence of multimorbidity and reduced physi-
ological reserve associated with ageing and comorbidity. Recognising
and understanding factors that make them susceptible to nutritional risk
is crucial in order to undertake regular assessments and proactive meas-
ures to counteract cachexia.

Cancer-related Risk Factors

Different cancer sites and stages can have a different impact on the nutri-
tional status. The risk of developing cachexia is very high (80%-90%)
among patients with pancreatic, liver or lung cancer, high (50%-70%)
among patients with colon, gastric or head and neck cancer, moderate
(30%-40%) for patients with endometrial, bladder or renal cancer, and low
(20%-30%) for those with breast cancer, melanoma or prostate cancer.
The tumour itself may induce anorexia purportedly via the neuropeptide Y
signalling cascade, which may increase production of inflammatory
cytokines and compete with host cells for substrates; this process persists
in the presence of a progressive, metastatic disease.

80 Mukherjee et al.
Table 1 Steps to Screen, Assess and Manage Nutritional Impairments in
Older Adults with Cancer.
Assessment Suggested interventions
Step 1: Recognise the risk factors of cachexia in older adults with cancer
Assess disease- and treatment-related aetiology Early recognition of factors that increase risk of nutritional
• Cancer type and cancer stage. Certain cancers impairment and proactive referral for intervention
such as pancreatic, liver, lung, colon, gastric or Look for symptoms, side effects and other aggravating factors:
head and neck cancer increase risk of cachexia • Malnutrition
• Metastatic disease • Hydration status
• Toxicities from anticancer treatment: • Non-volitional weight loss
i.e. surgery, radiotherapy, chemotherapy, • Micronutrient deficiencies
targeted therapy, immunotherapy • Presence of nutrition impact symptoms
• Early satiety
• Ageusia
• Fatigue, frailty
• Mouth ulcers/sores/poor dentition
• Dry mouth
• Dysphagia/odynophagia
• Malabsorption
• Gastrointestinal (GI) dysfunction, constipation, diarrhoea,
vomiting, nausea, pancreatic exocrine insufficiency,
steatorrhoea, dumping syndrome
• Pain
Assess psychosocial-related aetiology Assess/monitor for any of the following:
• Anxiety/depression
• Cognitive impairment
• Financial constraints
• Poor access to food/mobility
• Functional impairment/falls
• Social isolation
Step 2: Perform nutritional screening and assessment in older adults with cancer
Use of validated screening tools: Screen opportunistically, periodically and on clinical need
• Mini Nutritional Assessment (MNA) Use tools that you are most familiar with and/or are widely
• Malnutrition Universal Screening Tool (MUST) accepted in your healthcare facility
• Short Nutritional Assessment Questionnaire
Key factors to assess include:
(SNAQ)
• Weight loss
• Patient-Generated Subjective Global
• >5% in 6 months
Assessment (PG-SGA)
• >10% beyond 6 months
• G-8 Questionnaire
• Low BMI (body mass index)
Use of comprehensive assessments: • <22 if more than 70 years old
• Geriatric Assessment (GA) • Reduced muscle mass (objective tests or physical examination,
Use of objective tools where available: functional tests, mid-arm or calf circumference)
• Computed tomography (CT) • Reduced food intake
• Magnetic resonance imaging (MRI) • <50% of requirements for >1 week
• Dual-energy X-ray absorptiometry (DEXA) • Any reduction for >2 weeks
• Bioelectrical impedance analysis (BIA) • GI disorder affecting nutrient absorption
• Frailty

Nutrition in the Older Patient with Cancer 81

Table 1 Steps to Screen, Assess and Manage Nutritional Impairments in
Older Adults with Cancer. (Continued)
Assessment Suggested interventions
Step 3: Managing nutritional impairments in older adults with cancer
Undertake a multidisciplinary approach • Meet energy and protein requirements:
involving the: • Protein: 1-1.5 g/kg body weight (BW)/day
• Patient • Energy: in malnourished patients, aim for 32-38 kcal/kg
• General practitioner BW/day
• Dietician • Individualise dietary strategies, dietary education, provision
• Physiotherapist of resources to include high protein and high energy foods:
• Pharmacist • Protein: eggs, chicken, fish, red meat, legumes, milk,
• Specialist physicians yoghurt, nuts, tofu
• Carers • Energy: cereals, starchy vegetables, fats, avocado, cheese,
• Social workers nuts, ice cream
• Provide oral nutritional supplements (ONSs), if indicated
• Suggest food fortification techniques, if indicated:
• Addition of ONS/protein/skimmed milk powder to full-cream
milk, porridge, scrambled eggs, breakfast cereal, soups
• Increasing cheese/oil/margarine content in dishes such as
pasta, curries, salads, mashed potato, vegetables, meat etc.
• Suggest shopping and cooking aids, meal delivery
programmes, shared and supervised meals, texture
modification of diet
• Consider enteral nutrition if inadequate intake persists
(e.g. less than 50% of their requirements for 1 week)
• Monitor and correct vitamin/mineral/micronutrient
deficiencies, as required
• Provision of pharmacological (e.g. antiemetics, corticosteroids,
prokinetics) and non-pharmacological (e.g. dry, bland and cold
foods, or avoiding fatty and very sweet foods) strategies to
manage nutrition impact symptoms
• Choose a less emetogenic regimen, if possible
• Manage treatment-related toxicities proactively
• Enable patients to self-manage their nutritional needs by
adapting meal-planning skills, engaging in healthy dietary
practices and improving access to support
• Exercise regimen
• Optimal management of comorbidities
Monitor and reassess: • Regular weight and nutritional status monitoring. Repeat
• Nutritional and hydration status screening weekly for inpatients, especially in presence of
• Disease state clinical concern
• Response to treatment • Monitor all factors mentioned in Step 1
• Patient preferences
• Routinely check micronutrient status, albumin and electrolytes
• Arrange for reviews with the multidisciplinary team, as indicated

82 Mukherjee et al.
Treatment-related Risk Factors
The provision of anticancer treatment can cause nutrition impact symp-
toms (Table 1). This can result in decreased dietary intake, sarcopenia
and frailty, exacerbating the risk of cachexia.
Chemotherapy drugs can also induce micronutrient imbalances. For exam-
ple, cisplatin can increase renal excretion of magnesium, potassium and
L-carnitine; methotrexate and pemetrexed could lead to folic acid deple-
tion; and certain anticancer drugs metabolised by CYP3A4, such as cyclo-
phosphamide and paclitaxel, could potentially alter the synthesis or degra-
dation of vitamin D. Immunotherapy can enhance proinflammatory status
and alteration of gut flora, leading to colitis. Surgical resection can cause
alterations in gut motility leading to nutrient malabsorption and subse-
quent deficiencies in macronutrients and fat- and water-soluble vitamins.

Age-related and Other Factors

Common geriatric symptoms such as frailty, functional impairment and
cognitive and/or mood disorders are associated with a greater risk of
malnutrition and poor prognosis. For example, according to Poisson et al
(2021), in hospitalised older adults with cancer, poor physical function,
dementia and depression increased the risk of cachexia, and were associ-
ated with an increased length of stay and mortality.
Several socioeconomical, psychological, religious and cultural factors,
including poverty, poor education and self-imposed dietary restrictions,
can also contribute to malnutrition. Nutritional status may decline fur-
ther in the presence of social isolation.
Functional impairments may limit the ability to self-feed, or to access
food. Even in supported environments such as nursing homes, super-
vised feeding may be necessary to meet the nutritional requirements.

Step 2: Perform Nutritional Screening and

Assessment in Older Adults with Cancer
Table 1 shows widely available and validated subjective malnutrition
screening tools to help identify patients at risk of malnutrition. These

Nutrition in the Older Patient with Cancer 83

tools measure parameters such as BMI, non-volitional weight loss over
the previous 3 to 6 months, decrease in oral intake, muscle and fat loss,
and functional status. They are free to use and easily replicated. Con-
versely, there are also objective tools that can be used, if available.
Another tool, the G-8, which has been validated in geriatric oncology,
covers both nutritional and geriatric parameters to screen patients who
would benefit from a geriatric assessment (GA). GA evaluates several
domains such as demographic and social factors, comorbidities, func-
tion, geriatric syndromes, cognition, mood, nutrition and treatment-
related toxicity, which can help personalise cancer treatment decision-
making according to overall health status.
These tools may assist members of the multidisciplinary team in manag-
ing the nutritional needs of older adults with cancer.

Step 3: Manage Nutritional Impairments in

Older Adults with Cancer
Currently, there is no effective treatment to completely reverse cachexia,
highlighting the need for early diagnosis and intervention. As the causes
of decline in nutritional status are often dynamic and multifactorial,
interventions should be targeted to each contributing cause and personal-
ised according to the patient’s needs. Under some circumstances, pallia-
tive care alone may be appropriate.
For older adults with cancer, the European Society for Clinical Nutri-
tion and Metabolism (ESPEN) guidelines recommend a protein intake of
1.0-1.5 g/kg body weight (BW)/day. The recommended energy intake is
32-38 kcal/kg BW/day if malnourished and 27-30 kcal/kg BW/day if
not. Malnutrition can be treated, and nutrition impact symptoms allevi-
ated, through a dietician's prescription of an individualised diet including
food fortification and/or oral nutritional supplements (ONSs) that meet the
energy, protein and micronutrient requirements of the patient (Table 1).
In the absence of specific deficiencies, supply of micronutrients in accord-
ance with the recommended daily allowance is suggested. Surgeries
involving gastrectomy or intestinal resection can increase the risk of

84 Mukherjee et al.
micronutrient deficiencies such as vitamin B12, calcium, magnesium,
folate and iron, which should be monitored every 3 months and corrected
as required. Similarly, the Whipple procedure (pancreaticoduodenec-
tomy) for pancreatic cancer increases the risk of micronutrient deficien-
cies, such as fat-soluble vitamins A, D, E and K, and minerals such as
calcium, magnesium, folate, selenium and iron, and should be monitored
and supplemented as required. These are particularly relevant in older
adults with cancer, as iron deficiency (anaemia) increases the risk for
chemotherapy-related toxicities, and deficiencies in vitamin D and min-
erals exacerbate bone loss, osteoporosis, falls and fractures.
Treatment-induced nutrition impact symptoms can be alleviated by
modifying treatment regimens (i.e. reducing the drug dose or choosing
less emetogenic or gut-toxic regimens, if possible), and/or using adjunct
pharmacological and non-pharmacological strategies to manage symp-
toms and improve nutrition, as shown in Table 1.
Other interventions such as social support may help improve access to,
and facilitate the intake of, food. In cases of patients with sarcopenia
and frailty, the involvement of an exercise physiologist will aid the reha-
bilitation and optimisation of muscle and strength (Table 1).

Conclusion
Older adults with cancer are more vulnerable to cachexia and other nutri-
tional impairments which can cause adverse outcomes. Early recognition
of risk factors, routine and regular assessments of nutritional and overall
health status, as well as proactive provision of personalised interventions
are essential and must be incorporated in the routine oncological care.

Further Reading
Anker MS, Holcomb R, Muscaritoli M, et al. Orphan disease status of can-
cer cachexia in the USA and in the European Union: a systematic review.
J Cachexia Sarcopenia Muscle 2019; 10:22–34.
Caillet P, Liuu E, Raynaud Simon A, et al. Association between cachexia, chemo-
therapy and outcomes in older cancer patients: a systematic review. Clin Nutr
2017; 36:1473–1482.

Nutrition in the Older Patient with Cancer 85

Cederholm T, Jensen GL, Correia MITD, et al. GLIM criteria for the diagnosis of
malnutrition – a consensus report from the global clinical nutrition community.
Clin Nutr 2019; 38:1–9.
Cruz-Jentoft AJ, Bahat G, Bauer J, et al; Writing Group for the European Work-
ing Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended
Group for EWGSOP2. Sarcopenia: revised European consensus on definition
and diagnosis. Age Ageing 2019; 48:16–31.
D’Almeida CA, Peres WAF, de Pinho NB, et al. Prevalence of malnutrition in
older hospitalized cancer patients: a multicenter and multiregional study.
J Nutr Health Aging 2020; 24:166–171.
Dunne RF, Roussel B, Culakova E, et al. Characterizing cancer cachexia in the
geriatric oncology population. J Geriatr Oncol 2019; 10:415–419.
Evans WJ, Morley JE, Argilés J, et al. Cachexia: a new definition. Clin Nutr 2008;
27:793–799.
Fearon KP, Strasser FP, Anker SDP, et al. Definition and classification of cancer
cachexia: an international consensus. Lancet Oncol 2011; 12:489–495.
Gröber U, Holzhauer P, Kisters K, et al. Micronutrients in oncological interven-
tion. Nutrients 2016; 8:163.
Mislang AR, Di Donato S, Hubbard J, et al. Nutritional management of older adults
with gastrointestinal cancers: an International Society of Geriatric Oncology
(SIOG) review paper. J Geriatr Oncol 2018; 9:382–392.
Muscaritoli M, Arends J, Bachmann P, et al. ESPEN practical guideline: clinical
nutrition in cancer. Clin Nutr 2021; 40:2898–2913.
National Institute for Health and Clinical Excellence (NICE). Nutrition support
for adults: oral nutrition support, enteral tube feeding and parenteral nutrition;
2017. Available at: https://www.nice.org.uk/Guidance/CG32 (24 May 2023,
date last accessed).
Ni J, Zhang L. Cancer cachexia: definition, staging, and emerging treatments.
Cancer Manag Res 2020; 12:5597–5605.
Poisson J, Martinez-Tapia C, Heitz D, et al. Prevalence and prognostic impact of
cachexia among older patients with cancer: a nationwide cross-sectional sur-
vey (NutriAgeCancer). J Cachexia Sarcopenia Muscle 2021; 12:1477–1488.
Vigano A, Kasvis P, Di Tomasso J, et al. Pearls of optimizing nutrition and physical
performance of older adults undergoing cancer therapy. J Geriatr Oncol 2017;
8:428–436.
Volkert D, Beck AM, Cederholm T, et al. ESPEN guideline on clinical nutrition
and hydration in geriatrics. Clin Nutr 2019; 38:10–47.
Wildiers H, Heeren P, Puts M, et al. International Society of Geriatric Oncology
consensus on geriatric assessment in older patients with cancer. J Clin Oncol
2014; 32:2595–2603.

86 Mukherjee et al.
Zhang X, Edwards BJ. Malnutrition in older adults with cancer. Curr Oncol Rep
2019; 21:80.
Zhang X, Pang L, Sharma SV, et al. Malnutrition and overall survival in older
patients with cancer. Clin Nutr 2021; 40: 966–977.
Zopf Y, Schink K, Reljic D, et al. Assessing cachexia in older patients: different
definitions – but which one is the most practical for clinical routine? Arch Ger-
ontol Geriatr 2020; 86:103943.

Declaration of Interest:
Ms Mukherjee has declared no conflicts of interest.
Dr To reports being a member of the Board of Directors for the Hospital Research
Foundation and a Steering Committee member of The Hospital Research Foun-
dation Palliative Care Grant Funding; his institution has received research grants
from the Medical Research Futures Fund and the National Health and Medical
Research Collaborative, Adelaide, Australia.
Dr Mislang has declared no conflicts of interest.

Nutrition in the Older Patient with Cancer 87

Energy Balance, Nutrition,
Cancer Incidence and 10
Survivorship
J. Arends1
J.A. Ligibel2
Universitätsklinikum Freiburg, Freiburg, Germany
1

Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

2

‘Energy balance’ refers to the balance between energy ingested through

food, energy expended through physical activity and metabolism, and
energy stored as adipose tissue. These three aspects of the energy bal-
ance equation – diet, physical activity and adiposity – have increasingly
been linked to the risk of developing and dying from cancer. This chapter
provides an overview of the data linking energy balance to cancer risk
and outcomes, from observational and interventional trials, as well as a
brief exploration of the biological mechanisms through which energy
balance is believed to impact cancer.

Energy Balance and Cancer Risk

Observational Evidence
Obesity, inactivity and poor dietary quality are well-established risk fac-
tors for the development of cancer. The World Cancer Research Fund
(WCRF) estimates that 30%-50% of cancer cases around the world occur
due to preventable causes, with obesity, which impacts more than 640
million people worldwide, rapidly becoming one of the most common
preventable causes of cancer in the developed world. Current analyses of
more than 1000 reports linking obesity to cancer risk by the International
Agency for Research on Cancer (IARC) and the WCRF suggest that
obesity increases the risk of more than a dozen malignancies, including

88
common cancers such as those of the breast, colon, endometrium,
kidney and oesophagus.
Although not as well studied as the relationship between obesity and can-
cer, physical inactivity has also increasingly been linked to higher cancer
risk. In 2018, the United States Physical Activity Guidelines Advisory
Committee reviewed 45 systematic reviews and meta-analyses of obser-
vational data evaluating the relationship between physical activity patterns
and cancer risk, and concluded that there was strong evidence that higher
levels of physical activity were associated with lower risk of several cancers,
including cancers of the breast, colon, endometrium, oesophagus, kidney
and stomach.
The relationship between diet and cancer risk has been somewhat less
consistent, likely due in part to the complexities of measuring diet and
the vast number of potential dietary factors for consideration. A 2018
update of the relationship between diet and cancer risk conducted by the
WCRF suggested that alcohol intake increased the risk of several differ-
ent cancers, including cancers of the mouth, pharynx, larynx, oesopha-
gus, liver, colorectum and breast. Processed and red meat intake were
also associated with increased risk of colorectal cancer, and coffee con-
sumption was associated with a decreased risk of endometrial and liver
cancers. Current research focuses on the relationship between cancer
risk and broader dietary patterns, such as the Healthy Eating Index and
Mediterranean diet and Dietary Approaches to Stopping Hypertension
(DASH), in an effort to better understand the totality of diet in relation
to cancer risk.

Interventional Evidence
Despite the extensive observational data linking energy balance factors
to cancer risk, there has been only one randomised controlled trial (RCT)
that was designed to test the impact of dietary change on cancer risk, and
no RCTs designed to test the impact of weight loss or increased physical
activity. The US-based Women’s Health Initiative Dietary Modification
(WHIDM) trial randomised 48 835 postmenopausal women with no his-
tory of cancer to a dietary intervention designed to reduce fat intake and
increase daily servings of fruits and vegetables, or to a usual diet control

Energy Balance, Nutrition, Cancer Incidence and Survivorship 89

group, with co-primary endpoints testing the impact of the dietary inter-
vention on breast and colorectal cancers. The dietary intervention was
successful in changing dietary patterns, with a significant reduction in
the percentage of calories consumed as fat and an increase in fruits and
vegetable servings in the intervention group, and induced modest weight
loss of 2.2 kg at 1 year and 0.8 kg at 6 years. However, there was no
significant reduction in breast (hazard ratio [HR] 0.91, 95% confidence
interval [CI]: 0.83-1.0) or colorectal cancers (HR 1.08, 95% CI: 0.90-
1.29) after a median follow-up of 8.1 years.
A few RCTs designed to evaluate the impact of energy balance interven-
tions on other endpoints have included cancer incidence as a secondary
endpoint, providing provocative preliminary evidence that weight loss,
dietary change and/or increased physical activity could lower cancer risk.
The Look AHEAD (Action for Health in Diabetes) trial randomised 4859
people with type 2 diabetes and a body mass index (BMI) ≥25 kg/m2 to a
diet- and exercise-based weight loss intervention or to a diabetes support
and education control group; results showed a 16% reduction in obesity-
related cancers in the weight loss group, though this comparison was not
statistically significant (HR 0.84, 95% CI: 0.68-1.04). The Prevención
con Dieta Mediterránea (PREDIMED) study evaluated the impact of a
Mediterranean diet, supplemented with either nuts or extra virgin olive
oil (EVOO), on the risk of heart disease in older individuals with cardio-
vascular risk factors such as hypertension and diabetes and found a 62%
reduction in breast cancer incidence in women randomised to the Medi-
terranean diet plus EVOO versus controls (HR 0.38, 95% CI: 0.16-0.87).

Energy Balance in Cancer Survivorship

Observational Evidence
Growing evidence suggests that energy balance factors influence not
only the risk of developing cancer, but also outcomes such as cancer-
related mortality and cancer recurrence. Obesity in particular has been
the focus of many reports. A recent systematic review and meta-anal-
ysis of 203 studies looking at the relationship between BMI and can-
cer outcomes, including both individuals with early-stage and advanced
cancers, found that obesity was associated with a higher risk of overall
90 Arends and Ligibel
mortality (HR 1.14, 95% CI: 1.09-1.19), higher cancer-specific mortal-
ity (HR 1.17, 95% CI: 1.12-1.23) and, in individuals with early-stage
disease, increased risk of cancer recurrence (HR 1.13, 95% CI: 1.07-
1.19). Notably, poor outcomes associated with obesity were primarily
seen in individuals with cancers of the breast, colorectum and prostate,
whereas obesity was associated with better outcomes in individuals with
melanoma, lung cancer and renal cell cancer, potentially due in part to
better outcomes with immunotherapy in individuals with obesity in some
cancers.
A number of reports have also looked at the relationship between physi-
cal activity patterns after cancer diagnosis and the risk of cancer-related
and all-cause mortality in cancer survivors. The 2018 US Physical Activ-
ity Guidelines Advisory Committee summarised 18 systematic reviews
and meta-analyses looking at the relationship between physical activity
patterns and all-cause and cancer-specific mortality and concluded that
there was moderate-level evidence that higher levels of physical activ-
ity were associated with a relative 38% reduction in the risk of cancer-
specific mortality in individuals with cancers of the colorectum, breast
and prostate. Higher levels of physical activity were also associated with
a 40%-50% lower risk of all-cause mortality in breast and colorectal
cancers, but evidence for prostate cancer was more limited.
Finally, observational evidence suggests that healthier dietary patterns
after cancer diagnosis are associated with improved disease-free and
overall survival in some cancers, although evidence suggesting that
intake of specific foods impacts cancer outcomes is largely lacking. In
particular, Western-pattern diets, those with a higher intake of red meats
and processed foods, are associated with worse survival outcomes in
colorectal cancer and prostate cancer. The one individual beverage that
has been more consistently linked to outcomes after diagnosis of some
cancers is alcohol, for which higher intakes (more than 2 drink equiva-
lents/day, i.e. more than 30 g/day) have been associated with increased
risk of all-cause mortality in individuals with hepatocellular cancer (risk
ratio [RR] 1.21, 95% CI: 1.07-1.36), laryngeal and pharyngeal cancers
(RR 1.48, 95% CI: 1.08-2.02) and head and neck cancers (RR 1.39, 95%
CI: 1.10-1.76).

Energy Balance, Nutrition, Cancer Incidence and Survivorship 91

Interventional Evidence
A number of RCTs have been designed to evaluate the impact of weight
loss, increased physical activity and dietary change after cancer diag-
nosis on the risk of cancer recurrence and mortality. Two trials, the
Women’s Healthy Eating and Living (WHEL) study and the Women’s
Intervention Nutrition Study (WINS), enrolled women with early-stage
breast cancer and evaluated the impact of reducing dietary fat, with or
without increasing the intake of vegetables, fruits and dietary fibre, on
the risk of breast cancer recurrence. The trials had somewhat disparate
results, with the WINS trial showing a 24% improvement in disease-free
survival at a median follow-up of 60 months in individuals participating
in the low-fat dietary programme relative to controls (HR 0.76, 95% CI:
0.60-0.98), whereas there was no reduction in recurrence in the low-fat
diet group in WHEL (16.7% versus 16.9%, p = 0.63) at a mean follow-
up of 7.3 years. Notably, participants in the WINS trial randomised to
the low-fat diet intervention lost an average of ≈2.7 kg versus controls,
whereas the WHEL intervention did not result in weight loss.
A number of ongoing trials will test the impact of weight loss, dietary
change and physical activity on cancer recurrence and mortality in
breast, colon, prostate and ovarian cancers (Table 1). The results of these
trials will help define the role of energy balance interventions in cancer
survivorship over the years to come.

Mechanisms
The energy imbalance resulting from an overabundance of foods (espe-
cially processed) for increasingly inactive populations may be seen as
the main driver for the spreading of (the global pandemic of) obesity,
metabolic syndrome and type 2 diabetes to sizeable fractions of popu-
lations across the globe. All are characterised by chronically activated
low-grade systemic inflammation, insulin resistance and hyperglycaemia
as well as complex endocrine derangements, including increased levels
of sex-steroid hormones (oestrogen and testosterone) and insulin-like
growth factor 1 (IGF-1), their respective binding proteins (sex hormone-
binding globulin, IGF-binding protein-1 and -2) and, finally, increased
oxidative stress at the cellular level.
92 Arends and Ligibel
Table 1 Ongoing Phase III Randomised Controlled Trials of Energy Balance
Interventions in Cancer Survivors.
Study Population Location Intervention Status Primary
Outcome
Breast Cancer
Breast Cancer Breast cancer USA, Weight loss Accrual completed Invasive
WEight Loss (BWEL) - Stage II-III Canada intervention (diet disease-free
(A011401) - HER2-negative plus physical activity) survival
NCT02750826 - BMI ≥27 kg/m2 plus health education
(N=3181) versus health
education attention
control
SUCCESS C Breast cancer Germany Weight loss Accrual completed; Disease-free
NCT00847444 - Stage II-III intervention (diet preliminary survival
- HER2-negative and physical activity) findings
- BMI 24-40 kg/m2 versus general lifestyle presented at
(N=2292) education 2018 San Antonio
Breast Cancer
Symposium
Diet and Breast cancer Italy Mediterranean, Accrual completed Disease-free
Androgens - Stage I-III macrobiotic diet survival
(DIANA-5) - ER-negative cancer pattern plus physical
NCT05019989 and/or metabolic activity versus general
syndrome or elevated lifestyle intervention
testosterone
(N=1542)
Ovarian Cancer
Lifestyle Ovarian cancer USA Diet and physical Accrual completed Progression-
Intervention for - Stage II-IV activity intervention free survival
Ovarian Cancer - No evidence of versus general health
Enhanced Survival disease by CT scan education attention
(LIVES) (GOG-225) and CA125 control
NCT00719303 (N=1205)
Colon Cancer
Colon Health Colon cancer Canada, Supervised, Enrolling Disease-
and Life-Long - High-risk stage II UK, structured physical free survival
Exercise Change and stage III Australia activity intervention
(CHALLENGE) - Performing <150 versus attention
(CO.21) minutes of moderate control condition
NCT00819208 intensity or 75
minutes of vigorous
physical activity/
week
(N=962)

Energy Balance, Nutrition, Cancer Incidence and Survivorship 93

Table 1 Ongoing Phase III Randomised Controlled Trials of Energy Balance
Interventions in Cancer Survivors. (Continued)
Study Population Location Intervention Status Primary
Outcome
Prostate Cancer
Intense Exercise Prostate cancer Australia, Supervised exercise Enrolling Overall
for Survival - Stage IV USA, (high intensity) survival
among Men - Castrate-resistant Canada, intervention versus
with Metastatic - No prior UK, self-directed
Castrate-Resistant chemotherapy Europe exercise (provision of
Prostate Cancer (N=866) guidelines)
(INTERVAL-GAP4)
NCT04507698
Abbreviations: BMI, body mass index; CA125, cancer antigen 125; CT, computed tomography; ER, oestrogen receptor;
GOG, Gynecologic Oncology Group; HER2, human epidermal growth factor receptor 2.

Cellular regulation is altered by these metabolic changes, including the bal-

ance between cell differentiation and proliferation, deregulated epigenetic
mechanisms (especially site-specific DNA hypermethylation in parallel
with global hypomethylation) initiating genetic instability and leading to
aberrant gene expression. Further, histone acetylation may be disturbed,
again initiating aberrant gene expression with silencing of tumour suppres-
sor genes and/or activation of oncogenes. While connections between diet
and epigenetic alterations, on the one hand, and between epigenetic altera-
tions and cancer, on the other, are supported by both observational studies
in humans as well as animal models, it is still less certain whether diet
is directly linked to epigenetic alterations and whether these epigenetic
alterations directly increase or decrease the risk of human cancer.
To counteract and slow these developments, it has been proposed to aim
for lowering cell proliferation and increasing differentiation by decreasing
sex hormone and growth hormone levels and inflammation. To achieve
this, energy imbalances, obesity and other metabolic derangements need
to be avoided or minimised. This will require lifestyle changes in the direc-
tion of earlier periods of human evolution, including generally increasing
physical activity, adapting food intake to actual energy requirements and
preferring natural over processed foods. The arguments to avoid overfeed-
ing are supported by observations showing that moderate caloric restric-
tion may increase health and survival in a large number of animal models.

94 Arends and Ligibel

Further Reading
Beresford SAA, Johnson KC, Ritenbaugh C, et al. Low-fat dietary pattern and risk
of colorectal cancer: the Women's Health Initiative Randomized Controlled
Dietary Modification Trial. JAMA 2006; 295:643–654.
Blackburn GL, Wang KA. Dietary fat reduction and breast cancer outcome: results
from the Women's Intervention Nutrition Study (WINS). Am J Clin Nutr 2007;
86:s878–s881.
Brandhorst S, Longo VD. Fasting and caloric restriction in cancer prevention and
treatment. Recent Results Cancer Res 2016; 207:241–266.
Eaton SB, Eaton SB. An evolutionary perspective on human physical activity:
implications for health. Comp Biochem Physiol A Mol Integr Physiol 2003;
136:153–159.
Hurtado-Barroso S, Trius-Soler M, Lamuela-Raventós RM, Zamora-Ros R. Veg-
etable and fruit consumption and prognosis among cancer survivors: a system-
atic review and meta-analysis of cohort studies. Adv Nutr 2020; 11:1569–1582.
Jochems SHJ, Van Osch FHM, Bryan RT, et al. Impact of dietary patterns and the
main food groups on mortality and recurrence in cancer survivors: a systematic
review of current epidemiological literature. BMJ Open 2018; 8:e014530.
Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body fatness and cancer – view-
point of the IARC Working Group. N Engl J Med 2016; 375:794–798.
Look AHEAD Research Group, Yeh HC, Bantle JP, Cassidy-Begay M, et al. Inten-
sive weight loss intervention and cancer risk in adults with type 2 diabetes:
analysis of the Look AHEAD randomized clinical trial. Obesity (Silver Spring)
2020; 28:1678–1686.
Malik VS, Willett WC, Hu FB. Global obesity: trends, risk factors and policy
implications. Nat Rev Endocrinol 2013; 9:13–27.
Manna P, Jain SK. Obesity, oxidative stress, adipose tissue dysfunction, and the
associated health risks: causes and therapeutic strategies. Metab Syndr Relat
Disord 2015; 13:423–444.
McTiernan A, Friedenreich CM, Katzmarzyk PT, et al. Physical activity in can-
cer prevention and survival: a systematic review. Med Sci Sports Exerc 2019;
51:1252–1261.
NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass index
in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-
based measurement studies with 19.2 million participants. Lancet 2016;
387:1377–1396.
Petrelli F, Cortellini A, Indini A, et al. Association of obesity with survival out-
comes in patients with cancer: a systematic review and meta-analysis. JAMA
Netw Open 2021; 4:e213520.

Energy Balance, Nutrition, Cancer Incidence and Survivorship 95

Pierce JP, Natarajan L, Caan BJ, et al. Influence of a diet very high in vegetables,
fruit, and fiber and low in fat on prognosis following treatment for breast can-
cer: the Women's Healthy Eating and Living (WHEL) randomized trial. JAMA
2007; 298:289–298.
Prentice RL, Caan B, Chlebowski RT, et al. Low-fat dietary pattern and risk of
invasive breast cancer: the Women's Health Initiative Randomized Controlled
Dietary Modification Trial. JAMA 2006; 295:629–642.
Sapienza C, Issa JP. Diet, nutrition, and cancer epigenetics. Annu Rev Nutr 2016;
36:665–681.
Schwedhelm C, Boeing H, Hoffmann G, et al. Effect of diet on mortality and can-
cer recurrence among cancer survivors: a systematic review and meta-analysis
of cohort studies. Nutr Rev 2016; 74:737–748.
Steck SE, Murphy EA. Dietary patterns and cancer risk. Nat Rev Cancer 2020;
20:125–138.
Toledo E, Salas-Salvadó J, Donat-Vargas C, et al. Mediterranean diet and invasive
breast cancer risk among women at high cardiovascular risk in the PREDIMED
trial: a randomized clinical trial. JAMA Intern Med 2015; 175:1752–1760.
World Cancer Research Fund International/American Institute for Cancer
Research. Diet, Nutrition, Physical Activity and Cancer: a Global Perspective.
Continuous Update Project Expert Report 2018. Available at: https://www.
wcrf.org/diet-activity-and-cancer/ (24 May 2023, date last accessed).

Declaration of Interest:
Dr Arends reports speaker honoraria from Baxter, B. Braun Melsungen, Danone,
Fresenius Kabi, Nestlé and SPCC (Sharing Progress in Cancer Care).
Professor Ligibel reports that her institution received sample products from
Fitbit Corporation and Nestlé Health Sciences for a research project that she has
conducted.

96 Arends and Ligibel

Navigating Nutritional
Decision-Making 11
M. Lee1
A. Jatoi2
J.G. Le-Rademacher1,2
Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, USA
1

Department of Oncology, Mayo Clinic, Rochester, MN, USA

2

A New York Times article from a few years ago began with the statement:
There’s a decent chance you’ll be reading about diet soda studies
until you die, [but] the odds are exceedingly good it won’t be the
soda that kills you.
Indeed, nutritional research – much of which focuses on decreasing can-
cer risk and on improving outcomes after a cancer diagnosis – is seem-
ingly ubiquitous and, at times, seemingly contradictory in its findings
and recommendations. Understanding study designs and the data they
generate can be daunting for patients as well as for clinicians. Here we
outline three illustrative points that clinicians should consider when dis-
cussing scientific findings on nutrition and cancer with patients. We also
allude to other points of importance and provide resources that may help
clinicians help patients (Tables 1 and 2).

An Association Should Not Imply Causation:

Understanding Studies with Different Designs
Statistically significant associations abound, but proof of causality relies
on well-conducted, well-reported placebo-controlled trials. A relevant case
in point focuses on beta (β)-carotene and its previously touted role in lung
cancer prevention. Carotenoids, such as β-carotene, are abundant in plants,

97
Table 1 Partial List of Trial Issues to Consider.
Trial design issue
Potential disconnect between association and causality
Undue focus on secondary endpoints
Ignoring patient dropout and data absence
Single-site or multi-site study
Confirmation of outcome measures during trial conduct
Appropriate degree of monitoring and reporting of toxicity
High degree of intervention fidelity from patient to patient
Slow or swift patient recruitment

Table 2 Relevant Databases.

Center for Food Safety and Applied https://www.fda.gov/about-fda/fda-organization/center-food-safety-and-
Nutrition (CFSAN) applied-nutrition-cfsan
FDA Adverse Event Reporting https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-
System (FAERS): Latest Quarterly reporting-system-faers/fda-adverse-event-reporting-system-faers-latest-
Data Files quarterly-data-files
Licensed Natural Health Products https://www.canada.ca/en/health-canada/services/drugs-health-products/
Database (LNHPD) natural-non-prescription/applications-submissions/product-licensing/
licensed-natural-health-products-database.html
Natural Medicines databases https://naturalmedicines.therapeuticresearch.com/databases.aspx
Dietary Supplement Label Database https://ods.od.nih.gov/Research/Dietary_Supplement_Label_Database.aspx
(DSLD)
The Committee on Herbal Medicinal https://www.ema.europa.eu/en/human-regulatory/herbal-medicinal-products
Products (HMPC)
European Food Safety Authority https://www.efsa.europa.eu/en/topics/topic/health-claims
(24 May 2023, date last accessed)
Abbreviation: FDA, Food and Drug Administration.

functioning as antioxidants, modulators of cell proliferation and regula-

tors of immune function. Such preclinical data support the hypothesis that
an inverse relationship exists between carotenoid consumption and lung
cancer development. Epidemiological studies that examined such associa-
tions did in fact find such an inverse relationship. For example, Abar et al
(2016) focused on 17 prospective studies with 3603 patients who developed

98 Lee et al.
lung cancer within a cohort of 458 434 participants. Examining blood lev-
els of alpha (α)-carotene, β-carotene, total carotenoids and retinol, these
investigators observed an inverse relationship between lung cancer risk or
mortality and carotenoid concentrations, with lower risk ratios indicative
of lower cancer risk: 0.66 (95% confidence interval [CI]: 0.55–0.80) per
5 μg/100 mL of α-carotene (in five studies), 0.84 (95% CI: 0.76–0.94) per
20 μg/100 mL of β-carotene (in nine studies), 0.66 (95% CI: 0.54–0.81)
per 100 μg/100 mL of total carotenoids (in four studies) and 0.81 (95% CI:
0.73–0.90) per 70 μg/100 mL of retinol (in eight studies). Clearly, such
findings invite further study.
However, double-blind, randomised, placebo-controlled clinical trial data
warn against advising patients at high risk for cancer to take carotenoid
supplements. The Beta-Carotene and Retinol Efficacy Trial (CARET)
randomly assigned 18 000 individuals at high risk for lung cancer to
β-carotene 30 mg per day and 25 000 IU of retinol palmitate per day
versus matching placebos, only to conclude that the carotenoid sup-
plementation had an opposite effect of that hypothesised: after a mean
follow-up of 4 years, individuals who received the β-carotene and retinol
manifested a relative risk of lung cancer of 1.28 (95% CI: 1.04–1.57),
compared with placebo-exposed patients. Furthermore, in an almost
simultaneously conducted interventional trial – the Alpha-Tocopherol,
Beta-Carotene Cancer Prevention Study – which tested β-carotene 20 mg
per day (in conjunction with vitamin E) in individuals at high risk for
lung cancer, these other investigators generated similar findings: “Unex-
pectedly, we observed a higher incidence of lung cancer among the men
who received beta-carotene than among those who did not (change in
incidence, 18%; 95% CI: 3%–36%).” Additionally, “Total mortality was
8% higher (95% CI: 1%–16%) among the participants who received
beta-carotene than among those who did not…”
These two studies underscore the importance of double-blind, randomised,
placebo-controlled trials for final nutritional recommendations. Observa-
tional studies may be subject to selection bias or confounding effects while
randomised trials minimise these risks, hence making selection bias and
unknown confounders less of an influence on trial outcomes. Admittedly,
the above two trials raise other issues – such as concerns about ingesting

Navigating Nutritional Decision-Making 99

discrete supplements, such as pills as opposed to consuming whole foods
that presumably contain just the necessary tincture and combination of
multiple micronutrients; how investigators choose the ‘right dose’ of a
supplement; alarms about taking ‘high dose’ supplements, as ostensibly
prescribed in the two trials referenced above; and the rationale for admin-
istering a nutrient to an individual with no apparent deficiency of that
nutrient. For the purposes of this chapter, the main illustrative point is that
observational nutritional studies can be misleading and that placebo-con-
trolled, randomised, controlled data carry guiding value.

Secondary Outcomes Should Not Guide

Definitive Clinical Recommendations
On 25 December 1996, the Journal of the American Medical Association
(JAMA) reported on a randomised, placebo-controlled trial (Clark et al)
that sought to determine if oral selenium (200 μg per day) decreased the
risk of basal or squamous cell carcinomas of the skin. The trial included
1312 patients, clearly stated its primary endpoint, reported 377 new
cases of basal cell skin cancer with selenium versus 350 with placebo
(risk ratio [RR] 1.10; 95% CI: 0.95–1.28) along with 218 new squamous
cell skin cancers with selenium and 190 with placebo (RR 1.14; 95%
CI: 0.93–1.39), and appropriately concluded: “Selenium treatment did
not protect against development of basal or squamous cell carcinomas
of the skin.”
Twenty-five years later, if one searches the internet for information on
that study, the following can be found:
Just last Christmas Eve was a memorable date for people who have
been taking antioxidants to prevent disease. CNN and other networks
reported on a study from the Dec. 25, 1996, issue of the Journal of
the American Medical Association (JAMA) showing that selenium
reduced cancer mortality in humans by 50 percent over a 10-year
period of time. CNN carried a more extensive report and emphasized
that Americans could buy in health food stores the selenium tablets
used in the JAMA study.

100 Lee et al.

This directly quoted commentary makes two important points. First,
the findings from secondary endpoints can become overinflated in their
importance. Although the secondary endpoints from Clark et al did, in
fact, suggest selenium-treated individuals manifested a statistically sig-
nificant decrease in the incidence of prostate cancer, lung cancer and
colorectal cancer, these findings were just that: secondary endpoints,
which can generate spurious findings, as appears to have been the case
here and as further explained below. Importantly, secondary outcomes
need to be interpreted with caution, because among other issues, studies
are not always specifically powered to assess them and there are risks
of type I errors when there are multiple secondary endpoints. Second,
the viability of digitised memory banks, which can keep obsolete data
and erroneous conclusions alive on the internet, underscores the role of
clinicians as educators in such matters as the de-emphasis of secondary
endpoints.
Since the publication of the original trial from Clark et al, three other
large, definitive studies have focused on selenium and its respective and
purported roles in the prevention of prostate cancer, lung cancer and
colon cancer. Each of these trials examined cancer incidence (or, as in
the case of colon cancer, polyps) as the primary endpoint for each of the
cancers of interest, but each showed selenium does not prevent cancer
(or polyps). In effect, these statistically significant secondary endpoints
in the study from Clark et al eventually proved to be of no consequence.
As a case in point, the Selenium and Vitamin E Cancer Prevention Trial
(SELECT) for prostate cancer recruited 35 533 healthy men, and ran-
domly assigned these men in a double-blinded manner to selenium 200 μg
per day + placebo versus daily vitamin E + placebo versus both versus
neither (double-dummy design). It demonstrated that these interventions
“did not prevent prostate cancer;” cost over $110 million; appeared to
put to rest the hypothesis that selenium, as prescribed in the trial, serves
as a cancer chemopreventive agent; and at times even suggested adverse
effects from such supplementation. This evolution of information under-
scores the clinician’s role in providing patients with up-to-date and accu-
rate information.

Navigating Nutritional Decision-Making 101

Missing Data Can Mislead
Patients who have an advanced cancer are often too ill to continue with
clinical trial participation, despite their best efforts; these patients some-
times choose to cease trial participation – a decision that results in miss-
ing data. Through no fault of their own, these patients who drop out can
create challenges in the interpretation of trial results. For example, in
1999, Barber et al reported on a single-arm study that tested an omega-3
fatty acid product to treat cancer-associated weight loss. Twenty patients
were enrolled, but by week 3, two patients had dropped out; and by
week 7, seven patients had dropped out. Not surprisingly, comparisons
between baseline and 7-week data showed improvements in weight
(p = 0.033), in lean body mass with bioelectrical impedance (p = 0.0047)
and in Karnofsky scores (p = 0.046). However, one might wonder
whether these favourable findings could be artefactual and the result of
only dropout bias. Presumably, the more robust patients remained in the
trial, driving the 7-week results in a more favourable direction. Small
pilot studies – such as this one – yield important data, but their findings
should not be overstated. Although Barber et al reported their results
with an appropriate degree of caution, it is perhaps too easy for others to
ignore how patient dropout can incur a potential for bias. Following this
trial, a few hundred patients with advanced cancer and weight loss were
treated with a similar omega-3 fatty acid product within the context of
large phase III trials; none reported product efficacy.

Managing an Absence of Data

Still other aspects of study design come into play when deciding whether
a nutritional intervention should be recommended to a patient with can-
cer or at risk for cancer. These other aspects of study design also include
but are not limited to the following: whether a trial was conducted as a
single-site or multi-site study with the latter allowing for greater gener-
alisability of results, whether a trial was undertaken with the appropriate
degree of confirmation of outcome measures and an appropriate degree
of monitoring and reporting of toxicity, whether the intervention was
prescribed with a high degree of fidelity (or a well-monitored, repro-
ducible administration of the intervention) from patient to patient, and

102 Lee et al.

whether recruitment was slow or swift, with the latter more likely to
allow for the generalisability of findings.
But perhaps the most vexing problem is an absence of relevant data.
Often no definitive clinical trials are available to provide guidance,
leaving patients and clinicians to make decisions with little or no data.
Under such circumstances, we recommend that discussions with patients
consider the goals of cancer therapy. A patient who is receiving cancer
therapy with curative intent should perhaps be advised against taking an
understudied nutritional intervention, such as a high-dose supplement. In
contrast, patients who are no longer receiving curatively intended cancer
therapy may find that a nutritional intervention helps them feel more
empowered, more in control of their circumstances. Clinicians should
partner with patients to discuss the cost of nutritional interventions and
to review resources, such as those in Table 2, to provide guidance on
side effects. Clinicians should also work to build trust so that patients
are comfortable in reporting to their healthcare providers what they are
taking. The recruitment of a dietician to the study team can also be most
helpful. This absence of data can make the bond between patients and
clinicians stronger at a time when patients need it the most.

Further Reading
Abar L, Vieira AR, Aune D, et al. Blood concentrations of carotenoids and retinol
and lung cancer risk: an update of the WCRF-AICR systematic review of pub-
lished prospective studies. Cancer Med 2016; 5:2069–2083.
Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of
vitamin E and beta carotene on the incidence of lung cancer and other cancers
in male smokers. N Engl J Med 1994; 330:1029–1035.
Barber MD, Ross JA, Voss AC, et al. The effect of an oral nutritional supplement
enriched with fish oil on weight-loss in patients with pancreatic cancer. Br J
Cancer 1999; 81:80–86.
Carroll AE. Five reasons the diet soda myth won't die. The New York Times,
14 October 2019. https://www.nytimes.com/2019/10/14/upshot/diet-soda-
health-myths.html (24 May 2023, date last accessed).
Clark LC, Combs GF Jr, Turnbull BW, et al. Effects of selenium supplementation for
cancer prevention in patients with carcinoma of the skin. A randomized controlled
trial. Nutritional Prevention of Cancer Study Group. JAMA 1996; 276:1957–1963.

Navigating Nutritional Decision-Making 103

Fearon KC, Barber MD, Moses AG, et al. Double-blind, placebo-controlled, rand-
omized study of eicosapentaenoic acid diester in patients with cancer cachexia.
J Clin Oncol 2006; 24:3401–3407.
Fearon KC, Von Meyenfeldt MF, Moses AG, et al. Effect of a protein and energy
dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue
in cancer cachexia: a randomised double blind trial. Gut 2003; 52:1479–1486.
Goodman GE, Thornquist MD, Balmes J, et al. The Beta-Carotene and Retinol
Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality
during 6-year follow-up after stopping beta-carotene and retinol supplements.
J Natl Cancer Inst 2004; 96:1743–1750.
Jatoi A, Rowland K, Loprinzi CL, et al. An eicosapentaenoic acid supplement
versus megestrol acetate versus both for patients with cancer-associated wast-
ing: a North Central Cancer Treatment Group and National Cancer Institute of
Canada collaborative effort. J Clin Oncol 2004; 22:2469–2476.
Karp DD, Lee SJ, Keller SM, et al. Randomized, double-blind, placebo-controlled,
phase III chemoprevention trial of selenium supplementation in patients with
resected stage I non-small-cell lung cancer: ECOG 5597. J Clin Oncol 2013;
31:4179–4187.
Klein EA, Thompson IM Jr, Tangen CM, et al. Vitamin E and the risk of pros-
tate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).
JAMA 2011; 306:1549–1556.
Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on
risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer
Prevention Trial (SELECT). JAMA 2009; 301:39–51.
Thompson PA, Ashbeck EL, Roe DJ, et al. Selenium supplementation for pre-
vention of colorectal adenomas and risk of associated type 2 diabetes. J Natl
Cancer Inst 2016; 108:djw152.

Declaration of Interest:
Dr Lee has declared no conflicts of interest.
Dr Jatoi reports institutional funding for advisory board membership from
Novartis and Meter Health and an institutional research grant from AstraZeneca
for an investigator-initiated research study.
Dr Le-Rademacher has declared no conflicts of interest.

104 Lee et al.

Implementation Science to
Advance Nutritional Care 12
in Cancer
M.J. Hjermstad
O. Dajani
S. Kaasa
Oncology and Palliative Medicine, University of Oslo, Oslo; Department of
Oncology, Oslo University Hospital, Oslo; European Palliative Care Research
Centre (PRC), Oslo University Hospital and Oslo University, Oslo, Norway

Evidence-based guidelines emphasise the importance of routine screen-

ing for nutritional deficits in patients with cancer, not only in those at risk
of malnutrition. These guidelines target all adults at all stages of disease
including survivors, irrespective of whether the treatment intention is
curative, life-prolonging or palliative. However, given the high preva-
lence of malnutrition in cancer patients, varying between 20% and 70%,
the European Society for Clinical Nutrition and Metabolism (ESPEN)
guidelines documented that the nutrition guidelines regarding routine
assessment, patient-centred advice and/or provision of nutritional sup-
port are not adhered to in daily clinical practice. More specifically,
routine screening for nutritional deficits using objective measures and
patient-reported outcomes is not performed.
The main objective of this chapter is to emphasise the need for a thor-
ough, well-planned strategy to increase the chances for success in imple-
menting better routines for nutritional screening into clinical practice. We
strongly advocate using the basic principles of implementation science,
which aims to close the gap between academia and practice by evaluat-
ing the most suitable strategies to implement evidence-based knowledge
into the given setting.

105
This chapter focuses on how to implement the evidence-based recom-
mendations for nutritional care into routine clinical practice at all institu-
tions treating cancer patients. This goal is explicitly stated in the ESPEN
guidelines on nutrition in cancer patients.
Nutritional deficits must be assessed and managed according to the nutri-
tional care process of screening, assessment, intervention, monitoring
and evaluation. For patients to benefit from the nutritional advice given,
a patient-centred care approach is paramount: acknowledging the per-
ceptions, needs and values of the individual patient, and ensuring patient
participation in all clinical decisions. This is not only important from
the patient’s point of view, but also increases the chances for success-
ful implementation in clinical cancer care. Practical nutrition guidelines
encompass validated, stepwise and consensus-based recommendations
about when, who and how to screen, and procedures for subsequent inter-
ventions. Examples are when and how to offer patients basic nutritional
support and treatment, how to modify the anticancer and supportive
treatments to improve nutritional status, when to refer to the dieticians,
and guiding patients in how to optimise their diet and exercise regularly.

Why Do We See These Evidence-Practice Gaps

in Nutritional Care in Cancer?
Given the positive clinical effects of routine malnutrition screening,
it is surprising that this is not part of the clinical routine in cancer care.
However, this complies with the generally dismal incorporation of
evidence-based knowledge into clinical practice, with common time lags
of 10 years or more.
We believe that several factors may explain the poor integration of nutri-
tional care in cancer, albeit not being excuses thereof:
n Low awareness of the importance of nutritional status on the effec-

tiveness of cancer treatment

n Inconsistent outcome data from studies on the benefits of nutritional

support

106 Hjermstad et al.

n Limited knowledge of nutrition science among medical oncology,


surgery, radiotherapy and nursing staff, reinforced by little emphasis

in basic and specialist curricula
n A predominant disease-centred focus in cancer care, which to a small

extent incorporates the patient’s evaluation of nutritional problems

and other symptoms in the treatment decisions
n Unsystematic use of patient-reported outcome measures (PROMs)

that supplement the clinical data with valuable patient-centred infor-

mation
n Poor compliance with routine malnutrition screening

n Disproportionately low engagement in clinical studies on nutrition in

oncology, as opposed to other oncological trials

n The siloed organisation in medicine, with nutritional expertise and

dieticians separated from the core clinical team

n Economic considerations, with marginal numbers of dieticians, even

in university hospitals

The Rationale for Using an Implementation

Science Strategy to Improve Adherence to
Evidence-Based Nutrition Guidelines?
An explicit, consensus-based strategy for the delivery of patient-cen-
tred care including nutritional care is, to the best of our knowledge, not
implemented in routine cancer care. Furthermore, it is time to admit that
the poor adherence to nutrition guidelines represents a profound problem
that necessitates a significant change. This applies to all organisational
levels such as managerial, professional and individual, with robust top-
down and bottom-up implementation plans.
A wide array of both passive and active strategies has been used to improve
practice. However, when these actions are not performed systemati-
cally, chances for success are small. Our impression is that the two most
neglected factors in any change plan are a thorough identification of bar-
riers and facilitators and the anchoring of the change activities at all levels
involved. A traditional assumption has been that presenting convincing
Implementation Science to Advance Nutritional Care in Cancer 107
evidence-based results would suffice to see an uptake in practice. How-
ever, this is the exception rather than the rule, as the traditional research
methods with control of context, followed by interventions and analyses,
most often fall short in producing sustainable changes in practice.
The slow uptake of new evidence and technologies in clinical practice
as well as the opposite, namely ending medications with little effects
(e.g. extensive tube feeding at end-of-life), has led to the growing field
of research on knowledge transfer. Implementation science has been
defined as: ‘The scientific study of methods to promote the systematic
uptake of research findings and other evidence-based practices into
routine practice, and, hence, to improve the quality and effectiveness
of health services’; in other words, testing strategies to move evidence-
based clinical innovations into practice, given the actual context.
In conventional clinical trials, the outcomes are either objectively meas-
ured clinical parameters, for example, lower blood pressure or the effect
of chemotherapy on tumour size, or they may be patient-reported, such as
less dysphagia after radiotherapy, reduced pain after opioid switch, etc.
This contrasts with the outcome measures in implementation projects
that focus on how the implementation process goes, and how healthcare
providers adhere to the plan. Furthermore, the strategy is not to control
the context as in randomised clinical trials, but to plan the process of
change, repeatedly evaluate changes at all levels involved and adjust as
necessary in iterative processes.
A prerequisite for success is to acknowledge that most changes in health-
care represent complex changes, given the complexity of organisational
dynamics and the formal and informal social subsystems and rules. How
these systems act and interact must be fully understood and all expected
and potential barriers and facilitators must be identified upfront, with
action plans at hand. Using a validated framework from implementation
science can be beneficial when evaluating an implementation or design-
ing an implementation study.
Important aspects in this context are:
n Performing a gap analysis that assesses the current situation, deter-

mines the goal state and shows the gap between the two

108 Hjermstad et al.

n The results of this analysis form the basis for the actions needed and


the implementation plan

n Scoping the context in which the changes will take place

n Scoping available evidence-based guidelines

n Anchoring the project at all levels involved

n Identifying local barriers/facilitators

n Establishing an implementation team and identifying champions

n Developing the communication information and education plan

n Developing the evaluation plan

Some implementation science strategies are relatively similar and devel-

oped as an inherent part of the implementation process itself. One exam-
ple is the Integrated Promoting Action on Research Implementation in
Health Services (i-PARIHS) framework, which claims that successful
implementation relies on essential factors of the context, the quality and
type of evidence, and the facilitation of the evidence into practice. The
phases of facilitation are related: review and share, clarify and engage,
assess and measure, act and implement, in iterative cycles until uptake
in practice. These principles are not very different from the Plan-Do-
Study-Act model (the Deming or Shewhart Cycle), also emphasising
the iterative process that creates more knowledge by each iteration. As
most implementation projects are iterative by nature, changes underway
provide important information about the best steps to succeed with the
implementation.
An implementation plan that is specifically designed for the context
in which the changes will take place, approved and supported in full
by management at all levels, is instrumental. Implementing the use of
checklists after hip surgery is fundamentally different from implement-
ing mandatory nutritional screening in a cancer outpatient clinic. Failure
to perform thorough and detailed planning bounces back with unexpected
determinants that prevent the success of the implementation. Thus, it is
essential to focus on, define and approach facilitators and barriers at all
levels before start and during the process of change, and document the
planned and the unexpected changes along the way to move forward.

Implementation Science to Advance Nutritional Care in Cancer 109

Thus, any implementation, be it large or small, must focus on multiple
organisational and individual levels, bottom-up and top-down, through-
out the actual department, clinic or unit, and not only the patient–health-
care provider dyads. Common mistakes that prevent success are insuf-
ficient attention to the central role of the individual healthcare provider
in determining the process and outcomes of implementation, and to the
wider social and administrative consequences of the implementation.

How to Implement Nutritional Care as Part of

Cancer Care, the Practical Perspective
First, it must be acknowledged by management at all levels that quality
cancer care is not provided without nutritional care as an integrated part,
followed by a decision to change prior to defining the project group. The
intention and rationale must be understood by managers and stakehold-
ers, and anchoring of the entire project, including the need for resources
and the anticipated timeline, must be ensured at all relevant levels of the
institution (Figure 1). These factors must also be shared and discussed
with the multidisciplinary teams involved, on multiple occasions.
Barriers and facilitators must be identified, with plans for handling these.
Notably, these may vary across the involved hospitals and units.
Following the implementation science way of thinking, the final out-
come is the uptake of nutritional screening routines in the participating
units: clinic, department and wards, by the individual healthcare provid-
ers. The latter is the unit of observation, whose performance and fidel-
ity to the project serve as process indicators, coupled with descriptive
data on the prevalence of screening to substantiate compliance. Thus,
the selected multicomponent implementation strategy must be presented,
discussed and revised as necessary prior to project start, supported by
iterative educational and informational activities. These can focus on the
evidence-based data from a scoping of current practice on nutritional
assessment in the actual unit(s) and can consist of presentations about
the experiences, change of professional roles, and how this improved
patient outcomes by early adopters of nutritional screening programmes.

110 Hjermstad et al.

 Key implementation strategies Key recipients
Disseminate results to a wider audience Healthcare providers
n Focus on under- and post-graduate education n Patient advocacy groups

n Handbooks, guidelines, treatment n NGOs

Step 3 recommendations, patient pamphlets, n Oncologists, nurses,

educational programmes, e-learning dieticians, students

The implementation process Healthcare sector

n Develop, test, evaluate and revise the implementation n Public

plan n Private

n Develop nutritional pathways: n Pharmaceutical industry

n Screening – extended assessments – referrals n Universities

n Templates for nutritional outcomes in the EMR n Professional organisations

n Weight, nutritional intake, appetite loss (ESMO, ASCO, EAPC, etc.)

n Regular use of PROMs/(e)PROMs
Step 2

n Repeated evaluations of use

Preparatory work Policymakers/stakeholders

n Acknowledge the need for change n National authorities

n Decide and anchor the implementation strategy at all levels n Professional organisations

n Define the project group: roles and allocated resources n Patient organisations

n Information, education and training – iteratively n Management level

Step 1

n Map current situation, resources and practice prior to start

Figure 1 The nutritional care implementation ladder.

Abbreviations: ASCO, American Society of Clinical Oncology; (e)PROM, (electronic) PROM; EAPC, European Association
of Palliative Care; EMR, electronic medical record; ESMO, European Society for Medical Oncology; NGO, non-governmental
organisation; PROM, patient-reported outcome measure.

Provision of resources may facilitate uptake. This includes nomination

and training of champions and super-users who can provide interactive
assistance and clinical supervision, with allocated time to do this. Cer-
tain changes in the infrastructure are advantageous, for example, tem-
plates for mandatory registrations such as weight, nutritional intake and
appetite loss in the electronic medical records (EMRs), alert functions
connected to aberrant values in, for example, weight, body mass index
(BMI) and metabolic risk factors, facilitated referral procedure to dieti-
cians, etc. Developing standardised nutritional pathways in the EMRs
for time- and/or needs-based nutritional screening, extended assessment
and referrals is advantageous.

Implementation Science to Advance Nutritional Care in Cancer 111

It is advisable to set a starting point early in the process, to ensure timely
planning of the implementation strategy and assess for readiness at all
levels before start. The overall implementation plan defines how the pro-
ject or change will be executed, describes the reason behind the project
and its defined goals, delineates all steps involved, presents the time-
line and lists the resources, financial and human, that are necessary. In a
clinical setting, the plan must be adapted to the different departments and
units and be specified in detail.
In short, the implementation of nutritional care as an integrated part of
cancer care is a stepwise and iterative process directed at multiple lev-
els of healthcare, not only the healthcare provider­­–cancer patient dyads.
Addressing the scientific importance of nutrition on treatment and patient-
centred outcomes must go further than the individual clinical unit. Thus,
recipients also include managers and policy makers, stakeholders, pro-
fessional and lay healthcare organisations, and the pharmaceutical indus-
try for initiation of substantially more clinical studies with nutrition-
related primary outcomes.

Conclusion
Placing nutritional care higher on the agenda at all levels of healthcare in
cancer gives momentum. The use of implementation science strategies
increases the chances of successfully improving the quality of cancer
care. This adheres to the explicit requirements of nutrition guidelines:
that screening, prevention, detailed assessment, monitoring and treating
of malnutrition should be done at all cancer clinics.

Further Reading
Arends J, Bachmann P, Baracos V, et al. ESPEN guidelines on nutrition in cancer
patients. Clin Nutr 2017; 36:11–48.
Baker, A. Crossing the Quality Chasm: A New Health System for the 21st Century.
Institute of Medicine IOM, (US) Committee on Quality of Health Care in Amer-
ica. Washington DC: National Academies Press, 2001; Volume 323, p.1192.
Bauer MS, Damschroder L, Hagedorn H, et al. An introduction to implementa-
tion science for the non-specialist. BMC Psychol 2015; 3:32.

112 Hjermstad et al.

de Las Peñas R, Majem M, Perez-Altozano J, et al. SEOM clinical guidelines on
nutrition in cancer patients. Clin Transl Oncol 2019; 21:87–93.
Deming WE. Out of the Crisis. Cambridge, MA: MIT Press, 1986.
Eccles MP, Mittman BS. Welcome to implementation science. Implementation
Sci 2006; 1:1.
Grimshaw JM, Thomas RE, MacLennan G, et al. Effectiveness and efficiency
of guideline dissemination and implementation strategies. Health Technol
Assess 2004; 8:iii–iv, 1–72.
Grol R, Wensing M. What drives change? Barriers to and incentives for achiev-
ing evidence-based practice. Med J Aust 2004; 180(S6):S57–S60.
Harvey G, Kitson A. PARIHS revisited: from heuristic to integrated framework
for the successful implementation of knowledge into practice. Implement Sci
2016; 11:33.
Kaasa S, Hjermstad MJ, Sjøgren P. Commercial and social determinants in pal-
liative care. Eurohealth 2022; 28:22–27.
Kaasa S, Loge JH, Aapro M, et al. Integration of oncology and palliative care:
a Lancet Oncology Commission. Lancet Oncol 2018; 19:e588–e653.
Lee JLC, Leong LP, Lim SL. Nutrition intervention approaches to reduce malnu-
trition in oncology patients: a systematic review. Support Care Cancer 2016;
24:469–480.
Levonyak NS, Hodges MP, Haaf N, et al. Importance of addressing malnutrition
in cancer and implementation of a quality improvement project in a gastroin-
testinal cancer clinic. Nutr Clin Pract 2022; 37:215–223.
Liposits G, Orrevall Y, Kaasa S, et al. Nutrition in cancer care: a brief, practical
guide with a focus on clinical practice. JCO Oncol Pract 2021; 17:e992–e998.
Moore GF, Audrey S, Barker M, et al. Process evaluation of complex interven-
tions: Medical Research Council guidance. BMJ 2015; 350:h1258.
Moore GF, Evans RE, Hawkins J, et al. From complex social interventions to
interventions in complex social systems: future directions and unresolved
questions for intervention development and evaluation. Evaluation (Lond)
2019; 25:23–45.
Muscaritoli M, Arends J, Bachmann P, et al. ESPEN practical guideline: clinical
nutrition in cancer. Clin Nutr 2021; 40:2898–2913.
Roeland EJ, Bohlke K, Baracos VE, et al. Management of cancer cachexia:
ASCO guideline. J Clin Oncol 2020; 38:2438–2453.
Wensing M, Grol R. Knowledge translation in health: how implementation
science could contribute more. BMC Med 2019; 17:88.

Implementation Science to Advance Nutritional Care in Cancer 113

Declaration of Interest:
Dr Hjermstad has declared no conflicts of interest.
Dr Dajani has declared no conflicts of interest.
Professor Kaasa reports institutional funding for advisory board membership
from Helsinn Healthcare, webinar lectures from Pfizer Norway and Nutricia
Norway, a writing engagement from Nutricia Norway, invited speaker fees from
MEDIDEO and Fresenius Kabi Deutschland, research grants from The Norwe-
gian Cancer Society and the South-Eastern Norway Regional Health Authority
for his work as coordinating principal investigator from Helseforsk, and from
Nutricia Research for his work on the PROTES Project. He reports personal roy-
alties from the Oxford Textbook of Palliative Medicine.

114 Hjermstad et al.

Health Economics in
Oncology Nutrition Research 13
M.T. Fallon1,2
D. Yi3
B.J.A. Laird1,2,4
Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK
1

2
Edinburgh Cancer Centre, NHS Lothian, Edinburgh, UK
3
Cicely Saunders Institute of Palliative Care, Policy & Rehabilitation,
King's College London, London, UK
4
St Columba’s Hospice Care, Edinburgh, UK

Health economics can be a very emotive topic, particularly for patients

and carers. Therefore, it is helpful to understand the general concepts,
which are much broader than simply the financial cost of a particular
medicine.
A key general concept is defining the value of healthcare, which can be
considered as ‘what is gained, relative to what is lost’. In this context,
there are three value dimensions:
1. Societal: how well assets are distributed to different subgroups of the
population (equity in resource distribution).
2. Technical: how well resources are used to improve outcomes for all
(improving quality and safety of services).
3. Personal: how well the outcome relates to the values of each individual
(understanding what matters most to the patient).
Contrary to popular misconception, value is not the same as quality of care
or how much money is spent. High-quality care to the wrong patient or at
the wrong time (or in the wrong place) is still low value. Similarly, bet-
ter value is not necessarily achieved by higher expenditure. Nevertheless,

115
even to the right person at the right time, there will still be an inevitable
cost. Clearly, maximising value in healthcare resources requires under-
standing both what we seek to achieve and the effectiveness of the means
to achieve it; this is the purpose of health economics. People used to a
universal healthcare system may struggle to see the value of healthcare,
rather than perceive it as a basic right, and rarely question where these
resources originate.

Defining Health Economics

So, what is health economics? ‘Economics is a science which studies
human behaviour as a relationship between ends and scarce means which
have alternative use’ (Robbins, 1932). Thus, economics is a science of
choice. Health economics is therefore the science of choice within the
healthcare context. The aim is to distribute a constrained health budget to
maximise overall population health, as public and third sector healthcare
providers have the objective of health maximisation using their fixed
budget. The budget is insufficient to reimburse all desired care costs,
therefore choices need to be made between interventions to prioritise
those that provide the best patient outcomes per unit of expenditure.
If investment is made in suboptimal treatments, then the benefits that
may have been obtained from alternative treatments that fall outside
the available budget are forgone. This ‘lost health’ is referred to as the
opportunity cost, defined as ‘the value of forgone benefit which could be
obtained from a resource in its next-best alternative use’. Fundamentally,
money that is spent on a certain intervention/treatment/drug cannot be
spent on something else.
In reality, healthcare systems are so complex that the opportunity cost is
typically not identifiable; that is, we do not know what other healthcare
intervention we may have displaced. Defining a perspective of the health
economic analysis is important as costs and benefits associated with
interventions can be narrowed down. The economic evaluation frame-
work quantifies the relevantly measured outcomes of specific health
interventions and balances them against the cost, from a predetermined
perspective of analysis (a societal or a national health system). With
such a framework, we can therefore minimise ‘waste’ by identifying and

116 Fallon et al.

exchanging treatments that may be of minimal benefit for more effec-
tive ones. The complexities above can be applied to nutrition in cancer
patients.

Measuring Economic Outcomes –

Potential Approaches
In the field of oncology, the importance of optimising nutrition is becom-
ing increasingly recognised. Many international guidelines advocate the
importance of nutritional assessment and interventions alongside sur-
gical and oncological treatments. However, there remains a paucity of
evidence to support nutritional interventions. In a bid to redress this, the
last decade has seen a rise in the number of oncology trials of nutritional
interventions.
Specifically, these have often focused on cancer cachexia: disease-
related malnutrition with systemic inflammation. Using lung cancer as
an example (where there are 50 000 cases in the United Kingdom [UK]
per year and, of these, approximately 20 000 have cachexia at diagno-
sis), the average patient incurs around £10 000 of secondary care costs
in their first year after diagnosis. Therefore, if successful, identifying
cachexia early in lung cancer has the potential to influence the care of
20 000 patients, and even a 25% reduction in costs associated with this
would save the National Health Service (NHS) £50 million annually.
To date, late-phase trials have assessed the efficacy of interventions
targeting appetite, muscle or combinations thereof, to prevent or treat
cachexia. Such studies have had varying measures of success; however,
with the potential for these therapies to enter routine oncology care, it is
critical that they are deemed to be cost-effective. Yet, inbuilt economic
evaluation of nutritional interventions in the field of oncology remains
the exception rather than the rule.

Cost-Benefit Analysis
Cost-benefit analysis (CBA) compares the costs and effects of inter-
ventions, placing a monetary value on health benefits. It is difficult to

Health Economics in Oncology Nutrition Research 117

determine how much value to put on ‘better appetite’ from an oncology
nutrition intervention, for example. However, results from CBA can be
used for resource allocation decision-making in different healthcare set-
tings. Cost-utility analysis (CUA) measures effects of interventions in
combined quantity and quality. If weight gains from nutritional interven-
tions enable cancer patients to better tolerate therapeutic interventions,
leading to extended days of life, quality-adjusted life year (QALY) is a
good outcome measurement in a trial. CUA studies are used routinely
to inform resource allocations across different healthcare settings, but
CUA does not include non-health effects (e.g. ability to work), which
can be a major drawback. The focus of cost-effectiveness analysis (CEA)
is the impact of interventions on the clinical outcome. Effects of inter-
ventions are measured in physical units (e.g. weight change, blood pres-
sure). Results from several CEA studies can be compared as long as they
employ the same outcome measurements (calorie intake or weight gain).
In contrast, budget allocations among different healthcare settings can-
not use the CEA results for decision-making.
The Consolidated Health Economic Evaluation Reporting Standards
(CHEERS) Task Force has developed a 24-item checklist of recommen-
dations which researchers should consider when designing trials which
have economic evaluation inbuilt. Specifically, model-based evaluation
(including primary and secondary care) considering potential risks/ben-
efits (e.g. survival advantage) may have relevance in oncology nutrition
trials. A key consideration here is value for money and, in the cancer
setting, where resources are finite in the face of increasingly expensive
therapies; this is critical. These approaches are being incorporated in
non-malignant trials but the principles are easily transferred to cancer.
Brown et al (2020) propose that data collection for economic evalua-
tion is prospectively planned alongside other assessments in randomised
nutrition trials. They argue that this will help inform decision-makers
about potential interventions to be implemented based on whether they
provide value for money, or not. The primary outcome of trials may be
of clinical interest and needs to be translated into health-related quality
measures to be used in economic evaluations. Collecting health-related
quality measures as a secondary outcome needs to be determined with a

118 Fallon et al.

consideration of characteristics of patients and interventions. Oncology
nutrition interventions for life extension can use the EuroQol 5 Dimen-
sion (EQ-5D) or the 36-Item Short Form Health Survey (SF-36). How-
ever, these health-related quality measurements are not sensitive enough
to record the possible changes made by interventions at the end of life.
The Palliative care Outcome Scale for Economic evaluations (POS-E)
based on the Integrated Palliative care Outcome Scale (IPOS) or ICECAP
Supportive Care Measure (SCM) have been suggested as alternatives.
It is also important to decide when to collect these outcome measures:
is the trial endpoint the most appropriate endpoint for the economic
evaluation?
This idea has been further conceptualised by O’Sullivan et al (2005).
Termed ‘piggyback’ evaluation, it involves health-economic data being
collected within the context of an otherwise typical clinical trial. The
authors highlight key design and potential limitations in conducting such
evaluations:
n Resource consumption in trials may differ from practice, and may not

resemble real-world practice

n Casefinding can occur due to monitoring requirements in trials

n Participant compliance is reinforced in trials

n Data are collected for intermediate health outcomes versus longer

term effects
These aspects present challenges for piggyback health-economic evalu-
ation in clinical trials; however, they can be addressed. One option is to
differentiate clearly between protocol costs and total costs. Casefinding
can be addressed through randomised approaches if a comparator arm
is present and even more so if blinding is included. However, one of the
main ways to attenuate limitations of piggyback evaluations in clinical
trials is to design studies that resemble clinical practice as much as pos-
sible. To illustrate, the control arm can be ‘standard care’ rather than any
specific ‘sham intervention’, allowing a direct assessment of economic
evaluation in as realistic a setting as possible.

Health Economics in Oncology Nutrition Research 119

Health Economics in Nutrition Research
In clinical nutrition, trial design is challenging for several reasons,
including the adjunct nature of nutritional interventions, stratification,
which is usually by disease rather than nutritional state, and the lack
of consensus on a nutrition trial control group. It has also been argued
that the key consideration is the choice of endpoints. Rather than using
the classical endpoints of a biomedical model (e.g. survival) or patient-
reported outcomes, a multi-component outcome model, where classical
and patient-reported endpoints are combined, may be used but is depend-
ent on study design and intervention.
Despite these observations, there remains a paucity of trials which
address nutritional interventions in the oncology setting. Therefore, the
practical application of nutritional evaluation in cancer nutrition trials
needs further elucidation. However, such work is possible. A recent
feasibility trial (Hall et al, 2021) examining an exercise and nutrition
intervention for people with advanced cancer included health-economic
analysis endpoints. This randomised trial with a standard-care control
arm incorporated real-life economic data including health professional
contact and hospital admissions. The analyses demonstrated that the
experimental arm (nutrition/exercise intervention) was less expensive
than the control arm. As such, should larger studies demonstrate efficacy
and the intervention be considered for clinical practice, cost-saving ten-
ets will support implementation in the clinic.
Another consideration is that the effect and objectives of a nutritional
intervention are different at different stages of the clinical pathway. Pre-
habilitation and on-treatment support are now common concepts based
on the theory that early identification and optimisation of nutritional sta-
tus will synergise with the curative or palliative treatments. Here a cost
per QALY endpoint is appropriate. Improved fitness for treatment will
generally increase treatment costs but decrease toxicity/complications
and related costs. At the other end of the spectrum is end-of-life care.
Here the objectives are not to extend life, therefore QALYs may not be
an appropriate outcome measure. Costs of care are borne by a mix of
agencies including primary and secondary healthcare services, the third

120 Fallon et al.

sector (e.g. government, insurance companies), family, social services
and the wider economy, for example where carers are taken out of the
workplace.
More effort (collecting additional data even at extra time points) and
resources (conducting economic analysis) can be challenging for cli-
nicians or researchers working in oncology nutrition. However, health
economics helps to cumulate evidence on the ‘value for money’ of nutri-
tional interventions in oncology, which is key to serving patients in need
and their families better. Developing guidelines or checklists for eco-
nomic evaluations in oncology interventions may come next.
When considering analyses, different approaches are applicable and will
be influenced by the stakeholder. Drug, device and food regulators will
look at the safety, efficacy and quality of manufacture, whereas health
technology assessors will evaluate efficacy and cost-effectiveness. This
contrasts with patients and carers, where patient-centred outcomes are of
most utility, while in routine clinical care, clinicians will value evidence-
based medicine. Industry stakeholders are most interested in profitability
and market access, whereas healthcare management will focus on budget
impact and compatibility with service configuration.
When assessing health economics in oncology nutrition trials, a combi-
nation of clinical-efficacy assessment with real-world studies is needed
to understand effectiveness. These should be embedded in the clinical
pathway using appropriate implementation models, variation in care and
outcomes. Such standards are achievable, but most importantly essential
to assess truly the impact of oncology nutritional interventions.

Further Reading
Arends J, Strasser F, Gonella S, et al; ESMO Guidelines Committee. Cancer
cachexia in adult patients: ESMO Clinical Practice Guidelines. ESMO Open
2021; 6:100092.
Arora C, Malhotra A, Ranjan P, Kumar A. Designing and conducting randomized
controlled trials: basic concepts for educating early researchers in the field of
clinical nutrition. Cureus 2021; 13:e17036.

Health Economics in Oncology Nutrition Research 121

Arthur ST, Noone JM, Van Doren BA, et al. One-year prevalence, comorbidities
and cost of cachexia-related inpatient admissions in the USA. Drugs Context
2014; 3:212265.
Brown V, Williams J, McGivern L, et al. Protocol for economic evaluation along-
side the SHINE (Supporting Healthy Image, Nutrition and Exercise) cluster
randomised controlled trial. BMJ Open 2020; 10:e038050.
Dzingina M, Higginson IJ, McCrone P, Murtagh FEM. Development of a patient-
reported palliative care-specific health classification system: the POS-E.
Patient 2017; 10:353–365.
EuroQol. EQ-5D. https://euroqol.org/eq-5d-instruments (24 May 2023, date
last accessed).
Hall CC, Skipworth RJE, Blackwood H, et al. A randomized, feasibility trial of
an exercise and nutrition-based rehabilitation programme (ENeRgy) in people
with cancer. J Cachexia Sarcopenia Muscle 2021; 12:2034–2044.
Husereau D, Drummond M, Augustovski F, et al. Consolidated Health Eco-
nomic Evaluation Reporting Standards 2022 (CHEERS 2022) statement:
updated reporting guidance for health economic evaluations. Clin Ther 2022;
44:158–168.
Jensen GL, Cederholm T, Correia MITD, et al. GLIM criteria for the diagnosis of
malnutrition: a consensus report from the global clinical nutrition community.
JPEN J Parenter Enteral Nutr 2019; 43:32–40.
Johannesson M, Jönsson B. Economic evaluation in health care: is there a role for
cost-benefit analysis? Health Policy 1991; 17:1–23.
Muscaritoli M, Arends J, Bachmann P, et al. ESPEN practical guideline: clinical
nutrition in cancer. Clin Nutr 2021; 40:2898–2913.
Mushkin SJ. Toward a definition of health economics. Public Health Rep (1896)
1958; 73:785–793.
National Cancer Registration and Analysis Service (NCRAS). https://www.
cancerdata.nhs.uk/ (24 May 2023, date last accessed).
Normand C. Measuring outcomes in palliative care: limitations of QALYs and the
road to PalYs. J Pain Symptom Manage 2009; 38:27–31.
O'Sullivan AK, Thompson D, Drummond MF. Collection of health-economic data
alongside clinical trials: is there a future for piggyback evaluations? Value
Health 2005; 8:67–79.
Robbins L. An Essay on the Nature and Significance of Economic Science. Lon-
don: MacMillian & Co. Limited, 1932.
Saygili M, Çelik Y. An evaluation of the cost-effectiveness of the different pal-
liative care models available to cancer patients in Turkey. Eur J Cancer Care
(Engl) 2019; 28:e13110.

122 Fallon et al.

Shizgal P. Scarce means with alternative uses: Robbins' definition of economics
and its extension to the behavioral and neurobiological study of animal deci-
sion making. Front Neurosci 2012; 6:20.
Solheim TS, Laird BJA, Balstad TR, et al. Cancer cachexia: rationale for the
MENAC (Multimodal-Exercise, Nutrition and Anti-inflammatory medication
for Cachexia) trial. BMJ Support Palliat Care 2018; 8:258–265.

Declaration of Interest:
Professor Fallon reports institutional funding for advisory board membership and
her work as local principal investigator from Pfizer, and institutional financial
support for a PhD student from Mentholatum.
Dr Yi reports personal speaker fees from MOGAM Institute for Biomedical
Research.
Dr Laird reports personal consultancy fees from Artelo and institutional funding
for scientific advisory board membership from Actimed, consultancy work from
Kyowa Kirin and an institutional research grant from Artelo.

Health Economics in Oncology Nutrition Research 123

Index
Note:
Abbreviations used in the index are listed on pages xvii-xix.
All entries pertain to cancer, unless specifically mentioned otherwise.
References to figures are indicated by page numbers suffixed by ‘f’.
References to tables are indicated by page numbers suffixed by ‘t’.

A Aerobic exercise, 19
Albumin, 49, 63
Actinomycin D, 62t Alcohol, 22–23, 89
Activity-induced energy expenditure cancer mortality-associated, 22, 91
(AEE), 15 Alpha-Tocopherol, Beta-Carotene
Acute phase reactants, 49, 53 Cancer Prevention Study, 99
Acute renal failure, 57 Altretamine, 60t
Adenosine triphosphate (ATP), 3 American Cancer Society, 18
Adipose tissue, 5 American Society of Clinical
chemotherapy-associated toxicity Oncology (ASCO), 49
prediction, 7 Amino acids, 4–6, 12
measurement, 7 branched-chain, 58, 74
normal body composition, 8t essential, 6, 74
reduction, stress starvation, 12 influence on metabolism, 6, 74
Advanced cancer Anabolism, 5, 6, 74
abnormal metabolism and wasting, Anamorelin, 49, 70
48 Anorexia (cancer), 12, 26, 49–50
exercise and nutrition intervention appetite stimulation, 4, 58
trial, 120 causes, 49–50
hydration, 72–73 neuropeptide Y and, 4, 80
muscle depletion, 48 nutritional support in, 70–71
nutritional support, 69–77, 103 in older adults, 80
general principles, 73–74, 74t see also Appetite
indications/situations, 70–71 Anorexigenic pathway, 4
initiation/withholding/withdrawal, Anthropometry, 8
72–73 ‘Anticancer’ diet, 15
ketones, role, 74–75 Anticancer drugs see Cancer treatment;
 see also Enteral nutrition (EN); Chemotherapy
Parenteral nutrition (PN) Antioxidants, 98, 100–101
refractory cachexia, 55 Appetite, 4
weight loss, 46, 47, 48 control, 4
see also End-of-life care

124
 mood relationship, 28–29 weight loss classification, 47f
poor/loss, in cancer, 28, 30, 32, 48, Body weight (BW)
49 eating relationship, 31
substances stimulating, 49, 53, 58 history-taking, 46
see also Anorexia (cancer); Food increased, cancer risk and, 18
intake loss see Weight loss
Arginine, 6 monitoring, by patients, 11
Artificial nutrition (AN), 72–73 nutritional requirements calculation,
L-Asparaginase, 60t 38
Associations, not implying causation, nutritional screening, 9
97–100, 98t resting energy expenditure
estimation, 15
see also Obesity
B Branched-chain amino acids (BCAAs),
BCNU (carmustine), 62t 58, 74
Bed rest, 5 Breast cancer
Behavioural change techniques, 30 alcohol-related, 22
Best supportive care, 69–70 dietary change impact on outcome, 92
Beta (β)-carotene, 97–99 dietary change impact on risk of, 20,
Beta-Carotene and Retinol Efficacy 90
Trial (CARET), 99 energy balance intervention trials, 93t
Bexarotene, 60t survivors, physical activity, 20
Bias, dropout, 102 Breast Cancer WEight Loss (BWEL)
Binge drinking, 22 trial, 93t
Bioimpedance analysis (BIA), 8 Busulfan, 60t
Bleomycin, 62t
Body compartments, changes, 8
Body composition C
assessment, 7–9, 11, 13 C-reactive protein, 10t, 11, 49, 63
estimated vs measured, 7, 8 Cachexia (cancer), 12, 49–50, 54, 73
in nutritional assessment, 11 cancer types, risk in, 80
regular measurement, 8–9 causes, 49–50, 73
Body fat, 18–19 communicating with family over,
Body image, 29 32, 33
Body mass index (BMI), 8, 9, 13, 54 definition, 12, 54, 73, 79, 117
cachexia diagnosis and, 55, 79 diagnosis, 79
cancer outcomes and, 90–91 distress related to, assessment, 29–30
cancer risk-associated, 18 emotional aspects, management, 30,
weight loss associated with 31
mortality, 47f, 69 inflammation in, 54, 73, 79, 80, 117

Index 125
 information/education about, 31, 33 physical activity, 19–20
in lung cancer, 117 plant food, 20
management, 49–50 processed meat avoidance, 21
clinical guidelines, 27 red meat reduction/levels, 21
home parenteral nutrition, 71 progression, diet reducing, 15
manifestations/criteria for, 55 risk
nutritional intervention trials, 117 caloric restriction reducing, 16
in older adults see Older patients dietary change impact, RCT, 89–90
with cancer risk factors, 18, 88
poor understanding about, 31 alcohol intake, 22, 23, 89
progressive nature, 79 body fatness/obesity, 18, 88–89
psychosocial consequences, 26 diet, 15, 20, 21, 88, 89
psychosocial help from energy balance and see Energy
professionals, 29–30 balance
refractory, 55 physical inactivity, 19, 88, 89
risk factors, 80–83, 81, 82t survivorship, energy balance in see
Cachexia syndrome, cancer, 26, 54 Energy balance
stages, 54–55 types associated with obesity, 88–89
Calf circumference (CC), 8 types associated with physical
Caloric intake inactivity, 89, 91
reduced in vegetarian diet, 20 see also specific cancer types
requirements, individualised dietary Cancer treatment, 53–68
counselling, 38, 43 cachexia risk factor in older adults,
target, 56f, 57 81t, 83
see also Energy, intake enteral nutrition indications, 63–64,
Caloric restriction, 94 65t
cancer growth impaired, 74 food impact on anticancer drugs,
reduced cancer risk, 16 59–61, 60t
Calorimetry, 3 nutrition as complement to, 41, 42
Cancer nutritional support during, 54–59,
cachexia see Cachexia (cancer) 70–71
disease-centred focus of care, 107  implementing guidelines see
mortality see Mortality, cancer Implementation science
outcomes, energy balance impact monitoring, 61–63
see Energy balance older adults, 82t, 84–85
preventable causes, 88 oral nutritional supplements
prevention, 18–25 (ONSs), 73–74
alcohol intake, reduction, 22–23  pharmaconutrients,
body fatness, reduction, 18–19 pharmacological agents, 58–59
dietary supplements, 23

126 Index
 nutritionally relevant adverse effects, Coffee, 89
62t Colon cancer see Colorectal cancer
parenteral nutrition indications, 64, Colon Health and Life-Long Exercise
66t, 67 Challenge (CHALLENGE) study,
see also Chemotherapy; 93t
Radiotherapy Colorectal cancer, 23
Cannabinoids, 58 dietary change reducing risk, RCT, 90
Capecitabine, 60t dietary fibre reducing risk, 20
Carbohydrates, 3, 18 energy balance intervention trials, 93t
eucaloric ketogenic diet, 75 psychosocial issues, 27
metabolism, 3, 4 risk, processed/red meat and, 21
Carbon dioxide, 3 selenium and, 101
Carboplatin, 60t, 62t survivors, physical activity benefit, 20
Carcinogens, dietary, 21 vegetarian diet reducing risk, 20
Carmustine (BCNU), 62t Colorectal polyps, 21
Carotenoids, 97–99 Committee on Herbal Medicinal
Catabolic crisis, 15 Products (HMPC), 98t
nutritional therapy during, 14, 15 Communication
Catabolic hormones, 4 culturally sensitive, 30–31
Center for Food Safety and Applied with family members, 32–34, 33t, 38
Nutrition (CFSAN), 98t indirect methods, 30
Chemotherapy before non-volitional feeding, 63
cachexia risk factor in older adults, Compliance, individualised nutrition,
81t, 83 38, 39–40
food impact on/interactions with, Computed tomography (CT), 7, 47
59–61, 60t Consolidated Health Economic
high-dose see High-dose Evaluation Reporting Standards
chemotherapy (CHEERS) Task Force, 118–119
muscle and fat catabolism, 49 Coping strategies, 30
side effects, 49, 50 Cost-benefit analysis (CBA), 117–119
see also Cancer treatment Cost-effectiveness analysis (CEA), 118
Chemotherapy with radiotherapy Cost-utility analysis (CUA), 118
parenteral nutrition indications, 66t Costs of care, 120–121
weight loss, 46 see also Health economics
Chlorambucil, 60t Counselling, nutritional see Nutritional
Chylomicrons, 5 counselling
Circadian rhythms, 16 CPT-11, 60t
Cisplatin, 62t, 83 Cultural aspects of nutrition, 26–37
Clinical nutritionist, 38, 40, 50 cachexia management, 27, 31

Index 127
 communicating with family balanced, 18, 23
members, 32–34, 33t cancer progression reduction, 15
communication to help patient, 30–31 cancer risk and, 15, 23, 88, 89
eating-related problems and help dietary change effect, RCT,
for, 29, 30, 31 89–90
factors affecting family carer role, 28 epigenetic alterations and, 94
humility, learning about patient, 31 eucaloric ketogenic, 75
information to dispel myths/ healthy, 18, 23, 27, 28
misunderstandings, 31 cancer survivorship and, 91
in older adults with cancer, 83 Mediterranean-style, 15, 89, 90
Cyclophosphamide, 62t, 83 older adults with cancer, 82t
Cytochrome P450 system, 59, 83 plant food, 20
Cytotoxic therapy see Chemotherapy prescribed, 40
PRO (problem, resources, outcome)
approach, 30
D processed/red meat, 21, 89, 91
Dacarbazine, 62t therapeutic, 40
Dactinomycin, 62t vegetarian, 20
Databases, 98t Diet and Androgens (DIANA-5) trial,
Decision-making, nutritional, 97–104 93t
association not implying causation, Diet-induced energy expenditure
97–100, 98t (DEE), 15
dropout bias, cautions, 102 Dietary Approaches to Stopping
evidence-based, nutritional support, Hypertension (DASH), 89
40, 40f Dietary counselling see Nutritional
importance of double-blind RCTs, counselling
99–100 Dietary fibre, 6, 20
missing data, misleading results, Dietary habits
102–103 pre-illness, maintaining, 28
resource allocation, cost-benefit see also Eating habits
analyses, 118 Dietary intake see Food intake
secondary outcomes, spurious Dietary patterns, 15–16, 39, 89–91
findings, 100–101 Dietary plan, 38
value for money basis, 118 Dietary Supplement Label Database
Dehydration, 6 (DSLD), 98t
Deming Cycle, 109 Dietary supplements, 23, 39, 58
Diabetes, type 2, 90, 92 Dietician, 38, 40, 50, 55, 103
Diet, 15–16 low numbers, cost aspects, 107
‘anticancer’, 15 Digestion, impaired, 12

128 Index
Direct calorimetry, 3 communicating with family on,
Disease-related malnutrition (DRM), 32–34, 33t
53, 54, 59 coping with, 29–30, 31–32
see also Malnutrition, cancer-related disagreements (family), managing,
Disease-related malnutrition with 31–32
inflammation, 12 Economics, 116
see also Cachexia (cancer) health see Health economics
Distress see Eating-related distress Educating patients/carers, 28, 30, 31, 50
Diuresis, 6 EFFORT study, 57
DNA hypermethylation, 94 Eicosapentaenoic acid (EPA), 58
Docetaxel, 60t, 62t Elderly patients see Older patients with
Docosahexaenoic acid (DHA), 58 cancer
Doxorubicin, 62t Electrolytes, 6, 60t, 82t
Dropout bias, 102 Electronic medical records (EMRs), 111
Drug interactions, with food, 59, 60t, 61 End-of-life care, 120
DTIC (dacarbazine), 62t artificial nutrition initiation/
Dual-energy X-ray absorptiometry withdrawal, 72–73
(DEXA), 7 hydration initiation/withdrawal, 72–73
parenteral nutrition, 64, 67
Energy, 3
E balance see Energy balance
Early-stage cancer deficiency, store loss, 11
energy balance and survivorship, expenditure, 3, 11, 14–15
90–91, 92 imbalance see under Energy balance
nutritional support, 54 intake, 4, 14, 37–38
nutritional support decision-making, during cancer therapy, 55, 57
40, 40f older adults with cancer, 84
parenteral nutrition, 50 production, 3, 4, 5
Eating habits requirements, 4, 11, 15, 43
changes due to cancer, 26, 27 calculation, 15
changing to reduce cancer risk, 89–90 individualised diet, 38, 39, 43
communicating with family about, older adults with cancer, 82t
32, 33, 33t simple starvation, 11
healthy, 18, 23, 27, 28, 89 stress starvation, 12
myths/misunderstandings, 31, 33t surgery/trauma increasing, 59
pre-illness, maintaining, 28 sources, 4, 5
see also Diet stores, normal, 8t
Eating-related distress, 28–29 Energy balance, 3, 14, 88–96
assessment, 29 cancer risk and, 88–90

Index 129
 interventional evidence, 89–90 nutritional assessment guidelines, 7,
mechanisms, 92, 94 53, 105, 106
observational evidence, 88–89 nutritional screening guidelines, 9, 53
cancer survivorship/outcomes, nutritional support, 49, 53, 59
90–92 in older adults, 82t, 84–85
interventional evidence, 92, parenteral nutrition indications, 66t
93t–94t European Society for Medical
observational evidence, 90–91 Oncology (ESMO), 7, 27, 42, 49
definition/description, 88 EuroQol 5 Dimension (EQ-5D), 119
imbalance, 11 Everolimus, 60t
avoidance, lifestyle changes, 94 Evidence-based decision-making, 40,
cancer risk mechanisms, 92, 94 40f
cellular regulation changes, 94 Evidence-based guidelines, 49, 51,
refractory cachexia, 55 105, 108
negative, undernutrition and, 11 adherence to, improving, 107–110
Enteral nutrition (EN), 56f, 57, 63–64 gaps in nutritional care in cancer,
in advanced cancer, 69 106–107
complications, 64 implementation, 105, 106, 108
contraindications, 64 poor uptake/adherence, 107, 108
in head and neck cancer, 64, 71 time lag, 106
in older adults with cancer, 82t see also Implementation science
parenteral nutrition vs, 74t nausea/vomiting management, 50
pros and cons, 74t Exercise see Physical activity
use and indications, 41, 50, 63–64, Exercise physiologists, 85
65t–66t Extra virgin olive oil (EVOO), 90
Epigenetic alterations, diet and, 94
Epirubicin, 62t
ERAS (enhanced recovery after
F
surgery) programme, 59 ‘Factory talk’, 31
Erlotinib, 60t Family, social aspects of eating, 26, 37
Essential amino acids, 6, 74 Family carers, 28, 32–34
Estramustine, 60t communicating with, 32–34, 33t, 38
Etoposide, 60t, 62t disagreements with patient, 28, 31
European Food Safety Authority, 98t managing, 28–29, 31–32
European Society for Clinical information on individualised diet, 38
Nutrition and Metabolism (ESPEN), mistaken ‘common sense’ beliefs,
49, 59 28, 32, 33t
enteral nutrition indications, 65t–66t pressure on patients to eat, 28, 32
individualised nutritional psychosocial issues related to
counselling, 42 nutrition, 28, 31–32

130 Index
 role, factors affecting, 28 nutritional assessment, 48
Family conflict, 28, 31–32 older adults, 81t, 84
Famine periods, 11 psychosocial factors, 27–28, 50
Fasting, energy production, 5 severe reduction, management, 57
Fat, dietary see Lipids specialist consultation and
Fat mass reserves, monitoring during support, 50
cancer treatment, 62 see also Nutritional assessment
Fatness, body, 3, 18–19 see also Nutritional intake
see also Obesity Food–drug interactions, 59, 60t, 61
Fatty acids, 5, 58 Force-feeding, 28, 33t
turnover, in cancer, 12 Frailty, 79, 85
FDA (Food and Drug Administration) Functional impairments, older adults
Adverse Event Reporting System with cancer, 83
(FAERS), 98t
Feeding, non-volitional see Enteral
nutrition (EN); Parenteral nutrition
G
(PN) G-8, screening in older adults, 84
‘Feel-good’ factors, 31 Gap analysis, 108–109
Fibre (dietary), 6, 20 Gastrectomy, 84
Fluorouracil, 60t, 62t Gastrointestinal toxicity, nutritional
Food support in, 70–71
aversion, 28, 38 Gefitinib, 60t
fortification, 57, 82t Geriatric assessment (GA), 84
impact on anticancer drugs, 59, 60t, Ghrelin receptors, 49
61 GLIM criteria, 10, 10t
refusal, 28 Global Leadership Initiative on
texture, modification, 57 Malnutrition (GLIM), 10, 10t
Food frequency questionnaire, 38 Gluconeogenesis, 4, 5, 12
Food intake, 3 Glucose, 4
adequacy and importance, 37–38 metabolism, 4
choice, comfort through eating, 28 normal (blood), 8t
energy and protein deficiency, 11 requirements, in cancer, 12
individualised dietary counselling, tolerance impairment, 53
38, 43 Glycogen, 3, 8t
nutritional screening, 9, 83–84
organic, PRO (problem, resources, H
outcome) stories and, 30 Haematopoietic stem cell
reduced in cancer, 4, 12, 39t, 43, 48, transplantation
50 enteral nutrition indications, 65t–66t
monitoring/demonstrating, 61 parenteral nutrition indications, 66t

Index 131
Head and neck cancer, enteral Hounsfield units, 7
nutrition, 64, 71 Hydration, of imminently dying
Head and Neck Patient Symptom patients, 72–73
Checklist, 48 Hyperglycaemia, 12, 92
Health budget, 116 Hyperketonaemic glucose deprivation,
Health economics, 115–123 75
analyses for different stakeholders, Hypermetabolism, 15
121 Hypodermoclysis, 73
cachexia in lung cancer, Hypothalamus, 4
interventions, 117
concepts/dimensions, 115–116
cost-benefit analyses, 117–119
I
data collection, 118 i-PARIHS framework, 109
definition, 116–117 Imatinib, 60t
measuring economic outcomes, 117, Immune-modulating oral/enteral
119 formulae, 59
in nutrition research, 120–121 Immune response, arginine role, 6
piggyback evaluations, 119 Immunotherapy, cachexia in older
purpose, 116 adults, 83
value of healthcare, 115–116, 121 Implementation science, 105–114
Health-related quality measures, barriers and facilitators,
118–119 identification, 107, 108, 109, 110
Healthcare, value of, 115–116, 121 definition, 108
Healthcare resources, value of, 116 evaluating or designing, 108–109
Healthy Eating Index, 89 facilitation phases, 109
Helplessness, sense of, 26 gap analysis, 108–109
Herbal supplements, 59 i-PARIHS framework, 109
Hexoses, 4 implementation plan, 109, 110, 112
High-dose chemotherapy mistakes preventing success, 110
enteral nutrition indications, 65t–66t nutritional care as part of cancer
parenteral nutrition indications, 66t care, 110–112
Histone acetylation, 94 goal/outcome, 110
HMB (beta-hydroxy-beta- ladder/steps, 111–112, 111f
methylbutyrate), 6 resources for, 110, 111
Hormones strategies and key recipients,
cancer risk-associated, 19, 92 111–112, 111f
catabolic, 4 outcome measures, 108
energy imbalance and, 92 planning the process of change, 108,
physical activity and, 19 109, 112
sex-steroid, 19, 92, 94 rationale for using, 107–110

132 Index
Incurable cancer, nutritional support International Agency for Research on
in, 70, 71 Cancer (IARC), 88–89
Indirect calorimetry, 3, 15 Intestinal microbiota, 6, 42
Individualised nutritional counselling Intestinal resection, 84
see Nutritional counselling, Intravenous fluids, 73
individualised Irinotecan, 60t, 62t
Inflammation/inflammatory response, 53 Iron-deficiency anaemia, 85
assessment, 11, 49, 63 Iso-osmolar fluids, 73
in cachexia, 12, 54, 73, 79, 80, 117 Isotonic balanced solutions, 73
see also Cachexia (cancer)
chronic low-grade systemic, 92
decreasing, energy imbalance
K
avoidance, 94 Ketogenic diet, eucaloric, 75
dietary supplementation in, 58 Ketone bodies, 11, 12
effects/impact (metabolic) of, 6, 12, Ketones, 74–75
53 Knowledge transfer, 108
insulin resistance and anorexia, 12, 92
measurement in nutritional
assessment, 11
L
N-nitroso compounds, processed Lean body mass, 12
meat and, 21 Leucine, 6, 74
omega-3 fatty acid modulating, 5 Licensed Natural Health Products
overweight and cancer risk Database (LNHPD), 98t
associated, 19, 92 Lifestyle, healthy, 20, 94
phytochemicals reducing, 20 healthy eating/balanced diet, 18, 20,
in stress starvation, 12 23, 27, 28
water/sodium retention, 6 physical activity, 19
weight loss associated, 48, 54, 55 recommended long-term changes, 15
 see also Cachexia (cancer); Lifestyle Intervention for Ovarian
Cachexia syndrome Cancer Enhanced Survival (LIVES)
Inflammatory cytokines, 4, 80 study, 93t
Information overload or confusion, Lipids, 3, 4–5
27, 28 emulsification, 4–5
Insulin, 4 eucaloric ketogenic diet, 75
resistance, 12, 53, 92 inflammatory response modulation, 5
Insulin-like growth factor 1 (IGF-1), 92 metabolism, 4–5, 74
Intense Exercise for Survival stores, 8t
among Men with Metastatic Lomustine, 62t
Castrate-Resistant Prostate Cancer Long-chain fatty acids, 5
(INTERVAL-GAP4), 94t Look AHEAD trial, 90

Index 133
‘Lost health’, 116 see also Nutritional screening
Lung cancer severe
beta (β)-carotene association, 97–99 incurable cancer, nutritional
cachexia, 117 support, 71
selenium and, 101 protein metabolism, 5
therapy-related, 53
Malnutrition screening tools, 48
M Meat
Macronutrients, 3, 18 processed, 21, 89, 91
metabolism, 4–6 red, 21, 89, 91
requirements during cancer therapy, Mechlorethamine hydrochloride, 62t
55, 57 Mediterranean diet, 15, 89, 90
see also Carbohydrates; Lipids; Melanoma, malignant, 6
Protein Melphalan, 60t, 62t
Magnesium, 6, 60t, 83, 85 Men, alcohol-related cancer, 22
Magnetic resonance imaging (MRI), 7 Metabolism
‘Malignant (sub)obstruction’, 71 abnormal, wasting due to, 48
Malnutrition, cancer-related, 13, 46, 51 macronutrients, 4–6
causes, 39t, 49–50, 53 micronutrients, 4–6
definition, 13, 78 Metastatic disease
diagnosis, 9–11, 46, 78–79 abnormal metabolism causing
disease-related (DRM), 53, 54, 59 wasting, 48
low phase angle (PhA), 8 see also Advanced cancer
management, 49–50, 51 Methotrexate, 60t, 62t, 83
 individualised nutritional Micelles, primary, and secondary, 4, 5
counselling, 41, 43 Microbiota, intestinal, 6, 42
nutritional support in, 70–71 Micronutrients
older adults with cancer, 84–85 deficiency, after surgery, 84–85
specialist consultation and intake, vegetarian diet and, 20
support, 50 metabolism, 4–6
mortality risk, in older adults, 79 recommended daily intake, 13
muscle mass loss, 47 requirements, 12–13, 56f
in older adults with cancer older adults with cancer, 84–85
management, 84–85 supplements, impact on anticancer
prevalence and mortality, 79 drugs, 59
screening/assessment, 81t, 83–84 Mood, appetite relationship, 28–29
prevalence, 79, 105 Mood disorders, 83
prognosis related to, 53–54, 79 Mortality, cancer
screening, 48, 106 alcohol intake associated, 22, 91
diet impact, 91

134 Index
 muscle mass loss associated, 47, 69 N
obesity increasing risk, 90–91
in older adults with cancer, 79 Nasogastric tube feeding, 63, 64
physical activity impact, 91 Natural Medicines database, 98t
weight loss and poor food intake, 69 Nausea and vomiting, 50
Mucositis, 62t, 63 cancer drugs causing, 62t
Multinational Association of Neuropeptide Y, 4, 80
Supportive Care in Cancer Nitrates, in processed meats, 21
(MASCC), 27 Nitrogen balance, 5
Muscle N-Nitroso compounds, 21
assessment, 7 Non-steroidal anti-inflammatory drugs
during cancer treatment, 62 (NSAIDs), 58
catabolism, therapies associated, 49 Nutrients
changes, chemotherapy toxicity balance, measurement, 10
prediction, 7 classes, 18
contraction, anabolism induction, 5 Nutrition
degradation, stress starvation, 12 basic concepts, 3–17, 18
function assessment, 55 psychosocial issues see
protein depletion, in disease-related Psychosocial aspects of nutrition
malnutrition (DRM), 54 Nutrition impact symptoms, 49, 81t
wasting, 4, 48, 49, 54, 55 Nutrition plan, individualised, 56f, 57
abnormal metabolism causing, 48 Nutrition research, 97
cachexia, in older adults, 79 association does not imply
 see also Cachexia (cancer); causation, 97–100, 98t
Malnutrition, cancer-related; health economics in, 120–121
Muscle mass, loss see also Randomised controlled
Muscle mass, 5, 7, 12 trials (RCTs)
calf circumference predictor of, 8 Nutrition science, knowledge limited,
fat infiltration, 7 107
loss, 48, 54 Nutritional advice, 31
cachexia diagnosis, 79 Nutritional assessment, 9–10, 38, 53,
guidelines for management, 49 56f, 105, 106
malnutrition criterion, 47, 54 definition and protocol, 9–10
mortality association, 47, 69 domains, 10–11
in obese patients, 48 early, guidelines, 7
stress starvation, 12 GLIM criteria, 10, 10t
see also Muscle, wasting malnutrition diagnosis, 9–10, 38,
measurement, 7 39t, 53, 56f, 105
Mustine hydrochloride, 62t monitoring/repeated measurement, 11
Myosteatosis, 7 nutritional status estimation, 7, 8–9

Index 135
 older adults with cancer, 81t, 83–84 older adults with cancer, 81t, 83–84
for reduced food intake, 48, 50 poor compliance with, 106, 107
Nutritional care see Nutritional Nutritional status, 46–52
support/therapy assessment/evaluation, 7, 8–9,
Nutritional counselling, individualised, 46–49, 53
37–45, 50, 55, 57 weight loss grading, 46–47, 47t
assessment for, 38, 39t, 43 see also Nutritional assessment
benefits, 41–42, 43 cancer anorexia/cachexia
compliance with recommendations, management, 49–50
38, 39–40 impaired, complications/outcomes, 54
decision-making process, 40, 40f importance in cancer treatment, 106
description, 37–38, 39, 41 older adults with cancer, 81t, 83
factors to consider, 40 preoperative, outcome, 58
as first choice of support, 43 Nutritional support/therapy, 12, 14, 40,
goals, 39–41 53–54
integration with treatment, 40 in advanced cancer see Advanced
intensive, 42 cancer
in older adults with cancer, 82t algorithm, 55, 56f
research and outcomes, 41 during best supportive care, 69–70
Nutritional decision-making see during cancer treatment, 41, 54–59,
Decision-making, nutritional 55f
Nutritional intake implementation of guidelines,
individualised dietary counselling, 110–112
37–38, 39, 41 monitoring, 61–63
qualitatively/quantitatively poor integration/use, reasons,
appropriate, 14 106–107
see also Food intake see also Implementation science
Nutritional requirements (adults), 14–15 consideration of malnutrition causes
individualised dietary counselling, 38 for, 12
Nutritional research see Nutrition cost, 103
research definition/therapy types included, 14
Nutritional risk, delay/failure of early initiation, 54
anticancer treatment, 55 effect/objectives at different clinical
Nutritional Risk Screening 2002 stages, 120
(NRS-2002), 53 in end-of-life phase, 64, 67, 103
Nutritional screening, 9, 56f, 106 enteral nutrition see Enteral nutrition
description, 9 (EN)
implementing better routines for, general principles, 73–74
105, 106, 109 goals/aim, 14, 37, 54
see also Implementation science health economics, 119, 120

136 Index
 inconsistent outcome data, 106 malnutrition prevalence, 79, 80
indications, 41, 70–71 management, 78
individualised, 41, 55, 57 nutritional impairment
older adults with cancer, 82t management, 78, 82t, 84–85
oral nutrition, 14, 40, 41, 56f, 57, 73 micronutrient deficiency, 84–85
goal, 14, 57 risk/risk factors, 80, 81t
as preferred route, 14, 37, 56f, 57, nutritional needs, 78
73 nutritional screening/assessment, 79,
 see also Oral nutritional 81t, 83–84
supplements (ONSs) Omega-3 fatty acids, 5, 58, 70
parenteral nutrition see Parenteral cancer-associated weight loss
nutrition (PN) treatment, 102
recommended long-term lifestyle supplementation, 5
changes, 15 Opportunity cost, 116
side-effects, databases, 98t, 103 Oral mucositis, 62t, 63
see also Nutritional counselling, Oral nutritional supplements (ONSs),
individualised 39, 41, 43, 57, 58
in advanced cancer, 70, 71, 73
indications, 39, 43, 73–74
O liquid formulae, 70
Obesity, 13, 18–19, 54 in older adults with cancer, 84
cancer outcomes and, 90–91 randomised controlled trials (RCTs)
cancer risk and, 18–19, 88 and outcomes, 70–71
cancer types associated, 88–89 timing of use, 70
muscle mass loss in cancer patients, Oral nutritional support see Nutritional
48 support/therapy
sarcopaenic, 13 Organic foods, 30
weight loss, 19, 54 Ovarian cancer, energy balance
in cancer patients, 47 intervention trials, 93t
Observational studies, misleading Overnutrition, 13
results, 97–99, 99–100 Overweight, 18–19, 54
Older patients with cancer, 78–87 see also Obesity
cachexia diagnosis/prevalence, 79 Oxygen, 3
cachexia risk factors, 80–83
age-related, other factors, 83
cancer-related, 80 P
treatment-related, 83 Paclitaxel, 83
cancer types, cachexia risk, 80 Pain, cancer-related malnutrition and,
frailty, and adverse outcome, 79 49, 50
malnutrition diagnosis, 78

Index 137
Palliative care Outcome Scale for increased, cancer risk reduction, 90
Economic evaluations (POS-E), 119 low levels, cancer risk association,
Parenteral nutrition (PN), 41, 50, 57, 19, 88, 89
64, 67 muscle mass and, 5
administration methods, 66t recommended levels, 19
in advanced cancer, 69, 71, 72, 74 reduction, in simple starvation, 11
enteral nutrition vs, 74t Physical inactivity, cancer risk and, 19,
home, 64, 71 88, 89
goal, 72 Physical performance
indications, 71, 72 grading, 61
survival with, 71, 72f monitoring during cancer treatment,
withdrawal, 73 62
impact on survival, 69–70, 71 Phytochemicals, 20
indications, 41, 50, 56f, 57, 64, 66t, 74 ‘Piggyback’ evaluation, 119
long-term, 64 Plan-Do-Study-Act model, 109
pros and cons, 74t Plant food, cancer prevention and, 20
short-term, 64 Plicamycin, 60t
Patient-adapted intervention plan, 56f, 57 Polyunsaturated fatty acids (PUFAs), 5
Patient-centred care approach, 106, 107 see also Omega-3 fatty acids
Patient-Generated Subjective Global Positron emission tomography (PET),
Assessment (PG-SGA), 53 75
Patient-reported outcome measures Potassium, 6
(PROMs), 107 Pre-cachexia, 55
Pemetrexed, 83 Prealbumin, 63
Percutaneous endoscopic gastrostomy Prevención con Dieta Mediterránea
(PEG), 63–64 (PREDIMED) trial, 90
Pharmacological therapy, 39, 58–59 Prevention of cancer see Cancer,
cachexia management in older prevention
adults, 82t PRO (problem, resources, outcome)
Pharmaconutrients, 58–59 approach, 30, 31–32
Phase angle (PhA), 8 Procarbazine, 60t
Phosphate, 6 Processed meat, 21, 89, 91
Physical activity, 6, 19–20 Progesterone analogue, 49
in cancer patients, 19–20, 57, 74 Prognostic factors, 63
 all-cause/cancer-specific Prostate cancer
mortality, 20, 91 energy balance intervention trials, 94t
overweight patients, 54 selenium and, 101
for cancer survivors, 19–20 survivors, physical activity, 20

138 Index
Protein, 5–6 Q
accumulation, 3
balance, 3, 55 Quality-adjusted life year (QALY),
deficiency, 11 118, 120
intake Quality of life (QoL)
high level, in disease-related eating-related problems, impact, 29
malnutrition, 54 home parenteral nutrition and,
 individualised dietary 72–73
counselling, 40, 41, 43 individualised dietary counselling,
older adults with cancer, 82t, 84 37
target, 56f, 57 measurement, 61
metabolism, 5–6 nutrition as key determinant, 42
normal body composition, 8t psychosocial factors affecting,
prescribing high-intake/high-protein 28–29
foods, 41, 54 Questionnaires, 38, 61
requirements, 5, 38, 43, 56f, 57
in older adults with cancer, 82t, 84 R
surgery/trauma increasing, 59
Radiotherapy
Psychosocial aspects of nutrition,
chemotherapy with see
26–37, 57
Chemotherapy with radiotherapy
choice of foods, 28
enteral nutrition indications, 65t
communicating with family
nutritional complications, 62t
members, 32–34, 33t
weight loss and, 46–47
eating-related distress, 28–29
see also Cancer treatment
coping with, 31–32
Randomised controlled trials (RCTs),
family carer, factors affecting role
107, 117
of, 28, 32
advanced cancer patients dropping
help from healthcare professionals,
out, 102
29–30
associations do not imply causation,
information overload or confusion,
99–100
27, 28
beta-carotene and lung cancer, 99
issues in cancer, 27–29
design, economic evaluation in, 118,
obstacles to seeking help, 29
120
oral intake, factors affecting, 27–28,
economic evaluation of nutritional
50
interventions, 117, 119, 120
quality of life and, 28–29
endpoints, choice of, 120
Psychosocial consequences, of
issues to consider in decision-
cachexia, 26
making, 98t
Psychosocial interventions, 29–30

Index 139
 missing data (drop out of patients), Small bowel obstruction, 71
102 Smoking, 22
managing, 102–103 Social aspects of meals, 37
multi-component outcome model, 120 see also Psychosocial aspects of
paucity for nutritional interventions nutrition
in cancer, 120 Social support, older adults with
secondary endpoints, interpretation, cancer, 82t, 85
100–101 Sodium, retention, acute stress, 6
selenium and skin cancer, 100–101 Starvation
study design issues, 102–103 simple, 11
see also specific trials stress, 12
Refeeding, after starvation, 6 Storytelling, 30
Refeeding syndrome, 6, 57 Streptozocin, 62t
Research see Nutrition research Stress
Resistance training, 19–20 acute, water/sodium retention, 6
Resource allocation decision-making, glucose metabolism, 5
cost-benefit analysis, 118 Stress starvation, 12
Resting energy expenditure (REE), 11, SUCCESS C trial, 93t
14, 15 Sunitinib, 60t
Retinol, 99 Supplements
Risk factors, for cancer see Cancer concerns about doses, 99–100
concerns over rationale for
administering, 100
S high-dose, concerns, 99, 100, 103
Sarcopenia, 6, 7, 55, 79 oral nutrient see Oral nutritional
management, 85 supplements (ONSs)
in obesity, 13 Supportive care, cachexia
progressive nature, 79 management, 27
Satiety, early, 26, 70 Surgery, cancer, 58, 83
Sedentary lifestyle, 19, 88, 89 ESPEN guidelines, 59
SELECT trial, 101 micronutrient deficiency, 84–85
Selenium, 100–101 Survival, prediction, by body mass
Selenium and Vitamin E Cancer index (BMI) and weight loss, 9
Prevention Trial (SELECT), 101 Survivorship (cancer) and energy
Sex-steroid hormones, 19, 92, 94 balance see Energy balance
Shewhart Cycle, 109 Swallowing difficulties, 63
Short Form Health Survey (SF-36), Symptom management, 49–50
119
Skin cancers, selenium and, 100–101

140 Index
T VP-16 (etoposide), 60t, 62t
Tamoxifen, 60t
Targeted therapy, muscle and fat W
catabolism, 49 Wasting see Muscle, wasting
Temozolomide, 60t Wasting syndrome see Malnutrition,
Therapy-related malnutrition, 53 cancer-related
Thioguanine, 60t Water
Topotecan, 60t intake, 6
Total energy expenditure (TEE), 14, 15 retention, 6
Trace elements, 12–13 Weight, body see Body weight (BW)
decrease in disease, 13 Weight gain, 31
supplementation, 13 Weight loss (non-volitional), 28, 46
Treatment toxicity, reduced by dietary advanced cancer, 46, 47, 48
counselling, 42 cachexia, 54, 55, 79
Tretinoin, 60t cancer-associated malnutrition, 46, 54
Triglycerides, 4, 5 cancer types-associated, 46
Tube feeding see Enteral nutrition (EN) communicating with family about,
32, 33, 33t
U concerns over dying, 28, 34
culturally sensitive communication
Ultrasound, 7 about, 30
Undernutrition, 11–12 drivers/mechanisms, 48
inappropriate self-management, 32 future risks, evaluation, 46–47
prevention, nutritional therapy goal, grading/classification, 46, 47f
14 inflammation association, 48, 54,
55, 79
V monitoring for, 11
myths and misunderstandings,
Value, of healthcare, 115–116
dispelling, 29, 31
Value for money, 118, 121
nutritional assessment, GLIM
Vegetables, cruciferous, 20
criteria, 10t
Vegetarian diet, 20
nutritional screening, 9
Vinblastine, 62t
in obese cancer patients, 29, 47
Vitamins, 12–13
omega-3 fatty acid trial and dropout
deficiency, older adults with cancer,
bias, 102
85
perceived social benefits and, 29
intake, vegetarian diet and, 20
pre-cachexia, 55
vitamin E, SELECT trial, 101
as prognostic factor, 9, 47, 69

Index 141
 progressive, evaluation, 46, 47f
as proxy for nutritional status
deterioration, 9
refractory cachexia, 55
Weight loss (volitional)
cancer risk reduction, 90
in obesity, 19, 54
Whipple procedure, 85
Wine, red, 22
Women, alcohol-related cancer, 22
Women’s Health Initiative Dietary
Modification Trial (WHIDM),
89–90
Women’s Healthy Eating and Living
(WHEL) study, 92
Women’s Intervention Nutrition Study
(WINS), 92
World Cancer Research Fund
(WCRF), 88, 89
World Health Organization (WHO),
21, 61

142 Index
 ESMO HANDBOOK OF
www.esmo.org

NUTRITION AND CANCER

ESMO HANDBOOK OF
NUTRITION AND CANCER
Edited by Aminah Jatoi, Stein Kaasa and Michiel Strijbos 2N D ED I TI O N

The second edition of the ESMO Handbook of Nutrition and Cancer

brings together dozens of experts from around the world to update
clinically important topics on the interface between nutrition and
cancer. Chapters cover the basic concepts of nutrition to the health
economics of nutrition, with numerous pertinent topics in between.
The tremendous effort that went into this fully revised edition is
intended to provide clinicians with the latest knowledge as they
provide state-of-the-art nutritional education to patients with cancer,
to those at risk for cancer, or to those with a history of cancer.

2ND EDITION
ESMO Press
ESMO HANDBOOK OF
ESMO Handbook Series
ISBN 978-88-944465-6-2

NUTRITION AND CANCER

ISBN 978-88-944465-6-2

9 788894 446562 Edited by Aminah Jatoi, Stein Kaasa and Michiel Strijbos 2N D ED I TI O N
[ S A M P LE B A R C O D E ]

ESMO Handbook Series

European Society for Medical Oncology
Via Ginevra 4, 6900 Lugano, Switzerland www.esmo.org ESMO Handbook Series

ESMO_handbook_nutrition.indd 1 05/06/2023 10:19