Psycho-Oncology 4th Edition William

Breitbart (Editor)
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Psycho-​Oncology
Psycho-​Oncology
FOURTH EDITION

EDITED BY

William S. Breitbart, MD, FAPOS

Phyllis N. Butow, BA(Hons), DipEd, MClinPsych,
MPH, PhD
Paul B. Jacobsen, PhD
Wendy W. T. Lam, RN, PhD, FFPH
Mark Lazenby, APRN, PhD
Matthew J. Loscalzo, MSW, LCSW, FAPOS

1
3
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Library of Congress Cataloging-in-Publication Data
Names: Breitbart, William S., 1951– editor.
Title: Psycho-oncology / [edited by] William S. Breitbart, Phyllis N. Butow, Paul B. Jacobsen, Wendy W. T. Lam,
Mark Lazenby, Matthew J. Loscalzo ; senior editor, William Breitbart.
Other titles: Psycho-Oncology (Holland)
Description: 4th edition. | New York, NY : Oxford University Press, [2021] |
Includes bibliographical references and index.
Identifiers: LCCN 2020029603 (print) | LCCN 2020029604 (ebook) |
ISBN 9780190097653 (hardback) | ISBN 9780190097677 (epub) | ISBN 9780190097684
Subjects: MESH: Neoplasms—psychology | Risk Factors | Neoplasms—prevention & control |
Neoplasms—therapy
Classification: LCC RC262 (print) | LCC RC262 (ebook) | NLM QZ 260 |
DDC 616.99/40019—dc23
LC record available at https://lccn.loc.gov/2020029603
LC ebook record available at https://lccn.loc.gov/2020029604
DOI: 10.1093/​med/​9780190097653.001.0001
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Dedication: Jimmie C. Holland, M.D. (1928–2017)
Psycho-​Oncology, 4th edition is solemnly dedicated to Professor Jimmie C. Holland, MD (1928–​2017), internationally recognized as the founder
of the field of psycho-​oncology. Dr. Holland, who was affectionately known by her first name, “Jimmie,” had a profound global influence on the
fields of psycho-​oncology, oncology, supportive care, psychiatry, behavioral medicine, and psychosomatic medicine. At the time of her passing,
Dr. Holland was the Attending Psychiatrist and Wayne E. Chapman Chair at Memorial Sloan Kettering Cancer Center (MSK) and Professor of
Psychiatry, Weill Medical College of Cornell University in New York.
In 1977, Jimmie was appointed Chief of the Psychiatry Service in the Department of Neurology at MSK, by Jerome Posner, MD, then Chairman of
Neurology at MSK. The Psychiatry Service at MSK was the first such clinical, research, and training service established in any cancer center in the
world. In 1996, Dr. Holland was named the inaugural Chairwoman of the Department of Psychiatry and Behavioral Sciences at MSK—​again,
the first such department created in any cancer center in the U.S. or the world. Dr. Holland had over a 40-​year career at MSK.
Jimmie created and nurtured the field of psycho-​oncology, established its clinical practice, advanced its clinical research agenda, and, through
her pioneering efforts, launched the careers of the leaders of a worldwide field who continue to work in what has become a shared mission to em-
phasize “care” in cancer care. Dr. Holland founded the International Psycho-​Oncology Society (IPOS) in 1984 and the American Psychosocial
Oncology Society in 1986. Over 25 years ago, Jimmie founded the international journal Psycho-​Oncology and coedited the journal for 30 years.
Dr. Holland received many awards recognizing her achievements over the course of her career. Some of her notable awards include the Medal
of Honor for Clinical Research from the American Cancer Society, the Clinical Research Award from the American Association of Community
Cancer Centers, the American Association for Cancer Research Joseph H. Burchenal Clinical Research Award, the Marie Curie Award from the
Government of France, the Margaret L. Kripke Legend Award for contributions to the advancement of women in cancer medicine and cancer
science from the MD Anderson Cancer Center, the T. J. Martell Foundation 2015 Women of Influence Award, and the Distinguished Alumnus
Award from Baylor College of Medicine in 2016. She served as President of the Academy of Psychosomatic Medicine (APM) in 1996 and was the
recipient of the APM’s Hackett Lifetime Achievement Award in 1994. She was the inaugural recipient of the Arthur Sutherland Award for Lifetime
Achievement from IPOS.
This 4th edition of Psycho-​Oncology is the first edition of this text that has not been edited by Dr. Holland. In 1989, Dr. Holland edited the
Handbook of Psychooncology: Psychological Care of the Patient with Cancer, the first major textbook in our field. This landmark book was no-
table for several reasons; it established our “new” field, and it was the first use, in a text, of the term “psychooncology” to name our field (thankfully
the hyphen was soon added). Psycho-​oncology was thus born and named with the publication of this textbook. Subsequently, Dr. Holland edited,
with a group of dedicated coeditors, several editions of what became known as the “Bible” of psycho-​oncology or, in many circles, the “Holland
Textbook of Psycho-​oncology.” The textbook Psycho-​Oncology was published in 1998 and represented the most comprehensive, multidiscipli-
nary, and international encyclopedia of a field entering its adolescence. The year 2010 saw the publication of the 2nd edition, followed by the 3rd
edition in 2015, both published by Oxford University Press in collaboration with IPOS and APOS. Every card-​carrying “psycho-​oncologist” in
over 60 countries with national psycho-​oncology societies around the world had to have the latest edition in their library. For many it represented
a valued link to Jimmie Holland. The task of editing this 4th edition of Psycho-​Oncology without Jimmie’s firm guidance and wise counsel was
daunting for all of us, but we were all deeply inspired to do so because of our loving debt to Jimmie. The torch has been passed.
Dedication: Ruth McCorkle, PhD, RN, FAAN (1941–​2019)
In January 1975, a 33-​year-​old Ruth McCorkle, a newly minted PhD from the University of Iowa and a new assistant professor at the University of
Washington, met Jimmie C. Holland at a conference on the behavioral dimensions of cancer that was organized by the National Cancer Institute
in San Antonio, Texas. This meeting began a lifelong friendship and collaboration, not least of which was this book.
Ruth McCorkle died on August 17, 2019, in her home in Hamden, CT, from cancer. At the time of her death, she was the Florence Schorske Wald
Professor of Nursing Emerita at Yale University.
From the earliest days of her career, Ruth was interested in the lived experiences of people diagnosed with cancer, including the effects of touch on
the seriously ill and how the attachments and goals of patients undergoing treatment for lung cancer—​and their families—​changed over time. At
the University of Washington, she and Jeanne Quint-​Benoliel developed the first multidisciplinary cancer unit in which patients and their families
would be seen from the time of diagnosis through the dying experience by an interprofessional team.
It was on this unit, in the mid 1970’s, that she developed the first scale that measured the distress cancer patients experienced, the Symptom
Distress Scale. As a student of history, she learned of how Sir William Osler had taken field notes on his dying experience, in which he wrote that,
because he had “no actual pain,” he felt “singularly free from mental distress” as he was dying. In the early 1970’s, when Ruth had gone to London
to study with Dame Cicely Saunders at St. Christopher’s Hospice, she was introduced to the British psychiatrist J. M. Hinton and his now justly
famous qualitative work on associations between dying patients’ physical and mental distress. From Saunders and Hinton, and from Osler’s field
notes, Ruth began to see that patients’ mental distress could be related to their physical symptoms. She thus became interested in the points at
which a physical symptom becomes emotionally unbearable. Hence, her scale measured the presence of a symptom as well as how distressed a
patient was by it. The development of the Symptom Distress Scale led to her intervention.
She developed and tested in 7 National Institutes of Health-​funded clinical trials the Standardized Nursing Intervention Protocol, an intervention
in which an advanced practice cancer nurse helped patients and families learn to manage distressing symptoms. In a breakthrough, one of those
trials resulted in a 7-​month survival benefit.
We will read much about distress in this 4th edition of Psycho-​Oncology. For the importance of identifying and intervening on the sources of
cancer patients’ distress—​and even for the presence of the word “distress” in the psycho-​oncologic lexicon—​we have Ruth—​and Jimmie—​to thank.
Ruth ended the last article she wrote with this: “. . . patients’ physical needs must be addressed before their psychosocial problems are identified. It
is not just about taking care of their physical needs first. Rather, it is that we may be creating distress by not doing so.” Over the last 6 weeks of her
life, she instructed her hospice care providers on how to manage her physical needs, and her close friends and family provided the physical touch
she knew would comfort her emotionally. In this experience, one can find the truth of Ruth’s entire scientific career.
In this 4th edition of Psycho-​Oncology, you will find this truth woven into the science the book reports on: For Ruth, psycho-​oncology was not
just about how to support patients and families living with cancer. It was also about enabling them to have deaths “singularly free from mental
distress.” It is thus fitting that, along with Jimmie C. Holland, we dedicate this edition to Ruth McCorkle.
Contents

Section editors xiii 8 Cervical Cancer Screening and HPV

Contributors xv Vaccination: Multilevel Challenges to Cervical
Cancer Prevention 61
Introduction: Our Past, Our Future—New Richard Fielding, Samara Perez, Zeev Rosberger, Ovidiu Tatar,
Frontiers in Psycho-​Oncology 1 and Linda D. L. Wang
William S. Breitbart (Senior Editor)
9 Breast Cancer Screening 68
Gabriel M. Leung, Irene O. L. Wong, Ava Kwong, and
Joseph T. Wu
SECTION I
10 Prostate Cancer Screening 74
Behavioral and Psychological Factors in Michael A. Diefenbach, Daniel Nethala, Michael Schwartz, and
Cancer Risk and Prevention Simon J. Hall
Paul B. Jacobsen (Section Editor) 11 Lung Cancer Screening 78
1 Tobacco Use and Cessation 7 Lisa Carter-​Harris and Jamie Ostroff
Thomas H. Brandon, Vani N. Simmons, Úrsula Martínez, and 12 Skin Cancer Screening 87
Patricia Calixte-​Civil Jennifer L. Hay and Stephanie N. Christian
2 Diet and Cancer 13
Marian L. Fitzgibbon, Lisa Tussing-​Humphreys, Angela Kong,
and Alexis Bains
SECTION III
3 Physical Activity, Sedentary Behavior, and Screening and Testing for Germ Line and
Cancer 21
Somatic Mutations
Christine M. Friedenreich, Chelsea R. Stone, and Jessica McNeil
Paul B. Jacobsen (Section Editor)
4 Sun Exposure and Cancer Risk 30
Suzanne J. Dobbinson, Afaf Girgis, Bruce K. Armstrong, and 13 Psychosocial Issues in Genetic Testing for
Anne E. Cust Breast/​Ovarian Cancer 95
Mary Jane Esplen, Jonathan Hunter, and Eveline M. A. Bleiker
5 Psychosocial Factors 36
Anika von Heymann and Christoffer Johansen 14 Psychosocial Issues in Genetic Testing for
Hereditary Colorectal Cancer 102
6 Viral Cancers and Behavior 43 Sukh Makhnoon and Susan K. Peterson
Susan T. Vadaparampil, Lindsay N. Fuzzell, Shannon M. Christy,
Monica L. Kasting, Julie Rathwell, and Anna E. Coghill 15 Psychosocial Issues in Genomic Testing, Including
Genomic Testing for Targeted Therapies 110
Megan Best
SECTION II 16 Psychosocial Issues Related to Liquid Biopsy for
Screening for Cancer in Normal and At-​Risk ctDNA in Individuals at Normal and Elevated
Populations Risk 116
Jada G. Hamilton, Amanda Watsula-​Morley, and
Wendy W. T. Lam (Section Editor)
Alicia Latham
7 Colorectal Cancer Screening 53
Caitlin C. Murphy and Sally W. Vernon
viii Contents

29 Head and Neck Cancer 215

SECTION IV Loreto Fernández González, Jonathan Irish, and Gary Rodin
Screening and Assessment in Psychosocial 30 Central Nervous System Tumors 221
Oncology Alan D. Valentine
Wendy W. T. Lam (Section Editor) 31 HIV Infection and AIDS-​Associated
17 Screening and Assessment for Distress 121 Neoplasms 226
Alex J. Mitchell Joanna S. Dognin and Peter A. Selwyn

18 Assessment, Screening, and Case Finding

for Depression and Anxiety in People with
Cancer 130
Kristine A. Donovan and Paul B. Jacobsen
19 Screening for Delirium and Dementia in the
Cancer Patient 137
Christian Bjerre-​Real, James C. Root, Yesne Alici,
Julia A. Kearney, and William S. Breitbart
20 Screening and Assessment for Cognitive
Problems 146
Alexandra M. Gaynor, James C. Root, Elizabeth Ryan, and
Tim A. Ahles
SECTION V
Psychological Issues Related to Site of
Cancer
Mark Lazenby (Section Editor)
21 Melanoma 155
Nadine A. Kasparian and Iris Bartula
SECTION VI
Management of Specific Physical
Symptoms
William S. Breitbart (Section Editor)
32 Cancer-​Related Pain 235
R. Garrett Key, Dustin Liebling, Vivek T. Malhotra,
Steven D. Passik, Natalie Moryl, and William S. Breitbart
33 Nausea and Vomiting 255
Laura J. Lundi and Kavitha Ramchandran
34 Cancer-​Related Fatigue 265
Daniel C. McFarland, Christian Bjerre-​Real, Yesne Alici, and
William S. Breitbart
35 Sexual Problems and Cancer 276
Jeanne Carter, Ashley Arkema, Andrew J. Roth, Sally Saban, and
Christian J. Nelson
36 Neuropsychological Impact of Cancer and Cancer
Treatments 283
Alexandra M. Gaynor, James C. Root, and Tim A. Ahles

22 Lung Cancer 162 37 Sleep and Cancer 291

Marianne Davies Amy E. Lowery-​Allison and E. Devon Eldridge-​Smith

23 Breast Cancer 169 38 Weight and Appetite Loss in Cancer 298

M. Tish Knobf and Youri Hwang Yesne Alici and Victoria Saltz

24 Colorectal Cancer 176 39 Body Image—​An Important Dimension in Cancer

Anne Miles and Claudia Redeker Care 303
Mary Jane Esplen and Michelle Cororve Fingeret
25 Prostate Cancer and Genitourinary
Malignancies 182
Andrew J. Roth and Alejandro Gonzalez-​Restrepo

26 Gastrointestinal Cancers 189

Daniel C. McFarland and William S. Breitbart
27 Gynecologic Cancers 196
Heidi S. Donovan and Teresa H. Thomas
28 Hematopoietic Dyscrasias and Stem Cell
Transplantation/​CAR-​T Cell Therapy 203
Jesse R. Fann and Nicole Bates
SECTION VII
Psychiatric Disorders
William S. Breitbart (Section Editor)
40 Adjustment Disorders in Cancer 313
Froukje de Vries, Sarah Hales, Gary Rodin, and Madeline Li
41 Depressive Disorders in Cancer 320
Christian Schulz-​Quach, Madeline Li, Kimberley Miller, and
Gary Rodin

42 Suicide and Medical Aid in Dying 329
Hayley Pessin, Elie Isenberg-​Grzeda, Reena Jaiswal, and
Monique James
43 Anxiety Disorders 338
Ashley M. Nelson, Chelsea S. Rapoport, Lara Traeger, and
Joseph A. Greer
44 Delirium 345
Yesne Alici and William S. Breitbart
45 Substance Use Disorders 355
Sameer Hassamal, Adam Rzetelny, and Steven D. Passik
46 Posttraumatic Stress Disorder Associated with
Cancer Diagnosis and Treatment 363
Matthew Doolittle and Katherine N. DuHamel
47 Psychiatric Toxicities of Cancer Therapies: Focus
on Immunotherapy and Targeted Therapy 374
Daniel C. McFarland, Mehak Sharma, and Yesne Alici
SECTION VIII
Evidence-​Based Interventions
William S. Breitbart and Phyllis N. Butow (Section Editors)
Models of Care Delivery
48 Delivering Integrated Psychosocial Oncology
Care: The Collaborative Care Model 385
Jesse R. Fann, Julia Ruark, and Michael Sharpe
49 The Engaged Patient: The Cancer Support
Community’s Comprehensive Model of
Psychosocial Programs, Services, and
Research 393
Mitch Golant, Alexandra K. Zaleta, Susan Ash-​Lee,
Joanne S. Buzaglo, Kevin Stein, M. Claire Saxton,
Marcia Donziger, Kim Thiboldeaux, and Linda Bohannon
50 The Role of Implementation Science in
Advancing Psychosocial Cancer Care 400
Paul B. Jacobsen and Wynne E. Norton
Interventions During Active Treatment
51 Supportive Psychotherapy in Cancer 409
Rosangela Caruso, Maria Giulia Nanni, and Luigi Grassi
52 Cognitive and Behavioral Interventions 416
Barbara L. Andersen, Nicole A. Arrato, and Caroline S. Dorfman
53 Metacognitive Approaches 424
Louise Sharpe and Leah Curran
Contents ix
54 Mindfulness-​Based Interventions 429
Linda E. Carlson
55 Acceptance and Commitment Therapy (ACT) for
Cancer Patients 438
Nicholas J. Hulbert-​Williams, Ray Owen, and Christian J. Nelson
56 Supportive-​Expressive and Other Forms of Group
Psychotherapy in Cancer Care 445
David W. Kissane
57 Emotion-​Focused Therapy 452
Sharon Manne
58 Interpersonal Psychotherapy and Cancer 459
Jennifer Sotsky, Hayley Pessin, and John C. Markowitz
59 Integrative Oncology 470
Santhosshi Narayanan, Gabriel Lopez, Jun J. Mao, Wenli Liu,
and Lorenzo Cohen
Interventions for Families and Couples
60 Psychosocial Interventions for Couples and
Families Coping with Cancer 481
Talia I. Zaider and David W. Kissane
Interventions for Advanced Cancer/​End of
Life/​Bereavement
61 Meaning-​Centered Psychotherapy 489
Melissa Masterson Duva, Wendy G. Lichtenthal,
Allison J. Applebaum, and William S. Breitbart
62 Dignity Therapy 495
Harvey Max Chochinov and Maia S. Kredentser
63 Managing Cancer and Living Meaningfully
(CALM) Therapy 502
Sarah Hales and Gary Rodin
64 Bereavement Interventions in the Setting of
Cancer Care 509
Wendy G. Lichtenthal, Kailey E. Roberts, Holly G. Prigerson, and
David W. Kissane
Interventions for Cancer Survivors
65 Meaning-​Centered Group Psychotherapy for
Cancer Survivors 521
Nadia van der Spek, Wendy G. Lichtenthal, Karen Holtmaat,
William S. Breitbart, and Irma M. Verdonck-​de Leeuw
66 Physical Activity and Exercise Interventions in
Cancer Survivors 528
Chloe Grimmett, Rebecca J. Beeken, and Abigail Fisher
x Contents
Digital Health Interventions
67 e-Health Interventions for Cancer Prevention
and Control 537
Kelly M. Shaffer, Elliot J. Coups,† and Lee M. Ritterband
68 Digital Health Interventions for Psychosocial
Distress (Anxiety and Depression) in Cancer 543
Lisa Beatty and Haryana Dhillon
69 e-​Health Interventions for Physical Symptom
Control 550
Robert Zachariae
70 e-​Health Interventions for Tobacco
Cessation 561
Chris Kotsen, Jamie Ostroff, and Lisa Carter-​Harris
SECTION IX
Psychosocial Issues at the Time of Diagnosis
Matthew J. Loscalzo (Section Editor)
71 Treatment Decision Making 573
Allison Marziliano and Michael A. Diefenbach
72 The Family Meeting: Communication across the
Continuum of Cancer Care 578
Stefanie N. Mooney and Marinel Olivares
SECTION X
Palliative and Supportive Care
Mark Lazenby (Section Editor)
73 Psychological and Psychiatric Aspects of Palliative
and End-​of-​Life Care: Synergies between Psycho-​
Oncology and Palliative Care 589
Scott A. Irwin, Nathan Fairman, Chase Samsel, Jeremy M. Hirst,
Jason A. Webb, and Manuel Trachsel
74 Prognostic Understanding in Advanced Cancer
Patients 599
Laura C. Polacek, Leah E. Walsh, Allison J. Applebaum, and
Barry Rosenfeld
SECTION XI
Diversities in the Experience of Cancer
Matthew J. Loscalzo (Section Editor)
75 Cancer, Culture, and Health Disparities 609
Marjorie Kagawa-​Singer and Annalyn Valdez-​Dadia
76 Financial Toxicity in Cancer Treatment 616
Victoria Blinder and Francesca M. Gany
77 The Experience of Cancer as an Immigrant 621
Francesca M. Gany and Jennifer Leng
78 Sexual and Gender Minority Health in
Psycho-​Oncology 627
Charles Kamen and Jennifer M. Jabson Tree
SECTION XII
Bio-​Behavioral Psycho-​Oncology
William S. Breitbart and Mark Lazenby (Section Editors)
79 Psycho-​Oncology, Stress Processes, and Cancer
Progression 637
Michael H. Antoni, Jennifer M. Knight, and Susan K. Lutgendorf
80 Depression, Inflammation, and Cancer 644
Daniel C. McFarland, Leah E. Walsh, and Andrew H. Miller
81 Biobehavioral Psycho-​Oncology
Interventions 654
Michael A. Hoyt and Frank J. Penedo
SECTION XIII
Geriatric Psycho-​Oncology
Matthew J. Loscalzo (Section Editor)
82 The Older Cancer Patient 663
Barbara A. Given and Charles W. Given
83 Geriatric Psycho-​Oncology Assessment Issues
and Interventions 671
Kelly M. Trevino, Rebecca M. Saracino, Andrew J. Roth,
Yesne Alici, and Christian J. Nelson
84 Communicating with the Older Adult Cancer
Patient 678
Patricia A. Parker, Smita C. Banerjee, and Beatriz Korc-​Grodzicki
SECTION XIV
Pediatric Psycho-​Oncology
William S. Breitbart (Section Editor)
85 Screening and Assessment in Pediatric
Psycho-​Oncology 687
Darcy E. Burgers, Sarah J. Tarquini, Anne E. Kazak, and
Anna C. Muriel
 Contents xi

86 Psychiatric Disorders in Pediatric Psycho-​

Oncology: Diagnosis and Management 696 SECTION XVII
Julia A. Kearney, Meredith E. MacGregor, and Maryland Pao
Building Supportive Care/​Psycho-​Oncology
87 Evidence-​Based Psychosocial Interventions in Teams
Pediatric Psycho-​Oncology 703 Phyllis N. Butow (Section Editor)
Lori Wiener, Marie Barnett, Stacy Flowers, Cynthia Fair, and
Amanda L. Thompson Building Supportive Care Teams: Working
88 Adolescent and Young Adult Patients 715 Together and Self-​Care
Christabel K. Cheung, Sheila J. Santacroce, and Bradley J. Zebrack
96 Integrating Interdisciplinary Supportive Care
Programs: Transforming the Culture of Cancer
Care 775
SECTION XV Matthew J. Loscalzo, Karen L. Clark, Barry D. Bultz, and
Psychological Issues for the Family and Juee Kotwal

Caregivers 97 Occupational Stress in Oncology Staff: Burnout,

Phyllis N. Butow (Section Editor) Resilience, and Interventions 782
Fay J. Hlubocky and Daniel C. McFarland
89 Including Family Members in Caring for
the Patient with Cancer: A Family-​Centered Health Provider/​Patient Communication
Approach 723
Douglas S. Rait 98 Principles of Communication Skills Training
in Cancer Care across the Life Span and Illness
90 Couples Facing Cancer 729
Trajectory 791
Hoda Badr and Courtney Bitz
David W. Kissane and Carma L. Bylund
91 Cancer Caregivers 737
Allison J. Applebaum, Erin Kent, Kristin Litzelman, Betty Ferrell,
J. Nicholas Dionne-​Odom, and Laurel Northouse
SECTION XVIII
92 Addressing the Needs of Children When a Parent Psycho-​Oncology in Health Policy
Has Cancer 745
Cynthia W. Moore, Greer J. Dent, and Paula K. Rauch Wendy W. T. Lam (Section Editor)

99 Distress, the Sixth Vital Sign: A Catalyst for

Standardizing Psychosocial Care Globally 801
Barry D. Bultz, Matthew J. Loscalzo, Alex J. Mitchell, and
SECTION XVI
Jimmie C. Holland†
Survivorship
100 Implementation of Clinical Practice Guidelines
Phyllis N. Butow and Wendy W. T. Lam (Section Editors)
for Psychosocial Cancer Care 806
93 Fear of Cancer Recurrence 755 Jane Turner and Nicole Rankin
Allan B. Smith, Joanna E. Fardell, and Phyllis N. Butow
101 Emerging International Directions for
94 Implementing the Survivorship Care Plan: A Psychosocial Care: Perspectives from Asia and
Strategy for Improving the Quality of Care for Low-​Middle-​Income Countries 813
Cancer Survivors 760 Jeff Dunn, Melissa Henry, and Maggie Watson
Erin E. Hahn and Patricia A. Ganz
Index 819
95 Adult Survivors of Childhood Cancer 767
Lisa A. Schwartz, Claire E. Wakefield, Jordana K. McLoone,
Branlyn Werba DeRosa, and Anne E. Kazak
Section editors
William S. Breitbart, MD, FAPOS
The Jimmie C. Holland Chair in Psychiatric Oncology
Chairman
Department of Psychiatry and Behavioral Sciences
Memorial Sloan Kettering Cancer Center
Professor of Clinical Psychiatry
Vice-Chairman
Department of Psychiatry
Weill Cornell Medical College
President Emeritus, International Psycho-oncology Society
Phyllis N. Butow, BA(Hons), DipEd, MClinPsych, MPH, PhD
Professor of Psychological Medicine
NHMRC Senior Principal Research Fellow
Founding Chair, PoCoG
School of Psychology
University of Sydney
Paul B. Jacobsen, PhD
Associate Director
Healthcare Delivery Research Program
Division of Cancer Control and Population Sciences
National Cancer Institute
Wendy W. T. Lam, RN, PhD, FFPH
Associate Professor, Head, Division of Behavioural Sciences,
School of Public Health
Director, Jockey Club Institute of Cancer Care, Li Ka Shing
Faculty of Medicine
Director, Centre for Psycho-oncology Research and
Training (CePORT)
The University of Hong Kong
Mark Lazenby, APRN, PhD
Associate Dean for Faculty and Student Affairs
Professor of Nursing and Philosophy
University of Connecticut School of Nursing
Matthew J. Loscalzo, MSW, LCSW, FAPOS
Liliane Elkins Professor in Supportive Care Programs
Administrative Director, Sheri and Les Biller Patient and Family
Resource Center
Executive Director, Department of Supportive Care Medicine
Professor, Department of Population Sciences
City of Hope National Medical Center
Contributors

Tim A. Ahles, PhD Hoda Badr, PhD

Attending Psychologist Associate Professor
Director, Neurocognitive Laboratory Department of Medicine
Psychiatry Service Baylor College of Medicine
Department of Psychiatry and Behavioral Sciences Houston, TX, USA
Member Alexis Bains, BSc Nutrition
Memorial Sloan Kettering Cancer Center Research Assistant
New York, NY, USA Department of Kinesiology and Nutrition
Yesne Alici, MD The University of Illinois at Chicago (UIC)
Associate Attending Psychiatrist Chicago, IL, USA
Clinical Director, Smita C. Banerjee, PhD
Co-​Director, Bio-​Behavioral Brain Clinic Associate Attending Behavioral Scientist
Psychiatry Service Behavioral Sciences Service
Department of Psychiatry and Behavioral Sciences Co-​Director, Comskils Laboratory
Memorial Sloan Kettering Cancer Center Department of Psychiatry and Behavioral Sciences
New York, NY, USA Memorial Sloan Kettering Cancer Center
Barbara L. Andersen, PhD New York, NY, USA
Distinguished University Professor Marie Barnett, PhD
Department of Psychology Assistant Attending Psychologist
Ohio State University Psychiatry Service
Columbus, OH, USA Department of Psychiatry and Behavioral Sciences &
Michael H. Antoni, PhD Department of Pediatrics
Professor Memorial Sloan Kettering Cancer Center
Department of Psychology New York, NY, USA
University of Miami and Sylvester Comprehensive Cancer Center Iris Bartula, DCP
Miami, FL, USA Head of Research Psychology
Allison J. Applebaum, PhD Melanoma Institute Australia
Assistant Attending Psychologist Senior Lecturer
Director, Caregiver’s Clinic Northern Sydney Medical School
Psychiatry Service Faculty of Medicine and Health
Department of Psychiatry and Behavioral Sciences University of Sydney
Memorial Sloan Kettering Cancer Center Sydney, NSW, Australia
New York, NY, USA Nicole Bates, MD
Ashley Arkema, MS Acting Assistant Professor
Nurse Practitioner Department of Psychiatry and Behavioral Sciences
Female Sexual Medicine University of Washington Attending Psychiatrist
Brooklyn, NY, USA Department of Psychosocial Oncology
Bruce K. Armstrong, BMedSci(Hons), MBBS(Hons), DPhil(Oxon), FRACP, FAFPHM Seattle Cancer Care Alliance
Retired Seattle, WA, USA
School of Population and Global Health Lisa Beatty, PhD
The University of Western Australia Senior Research Fellow
Perth, WA, Australia College of Medicine and Public Health
Nicole A. Arrato, MA Flinders University
Graduate Research Assistant Adelaide, SA, Australia
Department of Psychology Rebecca J. Beeken, PhD
Ohio State University Associate Professor of Behavioural Medicine
Columbus, OH, USA Leeds Institute of Health Sciences
Susan Ash-​Lee, MSW, LCSW University of Leeds
Vice President Leeds, Yorkshire, UK
Clinical Services Program
Cancer Support Community
Denver, CO, USA
xvi Contributors

Megan Best, PhD, MAAE, BMed(Hons), GradDipQHR Darcy E. Burgers, PhD

Senior Lecturer Psychologist
Department of Psycho-​Oncology Co-​operative Research Group Division of Pediatric Psychosocial Oncology
University of Sydney Department of Psychosocial Oncology and Palliative Care
Broadway, NSW, Australia Dana-​Farber Cancer Institute
Courtney Bitz, MSW, LCSW, OSW-​C Boston, MA, USA
Director of Clinical Social Work Phyllis N. Butow, BA(Hons), DipEd, MClinPsych, MPH, PhD
Department of Supportive Care Medicine Professor of Psychological Medicine
City of Hope NHMRC Senior Principal Research Fellow,
Duarte, CA, USA Founding Chair, PoCoG
Christian Bjerre-​Real, MD, MMCI School of Psychology
Research Fellow University of Sydney
Department of Psychiatry and Behavioral Sciences Sydney, NSW, Australia
Memorial Sloan Kettering Cancer Center Joanne S. Buzaglo, PhD
New York, NY, USA Executive Director, PRO Solutions
Eveline M. A. Bleiker, PhD Outcomes Sciences
Professor ConcertAI
Department of Psychosocial Research and Epidemiology Rydal, PA, USA
Netherlands Cancer Institute Carma L. Bylund, PhD
Amsterdam, The Netherlands Professor
Victoria Blinder, MD, MSc College of Journalism and Communications
Associate Attending Oncologist University of Florida
Associate Member Newberry, FL, USA
Immigrant Health and Cancer Disparities Service Patricia Calixte-​Civil, MA
Department of Psychiatry and Behavioral Sciences Doctoral Student
Breast Medicine Service Department of Psychology
Department of Medicine University of South Florida, Moffitt Cancer Center
Memorial Sloan Kettering Cancer Center Tampa, FL, USA
New York, NY, USA Linda E. Carlson, PhD
Linda Bohannon, MSM, BSN, RN Professor
President Department of Oncology
Global Headquarters University of Calgary
Cancer Support Community Cumming School of Medicine
Washington, DC, USA Calgary, AB, Canada
Thomas H. Brandon, PhD Jeanne Carter, PhD
Department Chair and Program Leader, Attending Psychologist
Health Outcomes and Behavior Director, Female Sexual Health Clinic
Moffitt Distinguished Scholar Gynecology Service
Director, Tobacco Research and Intervention Program Department of Surgery
Moffitt Cancer Center Psychiatry Service
Professor Department of Psychiatry and Behavioral Medicine
Departments of Psychology and Oncologic Sciences Memorial Sloan Kettering Cancer Center
University of South Florida New York, NY, USA
Tampa, FL, USA Lisa Carter-​Harris, PhD, APRN, ANP-​C , FAAN
William S. Breitbart, MD, FAPOS Associate Attending Behavioral Scientist
Jimmie C. Holland Chair in Psychiatric Oncology Behavioral Sciences Service
Chairman Department of Psychiatry and Behavioral Sciences
Department of Psychiatry and Behavioral Sciences Memorial Sloan Kettering Cancer Center
Member New York, NY, USA
Attending Psychiatrist Rosangela Caruso, MD, PhD
Supportive Care Service Doctor
Department of Medicine Biomedical and Specialty Surgical Sciences
Memorial Sloan Kettering Cancer Center University of Ferrara
Vice Chairman and Professor of Clinical Psychiatry Ferrara, Emilia Romagna, Italy
Department of Psychiatry
Christabel K. Cheung, PhD, MSW
Weill Cornell Medical College
Assistant Professor
New York, NY, USA
University of Maryland School of Social Work
Barry D. Bultz, AOE, PhD Member
Professor and Head, Division of Psychosocial Oncology University of Maryland Greenbaum Comprehensive Cancer Center
Daniel Family Leadership Chair in Psychosocial Oncology Baltimore, MD, USA
Department of Oncology
Harvey Max Chochinov, OM, OC, PhD, MD, FRCPC, FRSC, FCAHS
Cumming School of Medicine
Distinguished Professor
Department of Psychosocial Oncology
Department of Psychiatry
Tom Baker Cancer Center
University of Manitoba
University of Calgary
Winnipeg, MB, Canada
Calgary, AB, Canada
 Contributors xvii

Stephanie N. Christian, MPH Haryana Dhillon, BSc, MA(Psych), PhD

K. Leroy Irvis Fellow Associate Professor
Department of Behavioral and Community Health Sciences Centre for Medical Psychology and Evidence-​based Decision-​making,
University of Pittsburgh Graduate School of Public Health School of Psychology, Faculty of Science
Pittsburgh, PA, USA The University of Sydney
Shannon M. Christy, PhD Camperdown, NSW, Australia
Department of Health Outcomes and Behavior Michael A. Diefenbach, PhD
Division of Population Science H. Lee Moffitt Cancer Center and Research Professor
Institute Departments of Medicine, Urology and Psychiatry
Department of Oncologic Sciences Northwell Health
Morsani College of Medicine University of South Florida Manhasset, NY, USA
Center for Immunization and Infection Research in Cancer J. Nicholas Dionne-​Odom, PhD, RN, ACHPN
Lee Moffitt Cancer Center and Research Institute Assistant Professor
Tampa, FL, USA School of Nursing
Karen L. Clark, MS University of Alabama at Birmingham
Manager of Supportive Care Programs Hoover, AL, USA
Department of Supportive Care Medicine Suzanne J. Dobbinson, BSc, MSc, PhD
City of Hope National Medical Center Senior Research Fellow
Duarte, CA, USA Centre for Behavioural Research in Cancer
Anna E. Coghill, PhD, MPH Cancer Council Victoria
Assistant Member Kensington, VIC, Australia
Cancer Epidemiology Joanna S. Dognin, PsyD
Moffitt Cancer Center Psychologist
Tampa, FL, USA Department of Veterans Affairs
Lorenzo Cohen, PhD NYU Langone Medical Center
Professor and Director, Integrative Medicine Program White Plains, NY, USA
Department of Palliative, Rehabilitation and Integrative Medicine Heidi S. Donovan, PhD, RN
The University of Texas MD Anderson Cancer Center Professor
Houston, TX, USA Co-​Director National Rehabilitation Research and Training Center
Elliot J. Coups, PhD† on Family Support
Member Department of Health and Community Systems
Rutgers Cancer Institute of New Jersey University of Pittsburgh
Department of Medicine Pittsburgh, PA, USA
Rutgers Robert Wood Johnson Medical School Kristine A. Donovan, PhD, MBA
Rutgers, The State University of New Jersey Associate Member
New Brunswick, NJ, USA Department of Supportive Care Medicine
Leah Curran, DCP Moffitt Cancer Center
Clinical Psychologist Tampa, FL, USA
Department of Psychology Marcia Donziger, BA
The University of Sydney Vice President
Camperdown, NSW, Australia Digital Strategy and Business Development
Anne E. Cust, PhD, MPH(Hons), BSc, BA Cancer Support Community
Professor of Cancer Epidemiology Denver, CO, USA
Sydney School of Public Health Matthew Doolittle, MD
And the Melanoma Institute Australia Assistant Attending Psychiatrist
The University of Sydney Psychiatry Service
Camperdown, NSW, Australia Department of Psychiatry and Behavioral Sciences
Marianne Davies, DNP, ACNP, AOCNP Memorial Sloan Kettering Cancer Center
Associate Professor Yale School of Nursing New York, NY, USA
Department of Oncology Nurse Practitioner Caroline S. Dorfman, PhD
Smilow Cancer Hospital Assistant Professor
New Haven, CT, USA Department of Psychiatry and Behavioral Sciences
Greer J. Dent, BA Duke University Medical Center
Clinical Research Coordinator Durham, NC, USA
Department of Cancer Center Katherine N. DuHamel, PhD
Massachusetts General Hospital Director
Boston, MA, USA KND Consulting
Branlyn Werba DeRosa, PhD New York, NY, USA
Research Director Jeff Dunn, PhD, AO
Department of Research and Training Institute Professor
Cancer Support Community Department of Research and Innovation
Ardmore, PA, USA University of Southern Queensland
Toowoomba, Queensland, Australia
xviii Contributors

E. Devon Eldridge-​Smith, PhD Marian L. Fitzgibbon, PhD

Assistant Professor Professor
Department of Medicine Department of Pediatrics
National Jewish Health University of Illinois
Denver, CO, USA Chicago, IL, USA
Mary Jane Esplen, PhD Stacy Flowers, PsyD
Professor and Vice-​Chair Associate Professor
Department of Psychiatry Director of Behavioral Science
Faculty of Medicine Department of Family Medicine
University of Toronto Wright State University
Toronto, ON, Canada Columbus, OH, USA
Cynthia Fair, LCSW, MPH, DrPH Christine M. Friedenreich, PhD, FCAHS, FRSC
Professor and Department Chair Scientific Director
Department of Public Health Studies Department of Cancer Epidemiology and Prevention Research
Elon University Alberta Health Services
Elon, NC, USA Arnie Charbonneau Cancer Institute
Nathan Fairman, MD, MPH Adjunct Professor
Associate Clinical Professor The Faculties of Medicine and Kinesiology
Department of Psychiatry and Behavioral Sciences University of Calgary
UC Davis School of Medicine Calgary, AB, Canada
Sacramento, CA, USA Lindsay N. Fuzzell, PhD
Jesse R. Fann, MD, MPH Applied Research Scientist I
Professor Health Outcomes and Behavior
Department of Psychiatry and Behavioral Sciences Moffitt Cancer Center
Adjunct Professor Tampa, FL, USA
Departments of Rehabilitation Medicine and Epidemiology Francesca M. Gany, MD, MS
University of Washington Attending Physician
Medical Director Chief, Immigrant Health and Cancer Disparities Service
Department of Psychosocial Oncology Department of Psychiatry and Behavioral Sciences
Seattle Cancer Care Alliance Clinical Research Division Member
Fred Hutchinson Cancer Research Center Seattle, Washington Memorial Sloan Kettering Cancer Center
Seattle, WA, USA Professor
Joanna E. Fardell, PhD, MClinNeuropsych, BSc Department of Medicine and Department of Healthcare Policy & Research
Research Fellow Weill Cornell Medicine
Department of Behavioural Sciences Unit, Discipline of Paediatrics, New York, NY, USA
School of Women’s and Children’s Health, Faculty of Medicine Patricia A. Ganz, MD
University of New South Wales Distinguished Professor
Randwick, NSW, Australia Schools of Medicine and Public Health
Loreto Fernández González, BA, BSc, MPH University of California, Los Angeles (UCLA)
PhD Student and Connaught Scholar Los Angeles, CA, USA
Social and Behavioural Health Sciences Alexandra M. Gaynor, PhD
Dalla Lana School of Public Health Post-​Doctoral Neuropsychology Research Fellow
University of Toronto Department of Psychiatry and Behavioral Sciences
Toronto, ON, Canada Memorial Sloan Kettering Cancer Center
Betty Ferrell, RN, PhD, FAAN New York, NY, USA
Professor Afaf Girgis, PhD, BSc(Hons)
Nursing Research Professor
City of Hope National Medical Center Director, Psycho-​Oncology Research Group
Duarte, CA, USA University of New South Wales
Richard Fielding, BA(Hons), CPsychol, PhD, FFPH, FHKPsyS Sydney, Australia
Clinical Lead Barbara A. Given, PhD, RN, FAAN
Jockey Club Institute of Cancer Care, Li Ka Shing Faculty of Medicine University Distinguished Professor, Associate Dean Emeritus
Honorary Professor, School of Public Health College of Nursing
The University of Hong Kong Michigan State University
Hong Kong, China Okemos, MI, USA
Michelle Cororve Fingeret, PhD Charles W. Given, PhD
Fingeret Psychology Services Professor Emeritus
Houston, TX, USA College of Nursing
Abigail Fisher, PhD Michigan State University
Associate Professor Okemos, MI, USA
Department of Behavioural Science and Health Mitch Golant, PhD
University College London Senior Consultant, Strategic Initiatives
Bloomsbury, London, UK Research and Training Institute
Cancer Support Community
Los Angeles, CA, USA
 Contributors xix

Alejandro Gonzalez-​Restrepo, MD Melissa Henry, PhD

Attending Psychiatrist Associate Professor
Hartford Hospital/​Institute of Living Department of Oncology
Hartford Healthcare Faculty of Medicine
Simsbury, CT, USA McGill University
Luigi Grassi, MD Montreal, QC, Canada
Professor and Chair of Psychiatry Anika von Heymann, MSc, Psych, PhD
University of Ferrara Postdoctoral Fellow
Chairman of the Department of Biomedical and Specialty Surgical Sciences Department of Oncology
University of Ferrara Rigshospitalet
Ferrara, Italy København, Denmark
Joseph A. Greer, PhD Jeremy M. Hirst, MD
Associate Professor of Psychology Clinical Professor of Psychiatry; Palliative Care Psychiatry
Department of Psychiatry Department of Psychiatry; Palliative Medicine
Harvard Medical School UC San Diego School of Medicine
Program Director, Center for Psychiatric Oncology & La Jolla, CA, USA
Behavioral Sciences Fay J. Hlubocky, PhD, MA, CCTP
Massachusetts General Hospital Cancer Center Clinical Health Psychologist
Boston, MA, USA Research Project Professor
Chloe Grimmett, PhD Department of Medicine
Senior Research Fellow University of Chicago Medicine
School of Health Sciences Chicago, IL, USA
University of Southampton Jimmie C. Holland, MD†
Hampshire, UK Wayne E. Chapman Chair in Psychiatric Oncology
Erin E. Hahn, PhD, MPH Attending Psychiatrist
Research Scientist Psychiatry Service
Department of Research and Evaluation Department of Psychiatry and Behavioral Sciences
Kaiser Permanente Southern California Member
Pasadena, CA, USA Memorial Sloan Kettering Cancer Center
Sarah Hales, MD, PhD New York, NY, USA
Assistant Professor Karen Holtmaat, MSc, MA
Division of Psychosocial Oncology Assistant Professor in Psychosocial Oncology
Department Supportive Care Department of Clinical, Neuro-​and Developmental Psychology
Princess Margaret Cancer Centre Vrije Universiteit Amsterdam
Centre for Mental Health Amsterdam, NH, The Netherlands
University Health Network Michael A. Hoyt, PhD
University of Toronto Associate Professor
Toronto, ON, Canada Chao Cancer Center
Simon J. Hall, MD UC Irvine
Zucker Professor of Urologic Oncology Irvine, CA, USA
Smith Institute of Urology Nicholas J. Hulbert-​Williams, BSc, PhD, CPsychol, APBPsS, FHAE
Hofstra Northwell School of Medicine Professor of Behavioural Medicine
Lake Success, NY, USA School of Psychology
Jada G. Hamilton, PhD, MPH University of Chester
Assistant Attending Psychologist Chester, UK
Behavioral Sciences Service Jonathan Hunter, BSc, MD, FRCPC
Department of Psychiatry and Behavioral Sciences; Department of Medicine Professor
Assistant Member Department of Psychiatry
Memorial Sloan Kettering Cancer Center University of Toronto
New York, NY, USA Toronto, ON, Canada
Sameer Hassamal, MD Youri Hwang, MSN, RN, FNP-​C
Assistant Professor PhD Student
Department of Psychiatry School of Nursing
Arrowhead Regional Medical Center Yale University
Colton, CA, USA New Haven, CT, USA
Jennifer L. Hay, PhD Jonathan Irish, MD, MSc, FRCSC, FACS
Attending Psychologist Professor and Head
Behavioral Sciences Service Division of Head and Neck Oncology and Reconstructive Surgery
Department of Psychiatry and Behavioral Sciences Department of Otolaryngology-​Head and Neck Surgery
Member Princess Margaret Cancer Centre, University of Toronto
Memorial Sloan Kettering Cancer Center Toronto, ON, Canada
New York, NY, USA
xx Contributors

Scott A. Irwin, MD, PhD, FACLP, FAPA Anne E. Kazak, PhD, ABPP
Professor of Psychiatry and Behavioral Neurosciences Editor-​in-​Chief, American Psychologist
Department of Psychiatry and Behavioral Neurosciences Director, Center for Healthcare Delivery Science
Director of Patient and Family Support Program Nemours Children’s Health System Co-​Director
Samuel Oschin Comprehensive Cancer Institute, Center for Pediatric Traumatic Stress Professor
Cedars-​Sinai Health System Department of Pediatrics
Los Angeles, CA, US Thomas Jefferson University
Elie Isenberg-​Grzeda, MD, CM, FRCPC Wilmington, DE, USA
Assistant Professor Julia A. Kearney, MD
Department of Psychiatry Assistant Attending Psychiatrist
University of Toronto Clinical Director, Pediatric Psycho-​Oncology Program
Toronto, ON, Canada Department of Psychiatry and Behavioral Sciences &
Jennifer M. Jabson Tree, PhD, MPH Department of Pediatrics
Associate Professor Memorial Sloan Kettering Cancer Center
Department of Public Health New York, NY, USA
University of Tennessee Erin Kent, PhD, MS
Knoxville, TN, USA Associate Professor
Paul B. Jacobsen, PhD Health Policy and Management
Associate Director University of North Carolina
Division of Cancer Control and Population Sciences Chapel Hill, NC, USA
National Cancer Institute R. Garrett Key, MD, FAPA, FACLP
Bethesda, MD, USA Assistant Professor
Reena Jaiswal, MD Psychiatry and Behavioral Sciences
Assistant Attending Psychiatrist University of Texas at Austin Dell Medical School
Psychiatry Service Austin, TX, USA
Department of Psychiatry and Behavioral Sciences David W. Kissane, AC, MBBS, MPM, MD, FRANZCP, FAChPM, FACLP
Memorial Sloan Kettering Cancer Center UNDA Chair of Palliative Medicine Research
New York, NY, USA Cunningham Centre for Palliative Care, St Vincent’s Sydney
Monique James, MD University of Notre Dame Australia
Assistant Attending Psychiatrist Head of Szalmuk Family Psycho-​oncology Research Unit
Psychiatry Service Department of Palliative Care
Department of Psychiatry and Behavioral Sciences Cabrini Health, Melbourne, Australia
Memorial Sloan Kettering Cancer Center Head of Psycho-​Oncology Clinic
New York, NY, USA Monash Medical Centre
Monash University
Christoffer Johansen, MD, PhD, Dr. Med. Sci.
Clayton, VIC, Australia
Professor
Head, CASTLE—​Cancer Late Effect Research Oncology Clinic Jennifer M. Knight, MD, MS
Department of Oncology Associate Professor
Center for Surgery and Cancer Department of Psychiatry, Medicine, and Microbiology and Immunology
Rigshospitalet Medical College of Wisconsin
Copenhagen, Denmark Shorewood, WI, USA

Marjorie Kagawa-​Singer, PhD, MA, MN, RN M. Tish Knobf, PhD, RN, FAAN
Research Professor Professor
Community Health Sciences Department of Nursing
University of California, Los Angeles (UCLA) Yale University
Los Angeles, CA, USA New Haven, CT, USA
Charles Kamen, PhD, MPH Angela Kong, PhD, MPH, RD
Assistant Professor Assistant Professor
Department of Surgery Department of Pharmacy Systems, Outcomes, and Policy
University of Rochester University of Illinois Chicago
Rochester, NY, USA Chicago, IL, USA

Nadine A. Kasparian, PhD Beatriz Korc-​Grodzicki, MD, PhD, FAGS

Professor of Pediatrics Director, Cincinnati Children’s Center for Heart Disease Chief, Geriatrics Service
and Mental Health Heart Institute and Division of Behavioral Medicine and Department of Medicine
Clinical Psychology Memorial Sloan-​Kettering Cancer Center
Department of Pediatrics Professor of Medicine
University of Cincinnati College of Medicine Weill Cornell Medical College
Cincinnati, OH, USA New York, NY, USA

Monica L. Kasting, PhD Chris Kotsen, PsyD, NCTTP

Assistant Professor Associate Attending Psychologist
Department of Public Health Associate Director, Tobacco Treatment Program
Purdue University Department of Psychiatry and Behavioral Sciences
West Lafayette, IN, USA Memorial Sloan Kettering Cancer Center
New York, NY, USA
 Contributors xxi

Juee Kotwal, MBS, PMP Kristin Litzelman, PhD

Business Manager Assistant Professor
Department of Supportive Care Medicine Department of Human Development and Family Studies
City of Hope National Medical Center University of Wisconsin-​Madison
Duarte, CA, USA Madison, WI, USA
Maia S. Kredentser, PhD Wenli Liu, MD
Research Fellow Associate Professor
Clinical Health Psychology Department of Palliative, Rehabilitation and Integrative Medicine
University of Manitoba MD Anderson Cancer Center
Winnipeg, MB, Canada Houston, TX, USA
Ava Kwong, MBBS, BSc, PhD, FRCS, FRCS, FHKAM, FCSHK Gabriel Lopez, MD
Clinical Professor Associate Professor, Center Medical Director
Division of Breast Surgery, Department of Surgery Department of Palliative, Rehabilitation, and Integrative Medicine
The University of Hong Kong Li Ka Shing Faculty of Medicine University of Texas, MD Anderson Cancer Center
Pok Fu Lam, Hong Kong, China Houston, TX, USA
Wendy W. T. Lam, RN, PhD, FFPH Matthew J. Loscalzo, MSW, LCSW, FAPOS
Associate Professor, Head, Division of Behavioural Sciences, School of Liliane Elkins Professor in Supportive Care Programs
Public Health Administrative Director, Sheri & Les Biller Patient and Family
Director, Jockey Club Institute of Cancer Care, Li Ka Shing Faculty of Medicine Resource Center
Director, Centre for Psycho-​oncology Research and Training (CePORT) Executive Director, Department of Supportive Care Medicine
The University of Hong Kong Professor, Department of Population Sciences
Hong Kong, China City of Hope National Medical Center
Duarte, CA, USA
Alicia Latham, MD
Amy E. Lowery-​Allison, PhD
Assistant Attending Physician
Associate Attending Psychologist
Department of Medicine
Psychiatry Service
Memorial Sloan Kettering Cancer Center
Department of Psychiatry and Behavioral Sciences
New York, NY, USA
Memorial Sloan Kettering Cancer Center
Mark Lazenby, APRN, PhD New York, NY, USA
Professor of Nursing and Philosophy
Laura J. Lundi, BS
Associate Dean for Faculty and Student Affairs
Administrative Clinical Research Coordinator
University of Connecticut School of Nursing
Department of Medicine
Storrs, CT, USA
Stanford University
Jennifer Leng, MD, MPH Stanford, CA, USA
Associate Attending Physician Susan K. Lutgendorf, PhD
Associate Member Professor and Starch Faculty Fellow
Immigrant Health and Cancer Disparities Service Departments of Psychological and Brain Sciences, Obstetrics and Gynecology,
Department of Psychiatry and Behavioral Sciences and Urology
Memorial Sloan Kettering Cancer Center University of Iowa
New York, NY, USA Iowa City, IA, USA
Gabriel M. Leung, MD Irma M. Verdonck-​de Leeuw, PhD
Dean of Medicine Full Professor in Psychosocial Oncology
LKS Faculty of Medicine Department of Otolaryngology/​Head and Neck Surgery
The University of Hong Kong Vrije University Medical Center/​Cancer Center Amsterdam
Pok Fu Lam, Hong Kong Section of Clinical, Neuro-​and Developmental Psychology
Madeline Li, MD, PhD, FRCP(C) Vrije Universiteit Amsterdam
Attending Psychiatrist Amsterdam, The Netherlands
Department of Supportive Care Meredith E. MacGregor, MD
Princess Margaret Cancer Centre Assistant Attending Psychiatrist
University Health Network Department of Child and Adolescent Psychiatry and Behavioral Sciences
Associate Professor Children’s Hospital of Philadelphia
Department of Psychiatry Philadelphia, PA, USA
Faculty of Medicine Sukh Makhnoon, PhD, MS
University of Toronto Postdoctoral Fellow
Toronto, ON, Canada Department of Behavioral Science
Wendy G. Lichtenthal, PhD, FT University of Texas MD Anderson Cancer Center
Associate Attending Psychologist Houston, TX, USA
Director, Bereavement Clinic, Vivek T. Malhotra, MD, MPH
Psychiatry Service Chief, Anesthesiology Pain Service
Department of Psychiatry and Behavioral Sciences Associate Attending
Memorial Sloan Kettering Cancer Center Department of Anesthesiology and Critical Care Medicine
New York, NY, USA Memorial Sloan Kettering Cancer Center
Dustin Liebling, MD New York, NY, USA
Clinical Fellow Sharon Manne, PhD
Anesthesia Pain Management Service Section Chief, Professor of Medicine
Department of Anesthesiology and Critical Care Medicine Department of CINJ, Behavioral Sciences
Memorial Sloan Kettering Cancer Center Rutgers, The State University of New Jersey
New York, NY, USA New Brunswick, NJ, USA
xxii Contributors

Jun J. Mao, MD, MSCE Alex J. Mitchell, MBBS, MSc, MD, MRCPsych
Laurance S. Rockefeller Chair in Integrative Medicine Professor
Chief, Integrative Medicine Service Department of Psycho-​Oncology and Cancer Care
Attending Physician University of Leicester
Department of Medicine Leicester, UK
Memorial Sloan Kettering Cancer Center, Bendheim Integrative Medicine Center Stefanie N. Mooney, MD
New York, NY, USA Assistant Clinical Professor of Medicine
John C. Markowitz, MD Division of Supportive Medicine
Research Psychiatrist Department of Supportive Care Medicine
New York State Psychiatric Institute City of Hope National Medical Center
Professor of Clinical Psychiatry Duarte, CA, USA
Columbia University College of Physicians and Surgeons Cynthia W. Moore, PhD
New York, NY, USA Psychologist
Úrsula Martínez, PhD Department of Child and Adolescent Psychiatry
Applied Research Scientist Massachusetts General Hospital
Department of Health Outcomes and Behavior Boston, MA, USA
H. Lee Moffitt Cancer Center and Research Institute
Natalie Moryl, MD
Tampa, FL, USA
Associate Attending Physician
Allison Marziliano, PhD Supportive Care Service
Postdoctoral Fellow Department of Medicine
Department of Medicine Memorial Sloan Kettering Cancer Center
Northwell Health Associate Professor
Bethpage, NY, USA Department of Medicine
Melissa Masterson Duva, PhD Weill Cornell Medical College
Senior Psychologist New York, NY, USA
WTC Health Program Clinical Center of Excellence Anna C. Muriel, MD, MPH
New York University School of Medicine Chief, Division of Pediatric Psychosocial Oncology
New York, NY, USA Associate Psychiatrist
Daniel C. McFarland, DO Department of Psychosocial Oncology and Palliative Care
Research Fellow Dana Farber Cancer Institute
Department of Psychiatry and Behavioral Sciences Assistant Professor of Psychiatry
Memorial Sloan Kettering Cancer Center Harvard Medical School
New York, NY, USA Boston, MA, USA
Jordana K. McLoone, PhD Caitlin C. Murphy, PhD, MPH
Post-​Doctoral Research Fellow Assistant Professor
Women’s and Children’s Health, Faculty of Medicine Department of Population and Data Sciences
University of New South Wales UT Southwestern Medical Center
NSW, Australia Dallas, TX, USA
Jessica McNeil, PhD
Maria Giulia Nanni, MD
Postdoctoral Fellow Associate Professor
Cancer Epidemiology and Prevention Research Department of Biomedical and Specialty Surgical Sciences
Alberta Health Services University of Ferrara
Russell, ON, Canada Ferrara, Italy
Anne Miles, BSc, PhD
Santhosshi Narayanan, MD
Reader in Psychology
Assistant Professor
Department of Psychological Sciences
Department of PRIM
Birkbeck, University of London
MD Anderson Cancer Center
Bloomsbury, London, UK
Houston, TX, USA
Andrew H. Miller, MD
Ashley M. Nelson, PhD
William P. Timmie Professor of Psychiatry and Behavioral Sciences
Postdoctoral Fellow
Department of Psychiatry and Behavioral Sciences
Department of Psychiatry
Emory University School of Medicine
Massachusetts General Hospital/​Harvard Medical School
Atlanta, GA, USA
Boston, MA, USA
Kimberley Miller, MD, FRCPC
Attending Psychiatrist Christian J. Nelson, PhD
Department of Supportive Care Chief, Psychiatry Service,
Princess Margaret Cancer Centre, Associate Attending Psychologist
University Health Network Department of Psychiatry and Behavioral Sciences
Assistant Professor of Psychiatry Associate Member
Department of Psychiatry Memorial Sloan Kettering Cancer Center
Faculty of Medicine New York, NY, USA
University of Toronto
Toronto, ON, Canada
 Contributors xxiii

Daniel Nethala, MD Hayley Pessin, PhD

Resident Psychologist
Department of Urology Department of Psychiatry and Behavioral Sciences
Smith Institute for Urology at Northwell Health Memorial Sloan Kettering Cancer Center
Lake Success, NY, USA New York, NY, USA
Laurel Northouse, PhD Susan K. Peterson, PhD, MPH
Professor Emerita Professor
School of Nursing Department of Behavioral Science
University of Michigan The University of Texas MD Anderson Cancer Center
Ann Arbor, MI, USA Houston, TX, USA
Wynne E. Norton, PhD Laura C. Polacek, MA
Program Director Graduate Student
Division of Cancer Control and Population Sciences Department of Psychology
National Cancer Institute Fordham University
Bethesda, MD, USA The Bronx, NY, USA
Marinel Olivares, LCSW, ACHP-​SW Holly G. Prigerson, PhD
Clinical Social Worker Irving Sherwood Wright Professor in Geriatrics
Adult Hematology/​Hematopoietic Cell Transplantation Professor of Sociology in Medicine
Director, Family Meeting Program Director
Department of Supportive Care Medicine Cornell Center for Research on End-​of-​Life Care
City of Hope National Medical Center New York, NY, USA
Duarte, CA Douglas S. Rait, PhD
Jamie Ostroff, PhD Clinical Professor of Psychiatry and Behavioral Sciences
Chief, Behavioral Sciences Service Chief, Couples and Family Therapy Clinic
Vice Chair for Research Department of Psychiatry and Behavioral Sciences
Member and Attending Psychologist Stanford University
Director, Tobacco Treatment Program Stanford, CA, USA
Department of Psychiatry and Behavioral Sciences Kavitha Ramchandran, MD
Memorial Sloan Kettering Cancer Center Clinical Associate Professor
New York, NY, USA Department of Medicine
Ray Owen, DClinPsych, Cpsychol, FHEA Stanford University
Consultant Clinical Psychologist Stanford, CA, USA
Health Psychology Department Nicole Rankin, BA(Hons), MSc, PhD
Wye Valley NHS Trust Senior Research Fellow
Hereford, UK Faculty of Medicine and Health
Maryland Pao, MD The University of Sydney
Clinical and Deputy Scientific Director Camperdown, NSW, Australia
Department of NIMH Chelsea S. Rapoport, BA
National Institutes of Health (NIH) Clinical Research Coordinator
Bethesda, MD, USA Department of Psychiatry
Patricia A. Parker, PhD Massachusetts General Hospital
Attending Psychologist Boston, MA, USA
Behavioral Sciences Service Julie Rathwell, MPH
Director, Communication Skills Training and Research Program Research Project Specialist, Sr.
Department of Psychiatry and Behavioral Sciences Department of Cancer Epidemiology
Member, Memorial Hospital Moffitt Cancer Center
Memorial Sloan-​Kettering Cancer Center Tampa, FL, USA
New York, NY, USA
Paula K. Rauch, MD
Steven D. Passik, PhD Director, Marjorie E. Korff Parenting at a Challenging Time Program
Vice President, Department of Psychiatry
Scientific Affairs, Education and Policy Massachusetts General Hospital
Collegium Pharmaceuticals Boston, MA, USA
Stoughton, MA, USA
Claudia Redeker, MSc
Frank J. Penedo, PhD PhD Student
Professor Department of Psychology
Department of Psychology and Medicine Birkbeck College
University of Miami Bloomsbury, London, UK
Miami, FL, USA
Lee M. Ritterband, PhD
Samara Perez, PhD Professor
Research Associate Department of Psychiatry and Neurobehavioral Sciences
Department Lady Davis Institute for Medical Research Jewish University of Virginia
General Hospital Charlottesville, VA, USA
Clinical Psychologist
Psychosocial Oncology Program
McGill University Health Center
Montreal, QC, Canada
xxiv Contributors

Kailey E. Roberts, PhD Sally Saban, BA

Research Fellow Clinic Research Coordinator
Department of Psychiatry and Behavioral Sciences Department of Surgery
Memorial Sloan Kettering Cancer Center New York, NY, USA
New York, NY, USA Victoria Saltz
Gary Rodin, MD Student
Head of Department Williams College
Department of Supportive Care New York, NY, USA
Princess Margaret Cancer Centre Chase Samsel, MD
University Health Network Attending Physician
Professor Department of Psychiatry
Department of Psychiatry Boston Children’s Hospital and Dana-​Farber Cancer Institute
Faculty of Medicine Boston, MA, USA
Director
Sheila J. Santacroce, PhD, RN, CPNP, FAANP
Global Institute of Psychosocial, Palliative and End-​of-​Life Care
Associate Professor
University of Toronto
School of Nursing
Toronto, ON, Canada
University of North Carolina
James C. Root, PhD Chapel Hill, NC, USA
Associate Attending Neuropsychologist
Rebecca M. Saracino, PhD
Psychiatry Service
Assistant Attending Psychologist
Department of Psychiatry and Behavioral Sciences
Psychiatry Service
Memorial Sloan Kettering Cancer Center
Department of Psychiatry and Behavioral Sciences
New York, NY, USA
Memorial Sloan Kettering Cancer Center
Zeev Rosberger, PhD New York, NY, USA
Senior Investigator and Associate Professor
M. Claire Saxton, MBA
Departments of Oncology, Psychiatry, and Psychology
Vice President
Lady Davis Institute for Medical Research
Department of Education and Outreach
Institute of Community and Family Psychiatry
Cancer Support Community
Jewish General Hospital
Washington, DC, USA
Gerald Bronfman Department of Oncology
McGill University Christian Schulz-​Quach, MD, MSc, MA
Montréal, QC, Canada Assistant Professor
Department of Psychiatry
Barry Rosenfeld, PhD
University of Toronto
Professor
Toronto, ON, Canada
Chairman
Department of Psychology Lisa A. Schwartz, PhD
Fordham University Associate Professor
Consultant Psychologist Department of Pediatrics/​Oncology
Psychiatry Service The Children’s Hospital of Philadelphia
Department of Psychiatry and Behavioral Sciences Philadelphia, PA, USA
Memorial Sloan Kettering Cancer Center Michael Schwartz, MD, FACS
New York, NY, USA Associate Professor
Andrew J. Roth, MD Smith Institute for Urology
Attending Psychiatrist Northwell Health
Psychiatry Service New Hyde Park, NY, USA
Department of Psychiatry and Behavioral Sciences Peter A. Selwyn, MD, MPH
Memorial Sloan Kettering Cancer Center Professor and Chair
Professor of Clinical Psychiatry Department of Family and Social Medicine
Weill Cornell Medical College Director, Palliative Care Program
New York, NY, USA Montefiore Medical Center
Julia Ruark, MD, MPH Albert Einstein College of Medicine
Attending Psychiatrist The Bronx, NY, USA
Department of Psychosocial Oncology Kelly M. Shaffer, PhD
Seattle Cancer Care Alliance Assistant Professor
Seattle, WA, USA Center for Behavioral Health and Technology, Department of Psychiatry and
Elizabeth Ryan, PhD, ABPP-​CN Neurobehavioral Sciences
Associate Attending Neuropsychologist University of Virginia School of Medicine
Psychiatry Service Charlottesville, VA, USA
Department of Psychiatry and Behavioral Sciences Mehak Sharma, MD
Memorial Sloan Kettering Cancer Center Assistant Attending Psychiatrist
New York, NY, USA Psychiatry Service
Adam Rzetelny, PhD Department of Psychiatry and Behavioral Sciences
Senior Medical Science Liaison Memorial Sloan Kettering Cancer Center
Department of Medical Affairs New York, NY, USA
Collegium Pharmaceuticals
Maplewood, NJ, USA
 Contributors xxv

Louise Sharpe, BA(Hons), MPsychol, PhD Manuel Trachsel, MD, PhD

Professor of Clinical Psychology Head Clinical Ethicist
Department of Psychology Clinical Ethics Unit
The University of Sydney University Hospital of Basel/​University of Zurich
Camperdown, NSW, Australia Zürich, ZH, Switzerland
Michael Sharpe, MA, MD Lara Traeger, PhD
Professor of Psychological Medicine Assistant Professor
Department of Psychiatry Department of Psychiatry
University of Oxford Massachusetts General Hospital/​Harvard Medical School
Oxford, UK Boston, MA, USA
Vani N. Simmons, PhD Kelly M. Trevino, PhD
Senior Member Associate Attending Psychologist
Department of Health Outcomes and Behavior Psychiatry Service
Moffitt Cancer Center Department of Psychiatry and Behavioral Sciences
Tampa, FL, USA Memorial Sloan Kettering Cancer Center
Allan B. Smith, PhD New York, NY, USA
Co-​Deputy Director (Policy and Practice) Jane Turner, MBBS, PhD, FRANZCP
Centre for Oncology Education and Research Translation (CONCERT) Professor
Ingham Institute for Applied Medical Research Department of Psychiatry
Liverpool, NSW, Australia The University of Queensland
Jennifer Sotsky, MD, MS Brisbane, Australia
Clinical Fellow Lisa Tussing-​Humphreys, PhD, MS, RD
Department of Psychiatry Associate Professor
New York State Psychiatric Institute Department of Medicine Co-​leader, Cancer Prevention and Control Program,
New York, NY, USA Cancer Center
Nadia van der Spek, PhD University of Illinois
Assistant Professor Chicago, IL, USA
Licensed Mental Health Care Psychologist Susan T. Vadaparampil, PhD, MPH
Department of Clinical Psychology Associate Center Director, Community Outreach, Engagement, and Equity
Vrije Universiteit Amsterdam Department of Health Outcomes and Behavior
Amsterdam, The Netherlands Moffitt Cancer Center
Kevin Stein, PhD, FAPOS Tampa, FL, USA
Associate Professor (Adjunct) Annalyn Valdez-​Dadia, DrPH, MPH
Department of Behavioral Sciences and Health Education Assistant Professor
Rollins School of Public Health Department of Human Services
Snellville, GA, USA California State University, Dominguez Hills
Chelsea R. Stone, MSc Carson, CA, USA
Research Associate Alan D. Valentine, MD
Department of Cancer Epidemiology and Prevention Research Professor and Chair
Alberta Health Services Department of Psychiatry
Calgary, AB, Canada MD Anderson Cancer Center
Sarah J. Tarquini, PhD The University of Texas
Senior Psychologist Houston, TX, USA
Department of Psychosocial Oncology and Palliative Care Sally W. Vernon, MA, PhD
Dana-​Farber Boston Children’s Cancer and Blood Disorders Center Professor
Boston, MA, USA Department of Health Promotion and Behavioral Science
Ovidiu Tatar, MD, MSc University of Texas School of Public Health
Research Associate Houston, TX, USA
Psychosocial Oncology Lady Davis Institute for Medical Research Froukje de Vries, MD, PhD
Jewish General Hospital Research Center-​Centre Hospitalier Psychiatrist
de l'Université de Montréal (CRCHUM) Department of Supportive Care
Montréal, QC, USA Princess Margaret Cancer Centre, University Health Network
Kim Thiboldeaux, BA Communications Toronto, ON, Canada
CEO Claire E. Wakefield, BPsych(Hons), MPH, PhD
Cancer Support Community Professor
Washington, DC, USA School of Women’s and Children’s Health and Kids Cancer Centre
Teresa H. Thomas, PhD, RN UNSW Sydney and Sydney Children’s Hospital
Assistant Professor North Willoughby, NSW, Australia
School of Nursing Leah E. Walsh, MS
University of Pittsburgh Doctoral Student
Pittsburgh, PA, USA Department of Psychology
Amanda L. Thompson, PhD Fordham University
Chief, Pediatric Psychology The Bronx, NY, USA
Department of Life with Cancer
Inova Schar Cancer Institute
Fairfax, VA, USA
xxvi Contributors

Linda D. L. Wang, PhD Joseph T. Wu, PhD, BS

Associate Professor Professor
Department of Clinical Medicine School of Public Health
Medical College of Yangzhou University The University of Hong Kong
Yangzhou, Jiangsu, China Hong Kong, China
Maggie Watson, BSc, Dip Clin Psych, PhD Robert Zachariae, DMSc
Honorary Professor Professor
Research Department of Clinical, Educational and Health Psychology Unit for Psycho-​oncology and Health Psychology
University College London Aarhus University
Institute of Cancer Research Aarhus, Denmark
London, UK Talia I. Zaider, PhD
Amanda Watsula-​Morley, MA Assistant Attending Psychologist
Clinical Research Supervisor Psychiatry Service
Department of Psychiatry and Behavioral Sciences Department of Psychiatry and Behavioral Sciences
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center
New York, NY, USA New York, NY, USA
Jason A. Webb, MD, FAPA, FAAHPM Alexandra K. Zaleta, PhD
Director of Education, Duke Center for Palliative Care Associate Professor Senior Director of Research
Department of Medicine, Department of Psychiatry and Behavioral Sciences Department of Research and Training Institute
Duke University Cancer Support Community
Durham, NC, USA Philadelphia, PA, USA
Lori Wiener, PhD, DCSW, FAPOS Bradley J. Zebrack, MSW, MPH, PhD
Co-​Director, Behavioral Health Care, Professor
Director, Psychosocial Support and Research Program School of Social Work
Department of Pediatric Oncology Branch, University of Michigan
National Cancer Institute, Center for Cancer Research Ann Arbor, MI, USA
National Institutes of Health
Bethesda, MD, USA
Irene O. L. Wong, BSc, MPhil, MMedSci, PhD
Scientific Officer
School of Public Health
The University of Hong Kong
Hong Kong, China
Introduction
Our Past, Our Future—New Frontiers in Psycho-​Oncology
William S. Breitbart (Senior Editor)
Introduction
This textbook, Psycho-​Oncology, 4th edition, is the first edition of this
series of textbooks, which have defined the field of psycho-​oncology,
to be edited without Jimmie C. Holland as the senior editor. Jimmie’s
imprint on these textbooks and on our international field has resulted
in these textbooks often being referred to as the “Holland Textbook
of Psycho-​Oncology”—​that is, when it isn’t, perhaps somewhat sacri-
legiously, being referred to as the “Bible of Psycho-​Oncology.” Hence,
those of us who have taken on the both sacred and significant responsi-
bility of editing this 4th edition of Psycho-​Oncology have done so with a
sense of both sadness and honor. The field of psycho-​oncology is truly
interdisciplinary and international, and so it is fitting that the editors
and contributors to this 4th edition are indeed truly international and
represent multiple disciplines. As senior editor, I have been blessed to
have the magnificent talents of the following luminaries in our field
as associate editors: Phyllis N. Butow, BA(Hons), DipEd, MClinPsych,
MPH, PhD, of the University of Sydney; Paul B. Jacobsen, PhD, of the
U.S. National Cancer Institute; Wendy W. T. Lam, RN, PhD, FFPH,
of the University of Hong Kong; Mark Lazenby, APRN, PhD, of the
University of Connecticut School of Nursing; and Matthew J. Loscalzo,
MSW, LCSW, FAPOS, of the City of Hope. Their contributions to the
quality of this textbook will be quite evident to the reader. Each of the
editors of this textbook has had a direct and often life-​changing expe-
rience through a long-​standing relationship with Jimmie Holland, and
our dedication to preserving her legacy is on every page of this text.
I do want to take a moment to personally thank Andrea Knobloch,
our editor at Oxford University Press, and her team; the personal as-
sistants of many of the editors and contributors; and most significantly
Laurie Schulman, who served as managing editor of this textbook
and dedicated more than a year of time, energy, and devotion to as-
sisting me in seeing this project through—​even through the interrup-
tions of the coronavirus pandemic. Lastly, our deep appreciation goes
to the International Psycho-​Oncology Society (IPOS), the American
Psychosocial Oncology Society (APOS), and the several hundred au-
thors who contributed more than 100 chapters to this textbook.
Our Past
Jimmie C. Holland, or “Jimmie,” as the world of psycho-​oncology
knew her, is often credited as being the founder or “mother” of
psycho-​ oncology. Interestingly, Jimmie hated being called the
“mother” of psycho-​oncology. It particularly irked her when, as she
got older, this term changed to “grandmother” of psycho-​oncology.
Jimmie much preferred these titles/​roles to be reserved for her per-
sonal life—​her family, her beloved children and grandchildren. But
after all, she was a “Cicely Saunders–​type” figure in a new movement
within oncology, and so she was revered and mythologized in ways
that did not make her comfortable. As many who knew Jimmie will
attest, she was in fact somewhat shy and quite humble, quick to give
credit to others, and eager to accelerate the career trajectories of the
next generations of clinicians, scientists, and leaders of our field. That
isn’t to imply that she didn’t have very strong opinions or have envi-
able political skills, but she clearly used those skills for the benefit of
patients, the field, and the movement. Jimmie and I would often sit
in her office at the end of the day and discuss just about everything
one can imagine related to work, projects, our field, and politics (and
some gossip). There was nothing off limits. Interestingly, we did fre-
quently talk about the origins of psycho-​oncology and individuals
she felt never quite received enough recognition for their roles in the
creation of our field. That is, in part, why she urged the creation of
the IPOS Arthur Sutherland Award. Jimmie always felt that she had
received too much credit for founding the field of psycho-​oncology
and was eager for there to be recognition of such pioneers in our
field as Margit Von Kerekjarto, Robert Zitoun, Hiroomi Kawano,
Steven Greer, Lea Baider, Peter Maguire, Bernard Fox, Juan Ignacio
Romero, Avery Weissman, Edwin Cassem, Noemi Fisman, Maria
Margarida Carvalho, Morton Bard, and Arthur Sutherland himself.
One early pioneer has remained quite obscure and
underrecognized for over 50 years, and Jimmie and I became quite
fascinated with this figure. I became interested because he, like my
parents, was a Holocaust survivor. Jimmie, I believe, became fascin-
ated because he was also someone who had overcome severe phys-
ical disabilities (reminding Jimmie of her early days working with
polio patients). Loma Feigenberg was a physician at the Karolinska
Institute in Stockholm. In the 1950s, as an oncologist and radiother-
apist, he noted the lack of attention in addressing the psychological
responses of patients with advanced cancer. He later studied psy-
chiatry and began to work with cancer patients at the Karolinska.
He made what he called a “friendship contract” with them in which
he agreed to “confidentiality” of the content of their “sessions” and
made a commitment to ongoing care and support during their cancer
treatment. His book, Terminal Care: A Method for Psychological Care
2 Psycho-Oncology
of Dying Patients, is a landmark text.1 Feigenberg did finally receive
the Distinguished Life Service Award from the IPOS in 1987. He
also founded the International Work Group for Death, Dying and
Bereavement (IWG), an early beginning of thanatology.
However, Dr. Holland’s efforts over the last 43 years, since be-
coming the founding chief of the Psychiatry Service at Memorial
Sloan Kettering Cancer Center, have indeed brought her well-​
deserved recognition as the founder and past leader of the field of
psycho-​oncology. Having founded the IPOS in 1984 and the APOS in
1986, Dr. Holland went on to edit the first major textbooks of psycho-​
oncology for our field. This textbook, Psycho-​Oncology, 4th edition,
was preceded by four major textbooks that defined our field. In 1989,
Dr. Holland edited the Handbook of Psychooncology: Psychological
Care of the Patient with Cancer, the first major textbook in our field.2
This landmark book (coedited with Julia Rowland, PhD) established
our “new” field and virtually named the field “psycho-​oncology.” The
follow-​up textbook Psycho-​Oncology was published in 1998 and rep-
resented the most comprehensive, multidisciplinary, and interna-
tional encyclopedia of a field entering its adolescence.3 The year 2010
saw the publication of the 2nd edition,4 followed by the 3rd edition5
in 2015, both published by Oxford University Press in collaboration
with the IPOS and APOS. The field of psycho-​oncology was now
mature, rich, and filled with talented, creative, and innovative clin-
icians, scientists, advocates, and global leaders like Maggie Watson,
Luigi Grassi, Uwe Koch, David Kissane, Christoffer Johansen, Luzia
Travado, Barry Bultz, Maria Die Trill, Gary Rodin, Cristina Bolund,
Bill Redd, Anja Mehnert, Francisco Gil, David Spiegel, Joan Bloom,
Harvey Chochinov, Barbara Andersen, Jamie Ostroff, Phyllis Butow,
Paul Jacobsen, Richard Fielding, Matt Loscalzo, Leslie Fallowfield,
Pierre Gagnon, Jeff Dunn, Mitch Golant, Mary Jane Esplen, Sharon
Manne, Jane Turner, David Cella, Elisabeth Andritsch, Pat Fobair,
Irma Verdonck-​de Leeuw, Michael Antoni, James Zabora, and nu-
merous others (apologies to anyone who deserved mention and was
omitted unintentionally; noninclusion in this list means you’re not
an old-​timer and are part of the new wave, the vital leaders of the
future of our field).
With the publication of this textbook, Psycho-​Oncology, 4th edi-
tion, we take this moment to both look to our past and start to ex-
amine our future as a field. We have a rich legacy given to us by so
many of the pioneers of psycho-​oncology mentioned earlier. In fact,
this textbook is dedicated to the memory of Jimmie C. Holland and
we honor her and all the past editors and contributors to the prior
editions of this text by moving forward with the creation of what
we hope readers will someday view as a milestone textbook itself.
Of note, two former associate editors of several of the prior editions
of this series of textbooks died in 2019 as this 4th edition was being
prepared. We are indebted to and honor the contributions and lives
of Ruth McCorkle and Marguerite Lederberg—​ two remarkable
women who were cherished by so many of us, worldwide. Ruth was
an editor of several editions of the textbook and so we also dedicate
this textbook in her honor as well as in Jimmie’s.
Our Future
We, the editors of this 4th edition of Psycho-​Oncology, undertook
a careful examination of the content of the 3rd edition of Psycho-​
Oncology, as well as the expert authors who contributed their
expertise. We were particularly interested in two aspects of the
purpose of the Psycho-​Oncology textbook’s purpose: (1) to serve
as the source textbook that provided the broadest and most mul-
tidisciplinary and essential science and practice of the field of
psycho-​oncology, and (2) to bring to our field the newest and latest
innovations and cutting-​edge research and clinical practice that
would equip our readers with the knowledge and resources to be
knowledgeable and to participate in the “new frontiers of psycho-​
oncology.” We feel we have accomplished this delicate but critical
balance in the 4th edition of Psycho-​Oncology.
We’ve maintained many of the basic but critical aspects of pre-
vention, screening, assessment, and management of basic common
psychosocial and psychiatric issues in psycho-​oncology, including
cancer site–​specific psychosocial issues and management. As much
as possible, these cancer site–​specific chapters also include some
basic, updated oncological diagnostic and treatment-​related infor-
mation that is vital for clinicians and clinical researchers in our field.
There are, however, a number of new sections that represent new
developments in basic psycho-​oncology science, breakthroughs in
health care delivery, growth in treating special cancer populations,
and innovative and novel evidence-​based interventions that are
changing the landscape of treatment, and a growing international
perspective that our field has developed over recent years.
Allow me to briefly highlight some of the updates and new sections
in the 4th edition of Psycho-​Oncology that are designed to prepare
psycho-​oncologists for the “new frontiers of psycho-​oncology”:
1. Evidence-​Based Interventions: We have dramatically expanded
this section of the textbook and now include a variety of inno-
vative novel interventions with a significant evidence base for
efficacy. We’ve divided the interventions into models of care
delivery and phases of illness. Models of Care Delivery now in-
cludes the following:
(a) Collaborative and Integrated Models of Psychosocial
Oncology Care, Community-​ Based Care, and
Implementation Science’s Role in Care Delivery
(b) Family and Couples Interventions
(c) Interventions at various stages of illness including Active
Treatment, Advanced Disease, and Survivorship, as well
as novel interventions including Cognitive-​ Behavioral
Interventions, Mindfulness-​Based Interventions, Acceptance
and Commitment Therapy, Interpersonal Therapy,
Supportive-​ Expressive Psychotherapy, and Meaning-​
Centered Psychotherapy for advanced cancer patients, for
bereavement, survivors, and for caregivers, in addition to
CALM Therapy, Dignity Therapy, Emotionally Focused
Therapy, Metacognitive Approaches, Integrative Oncology
Interventions, and Physical Activity Interventions. We had
hoped to include Light Therapy, but that was not possible.
2. Digital Health Interventions: We have an expanded section
on e-​health intervention delivery, which ranges from preven-
tion, smoking cessation, and psychosocial distress to Physical
Symptom Control.
3. Biobehavioral Psycho-​Oncology: We have included the first
ever section on the science of stress and cancer risk and pro-
gression. We have wonderful contributions from Mike Antoni
and coauthors of Stress Processes and Cancer Progression;
Depression, Inflammation, and Cancer from Andrew Miller and

coauthors; and Biobehavioral Psycho-​Oncology Interventions
from Michael Hoyt and Frank Penedo. This somewhat contro-
versial area of psycho-​oncology research has now reached a
level of maturity and there are evidence-​based findings of which
all psycho-​oncologists must be aware.
4. Geriatric Oncology: This is a growing field in psycho-​oncology.
This section includes chapters on screening, assessment, inter-
ventions, and communications issues specific to managing
older cancer patients. Christian Nelson, Andrew Roth, Kelly
Trevino, Patricia Parker, Beatriz Korc-​Grodzicki, and Yesne
Alici were the primary contributors to this section. Their con-
tributions acknowledge the pioneering work of our late friend
and colleague Arti Hurria.
5. Pediatric Psycho-​Oncology: For the very first time, Pediatric
Psycho-​Oncology is fully included and represented in the
Psycho-​Oncology series of textbooks. This section has chap-
ters on pediatric psycho-​oncology screening and assessment,
management of common psychiatric disorders, evidence-​
based interventions in pediatric psycho-​oncology, and ad-
olescent and young adults with cancer. The contributors to
these sections include the leaders of the field—​Anne Kazak,
Maryland Pao, Julia Kearney, Lori Wiener, Anna Muriel, and
Bradley Zebrack.
6. Survivorship: This section has been expanded and has inter-
esting new information on approaches to Fear of Recurrence in
Cancer Survivors.
7. Palliative Care and Advanced Planning: These chapters focus
on the need to focus on treatment decision making; discus-
sion of advance care planning and care goals at the time of
diagnosis—​early in the course of life-​threatening cancer; and
prognostic awareness and the role of the psycho-​oncologist in
palliative care. The interface of psycho-​oncology and palliative
care is a critically important one that needs to be navigated with
a sense of collaboration and integration. Michael Diefenbach,
Stefanie Mooney, Scott Irwin, Barry Rosenfeld, and Allison
Applebaum and their coauthors have contributed outstanding
chapters.
8. Diversities in the Experience of Cancer: This expanded new
section addresses the important issues of cancer and cul-
ture; cancer disparities; access to care and food; financial and
housing insecurities; cancer and sexual minorities; and the ex-
perience of cancer as an immigrant. The contributors to this
section include leaders in these areas such as Marjorie Kagawa-​
Singer, Francesca Gany, Victoria Blinder, Jennifer Leng, and
Charles Kamen.
9. Behavioral and Psychological Factors in Cancer Risk;
Screening for Cancer in Normal and At-​Risk Populations:
These sections have been expanded and include a broad inter-
national perspective. Contributors include many luminaries
such as Christoffer Johansen, Jamie Ostroff, Richard Fielding,
Jennifer Hay, Gabriel Leung, and many others.
10. Screening and Testing for Germ Line and Somatic Mutations:
With the advent of precision oncology and therapies targeted
at actionable tumor mutations, psycho-​oncologists have had
to learn a great deal about genetics, and now we have begun
to explore the various psychosocial sequelae and the need for
Our Past, Our Future 3
counseling presented by this revolution in medical oncology.
This section has chapters on genetic testing in breast and
ovarian cancer, testing in hereditary cancers, genomic testing
for targeted therapies, and psychosocial issues related to large-​
scale liquid biopsy screening for mutations in normal and at-​
risk populations. Mary Jane Esplen, Susan Peterson, Megan
Best, Jada Hamilton, and their coauthors have contributed out-
standing chapters.
11. Screening and Assessment in Psychosocial Oncology: We’ve
experienced a revolution in screening and brief assessments
of patients at risk for distress, anxiety, depression, delirium
and cognitive disorders, suicidal ideation, and uncontrolled
symptoms. This section addresses many of these issues. Paul
Jacobsen, Kristine Donovan, Alex Mitchell, Tim Ahles, James
Root, Bill Breitbart, Yesne Alici, and their colleagues have con-
tributed outstanding chapters.
12. Building Supportive Care Teams; Psycho-​Oncology in Health
Policy: These sections are expanded and have a broad interna-
tional perspective.
Informed by Our Past, Inspired to Create a
Better Future
We have a great legacy. That is the gift our field has received from its
pioneers. We human beings engage in what is termed “cumulative
learning.” We build upon the wisdom and knowledge chronicled by
those who came before us. Einstein’s work on gravity could not have
taken place without building upon our knowledge of the chronicled
work of Newton. We are building upon the knowledge accumulated
and documented by psycho-​oncologists who dedicated their work
to establishing and growing a base of research and clinical innova-
tion over the last 50 years. It is our responsibility to contribute to this
“cumulative” knowledge base and move our field forward to better
“care for the whole person with cancer.” Our hope is that you, the
readers of the 4th edition of Psycho-​Oncology, feel we have made a
valuable contribution to fulfilling the solemn responsibility we have
inherited: to create a better future.
William S. Breitbart, MD, FAPOS
Senior Editor
Psycho-​Oncology, 4th edition
REFERENCES
1. Feigenberg L. Terminal care: Friendship contracts with dying
cancer patients. New York, Brunner/​Mazel, 1980.
2. Holland JC, Rowland J, Eds: Handbook of Psychooncology.
New York, Oxford University Press, 1989.
3. Holland JC, Breitbart WS, Jacobsen PB, Lederberg MS, Loscalzo
M, Massie MJ, McCorkle R, Eds: Psycholo-​Oncology. New York,
Oxford University Press, 1998.
4. Holland JC, Breitbart WS, Jacobsen PB, Lederberg MS, Loscalzo
M, McCorkle R, Eds: Psycho-​Oncology 2nd Edition. New York,
Oxford University Press, 2010.
5. Holland JC, Breitbart WS, Butow PN, Jacobsen PB, Lederberg
MS, Loscalzo M, McCorkle R, Eds: Psycho-​Oncology 3rd Edition.
New York, Oxford University Press, 2015.
SECTION I
Behavioral and Psychological
Factors in Cancer Risk and
Prevention
Paul B. Jacobsen (Section Editor)

1 Tobacco Use and Cessation 7 4 Sun Exposure and Cancer Risk 30

Thomas H. Brandon, Vani N. Simmons, Úrsula Martínez, and Suzanne J. Dobbinson, Afaf Girgis, Bruce K. Armstrong,
Patricia Calixte-Civil and Anne E. Cust
2 Diet and Cancer 13 5 Psychosocial Factors 36
Marian L. Fitzgibbon, Lisa Tussing-Humphreys, Angela Kong, Anika von Heymann and Christoffer Johansen
and Alexis Bains
6 Viral Cancers and Behavior 43
3 Physical Activity, Sedentary Behavior, Susan T. Vadaparampil, Lindsay N. Fuzzell,
and Cancer 21 Shannon M. Christy, Monica L. Kasting, Julie Rathwell,
Christine M. Friedenreich, Chelsea R. Stone, and Anna E. Coghill
and Jessica McNeil
1
Tobacco Use and Cessation
Thomas H. Brandon, Vani N. Simmons, Úrsula Martínez, and Patricia Calixte-​Civil
Tobacco and Cancer
Each year over 7 million people die worldwide due to tobacco use.1
Smoking is responsible for about 22% of all cancer deaths globally.
It accounts for over two-​thirds of all lung cancer mortalities and
contributes significantly to mortality rates for oral cancer, as well as
bladder, stomach, liver, pancreas, kidney, cervical, and colorectal can-
cers.2 In addition to cancer, smoking contributes to coronary heart di-
sease, chronic obstructive pulmonary disease, cardiovascular disease,
stroke, and peptic ulcers. Indeed, about 20% of all deaths in the United
States can be attributed to smoking. From the individual perspective,
a given smoker has about a 50% chance of dying from smoking, with
the average smoker living 10 years less than a nonsmoker.3 Although
there are risks associated with noncombustible tobacco use (e.g., chew,
snuff), this chapter focuses on combustible tobacco use (i.e., smoking)
because of its much higher prevalence and relative risk. Nevertheless,
patients should be advised to cease all forms of tobacco use.
Smoking cessation is associated with decreased mortality and
morbidity from cancer and other diseases. Stopping smoking at age
30 restores nine years of life expectancy, whereas stopping at age 60
still restores an expected three years of life, compared to continuing
to smoke.3 Thus, great potential for cancer prevention lies with long-​
term cessation of smoking. In this chapter, we begin by noting the
changing demographic profile of current smokers. We then review
the evidence-​based treatments for tobacco use and dependence, em-
phasizing primarily qualitative and meta-​analytic reviews. We draw
upon the 2008 update of the U.S. Public Health Service’s Clinical
Practice Guideline, Treating Tobacco Use and Dependence,4 which is
based on a review of 8,700 research articles, with treatment recom-
mendations derived from meta-​analyses of most treatment modal-
ities. We then discuss special issues of relevance for treating cancer
patients. New to this update is a discussion of electronic cigarettes
(e-​cigarettes), the use of which has grown exponentially over the
past decade, including among cancer patients.
Evolving Landscape of Tobacco and Nicotine Use
Changing Demographics of Tobacco Users
Several countries have implemented strategies toward reducing
tobacco burden, such as monitoring tobacco use, offering access
to smoking cessation interventions, increasing tobacco taxes, or
introducing public warnings about the dangers of tobacco use.
Although these actions have led to a global reduction in tobacco use
in most developed countries, these nations still account for half of all
female daily smokers and roughly 75% of male daily smokers. Efforts
to reduce tobacco use have been successful in developed countries,
and they should be bolstered in developing countries (i.e., coun-
tries with historically lower education, per capita income, and life
expectancy). Developing countries have shown moderate smoking
prevalence across time, but many of these nations are showing in-
creases in the prevalence of smoking and smoking-​related mortality
that are commensurate with increases in income, decreases in the
cost of tobacco, heavier marketing from the tobacco industry, and
limited tobacco-​related public health policies. As such, developing
countries are vulnerable to assuming the burden of the tobacco
epidemic.1 Moreover, tobacco use burden is disproportionately af-
fecting certain segments of the population worldwide. For example,
tobacco use is rapidly increasing among youth, especially females,
in developing countries, and it is highly prevalent among individ-
uals with low income across nations, regardless of per capita gross
national income.5
In the U.S., since the seminal 1964 U.S. Surgeon General’s report,
the prevalence of smoking among adults has dramatically declined
from nearly half of adults to less than one in five.6 The current dem-
ographic profile of smokers is markedly different than decades ago
because the reduction in smoking prevalence has not been con-
sistent across demographic groups. These differences in prevalence
of tobacco use are associated with differential burdens of tobacco-​
related morbidity and mortality. In particular, a substantial body
of evidence demonstrates that lower educational attainment, being
below the poverty level, identifying as American Indian/​Alaska
Native, living in the Midwest or South, working in a blue-​collar or
service industry, having active military or veteran status, having a
disability, having a severe mental illness, and not having health in-
surance are associated with higher prevalence of smoking in the U.S.
There are also more recent changes in the demographics of to-
bacco users that coincide with shifts in the racial/​ethnic composition
of the U.S. and/​or more inclusive data collection. That is, subgroups
who identify as more than one race/​ethnicity, as sexual or gender
minorities, or as immigrants report greater tobacco use. Regarding
race/​ethnicity, although Hispanics and non-​Hispanic Asians have
8 SECTION I Factors in Cancer Risk and Prevention
among the lowest smoking prevalence by race/​ethnicity (12.7% and
8%, respectively), there is wide variation in smoking behavior within
the subgroups and across gender. Among foreign-​born men living
in the U.S., 24.8% of Mexicans, 47.7% of Filipinos, and 52.7% of
Chinese people reported being current smokers, which is of partic-
ular relevance to healthcare in the United States given that Mexico,
the Philippines, and China represent three of the top five countries
with the largest populations of foreign-​born individuals in the U.S.
In 2010 alone, 29.3% of all immigrants living in the U.S. were from
Mexico. Thus, the distribution of tobacco use and its consequent
health and economic burdens are unequal and shifting, requiring
attention by both researchers and clinicians.
The Emergence of Electronic Cigarettes
E-​cigarette use has grown dramatically in the last 10 years. E-​
cigarettes include a battery and heating element that aerosolizes a
liquid that typically contains nicotine, flavorants, propylene glycol,
and vegetable glycerin. Since their introduction, the available prod-
ucts have expanded and evolved in terms of their ease of use, their
sophistication, and their efficiency of nicotine delivery. The newest
devices deliver a nicotine dose similar to a combustible cigarette,
while also simulating the sensorimotor aspects of smoking (e.g.,
hand and arm movements, puffing and inhalation behavior, and
visible exhalation). Theoretically, these similarities should ease the
transition from combustible cigarettes to e-​cigarettes. Although
there have been regulatory barriers to conducting randomized con-
trolled trials of e-​cigarettes for smoking cessation, evidence of their
efficacy is now emerging.7 However, e-​cigarettes have generated a
magnitude of controversy and division never before seen in the to-
bacco control and research fields. The current scientific consensus
is that e-​cigarettes are substantially less harmful than combustible
cigarettes,8 and therefore complete switching from smoking to
“vaping” represents significant harm reduction at the individual and
population levels. However, there is growing concern about the re-
cent uptake of vaping by youth and the unknown long-​term health
outcomes of this behavior. The primary public health challenge re-
lated to tobacco use is to develop policy that promotes switching by
current smokers while minimizing uptake of vaping by youth who
would not have otherwise used nicotine products.
Treatment of Tobacco Use and Dependence
Tobacco dependence has multiple motivational influences within
and across individual smokers.9 Among these are physical depend-
ence on nicotine, operant and classical conditioning processes, en-
vironmental and social factors, cognitive expectancies about the
benefits of smoking, and desire for weight control. Given the com-
plexity of the factors influencing smoking, it is not surprising that
single-​treatment approaches have limited success, with the best
long-​term outcomes obtained from multimodal treatments. In this
section, we review pharmacological interventions, followed by so-
cial/​behavioral interventions, broadly defined, and finally discuss
combination treatments.
Pharmacotherapy
Currently, there are seven pharmacotherapies approved by the U.S.
Food and Drug Administration (FDA) for smoking cessation. All of
these medications have been found to approximately double the odds
of long-​term abstinence (with one, varenicline, tripling the odds),
and the Clinical Practice Guideline issued by the U.S. Department of
Health and Human Services recommends that pharmacotherapy be
routinely offered to smokers attempting to quit.4
Nicotine Replacement Therapies
Nicotine replacement therapy (NRT) aids smoking cessation by
partially replacing plasma nicotine levels, thereby reducing symp-
toms of nicotine withdrawal (e.g., craving, depression, irritability,
difficulty concentrating) and possibly reducing the reinforcement
derived from any cigarettes smoked. Five types of NRT have FDA
approval: chewing gum, transdermal patch, intranasal spray, in-
haler device, and lozenge. In general, NRT is used during the first
8–​12 weeks of abstinence, when nicotine withdrawal symptoms are
greatest. Of the five NRT delivery methods, the nicotine nasal spray
reaches its peak concentration most rapidly, whereas the trans-
dermal patch provides the slowest, but most consistent, serum nico-
tine levels over the course of a day.
Meta-​analyses indicate roughly equivalent efficacies for the five
NRT products, with odds ratios ranging from 1.5 (for nicotine gum)
to 2.3 (for nasal spray) compared to placebo.4 Estimated six-​month
abstinence rates are approximately 20%–​25%. Each product is as-
sociated with specific contraindications and cautions, primarily re-
lated to its particular mode of drug delivery. Because NRT delivers
nicotine without the harmful byproducts of smoked tobacco, it is
considered a far safer alternative to smoking. The safety of NRT
during pregnancy has not been established.
Bupropion SR (Zyban®)
Bupropion was the first non-​nicotine medication to be approved
by the FDA for treating tobacco dependence. Also marketed as an
atypical antidepressant (Wellbutrin®), bupropion doubles tobacco
abstinence rates compared to placebo, with an average odds ratio
of 2.0, and an abstinence rate of approximately 24%.4 It attenu-
ates nicotine withdrawal and cigarette cravings, and can reduce
postcessation weight gain. Bupropion’s mechanism of action is not
fully understood, but it appears to inhibit the neuronal reuptake
of dopamine and norepinephrine—​key neurotransmitters in the
maintenance of nicotine dependence. It may also have antagonistic
effects on nicotinic receptors, attenuating perceived satisfaction
from smoking.
To reach steady-​state blood levels before quitting smoking, the
smoker should begin using bupropion SR one week before the
target quit date. Contraindications include a history of seizure dis-
orders or factors known to increase the risk of seizures (e.g., bu-
limia or anorexia nervosa, serious head trauma, alcoholism) and
concomitant use of monoamine oxidase (MAO) inhibitors. Because
of postmarketing reports of neuropsychiatric adverse events, in-
cluding suicidality, the FDA required “black box” warnings on
both bupropion and varenicline (see later) with respect to possible
neuropsychiatric adverse events, including depression, psychosis,
aggression, agitation, and anxiety, as well as suicidal ideation or be-
havior. Although the warning remains, the black box was rescinded
in 2016 following additional research that failed to find elevated
neuropsychiatric events for varenicline or bupropion compared to
NRT or placebo. The safety of bupropion during pregnancy has not
been established.

Varenicline (Chantix®)
Varenicline was the last pharmacotherapy approved for treating
nicotine dependence. It is an orally administered partial agonist of
α4β2 nicotinic acetylcholine receptors (nAChRs). Varenicline ap-
pears to reduce nicotine cravings and withdrawal symptoms, and
its agonistic properties appear to attenuate the reinforcing effects
of smoking, including perceived satisfaction.10 Similar to bupro-
pion, varenicline use should be initiated one week before the target
quit date. Evidence suggests that it has outperformed bupropion in
head-​to-​head studies and is the most effective of the smoking cessa-
tion medications, with an average odds ratio of 3.1, producing 33%
abstinence.4
The main adverse effect of varenicline is mild to moderate nausea.
However, as with bupropion, warnings of neuropsychiatric adverse
events are also included in labeling. In addition, there is some evi-
dence that varenicline may increase the risk of major cardiovascular
events. Varenicline is not approved for use with pregnant women.
Combination Pharmacotherapies
Recent research has tested the efficacy of combining different forms
of pharmacotherapy. The general model has been to combine a long-​
acting, relatively stable medication, such as the nicotine patch, with
a shorter-​acting medication that can be used ad libitum. In this
manner, both tonic and phasic nicotine cravings and withdrawal
symptoms can be addressed. The combination of nicotine patch with
gum, nasal spray, or inhaler has evidence of significant efficacy, as
does the combination of the patch and bupropion SR.4
Social/​Behavioral Treatments
The nonpharmacological therapies described in this section span a
wide range of intensity and duration, from minimal self-​help inter-
ventions to intensive individual counseling. Clinicians should be
aware of the availability of these options and should be willing to
refer patients for services that they are unable to provide themselves.
Self-​help
Self-​help refers to materials that can be provided to smokers, such
as pamphlets, booklets, or audiovisual media. Their primary ad-
vantages are low cost and ease of distribution. Unfortunately, the
efficacy of self-​help materials appears to be quite limited, with im-
proved cessation rates of about 1% compared to no-​treatment con-
trols.4 However, a self-​help intervention that extends over time (i.e.,
distribution of sets of materials over 12–​18 months) has recently
demonstrated long-​term efficacy.10
Telephone Quitlines
Smoking cessation quitlines are available throughout the United
States and most of the world. In the United States one number
(1-​800-​QUIT-​NOW) serves as a central access point that auto-
matically routes calls to the appropriate state or federal quitline
service. Approximately 400,000 smokers in the United States are
served annually by state quitlines, with an average utilization rate
of about 1%.11
Quitline services differ in the amount and frequency of coun-
seling offered, the provision of ancillary materials, referrals to local
smoking cessation agencies, the provision of free or subsidized
pharmacotherapies, and whether calls are proactive (call-​out), re-
active (call-​in), or both. Quitlines have the advantage of providing
CHAPTER 1 Tobacco Use and Cessation 9
more personal and intensive help than self-​help materials, while also
having greater potential reach than face-​to-​face counseling. Meta-​
analyses show that quitlines are effective, with overall odds ratios of
1.4–​1.6 compared to control conditions, which translates into differ-
ential long-​term abstinence rates of at least 3%–​5%.4
Brief Interventions
Healthcare providers have the opportunity to deliver relatively brief
face-​to-​face interventions. The U.S. Public Health Service (PHS)
Clinical Practice Guideline describes an effective brief smoking ces-
sation intervention model most commonly referred to as the “5’A’s.”4
The five key steps include (1) “Asking” every patient about tobacco
use at repeated visits, (2) “Advising” every tobacco user to quit by
providing clear and personalized advice to quit, (3) “Assessing” the
willingness of patients to quit, (4) “Assisting” patients with quitting,
and (5) “Arranging” follow-​up cessation support, ideally within a
few weeks of the quit attempt. Meta-​analyses have indicated that
physician advice alone increases abstinence rates by approximately
2.3%–​2.5%.4 Because 70% of smokers visit their physician each year,
the potential cumulative effect of even this small effect is sizable.
Moreover, there is a dose–​response relationship between contact time
and abstinence outcomes, with minimal counseling (< 3 minutes)
yielding 13.4% abstinence, low-​intensity counseling (3–​10 minutes)
yielding 16.0% abstinence, and higher-​intensity counseling (> 10
minutes) yielding 22.1% abstinence. Abstinence rates also increase
with the number of counseling meetings and/​or the number of cli-
nician types delivering the cessation messages.4 Alternative models
that reduce provider burden include Ask-​Advise-​Refer (AAR) and
Ask-​Advise-​Connect (AAC). In both abbreviated models, patients
are asked about their smoking and are delivered brief advice to quit.
However, in the AAR model, patients are then referred to evidence-​
based cessation programs for assistance in quitting (e.g., a quitline).
Designed to overcome patient barriers that exist with use of a pas-
sive referral model, the AAC model directly connects patients to the
smoking cessation resource via an automated connection system
within the electronic health record (EHR). The AAC method has
demonstrated greater impact over the AAR model with respect to a
higher proportion of smokers enrolling in treatment.12
Intensive Interventions
The most intensive interventions tend to be multisession treat-
ments typically offered through smoking cessation clinics, in either
group or individual formats. Of the empirically supported intensive
interventions, the most common approach is cognitive-​behavioral
counseling. Key elements of this approach include patient education
regarding tobacco dependence and withdrawal, advice for coping
with withdrawal symptoms, identifying high-​risk situations (“trig-
gers”) that produce urges to smoke, teaching and practicing cogni-
tive and behavioral responses for coping with urges, discussion of
long-​term risk factors such as depression and weight gain, and dis-
cussion of how to respond in the event of an initial “slip” or “lapse.” It
usually involves multiple sessions over several weeks and may begin
before the target quit date. Counseling has been found to be effec-
tive, with an odds ratio of 1.5 compared to no counseling and an
average abstinence rate of 16.2% compared to 11.2%.4 In addition
to counseling, the guideline also found evidence for intratreatment
social support, and it therefore recommends providing support and
encouragement as part of treatment.
10 SECTION I Factors in Cancer Risk and Prevention
Combining Counseling and Pharmacotherapy
A key conclusion of the most recent guideline is that the combina-
tion of counseling and medication is more effective than either alone
in producing long-​term tobacco abstinence. Moreover, as noted
earlier, higher abstinence rates tend to be produced with more in-
tensive counseling. Thus, the guideline meta-​analysis produced an
estimated abstinence rate of approximately 33% when medication
was combined with nine or more sessions of counseling, compared
to 22% when no more than one counseling session was provided.
Conversely, the guideline reported an odds ratio of 1.7 for the com-
bination of medication and counseling, compared to counseling
alone.4 Counseling and medication appear to provide complemen-
tary benefits. Whereas medication reduces withdrawal symptoms
and craving, counseling can teach cognitive and behavioral coping
strategies and can provide valuable social support. Therefore, when-
ever medication is recommended or provided to patients, they
should also be offered counseling.
Special Issues with Cancer Patients
There is a growing body of evidence that smoking following cancer
diagnosis has a negative impact on cancer treatment efficacy,
treatment-​related complications and side effects, cancer recurrence
and second malignancies, and overall survival.13 With advances in
cancer treatments, the number of cancer survivors is significantly
increasing, emphasizing the importance of improving health out-
comes and quality of life within this high-​risk population. In this
section, we will describe the benefits of smoking cessation in cancer
patients, review cessation and relapse rates among cancer patients,
and summarize the current knowledge regarding cessation inter-
ventions for cancer patients.
Benefits of Quitting Smoking
The last report of the U.S. Surgeon General concluded that con-
tinued smoking after cancer diagnosis is causally related to multiple
negative consequences, including increased risk of cancer-​specific
mortality as well as all-​cause mortality. Furthermore, persistent
smoking after a cancer diagnosis has been strongly associated
with cancer recurrence, poor treatment outcomes (e.g., poorer re-
sponse to treatment, treatment-​related toxicities), and higher risk of
hospitalization.13
Quitting smoking is associated with fewer medical complications,
decreased risk of subsequent malignancies, and increased survival
rate.14 Finally, some research indicates that patients who remain
smoke-​free following cancer treatment report lower levels of depres-
sion and fatigue, improving overall quality of life relative to patients
who continue to smoke.15 In summary, evidence is accumulating
that smoking cessation after a cancer diagnosis improves quality of
life, increases survival, and decreases cancer recurrence and psycho-
logical distress.
Smoking Cessation and Relapse among Cancer Patients
Despite the benefits of quitting, over 30% of cancer patients con-
tinue to smoke after diagnosis. However, cancer patients who smoke
are highly motivated to quit, and many make an attempt to quit at
the time of diagnosis.16 Because most quit attempts appear to occur
at the time of diagnosis and treatment, the period between cancer
diagnosis and end of treatment may represent the optimal window
of opportunity for provision of smoking cessation interventions.
There is less research on long-​term abstinence rates among cancer
patients. Estimates of smoking relapse range from 13% to 60%.
Unlike the general population of smokers for whom relapse most
often occurs within a week after cessation, the majority of relapses
among cancer patients occurs within the first few months following
a quit attempt, again reflecting the initial motivational impact of a
cancer diagnosis. Predictors of both persisting smoking and relapse
have included factors such as longer history of smoking, depression,
lower desire to quit, and alcohol use.17
Interventions for Cancer Patients
Few clinical trials have been conducted on smoking cessation inter-
ventions for cancer patients. Interventions tested have included a
variety of formats, such as nurse-​delivered inpatient counseling,
cognitive-​behavioral therapy, motivational interviewing, distribu-
tion of educational materials, and follow-​up phone calls. Several
studies have also tested pharmacological cessation treatments (nic-
otine replacement therapy, varenicline, or bupropion), either alone
or combined with counseling. The overall findings have not demon-
strated a significant treatment effect.18
More recently, some innovative interventions are being tested.
System-​ based interventions aim at introducing changes in the
overall organization to change smoking cessation practices (e.g.,
automatic referrals using EHRs). Also, interventions using mobile
technology have been pilot tested. However, evidence on the effec-
tiveness of these new types of interventions is still limited.
Finally, the use of e-​cigarettes has increased among cancer pa-
tients, paralleling trends in the general population.19 Overall, it seems
that cancer patients hold generally positive expectancies regarding
e-​cigarettes, as compared to both combustible cigarettes and NRT,
and find them an attractive way to quit smoking.20 The American
Association for Cancer Research (AACR) and the American Society
of Clinical Oncology (ASCO) recommend that healthcare providers
encourage use of FDA-​approved cessation methods, given the lack
of definitive data regarding the safety and efficacy of e-​cigarettes.
However, the American Cancer Society’s 2018 position statement on
e-​cigarettes recommends harm reduction, including e-​cigarettes, for
patients who have not otherwise been able to quit smoking.
When implementing smoking cessation interventions with
cancer patients, clinicians should be mindful of several unique
cancer-​related issues. For instance, the delay in relapse among
cancer patients described earlier may suggest a waning of motiva-
tion as patients physically recover and return to their prediagnosis
lifestyles. Thus, smoking relapse prevention interventions may be
particularly important as patients recover. Another issue relates to
potential contraindications with the use of smoking cessation phar-
macotherapy. With respect to NRT and e-​cigarettes, for example,
although nicotine is not itself carcinogenic, preclinical research sug-
gests that it can accelerate tumor growth, inhibit apoptosis induced
by several chemotherapy agents, and negatively impact response to
radiotherapy. Nevertheless, there is no evidence to date indicating
that NRT causes adverse events in cancer patients.14 In addition,
NRTs such as nicotine gum, spray, inhaler, or lozenge may not be
appropriate for individuals with oral cancers, whereas bupropion is
contraindicated for patients with a history of central nervous system
(CNS) tumors due to an increased risk of seizures. Hence, clinicians

must take extra care in selecting appropriate cessation medications
that address cancer patients’ unique needs.
Given the growing body of evidence demonstrating the substan-
tial risks of continued smoking among cancer patients, it is not
surprising that recognition and support of cessation services are
increasing. For example, the ASCO developed updated tobacco
guidelines that include recommendations for health professionals to
assess tobacco use and integrate cessation services in the oncology
setting.21 Similarly, a policy statement by the AACR called for im-
proved documentation of tobacco use among patients, as well as
improvements in evidence-​based cessation assistance provided to
all patients who use tobacco or have recently quit tobacco.22 The
National Comprehensive Cancer Network (NCCN) has also de-
veloped clinical practice guidelines for smoking cessation that in-
clude a thorough assessment of tobacco use and supports the use
of evidence-​based methods of smoking cessation (i.e., combined
pharmacologic and behavior therapy) for every cancer patient
throughout the continuum of cancer care.23 Finally, the U.S. National
Cancer Institute (NCI), in recognition of the need for system-​level
smoking cessation services, has provided competitive funding to
NCI-​designated cancer centers to develop comprehensive plans to
identify and offer cessation services to every cancer patient who
smokes, via enhanced EHR and other strategies.24
Improved comprehensive documentation of tobacco use would
further clinical support for smoking cessation as well as facilitate
research on the effects of tobacco on cancer-​related outcomes and
its impact on treatment response in clinical trials. With the aim
of improving the assessment of tobacco use in the oncology pa-
tient population, the Cancer Patient Tobacco Use Questionnaire
(C-​TUQ) was developed.25 This tool comprises up to 22 items for
standardized assessment of tobacco use among cancer patients. This
is particularly important within clinical trials of cancer therapies,
given that tobacco use is a treatment modifier.
In summary, the importance of quitting smoking for all cancer pa-
tients is clear. Clinicians who treat cancer patients must capitalize on
the window of opportunity during cancer diagnosis and treatment
to identify smokers and make cessation interventions readily avail-
able to these high-​risk patients. Cancer patients who stop smoking
and remain abstinent after treatment are likely to reap significant
benefits, including improved quality of life and prolonged survival.
Conclusion
Tobacco use by cancer patients appears to be influenced by the
same range of biopsychosocial factors as it is in the general popu-
lation. However, cancer diagnosis and treatment offer a unique and
potentially powerful opportunity for healthcare providers to inter-
vene by offering cessation advice and assistance. To date, there is
little research to recommend specialized smoking cessation inter-
ventions for cancer patients above and beyond the general recom-
mendations of the Clinical Practice Guidelines.7 However, it is likely
that targeted treatments that capitalize on the teachable moment
could be highly effective, and research has been increasing in this
area. Meanwhile, the greatest progress in both cancer prevention
and recovery depends on consistent action by all components of
the healthcare system to promote tobacco cessation. This includes
coverage of smoking cessation interventions by third-​party payers,
CHAPTER 1 Tobacco Use and Cessation 11
establishment of smoke-​free campuses by hospital administrators,
and strong cessation advice and assistance by every healthcare pro-
vider. Finally, the changing demographics of tobacco users along
with evolving noncombustible alternatives to smoking require on-
going monitoring and the updating of policies and clinical practices,
as needed.
ACKNOWLEDGMENTS
Preparation of this chapter was supported by National Cancer
Institute grants R01 CA154596, R01 DA037961, R01 CA199143,
and R03 CA227044.
Disclosure: Dr. Brandon has received research support from
Pfizer, Inc., and serves on the advisory board for Hava Health, Inc.
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2
Diet and Cancer
Marian L. Fitzgibbon, Lisa Tussing-​Humphreys, Angela Kong, and Alexis Bains
Overview
Research over the past several decades shows that 95% of cancers
can be attributed to environmental factors,1 including pollution, in-
fections, radiation, and other external factors as well as tobacco use,
alcohol, inactivity, diet, and other lifestyle factors.2 Diet, arguably
among the most modifiable of these factors, likely contributes to the
development of 30% to 35% of cancers.
Substantial shifts in the food landscape in developed countries
have contributed to changes in dietary intake, energy balance, in-
creases in body fat, and the development of obesity. Obesity, de-
fined as a body mass index (BMI) ≥ 30 kg/​m², is associated with
several cancers. Obesity exceeds 30% in both genders and is pre-
dicted to reach 51% by 2030 across all adult age groups in the United
States (U.S.). Thus, the World Cancer Research Fund (WCRF), the
American Institute for Cancer Research (AICR), the American
Cancer Society (ACS), and cancer researchers both in the U.S. and
globally are devoting significant time and resources to studying the
relationship between diet, dietary patterns, lifestyle risk factors, obe-
sity, and cancer.3
Advances in research methodology hold promise for reconciling
the complex literature on the role of diet and cancer risk. Prior re-
search focused more often on specific nutrients and foods in isola-
tion rather than examining the effects of dose, timing, exposure, and
overall nutritional status. However, more recent studies demonstrate
that dietary patterns are key to enhancing our knowledge of the rela-
tionship between diet and cancer. The consensus across studies sug-
gests that a healthy dietary pattern includes fruits, vegetables, fish,
whole-​grain cereals, nuts, legumes, and intake of healthy fats. This is
presumably due to the value of these foods in providing a combina-
tion of important vitamins, minerals, fiber, protein, and antioxidants
associated with reduced cancer risk. An unhealthy dietary pattern,
on the other hand, consists of red meat, processed meat, refined
sugars and sugar-​sweetened beverages, refined flours, alcohol, and
high saturated fat intake.
While diet is often a major contributor to the energy imbalance
that can lead to the development of obesity, physical activity pat-
terns also play a role. Extensive evidence shows increased physical
activity may reduce the incidence of and survival from various can-
cers and that inactivity is associated with many chronic diseases.
Strong evidence demonstrates that regular physical activity of all
types protects against excessive weight gain and obesity. Thus, the
interaction of energy intake (i.e., diet) and energy expenditure (i.e.,
physical activity) is fundamental to weight management and cancer
risk and control. This chapter (1) summarizes the role of dietary fac-
tors and cancer risk, (2) highlights the relationship between dietary
patterns and cancer, (3) summarizes the role of weight management
and energy balance, (4) identifies potential environmental barriers
to diet-​related cancer risk reduction, and (5) offers areas for future
research.
Diet-​, Physical Activity–​, and Body Composition–​
Related Factors and Cancer Risk
This section presents an overview of the best-​established associ-
ations (i.e., graded as “strong evidence”) reported by the WCRF and
the AICR between the leading causes of cancer death worldwide and
dietary factors, physical activity, and body fatness4 (summarized in
Table 2.1).
Lung Cancer. Lung cancer is the most common cause of cancer
and cancer death in both sexes combined worldwide. Smoking is the
main cause of lung cancer globally, accounting for an estimated 90%
of lung cancers among men and 80% in women. Arsenic in drinking
water is the most established dietary risk factor for lung cancer.
The World Health Organization (WHO) reports that contaminated
groundwater is the main source of arsenic.5 Beta-​carotene supple-
ments are also associated with increased risk for lung cancer, par-
ticularly among smokers. This association was discovered through
two large intervention trials, the Beta-​carotene and Retinol Efficacy
Trial (CARET) and the Alpha-​Tocopherol, Beta-​Carotene (ATBC)
Cancer Prevention Study.6 The CARET study was conducted in the
U.S. with male and female smokers and former smokers, as well as
men with occupational exposure to asbestos. The ATBC Cancer
Prevention Study was conducted in Finland with male smokers.
There is only limited evidence of specific foods decreasing (e.g.,
vegetables, fruits, foods containing carotenoids, etc.) or increasing
(e.g., red meat, processed meat, alcohol) lung cancer risk.
Liver Cancer. Liver cancer is the fourth most common cause of
cancer death worldwide and the fifth most commonly occurring
cancer. Established risk factors of liver cancer include cirrhosis of the
liver, long-​term use of high-​dose estrogen and progesterone, chronic
14 SECTION I Factors in Cancer Risk and Prevention

Table 2.1. Dietary-​, Physical Activity–​, and Weight-​Related Factors Showing Convincing or Probable Evidence of Association with the Top 10
Causes of Cancer Death Worldwide

Cancer Increases Risk Decreases Risk

Lung Arsenic in water**
High-​dose beta-​carotene supplements1**
Liver Exposure to aflatoxin2**
Alcohol (45 grams or 3 drinks a day)**
Body fatness (based on BMI)**
Coffee*
Stomach Body fatness (cardia) (based on BMI)*
Alcoholic drinks (45 grams or 3 drinks a day)*
Food preserved by salting3*
Colorectal Processed meat4** Physical activity7**
Alcoholic drinks (30 grams or 2 drinks a day)** Whole grains*
Body fatness5 Foods containing dietary fiber8*
Adult attained height6** Dairy products9*
Red meat (beef, pork, lamb, and goat from domesticated animals)* Calcium supplements* (supplemental dose of
200–​1,000 mg/​day) *
Breast Premenopausal Vigorous physical activity*
Adult attained height6** Body fatness11*
Alcoholic drinks (no amount/​limit was found)* Lactation12*
Greater birthweight10* Physical activity13*
Postmenopausal Body fatness in young adulthood11*
Alcoholic drinks (no amount/​limit was found)** Lactation12*
Body fatness5**
Adult weight gain**
Adult attained height6**
Esophageal Adenocarcinoma
Body fatness5**
Squamous Cell Carcinoma
Alcoholic drinks**
Mate14*
Pancreatic Body fatness15**
Adult attained height6*
Prostate Body fatness (advanced prostate cancer)16*
Adult attained height6*

** Indicates convincing evidence.

* Indicates probable evidence.
Based on the grading criteria reported in the Diet, Nutrition, Physical Activity and Cancer: A Global Perspective, Third Expert Report (2018).
** Convincing (strong evidence): Evidence strong enough to support a judgment of a convincing causal (or protective) relationship, which justifies making
recommendations designed to reduce the risk of cancer. The evidence is robust enough to be unlikely to be modifiable in the foreseeable future as new evidence
accumulates.
* Probable (strong evidence): Evidence strong enough to support a judgment of a probably causal (or protective) relationship, which generally justifies recommendation designed to reduce the
risk of cancer.
1
Based on studies testing high-​dose supplements on smokers and former smokers (beta carotene: 20 mg/​day or retinol: 25,000 IU/​day).
2
Grains (cereals), legumes (pulses), seeds, nuts, and some fruits and vegetables are foods that may be contaminated with aflatoxins.
3
Regarding traditionally prepared in East Asia, high-​salted foods and foods preserved with salt, such as pickled vegetables and salted or dried fish.
4
Regarding meat preserved by smoking, curing, slating, or adding chemical preservatives.
5
Body fatness represents BMI (body mass index), waist circumference, or waist-​hip ratio.
6
Adult attained height is an indicator of genetic, environmental, hormonal, and nutritional growth factors that have an influence on growth from preconception to completion of
linear growth.
7
Includes physical activity of all types: occupational, household, transport, and recreational. The panel judges that the evidence for colon cancer is convincing, but no conclusion was
drawn for rectal cancer.
8
Both foods that naturally have dietary fiber and foods with dietary fiber added.
9
Evidence from dairy, milk, cheese, and dietary calcium supplements.
10
“The Panel’s conclusion relates to the evidence for overall breast cancer (unspecified). The observed association was in estrogen-​receptor-​negative (ER–​) breast cancer only.”
11
Body fatness represents BMI, waist circumference, or waist-​hip ratio. Women 18 to 30 years old included in evidence. For young adults, body fatness represents BMI.
12
“The Panel’s conclusion relates to the evidence for overall breast cancer (unspecified). The evidence for premenopausal and postmenopausal breast cancers separately was less
conclusive, but consistent with the overall finding.”
13
“Physical activity including vigorous, occupational, recreational, walking and household activity.”
14
Beverage is consumed scalding hot and through a metal straw (as traditionally consumed in South America).
15
Body fatness referring to/​interconnected with fat distribution, BMI, abdominal girth, and adult weight gain.
16
Body fatness represents BMI, waist circumference, or waist-​hip ratio. This outcome was seen in advanced cancer only, meaning high-​grade and fatal prostate cancers.

viral hepatitis, and smoking. There is strong evidence that the fol-
lowing diet-​and weight-​related factors increase liver cancer risk: (1)
being overweight or obese (as assessed by BMI), (2) alcoholic drinks
(about 3 drinks/​day), and (3) exposure to aflatoxins. Aflatoxin, a
mold that develops on foods stored in hot, wet conditions, can con-
taminate foods such as cereals (grains), legumes, seeds, and nuts,
and some fruits and vegetables. Coffee consumption is the only diet-​
related factor that is protective. A dose-​response meta-​analysis of
existing studies conducted by the expert panel suggests that one cup
of coffee per day is associated with a 14% decreased risk.4
Stomach (Gastric) Cancer. Stomach cancer is the fourth most
common cancer worldwide, with the highest incidence noted
among men and in certain regions of Asia, and is the third most
common cause of cancer death. Based on the location of the tumor,
stomach cancer can be classified as cardia (top part and closest to
esophagus) and noncardia (all other regions). Stomach cardia can-
cers are more common in the U.S. and UK, while noncardia forms
of stomach cancer are more prevalent in Asia. However, incidence
rates of stomach cancer (particularly noncardia) are declining
worldwide due in part to more widespread use of refrigeration to
store foods (rather than salting) and a decrease in Helicobacter pylori
(H. pylori) infections. Smoking and exposure to industrial chemi-
cals are other established contributors to stomach cancer. Diet-​and
body composition–​related factors that increase the risk of stomach
cancer include alcoholic drinks (three drinks/​day), high-​salt foods,
and obesity. Being overweight or obese increases the risk of stomach
cardia cancer in particular.
Colorectal Cancer. Colorectal cancer is the third most commonly
diagnosed cancer and the second most common cause of cancer
deaths worldwide. Diet, physical activity, obesity, and alcohol con-
sumption influence risk. The factors with the strongest evidence for
increasing risk are (1) processed meat intake, (2) alcoholic drinks
(about two drinks/​day), (3) body fatness, (4) adult attained height,
and (5) red meat. Adult attained height is not a direct risk factor,
but rather a marker for factors (e.g., genetic, environmental, hor-
monal, and nutrition) that could impact growth during the develop-
mental years. Red meat contains the iron-​containing protein heme,
which can facilitate the formation of potentially carcinogenic com-
pounds. Also, red meat cooked at high temperatures can produce
heterocyclic amines and polycyclic aromatic hydrocarbons that may
contribute to colon cancer in people with a genetic predisposition.
Processed meats (e.g., ham, bacon, sausages, canned meats) are pre-
served by methods other than freezing, such as smoking, salting, air
drying, or heating. Strong evidence of factors decreasing risk include
(1) physical activity, (2) whole grains, (3) dietary fiber, (4) dairy
products, and (5) calcium supplements. Of these factors, the most
convincing evidence is based on studies examining physical activity
(e.g., occupational, household, transport, and recreational) and co-
lorectal cancer. Based on a meta-​analysis of over 30 studies, a re-
duced risk of about 14% for colon cancer was observed comparing
those in the highest vs. lowest groups for physical activity (risk ratio
[RR] = 0.85; 95% confidence interval [CI]: 0.78–​0.91).4 For whole-​
grain consumption there was a reduced risk of 17% per 90 g/​day
of whole-​grain intake (based on six studies consisting of n = 8,320
cases).4 For fiber-​containing foods, which include fiber that is added
and naturally occurring, there was a reduced risk of 9% per 10 g/​
day (based on 15 studies consisting of n = 14,876 cases).4 Calcium
CHAPTER 2 Diet and Cancer 15
and dairy products also appear to reduce colorectal cancer risk,
though the effect for milk is, in part, mediated by calcium. Evidence
for calcium’s protective effects is based on studies of supplements at
doses of 200 to 1,000 mg/​day.
Breast Cancer. Breast cancer is the most frequently occurring
cancer and the most common cause of cancer death for women
worldwide. Because it is a hormone-​related cancer, risk is most af-
fected by factors that influence exposure to estrogen, including
menopausal status. In a recent update by the WCRF/​AICR, the
following factors were considered strong evidence (convincing)
for increasing risk of postmenopausal breast cancer: (1) alcoholic
drinks (no amount identified), (2) body fatness, (3) adult weight
gain, and (4) adult attained height.4 Adult attained height (a marker
for factors affecting growth) and alcohol intake also increase risk
for premenopausal breast cancer. Additionally, greater birthweight,
which is an indicator of prenatal growth and fetal nutrition, is also
recognized as a risk factor for premenopausal women. While body
fatness increases breast cancer risk for postmenopausal women, it is
actually protective for premenopausal women. Lactation and phys-
ical activity decrease risk for both pre-​and postmenopausal women.
However, evidence is insufficient to confirm protective effects of any
specific dietary factors.
Esophageal Cancer. Cancer of the esophagus is the sixth most
common cause of cancer death and the seventh most common cancer
worldwide. There are two main types of esophageal cancer: squa-
mous cell carcinoma (affects the upper part of the esophagus) and
adenocarcinoma, which occurs in the region between the esophagus
and stomach. Risk factors vary by site. For instance, body fatness
increases the risk for esophageal adenocarcinoma but not squamous
cell. Squamous cell carcinoma can be impacted by diet-​related fac-
tors. For instance, intake of alcohol and mate are associated with
increased risk of squamous cell carcinoma rather than adenocar-
cinoma. Mate is a tea-​like beverage consumed in parts of South
America, usually scalding hot, through a metal straw.
Pancreatic Cancer. Pancreatic cancer is the seventh most
common cause of cancer deaths. Incidence is higher in men than
in women and higher in developed countries. The WCRF/​AICR’s
continuous update project concluded there is convincing evidence
that body fatness and adult attained height increase pancreatic
cancer risk.4 No convincing or probable evidence suggests that any
dietary factors increase risk, though limited data suggests that red
and processed meats, alcohol, high-​fructose foods/​beverages, and
foods containing saturated fatty acids increase risk. Coffee was pre-
viously considered a possible risk factor, but the updated report in-
dicates this is unlikely. No food or nutrition factors are identified as
decreasing pancreatic cancer risk.
Prostate Cancer. Prostate cancer is the second most common
cancer and fifth most common cause of cancer death in men.
Incidence is much higher in developed countries. The WCRF/​
AICR’s continuous update project report suggests there is strong
probable evidence that body fatness and adult attained height in-
crease prostate cancer risk. However, insufficient data exists to iden-
tify any dietary factor as risk promoting.4
Cervical Cancer. Cervical cancer ranks fourth in both mortality
and incidence for women worldwide. The primary risk factor is infec-
tion with human papilloma viruses. Food and nutrition do not play
a significant role in increasing or decreasing cervical cancer risk.4
16 SECTION I Factors in Cancer Risk and Prevention

Dietary Patterns and Cancer Risk
Single foods and nutrients are not typically consumed in isolation.
Because dietary nutrients are consumed in combination, syner-
gistic effects between food and nutrients may create a metabolic
milieu that prevents or promotes carcinogenesis. This section pre-
sents an overview of dietary patterns and associations with cancer
risk and risk of cancer-​related mortality as indicated by studies
that examined adherence to science-​based public health dietary re-
commendations such as the U.S. government’s Dietary Guidelines
for Americans (DGAs) and Mediterranean and vegetarian dietary
patterns. The DGAs and a Mediterranean diet (Med Diet) pattern
have corresponding index scores that are used to quantify adherence
using a standardized approach.7
The DGAs are designed to promote good health and reduce the
risk of chronic diseases, including cancer. The guidelines are re-
vised every five years to account for advances in scientific know-
ledge pertaining to diet and disease relationships (the current
DGAs are presented in Table 2.2). The Healthy Eating Index (HEI)
is a scoring tool that measures adherence to a given set of DGAs;
higher scores are indicative of greater adherence to the guidelines.8
A recent systematic review and meta-​analysis of prospective cohort
studies examining diet quality, using several metrics including
the HEI and various health outcomes, found that individuals con-
suming the highest-​quality diets compared to lowest-​quality diets
had a 16% reduction in cancer mortality or incidence (RR = 0.84;
95% CI: 0.82–​0.87).9
Ecological studies suggest overall cancer risk is lower in
Mediterranean countries versus northern Europe, the UK, and the
U.S. Many have attributed this distinction to the customary foods
consumed by people residing in this region. A Med Diet pattern
is one in which vegetables and whole grains feature prominently,
fresh fruit is a typical dessert, olive oil is the main fat source,
animal-​based protein intake is limited, and wine is consumed in
moderation, with meals. Mechanistically, it is hypothesized that
certain aspects of the Med Diet, including a healthy fatty acid ratio
and foods rich in antioxidants and anti-​inflammatory nutrients,
work synergistically to promote reduced systemic inflammation
and down-​regulation of pro-​carcinogenic pathways. Several re-
search groups have developed scoring indices to operationalize
and assess adherence to a Med Diet pattern to relate to disease
outcomes. The Alternate Mediterranean Diet (aMED) score is a
Med Diet adherence score developed specifically for U.S. popula-
tions.10 The aMED has nine components, with one point awarded

Table 2.2. Dietary and Lifestyle Recommendations for Good Health and Cancer Prevention

2015–​2020 Dietary Guidelines for Americans35 General Mediterranean Diet American Cancer Society37 American Institute for Cancer Research38
Characteristics36
5 overarching guidelines of a healthy eating • Daily abundance of plant-​ • Achieve and maintain • Be a healthy weight.
pattern: based foods including whole a healthy weight • Be physically active.
• Follow a healthy eating pattern across the grains, vegetables, fruits, and throughout life. • Eat a diet rich in whole grains,
lifespan. legumes. • Be physically active. vegetables, fruits, and beans.
• Focus on variety, nutrient density, and • Olive oil used daily as the • Limit time spent sitting. • Limit consumption of “fast food” and
amount. principal fat source. • Eat a healthy diet, with an other processed foods high in fat,
• Limit calories from added sugars and • Low to moderate daily emphasis on plant foods. starches, or sugars.
saturated fats and reduce sodium intake. consumption of low-​fat • Choose foods and drinks in • Limit consumption of red meat and
• Shift to healthier food and beverage choices. dairy foods. amounts that help you get processed meat.
• Support healthy eating patterns for all. • Animal-​based protein to and maintain a healthy • Limit consumption of sugar-​sweetened
A healthy eating pattern includes: consumed in low to moderate weight. beverages.
• A variety of vegetables from all the amounts weekly or monthly. • Limit how much processed • Limit alcohol consumption.
subgroups—​dark green, red and orange, • Sweets consumed in low meat and red meat you eat. • Do not use supplements for cancer
legumes (beans and peas), starchy, and other. amounts monthly. • Eat at least 2½ cups of prevention.
• Fruits, especially whole fruits. • Wine in moderation vegetables and fruits • For mothers: breastfeed your baby if
• Grains, at least half of which are whole grains. with meals. each day. you can.
• Fat-​free or low-​fat dairy, including milk, • Be physically active. • Choose whole grains • After a cancer diagnosis: follow our
yogurt, cheese, and/​or fortified soy beverage. instead of refined grain recommendations if you can.
• A variety of protein foods, including seafood, products.
lean meats and poultry, eggs, legumes (beans • If you drink alcohol, limit
and peas), and nuts, seeds, and soy products. your intake.
• Oils.
A healthy eating pattern limits:
• Saturated fats (<10% calories per day) and
trans fats, added sugars (<10% of calories per
day), and sodium (<2,300 mg per day).
• If alcohol is consumed, it should be
consumed in moderation—​up to one drink
per day for women, and up to two drinks
per day for men—​and only by adults of legal
drinking age.
Healthy Eating Patterns Dietary Principles:
• An eating pattern represents the totality of all
foods and beverages consumed.
• Nutritional needs should be met primarily
from foods.
• Healthy eating patterns are adaptable.
Meet the Physical Activity Guidelines for
Americans.

for scoring higher than the median intake within a given popula-
tion/​cohort for whole grains, fruits, vegetables (except potatoes),
nuts, fish, legumes, and monounsaturated versus saturated fat
ratio; one point is awarded for red and processed meat below the
median; and one point is awarded for consuming one alcoholic
beverage daily. In the National Institutes of Health–​American
Association of Retired Persons (NIH-​AARP) Diet and Health
observational cohort study, greater adherence to a Med Diet pat-
tern (aMED scores ranging from six to nine points) was associ-
ated with decreased risk of cancer-​related mortality in both men
and women.11 Regarding site-​specific cancers, greater adherence
to a Med Diet, based on aMED, was associated with lower colo-
rectal cancer risk in men in a combined analysis of the Nurses’
Health Study and Health Professionals Follow-​up Study,12 and
decreased risk of lung cancer in both men and women in the
NIH-​AARP cohort, with an even more profound risk reduction
in current and former smokers.13 However, not all studies have
shown a strong association between Med Diet adherence and
decreased cancer risk and mortality. For example, in the French
NutriNet-​Santé cohort study, greater adherence to a Med Diet,
based on the Medi-​Lite score, was not associated with decreased
risk of breast (women), colorectal, or prostate cancer (men).14 In
the Multiethnic Cohort study, greater adherence to a Med Diet,
based on aMED, was associated with lower colorectal cancer mor-
tality among African American cancer survivors but not Native
Hawaiian, Japanese American, Latino, and white survivors.15 An
important issue with the literature examining associations be-
tween Med Diet adherence and cancer risk and mortality is the
use of different scoring approaches to assess Med Diet adherence.
However, in the European Prospective Investigation into Cancer
and Nutrition (EPIC) study, researchers investigated three dif-
ferent Med Diet scores (Mediterranean Diet Score [MDS], rela-
tive Med Diet Score [rMED], and the Mediterranean Style Dietary
Pattern Score [MSDPS]) and associations with overall cancer
mortality. Comparing the highest versus lower quartile for each
score, higher Med Diet adherence was associated with signifi-
cantly lower risk of cancer-​related mortality irrespective of the
scoring approach used.16
The association between a vegetarian dietary pattern and re-
duced cancer risk stems from studies of the Seventh Day Adventist
religious sect whose doctrine advises against eating animal flesh.
Seventh Day Adventists adhering to a vegetarian eating pattern
had lower rates of cancer overall, lower rates at specific sites
such as the prostate and colon, and lower risk of cancer-​related
mortality compared to the general U.S. population.17 However,
Seventh Day Adventists also typically abstain from tobacco and
alcohol, which may contribute to the observed health effect. In
the EPIC cohort, vegetarianism was associated with lower overall
cancer risk and risk for stomach and bladder cancer, but no ef-
fect was observed for colorectal and prostate cancer incidence
compared to nonvegetarians.18 Studies of breast cancer incidence
and mortality have not demonstrated differences between vege-
tarians and nonvegetarians, although there is some evidence that
a vegan diet pattern can reduce breast cancer risk.19 Moreover,
a vegan diet pattern was associated with statistically significant
protection from overall cancer incidence in the Adventist Health
Study-​2.20
CHAPTER 2 Diet and Cancer 17
Diet and Weight Loss Intervention Trials: Effects
on Cancer-​Related Outcomes
This section presents an overview of several large randomized trials
designed to examine the effects of dietary factors and weight loss
on cancer prevention or control and cancer risk–​related biomarkers.
Increasing Fiber, Fruits, and Vegetables and Decreasing
Total Fat
The Women’s Health Initiative (WHI). The WHI was a study of
over 45,000 postmenopausal women (1993–​2004) that included a
clinical trial with three intervention arms, including two that were
diet and cancer related. The first of these tested a low-​fat eating pat-
tern (less than 20% of total calories; five servings/​day of fruits and
vegetables; six servings/​day of whole grains) on breast cancer and
colorectal cancer. Control participants received information con-
sistent with the U.S. Department of Agriculture DGAs. Follow-​up at
8.1 years showed no significant reduction in the incidence of breast
cancer or colon cancer among women in the intervention group.21
The second arm examined the effects of calcium and vitamin D sup-
plementation on colorectal cancer. Over an average of seven years,
no significant difference was observed in colorectal cancer incidence
between the intervention and control groups.22 The extended period
over which colorectal cancer develops may have led to these null
findings. In recent secondary analyses, vitamin D and calcium sup-
plementation were not associated with reduced invasive cancer risk
or mortality,23 whereas vitamin B6 and riboflavin intake were associ-
ated with lower colorectal cancer risk.23
Women’s Intervention Nutrition Study (WINS). This phase III
clinical trial (1994–​2001) was designed to examine the relationship
between dietary fat intake and breast cancer among 2,437 women
with resected, early-​stage breast cancer. Women in the intervention
group were counseled to reduce dietary fat intake to 15% of calories
during a four-​month intervention period. The comparison group re-
ceived no dietary counseling. Interim results at 60 months showed
dietary fat intake and body weight were significantly lower in the
intervention group compared to the control group.24
Women’s Healthy Eating and Living (WHEL) Study. This ran-
domized trial (1995–​2006) assessed whether a significant increase in
vegetable, fruit, and fiber intake and a decrease in dietary fat intake
could reduce the risk of recurrent and new primary breast cancer
and “all cause” mortality among 3,088 survivors of early-​stage breast
cancer. Women in the intervention were instructed to consume daily
five vegetable servings plus 16 ounces of vegetable juice, three fruit
servings, 30 grams of fiber, and 15% to 20% of energy intake from
fat. Women in the comparison group received written materials con-
sistent with the “5-​a-​Day” fruits and vegetables message. Although
the intervention group did adhere to the prescribed diet, there was
no effect on breast cancer events or mortality among early-​stage
breast cancer survivors.25
Mediterranean Diet
Only two studies have tested the effect of a Med Diet on cancer risk
in the context of a randomized controlled trial.
Lyon Diet and Heart Study. Six hundred and five adult survivors
of a first acute myocardial infarction were randomized to a Med
Diet–​type pattern or control (Step 1 diet of the American Heart
18 SECTION I Factors in Cancer Risk and Prevention
Association) over a four-​to five-​year timeframe.26 A secondary
outcome of the study was the occurrence of malignant tumors.
Seventeen cancers developed in the control group and seven in the
Med Diet group (RR = 0.39; 95% CI: 0.15–​1.01; p = 0.05). This study
demonstrated for the first time in a randomized trial the cancer pro-
tective effect of a Med Diet in a non-​Mediterranean population.
Prevención con Dieta Mediterránea (PREDIMED) Trial.
Briefly, the PREDIMED study randomized 7,447 participants (4,282
women) to a Med Diet supplemented with extra-​virgin olive oil,
Med Diet supplemented with mixed nuts, or control (low-​fat diet)
intervention with a median follow-​up of 4.8 years.27 A secondary
outcome of the trial was breast cancer incidence for women without
a history of breast cancer (n = 4,152). Breast cancer rates per 1,000
person-​years were 1.1 for the Med Diet plus extra-​virgin olive oil
group, 1.8 for the Med Diet nuts group, and 2.9 for the control group,
respectively. Although the results come from a secondary analysis,
findings suggest a protective effect of a Med Diet supplemented with
olive oil for the primary prevention of breast cancer.
Effect of Diet on Premalignant Lesions and
Cancer-​Related Biomarkers
Polyp Prevention Trial (PPT). The PPT28 was a randomized con-
trolled study of the effects of a low-​fat (20% of total energy intake),
high-​fiber (18 g/​1,000 calories), high-​fruit and -​vegetable (five to
eight daily servings) diet on the recurrence of colorectal adenomas
among individuals who had a polyp removed in the previous six
months. At the four-​year follow-​up, results suggested that adopting a
low-​fat, high-​fiber diet and increasing fruit and vegetable consump-
tion did not affect the risk of recurrence for colorectal adenomas.
Controlled Feeding Studies. In a two-​week strictly controlled
diet exchange study in which native black Africans consumed an
animal-​based diet and African Americans consumed a plant-​based
diet, colonic mucosal proliferation and inflammation were signif-
icantly lower in the African Americans and significantly higher
postdiet in the native black Africans.29 The authors attributed the ef-
fect in the African Americans to changes in gut microbial metabolic
function (i.e., increased short-​chain fatty acid production and de-
creases in secondary bile acids) that was related to the diet switch. In
a crossover feeding trial conducted with relatively healthy men and
women, consuming a high (i.e., refined grains and added sugars)
and low (i.e., high in whole grains, legumes, fruits, and vegetables)
glycemic index diet each for 28 days30 resulted in differing expres-
sion of plasma proteins related to carcinogenesis that was dependent
on the subject’s baseline body adiposity (high vs. low fat mass).
Specifically, in response to the high-​glycemic-​load diet, those with
high fat mass had increased expression of plasma proteins related to
cell cycle, DNA repair, and DNA replication that if sustained could
lead to carcinogenesis. These findings suggest that obesity’s effect
on cancer development may to some extent be tied to biological re-
sponse to differing dietary patterns.
Effect of Weight Loss on Cancer-​Related Outcomes
Surgically Induced Weight Loss. There is encouraging albeit
conflicting evidence regarding the effect of surgical weight loss
on cancer risk. In a study of obese patients undergoing laparo-
scopic gastric banding (n = 327) or medically induced weight loss
(n = 681), gastric banding was associated with significantly lower
incidence of cancer and cancer-​related mortality in the surgical
patients31 over a 23-​year period. In a large population-​based co-
hort study in the United Kingdom of 8,794 obese patients that
underwent bariatric surgery (gastric banding, sleeve gastrectomy,
and gastric bypass), decreased risk of hormone-​related cancers in-
cluding breast (odds ratio [OR] = 0.25; 95% CI: 0.19–​0.33), endo-
metrium (OR = 0.21; 95% CI: 0.13–​0.35), and prostate (OR = 0.37;
95% CI: 0.17–​0.76)32 was observed compared to obese patients not
undergoing a bariatric procedure that were propensity matched for
age, sex, comorbidity, and duration of follow-​up. However, in the
same study, there was no effect of gastric banding or sleeve gas-
trectomy on esophageal or colorectal cancer and an increased risk
of colorectal cancer in patients receiving gastric bypass. Suggested
mechanisms associated with this increase in risk include inflamma-
tion and hyperproliferation and gut microbiota changes following
the surgical bypass procedure.
Weight Management Lifestyle Interventions. Several studies
have examined how weight loss through calorie restriction, dietary
changes, and increased physical activity affects biological markers
related to cancer risk. For example, in the Nutrition and Exercise in
Women (NEW) study, 439 overweight and obese postmenopausal
women were randomized to aerobic exercise, dietary weight man-
agement, or both versus control for 12 months.33 Compared to
control, exercise plus diet-​induced weight loss was associated with
significantly decreased BMI, insulin resistance, systemic inflam-
mation, sex steroid hormones, and genes related to growth factor
signaling. Nonetheless, few studies have been able to discern the
effect of behavioral weight management interventions on cancer-​
specific outcomes (e.g., cancer risk, disease-​free survival).
Challenges to Healthy Eating and Weight
Management for Cancer Risk Reduction and
Cancer Health Equity
As noted earlier and highlighted in consensus reports from leading
cancer organizations, modifiable lifestyle behavioral risk factors,
including diet and physical inactivity, account for between 30%
and 50% of cancers. Often, the combination of less healthful diets
and physical inactivity leads to excessive weight gain and obesity,
increasing cancer risk. Recent estimates reflect that obesity accounts
for 14% to 20% of the attributable cancer risk for U.S. adults and
as much as 50% of all cancers for individuals under age 65 years.
In the most recent nationally representative survey of adults in the
U.S. (2013–​2014), the age-​adjusted prevalence of obesity was 35.2%
among men and 40.4% among women. There were differences, how-
ever, across race/​ethnicity, with prevalence rates of 38.7%, 57.2%,
and 46.6% among non-​Hispanic white, Non-​Hispanic black, and
Hispanic women, respectively.34 The differences in prevalence
rates among men were not as striking, with rates of 35.4%, 38.2%,
and 38.8% among non-​Hispanic white, non-​Hispanic black, and
Hispanic men, respectively.34
Unfortunately, minorities and low-​income individuals are at a
significant disadvantage when it comes to making healthier dietary
choices, driving obesity rates. For example, the main components of
the Med Diet, which is embraced by the scientific community and
associated with an inverse association with total mortality incidence
of coronary heart disease, stroke, and several cancers, are charac-
terized by a high consumption of vegetables, fruits, whole grains,
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 First Inter-allied Gas Conference. The first inter-allied gas
conference was held in Paris on September 16th, and consisted of
American, British, French, Italian, and Belgian delegates. The
conference busied itself mainly with questions of the medical
treatment of gassed cases and of defense against gas.
Mustard Gas. The principal topic under consideration at this
conference was the effects of the new mustard gas first used at
Ypres against the British on the nights of the 11th and 12th of July,
1917. The British suffered nearly 20,000 casualties from this gas
during the first six weeks of its use, and were so worried over it that
the start of the attacks carried out later in the fall of 1917 against
Ypres were delayed several days. The casualties were particularly
heavy because the smell of the gas was entirely new and not
unpleasant and because of the delayed action of the gas, whereby
men got no indication of its seriousness until 4 to 8 hours after
exposure. For these reasons men simply took shelter from the
bombardment without putting on masks or taking other precautions.
As a result of the Paris conference a long cable was sent to the
United States asking among other things that immediate report be
made on the possibilities of producing ethylene chlorhydrin, one of
the essentials in the manufacture of mustard gas by the only method
then known.
Within two weeks after this conference, there occurred an
incident which illustrates the very great danger in taking the views of
any one man unless certain that he is in a position to be posted on
all sides of the question under discussion. A high British official was
asked what he had heard in regard to the new mustard gas, and
what and how it was considered. He said with emphasis that the
British had no further fear of it since they had learned what it was
and how to take care of themselves and that it had ceased to be any
longer a problem with them.
Fries, knowing what he did, was convinced that this did not
represent the attitude of the British authorities who knew what the
gas was doing, and the statement was not allowed to influence the
American Gas Service in the least. This was a very fortunate thing
as events later proved. It should also be added that a quite similar
report was made by a French officer in regard to mustard gas some
time in the month of October. The French officer had more reason for
his attitude than the British officer as up to that time mustard gas had
not been largely used against the French. However, both cases
simply emphasize the danger of accepting the views of any man who
has seen but one angle of a problem so complicated as gas in war.

Training
Training in Gas Defense. In the latter part of October seventeen
young engineer officers, who had just arrived in France, were
assigned to the Gas Service and were promptly sent to British Gas
Schools for training in mask inspection, salvage and repair and in
training men to wear masks and take other necessary precautions
against gas in the field. It was also necessary at this time to establish
gas training in the First Division, and Captain Boothby was assigned
to that work.
Fig. 9.—Destroying Mustard Gas on the Battle Field.

It is important to note that the Gas Service had to begin

operations immediately upon its organization although it had almost
no facilities of any kind to work with. At one and the same time it was
necessary to decide upon the kinds of masks to be used and then to
obtain them; to decide upon methods of training troops in gas
defense and start at once to do it; to decide upon gases to be used
and manufactured in the United States and then obtain and send the
necessary data and finally to decide what weapons gas troops were
to use and to purchase those weapons, since none of them existed
in the United States. Worse still no one in the United States was
taking any interest in them.
New Mask. About November 1, Major Karl Connell of the Medical
Department, National Guard of New York, reported for duty in
response to a cablegram that had been sent asking for him by name.
It was intended to send him to a British School to learn the art of
teaching gas defense. However, learning after a short talk with him
that he had been interested in making masks for administering
anæsthesia, there was at once turned over to him samples of all the
masks in use by both the Allies and the Germans, with a view to
getting his ideas for a new mask. Within two or three hours he
suggested a new mask having a metal face piece with sponge
rubber against the face and with a canister to be carried on the back
of the head.
At that early date it was realized that a new mask must be
invented which would be far more comfortable and give better vision
than the British respirators adopted for use. Connell, thirty-six hours
after reporting, had so far developed his idea that he was sent to
Paris to make the first model, which he succeeded in doing in about
three weeks. This first mask was good enough to risk testing in a
high concentration of chlorine and while it leaked to some extent it
indicated that the idea was sound. The problem then was to perfect
the mask and determine how it could be produced commercially on
the large scale necessary to equip an army.
Since the British at this time and practically throughout the war
were much ahead of the French in all phases of gas warfare, Connell
was sent to London. There he succeeded in getting additional
models in such shape that one of them was sent to the United States
during the first few days of January, 1918. Connell’s work and
experiments were continued so successfully that after a model had
been submitted to the General Staff, as well as to General Pershing
himself, one thousand were ordered to be made early in May with a
view to an extensive field test preparatory to their adoption for
general use in the United States Army.
In this connection, during November, 1917, a letter was written to
the United States stating that while the Gas Service in France
insisted on the manufacture of British respirators exactly as the
British were making them, they desired to have experiments pushed
on a more comfortable mask to meet the future needs of the Army.
 The following four principles were set down in that letter: (a) That
the mask must give protection and that experience had shown that
suitable protection could only be obtained by drawing the air through
a box filled with chemicals and charcoal. (b) That there must be clear
vision and that experience to date indicated that the Tissot method of
bringing the inspired air over the eyepieces was by far the best, (c)
That the mask must be as comfortable as compatible with
reasonable protection, and that this meant the mouthpiece and
noseclip must be omitted. (d) That the mask must be as nearly fool
proof as it could be made. That is, it should be of quick and accurate
adjustment, in the dark or in the trenches, and be difficult to
disarrange or injure once in position.
Gas Training and Battle of Picardy Plains. On March 21, 1918,
as is known to everyone, the Germans began their great drive from
Cambrai across the Picardy Plains to Amiens. While the battle was
expected it came as a complete surprise so far as the tactics used,
and the extent and force of the attack, were concerned. Lieutenant
Colonel G. N. Lewis, who had been sent about March 1 to British
Gas Schools, and had been assigned to one of the schools run by
the Canadians, was thus just on the edge of the attack. This gave
him an opportunity to actually observe some of that attack and to
learn from eye-witnesses a great deal more. The school, of course,
was abandoned hurriedly and the students ordered back to their
stations. Lewis submitted two brief reports covering facts bearing on
the use of gas and smoke by the Germans. These reports exhibited
such a grasp of gas and smoke battle tactics that he was
immediately ordered to headquarters as assistant on the Defense
side of gas work, that is, on training in gas defense. Up to that time
no one had been able to organize the Defensive side of gas work in
the way it was felt it must be organized if it were to prove a thorough
success. A month later he was put at the head of the Gas Defense
Section, and in two months he had put the Defense Division on a
sound basis. He was then ordered to the United States to help
organize Gas Defense Training there.
 Fig. 10.—Close Burst of a Gas Shell.
The 6th Marines in the Sommediene Sector
near Verdun, April 30, 1918.

Cabled Report on Picardy Battle. Based partly on Colonel

Lewis’s written and oral reports, and also on information contained in
Intelligence dispatches and the newspapers, a cablegram of more
than 300 words was drafted reciting the main features of the battle
so far as they pertained to the use of gas. This cablegram ended
with the statement that “the above illustrates the tremendous
importance of comfort in a mask” and that “the future mask must
omit the mouthpiece and noseclip.”
Keeping the General Staff Informed of Work. In the early part
of May, 1918, the Americans arrived in the vicinity of Montdidier,
south of Amiens, on the most threatened point of the western front. It
was on May 18, 1918, that the Americans attacked, took, and held
against several counter-attacks the town of Cantigny. Shortly
afterward they were very heavily shelled with mustard gas and
suffered in one night nearly 900 casualties. Investigation showed
that these casualties were due to a number of causes more or less
usual, but also to the fact that the men had to wear the mask 12 to
15 hours if they were to escape being gassed. Such long wearing of
the British mask with its mouthpiece and noseclip is practically an
impossibility and scores became gassed simply through exhaustion
and inability to wear the mask.
An inspector from General Headquarters in reporting on supplies
and equipment in the First Division, stated that one of the most
urgent needs was a more comfortable mask. The First Division
suggested a mask on the principles of the new French mask which
was then becoming known and which omitted the mouthpiece and
noseclip. The efforts of the American Gas Service in France to
perfect a mask without a mouthpiece and noseclip were so well
known and so much appreciated that they did not even call upon the
Gas Service for remark. The assistant to the Chief of Staff who drew
up the memorandum to the Chief simply said the matter was being
attended to by the Gas Service. This illustrates the value of keeping
the General Staff thoroughly informed of what is being done to meet
the needs of the troops on the firing line.
Then, as always, it was urged that a reasonably good mask was
far more desirable than the delay necessary to get a more perfect
one. Based on these experiences with mask development, the
authors are convinced that the whole tendency of workers in general,
in laboratories far from the front, is to over-estimate the value of
perfect protection based on laboratory standards. It is difficult for
laboratory workers to realize that battle conditions always require a
compromise between perfection and getting something in time for
the battle. It was early evident to the Gas Service in France that we
were losing, and would continue to lose, vastly more men through
removal of masks of the British type, due to discomfort and
exhaustion, than we would from a more comfortable but less perfect
mask. In other words when protection becomes so much of a burden
that the average man cannot or will not stand it, it is high time to find
out what men will stand, and then supply it even at the expense of
occasional casualties. Protection in battle is always relative. The only
perfect protection is to stay at home on the farm. The man who
cannot balance protection against legitimate risks has no business
passing on arms, equipment or tactics to be used at the Front.
As early as September, 1917, gas training was begun in the First
Division at Condrecourt. This training school became the First Corps
School. Later a school was established at Langres known as the
Army Gas School while two others known as the Second and Third
Corps Gas Schools were established elsewhere. The first program of
training for troops in France provided for a total period of three
months. Of this, two days were allowed the Gas Service. Later this
was reduced to six hours, notwithstanding a vigorous protest by the
Gas Service. However, following the first gas attacks against the
Americans with German projectors in March, 1918, followed a little
later by extensive attacks with mustard gas, the A. E. F. Gas
Defense School was established at the Experimental Field.
Arrangements were made for the accommodation of 200 officers for
a six-day course. The number instructed actually averaged about
150, due to the feeling among Division Commanders that they could
not spare quite so many officers as were required to furnish 200 per
week.
This school was conducted under the Commandant of Hanlon
Field, Lieutenant Colonel Hildebrand, by Captain Bush of the British
Service. This Gas Defense School became one of the most efficient
schools in the A. E. F., and was developing methods of teaching that
were highly successful in protecting troops in the field.
Failure of German Gas. The losses of the Americans from
German gas attacks fluctuated through rather wide limits. There
were times in the early days during training when this reached 65 per
cent of the total casualties. There were other times in battle, when
due to extremely severe losses from machine gun fire in attacks, that
the proportion of gas losses to all other forms of casualties was very
small. On the whole the casualties from gas reached 27.3 of all
casualties. This small percentage was due solely to the fact that
when the Americans made their big attacks at San Mihiel and the
Argonne, the German supply of gas had run very low. This was
particularly true of the supply of mustard gas.
 Fig. 11.—German Gas Alarms.

Fries was at the front visiting the Headquarters of the First Army
and the Headquarters of the 1st, 3d, and 5th Corps from two days
before the beginning of the battle of the Argonne to four days
afterwards. He watched reports of the battle on the morning of the
attack at the Army Headquarters and later at the 1st, 5th and 3d
Corps headquarters in the order named. No reports of any gas
casualties were received. This situation continued throughout the
day. It was so remarkable that he told the Chief of Staff he could
attribute the German failure to use gas to only one of two possible
conditions; first, the enemy was out of gas; second, he was
preparing some master stroke. The first proved to be the case as
examination after the Armistice of German shell dumps captured
during the advance revealed less than 1 per cent of mustard gas
shell. Even under these circumstances the Germans caused quite a
large number of gas casualties during the later stages of the fighting
in the Argonne-Meuse sector.
Evidently the Germans, immediately after the opening of the
attack, or more probably some days before, began to gather together
all available mustard gas and other gases along the entire western
battle front, and ship them to the American sector. This conclusion
seems justified because the enemy never had a better chance to use
gas effectively than he did the first three or four days of the Argonne
fight, and knowing this fact he certainly would never have failed to
use the gas if it had been available. Had he possessed 50 per cent
of his artillery shell in the shape of mustard gas, our losses in the
Argonne-Meuse fight would have been at least 100,000 more than it
was. Indeed, it is more than possible we would never have
succeeded in taking Sedan and Mezieres in the fall of 1918.
Officers’ Training Camp. The first lot of about 100 officers were
sent to France in July, 1918, with only a few days’ training, and in
some cases with no training at all. Accordingly, arrangements were
made to train these men in the duties of the soldier in the ranks, and
then as officers. Their training in gas defense and offense followed a
month of strenuous work along the above mentioned lines.
This camp was established near Hanlon (Experimental) Field, at
a little town called Choignes. The work as laid out included squad
and company training for the ordinary soldier, each officer taking
turns in commanding the company at drill. They were given work in
map reading as well as office and company administration.
This little command was a model of cleanliness and military
discipline, and attracted most favorable comment from staff officers
on duty at General Headquarters less than two miles distant. Just
before the Armistice arrangements were made to transfer this work
to Chignon, about 25 miles southeast of Tours, where ample
buildings and grounds were available to carry out not alone training
of officers but of soldiers along the various lines of work they would
encounter, from the handling of a squad, to being Chief Gas Officer
of a Division.
Educating the Army in the Use of Gas. As has been remarked
before, the Medical Department in starting the manufacture of gas
masks and other defensive appliances, and the Bureau of Mines in
starting researches into poisonous gases as well as defensive
materials, were the only official bodies who early interested
themselves in gas warfare. Due to this early work of the Bureau of
Mines and the Medical Department in starting mask manufacture as
well as training in the wearing of gas masks, the defensive side of
gas warfare became known throughout the army very far in advance
of the offensive side. On the other hand, since the Ordnance
Department, which was at first charged with the manufacture of
poisonous gases, made practically no move for months, the
offensive use of gas did not become known among United States
troops until after they landed in France.
Moreover, no gas shell was allowed to be fired by the artillery in
practice even in France, so that all the training in gas the artillery
could get until it went into the line was defensive, with lectures on the
offensive.
The work of raising gas troops was not begun until the late fall of
1917 and as their work is highly technical and dangerous, they were
not ready to begin active work on the American front until June,
1918.
By that time the army was getting pretty well drilled in gas
defense and despite care in that respect were getting into a frame of
mind almost hostile to the use of gas by our own troops. Among
certain staff officers, as well as some commanders of fighting units,
this hostility was outspoken and almost violent.
Much the hardest, most trying and most skillful work required of
Chemical Warfare Service officers was to persuade such Staffs and
Commanders that gas was useful and get them to permit of a
demonstration on their front. Repeatedly Chemical Warfare Service
officers on Division staffs were told by officers in the field that they
had nothing to do with gas in offense, that they were simply
defensive officers. And yet no one else knew anything about the use
of gas. Gradually, however, by constantly keeping before the
General Staff and others the results of gas attacks by the Germans,
by the British, by the French, and by ourselves, headway was made
toward getting our Armies to use gas effectively in offense.
But so slow was this work that it was necessary to train men
particularly how to appeal to officers and commanders on the
subject. Indeed the following phrase, used first by Colonel Mayo-
Smith, became a watchword throughout the Service in the latter part
of the war—“Chemical Warfare Service officers have got to go out
and sell gas to the Army.” In other words we had to adopt much the
same means of making gas known that the manufacturer of a new
article adopts to make a thing manufactured by him known to the
public.

Fig. 12.—A Typical Shell Dump near the Front.

 This work was exceedingly trying, requiring great skill, great
patience and above all a most thorough knowledge of the subject. As
illustrating some of these difficulties, the Assistant Chief of Staff, G-3
(Operations) of a certain American Corps refused to consider a
recommendation to use gas on a certain point in the battle of the
Argonne unless the gas officer would state in writing that if the gas
was so used it could not possibly result in the casualty of a single
American soldier. Such an attitude was perfectly absurd.
The Infantry always expects some losses from our own high
explosive when following a barrage, and though realizing the
tremendous value of gas, this staff officer refused to use it without an
absolute guarantee in writing that it could not possibly injure a single
American soldier. Another argument often used was that a gas attack
brought retaliatory fire on the front where the gas was used. Such
objectors were narrow enough not to realize that the mere fact of
heavy retaliation indicated the success of the gas on the enemy for
everyone knows an enemy does not retaliate against a thing which
does not worry him.
But on the other hand, when the value of gas troops had become
fully known, the requests for them were so great that a single platoon
had to be assigned to brigades, and sometimes even to whole
Divisions. Thus it fell to the Lieutenants commanding these platoons
to confer with Division Commanders and Staffs, to recommend how,
when and where to use gas, and do so in a manner which would
impress the Commanding General and the Staff sufficiently to allow
them to undertake the job. That no case of failure has been reported
is evidence of the splendid ability of these officers on duty with the
gas troops. Efficiency in the big American battles was demanded to
an extent unheard of in peace, and had any one of these officers
made a considerable failure, it certainly would have been reported
and Fries would have heard of it.
Equally hard, and in many cases even more so, was the work of
the gas officers on Division, Corps and Army Staffs, who handled the
training in Divisions, and who also were required to recommend the
use of gas troops, the use of gas in artillery shell and in grenades,
and the use of smoke by the infantry in attack. However, the success
of the Chemical Warfare Service in the field with these Staff officers
was just as great as with the Regiment.
To the everlasting credit of those Staff Officers and the Officers of
the Gas Regiment from Colonel Atkisson down, both Staff Gas
officers and officers of the Gas Regiment worked together in the
fullest harmony with the single object of defeating the Germans.

Chemical Warfare Troops

Chemical Warfare troops were divided into two distinct divisions
—gas regiments and staff troops.

Fig. 13.—Firing a 155-Millimeter Howitzer.

 The men are wearing gas masks to keep out the enemy gas fired
at them in Oct., 1918.]
Staff Troops. The staff troops of the Chemical Warfare Service
performed all work required of gas troops except that of actual
fighting. They handled all Chemical Warfare Service supplies from
the time they were unloaded from ships to the time they were issued
to the fighting troops at the front, whether the fighting troops were
Chemical Warfare or any other. They furnished men for clerical and
other services with the Army, Corps and Division Gas Officers, and
they manufactured poisonous gases, filled gas shells and did all
repairing and altering of gas masks. Though these men received
none of the glamour or glory that goes with the fighting men at the
front, yet they performed services of the most vital kind and in many
cases did work as dangerous and hair raising as going over the top
in the face of bursting shell and screaming machine gun bullets.
Think of the intense interest these men must have felt when
carrying from the field of battle to the laboratory or experimental field,
shell loaded with strange and unheard of compounds and which
might any moment burst and end forever their existence! Or watch
them drilling into a new shell knowing not what powerful poison or
explosive it might contain or what might happen when the drill “went
through”!
And again what determination it took to work 12 or 16 hours a
day way back at the depots repairing or altering masks, and, as was
done at Chateroux, alter and repair 15,000 masks a day and be so
rushed that at times they had a bare day’s work of remodeled masks
ahead. But they kept ahead and to the great glory of these men no
American soldier ever had to go to the front without a mask. And
what finer work than that of these men who, in the laboratory and
testing room, toyed with death in testing unknown gases with
American and foreign masks even to the extent of applying the
gases to their own bodies.
Heroic, real American work, all of it and done in real American
style as part of the day’s work without thought of glory and without
hope of reward.
 The First Gas Regiment. In the first study of army organization
made by the General Staff it was decided to recommend raising
under the Chief of Engineers one regiment of six companies of gas
troops.
Shortly after the cable of August 17, 1917, was sent stating that
Lieut. Colonel Fries would be made Chief of the Gas Service, the
War Department promoted him to be Colonel of the 30th Engineers
which later became the First Gas Regiment. At almost the same
time, Captain Atkisson, Corps of Engineers, was appointed Lieut.
Col. of the Regiment. Although Colonel Fries remained the nominal
Commander of the regiment, he never acted in that capacity, for his
duties as Chief of the Gas Service left him neither time nor
opportunity. All the credit for raising, training, and equipping the First
Gas Regiment belongs to Colonel E. J. Atkisson and the officers
picked by him.
Immediately upon the formation of the Gas Service, the Chief
urged that many more than six companies of gas troops should be
provided. These recommendations were repeated and urged for the
next two months or until about the first of November, when it became
apparent that an increase could not be obtained at that time and that
any further urging would only cause irritation. The matter was
therefore dropped until a more auspicious time should arrive. This
arrived the next spring when the first German projector attack
against United States troops produced severe casualties, exactly as
had been forecasted by the Gas Service. About the middle of March,
1918, an increase from two battalions to six battalions (eighteen
companies) was authorized. A further increase to three regiments of
six battalions each (a total of fifty-four companies) was authorized
early in September, 1918, after the very great value of gas troops
had been demonstrated in the fight from the Marne to the Vesle in
July.
 Fig. 14.—Receiving and Transmitting Data
for Firing Gas Shell while Wearing Gas Masks.
Battlefield of the Argonne, October, 1918.

No Equipment for Gas Troops. About the first of December a

cablegram was received from the United States stating that due to
lack of equipment the various regiments of special engineers
recently authorized, including the 30th (Gas and Flame) would not
be organized until the spring of 1918. An urgent cablegram was then
sent calling attention to the fact that gas troops were not service of
supply troops but first line fighting troops, and consequently that they
should be raised and trained in time to take the field with the first
Americans going into the line. At this same time the 30th regiment
was given early priority by the General Staff, A. E. F., on the priority
lists for troop shipments from the United States. The raising of the
first two companies was then continued under Colonel Atkisson at
the American University in Washington.
About January 15 word was received that the Headquarters of
the regiment and the Headquarters of the First Battalion together
with Companies A and B of the 30th Engineers (later the First Gas
Regiment) were expected to arrive very soon. Some months prior
General Foulkes, Chief of the British Gas Service in the field, had
stated that he would be glad to have the gas troops assigned to him
for training. It was agreed that the training should include operations
in the front line for a time to enable the American Gas Troops to
carry on gas operations independently of anyone else and with entire
safety to themselves and the rest of the Army.
Due to the fact that the British were occupying their gas school,
the British General Headquarters were a little reluctant to take the
American troops Feb. 1. However, General Foulkes made room for
the American troops by moving his own troops out. He then placed
his best officers in charge of their training and at all times did
everything in his power to help the American Gas Troops learn the
gas game and get sufficient supplies to operate with. Colonel
Hartley, Assistant to General Foulkes, also did everything he could to
help the American Gas Service. These two officers did more than
any other foreign officers in France to enable the Chemical Warfare
Service to make the success it did.
Second Battle of the Marne. The Chief of the Gas Service,
following a visit to the British Gas Headquarters, and the
Headquarters of the American 2d Corps then operating with the
British, arrived on the evening of July 17, 1918, at 1st Corps
Headquarters at La Ferte sous Jouarre about 10 miles southeast of
Château-Thierry.
Two companies of the First Gas Regiment would have been
ready in 48 hours to put off a projector attack against an excellent
target just west of Belleau Wood had not the 2d battle of the Marne
opened when it did. It is said that General Foch had kept this special
attack so secret that the First American Corps Commander knew it
less than 48 hours prior to the hour set for its beginning. Certainly
the Chief of the Gas Service knew nothing of it until about 9:00 p.m.,
the night of July 17th. Consequently the gas attack was not made. At
that time so little was known of the usefulness of gas troops that they
were started on road work. At Colonel Atkisson’s suggestion that gas
troops could clean out machine gun nests, he was asked to visit the
First Corps headquarters and take up his suggestion vigorously with
the First Corps Staff.
Attacking Machine Gun Nests. Thereupon the Gas troops were
allowed to try attacking machine gun nests with phosphorus and
thermite. This work proved so satisfactory that not long afterwards
the General Staff authorized an increase in gas troops from 18
companies to 54 companies, to be formed into three regiments of
two battalions each. The 6 companies in France did excellent work
with smoke and thermite during all the second battle of the Marne to
the Vesle river, where by means of smoke screens they made
possible the crossing of that river and the gaining of a foothold on
the north or German side.
With the assembling of American troops in the sector near
Verdun in September, 1918, the gas troops were all collected there
with the exception of one or two companies and took a very active
part in the capture of the St. Mihiel salient. It was at this battle that
the Chemical Warfare Service really began to handle offensive gas
operations in the way they should be handled. Plans were drawn for
the use of gas and smoke by artillery and gas troops both. The use
of high explosives in Liven’s bombs was also planned. Those plans
were properly co-ordinated with all the other arms of the service in
making the attack. Gas was to be used not alone by gas troops but
by the artillery. Plans were made so that the different kinds of gases
would be used where they would do the most good. While these
plans and their execution were far from perfect, they marked a
tremendous advance and demonstrated to everyone the possibilities
that lay in gas and smoke both with artillery and with gas troops.
Following the attack on the St. Mihiel salient, came the battle of
the Argonne, where plans were drawn as before, using the added
knowledge gained at St. Mihiel. The work was accordingly more
satisfactory. However, the attempt to cover the entire American front
of nine divisions with only six companies proved too great a task.
Practically all gas troops were put in the front line the morning of the
attack. Due to weather conditions they used mostly phosphorus and
thermite with 4 inch Stokes’ mortars. Having learned how useful
these were in taking machine gun nests, plans were made to have
them keep right up with the Infantry. This they did in a remarkable
manner considering the weight of the Stokes’ mortar and the base
plates and also that each Stokes’ mortar bomb weighed about 25
pounds. There were cases where they carried these mortars and
bombs for miles on their backs, while in other cases they used pack
animals.

Fig. 15.—Setting Up a Smoke Barrage with Smoke

Pots.

Not expecting the battle to be nearly continuous as it was for

three weeks, the men, as before stated, were all put in the front line
the morning of the attack. This resulted in their nearly complete
exhaustion the first week, since they fought or marched day and