Holland-Frei Cancer Medicine

The latest edition of the gold-standard in cancer science and clinical oncology references

In the newly revised Tenth Edition of Holland-Frei Cancer Medicine, a team of distinguished researchers and practitioners delivers a comprehensive and up-to-date discussion of cancer science and clinical oncology practice. The book contains timely and indispensable information on epidemiology, etiology, cancer biology, immunology, prevention, screening, clinical presentation, pathology, imaging, and therapy.

Grounded in a fundamental understanding of cancer biology, Holland-Frei Cancer Medicine combines scientific principles with clinical practice. It contains hundreds of full-color illustrations and photographs, tables, graphs, and algorithms that complement and enhance the complex topics discussed within the book. This book is an invaluable clinical tool that provides readers with overview boxes, additional references, and other pedagogic features designed to make the content easy to access and comprehend.

Readers will also find:

• A translational and integrated approach throughout the book that combines cancer biology with cancer management
• A strong emphasis on multidisciplinary, research-driven patient care that improves outcomes and allows for the optimal use of all clinically appropriate therapies
• Discussions of the most current personalized cancer care, including molecular diagnostics and therapeutics

Perfect for medical oncologists, radiation oncologists, and internists, Holland-Frei Cancer Medicine, Tenth Edition will also earn a place in the libraries of allied health professionals involved in the treatment of cancer patients.

This book is published in collaboration with the American Association for Cancer Research: https://www.aacr.org/

Robert C. Bast Jr, MD, Vice President for Translational Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

John Byrd, MD, The Gordon and Helen Hughes Taylor Professor and Chair, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA

Carlo M. Croce, MD, Distinguished University Professor, The Ohio State University, The John W. Wolfe Chair in Human Cancer Genetics, Professor and Chair, Department of Cancer Biology and Genetics The Wexner Medical Center, The Ohio State University, Columbus, OH, USA

Ernest Hawk, MD, MPH, Vice President for Cancer Prevention & Head, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Fadlo R. Khuri, MD, President and Professor of Internal Medicine, Hematology and Medical Oncology, The American University of Beirut, Beirut, Lebanon

Raphael E. Pollock, MD, PhD, FACS, Director, The Ohio State University Comprehensive Cancer Center, Kathleen Wellenreiter Klotz Chair in Cancer Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA

Apostolia M. Tsimberidou, MD, PhD, Professor, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Christopher Willett, MD, Professor and Chair, Department of Radiation Oncology, Duke University School of Medicine, Boston, Massachusetts, USA

Cheryl Willman, MD, Executive Director, Mayo Clinic Cancer Center Programs: Mayo Rochester/Midwest, Mayo Arizona, Mayo Florida, London, Abu Dhabi, Director, Mayo Clinic Comprehensive Cancer Center, Professor of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic Cancer Center, Rochester, NY, USA

List of contributors xi

Preface xxvii

Acknowledgments xxix

Part 1: INTRODUCTION

1 Cardinal manifestations of cancer 3

James F. Holland, Robert C. Bast, Jr., John C. Byrd,

Carlo M. Croce, Ernest Hawk, Fadlo R. Khuri, Raphael

E. Pollock, Apostolia M. Tsimberadou, Christopher G.

Willett, and Cheryl L.Willman

2 Biological hallmarks of cancer 7

Douglas Hanahan and Robert A.Weinberg

Part 2: TUMOR BIOLOGY

3 Molecular biology, genetics, and translational

models of human cancer 19

Benno Traub, Florian Scheufele, Srinivas R.

Viswanathan, Matthew Meyerson, and David A. Tuveson

4 Oncogenes 49

Marco A. Pierotti, Milo Frattini, Samantha Epistolio,

Gabriella Sozzi, and Carlo M. Croce

5 Tumor suppressor genes 73

Fred Bunz and Bert Vogelstein

6 Epigenetic contributions to human cancer 89

Stephen B. Baylin

7 Cancer genomics and evolution 101

William P. D. Hendricks, Aleksandar Sekulic, Alan H.

Bryce, Muhammed Murtaza, Pilar Ramos, Jessica D.

Lang, Timothy G. Whitsett, Timothy K. McDaniel,

Russell C. Rockne, Nicholas Banovich, and Jeffrey M. Trent

8 Chromosomal aberrations in cancer 125

Megan E. McNerney, Ari J. Rosenberg, and Michelle M.

Le Beau

9 MicroRNA expression in cancer 143

Serge P. Nana-Sinkam, Mario Acunzo, and Carlo M. Croce

10 Aberrant signaling pathways in cancer 151

Luca Grumolato and Stuart A. Aaronson

11 Differentiation therapy 161

Sai-Juan Chen, Xiao-Jing Yan, Guang-Biao Zhou, and

Zhu Chen

12 Cancer stem cells 177

Grace G. Bushnell,Michael D. Brooks, andMax S.Wicha

13 Cancer and cell death 187

John C. Reed

14 Cancer cell immortality: targeting telomerase and

telomeres 201

Ilgen Mender, Zeliha G. Dikmen, and JerryW. Shay

15 Cancer metabolism 211

Natalya N. Pavlova, Aparna D. Rao, Ralph J.

DeBerardinis, and Craig B.Thompson

16 Tumor angiogenesis 223

John V. Heymach, Amado Zurita-Saavedra, Scott

Kopetz, Tina Cascone, MoniqueNilsson, and IreneGuijarro

Part 3: QUANTITATIVE ONCOLOGY

17 Cancer bioinformatics 247

John N.Weinstein

18 Systems biology and genomics 261

Saima Hassan, Joe W. Gray, and LauraM.Heiser

19 Statistical innovations in cancer research 269

J. Jack Lee and Donald A. Berry

20 Biomarker based clinical trial design in the era of

genomic medicine 285

R.Donald Harvey, Yuan Liu, Taofeek K.Owonikoko,

and Suresh S. Ramalingam

21 Clinical and research informatics data strategy for

precision oncology 293

Douglas Hartman, Uma Chandran, Michael Davis,

Rajiv Dhir,William E. Shirey, Jonathan C. Silverstein,

and Michael J. Becich

Part 4: CARCINOGENESIS

22 Chemical carcinogenesis 305

Lorne J. Hofseth, AinsleyWeston, and Curtis C. Harris

23 Ionizing radiation 325

David J. Grdina

24 Ultraviolet radiation carcinogenesis 333

James E. Cleaver, Susana Ortiz-Urda, and Sarah Arron

25 Inflammation and cancer 339

Jelena Todoric, Atsushi Umemura, Koji Taniguchi, and

Michael Karin

26 RNA tumor viruses 347

Robert C. Gallo and Marvin S. Reitz

27 Herpesviruses 359

Jeffrey I. Cohen

28 Papillomaviruses and cervical neoplasia 367

Michael F. Herfs, Christopher P. Crum, and KarlMunger

29 Hepatitis viruses and hepatoma 373

HongyangWang

30 Parasites 379

Mervat El Azzouni, Charbel F. Matar, Radwa Galal,

Elio Jabra, and Ali Shamseddine

Part 5: EPIDEMIOLOGY, PREVENTION, AND

DETECTION

31 Cancer epidemiology 391

Veronika Fedirko, Kevin T. Nead, Carrie Daniel, and

Paul Scheet

32 Hereditary cancer syndromes: risk assessment and

genetic counseling 403

Rachel Bluebond, Sarah A. Bannon, Samuel M. Hyde,

Ashley H.Woodson, Nancy Y.-Q. You, Karen H. Lu, and

Banu Arun

33 Behavioral approaches to cancer prevention 425

Roberto Gonzalez and Maher Karam-Hage

34 Diet and nutrition in the etiology and prevention

of cancer 433

Steven K. Clinton, Edward L. Giovannucci, Fred K.

Tabung, and Elizabeth M. Grainger

35 Chemoprevention of cancer 453

Ernest Hawk, Karen C. Maresso, Powel Brown, Michelle

I. Savage, and Scott M. Lippman

36 Cancer screening and early detection 473

OtisW. Brawley

Part 6: CLINICAL DISCIPLINES

37 Clinical cancer genomic diagnostics and modern

diagnostic pathology 493

Katherine Roth, Stephen B. Gruber, and Kevin McDonnell

38 Molecular diagnostics in cancer 505

Zachary L. Coyne, Roshni D. Kalachand, Robert C. Bast

Jr., Gordon B. Mills, and Bryan T. Hennessy

39 Principles of imaging 519

Lawrence H. Schwartz

40 Interventional radiology for the cancer patient 521

Zeyad A. Metwalli, Judy U. Ahrar, andMichael J. Wallace

41 Principles of surgical oncology 531

ToddW. Bauer, Kenneth K. Tanabe, and Raphael E. Pollock

42 Principles of radiation oncology 543

Scott R. Floyd, Justus Adamson, Philip P. Connell, Ralph

R.Weichselbaum, and Christopher G.Willett

43 Principles of medical oncology 553

Apostolia M. Tsimberidou, Robert C. Bast, Jr., Fadlo R.

Khuri, and John C. Byrd

44 Pain and palliative care 567

Laura Van Metre Baum and Cardinale B. Smith

45 Psycho-oncology 577

Diya Banerjee and Andrew J. Roth

46 Principles of cancer rehabilitation medicine 585

Michael D. Stubblefield, Miguel Escalon, Sofia A.

Barchuk, Krina Vyas, and David C.Thomas

47 Integrative oncology in cancer care 593

Gabriel Lopez,Wenli Liu, Santhosshi Narayanan, and

Lorenzo Cohen

48 Health services research 599

Michaela A. Dinan and Devon K. Check

Part 7: INDIVIDUALIZED TREATMENT

49 Precision medicine in oncology drug development 613

Apostolia M. Tsimberidou, Elena Fountzilas, and

Razelle Kurzrock

Part 8: CHEMOTHERAPY

50 Drug development of small molecule cancer

therapeutics in an Academic Cancer Center 631

Christopher C. Coss, Jeffrey T. Patrick, Damien Gerald,

Gerard Hilinski, Reena Shakya, and John C. Byrd

51 Principles of dose, schedule, and combination

therapy 641

Joseph P. Eder and Navid Hafez

52 Pharmacology of small-molecule anticancer agents 655

Zahra Talebi, Sharyn D. Baker, and Alex Sparreboom

53 Folate antagonists 667

Lisa Gennarini, Peter D. Cole, and Joseph R. Bertino

54 Pyrimidine and purine antimetabolites 679

Robert B. Diasio and StevenM. Offer

55 Alkylating agents and platinum antitumor

compounds 693

Zahid H. Siddik

56 DNA topoisomerase targeting drugs 701

AnishThomas, Susan Bates,William D. Figg, Sr., and

Yves Pommier

57 Microtubule inhibitors 717

Giuseppe Galletti and Paraskevi Giannakakou

58 Drug resistance and its clinical circumvention 731

Jeffrey A. Moscow, Shannon K. Hughes, Kenneth H.

Cowan, and Branimir I. Sikic

Part 9: BIOLOGICAL AND GENE THERAPY

59 Cytokines, interferons, and hematopoietic growth

factors 739

Narendranath Epperla,Walter Hanel, and Moshe Talpaz

60 Monoclonal antibody and targeted toxin therapy 755

Robert C. Bast, Jr. andMichael R. Zalutsky

61 Vaccines and immunomodulators 781

Jeffrey Schlom, Sofia R. Gameiro, Claudia Palena, and

James L. Gulley

62 T cell immunotherapy of cancer 789

M. Lia Palomba, Jae H. Park, and Renier Brentjens

63 Cancer immunotherapy 799

Padmanee Sharma, Swetha Anandhan, Bilal A.

Siddiqui, Sangeeta Goswami, Sumit K. Subudhi, Jianjun

Gao, Karl Peggs, Sergio Quezada, and James P. Allison

64 Cancer gene therapy 817

Haruko Tashiro, Lauren Scherer, and Malcolm Brenner

65 Cancer nanotechnology 825

Xingya Jiang, Yanlan Liu, Danny Liu, Jinjun Shi, and

Robert Langer

66 Hematopoietic cell transplantation 833

Qaiser Bashir, Elizabeth J. Shpall, and Richard E. Champlin

Part 10: SPECIAL POPULATIONS

67 Principles of pediatric oncology 847

Theodore P. Nicolaides, Elizabeth Raetz, andWilliam L.

Carroll

68 Cancer and pregnancy 867

Jennifer K. Litton

69 Cancer and aging 877

Ashley E. Rosko, Carolyn J. Presley, Grant R.Williams,

and Rebecca L. Olin

70 Disparities in cancer care 885

OtisW. Brawley

71 Neoplasms in people living with human

immunodeficiency virus 895

Chia-Ching J.Wang and Elizabeth Y. Chiao

72 Cancer survivorship 911

Lewis Foxhall

Part 11: DISEASE SITES

73 Primary neoplasms of the brain in adults 921

Matthew A. Smith-Cohn and Mark R. Gilbert

74 Neoplasms of the eye and orbit 933

Erica R. Alvarez, Claudia M. Prospero Ponce, Patricia

Chevez-Barrios, and Dan S. Gombos

75 Neoplasms of the endocrine glands and pituitary

neoplasms 943

Rui Feng, Chirag D. Gandhi, Margaret Pain, and

Kalmon D. Post

76 Neoplasms of the thyroid 949

Matthew D. Ringel

77 Malignant tumors of the adrenal gland 961

Jeffrey E. Lee, Mouhammed A. Habra, andMatthew T.

Campbell

78 Tumors of the diffuse neuroendocrine and

gastroenteropancreatic system 971

Evan Vosburgh

79 Neoplasms of the head and neck 981

Robert L. Ferris, AdamS. Garden, andNabil F. Saba

80 Cancer of the lung 1005

Daniel Morgensztern, Daniel Boffa, Alexander Chen,

Andrew Dhanasopon, Sarah B. Goldberg, Roy H.

Decker, Siddhartha Devarakonda, Jane P. Ko, Luisa M.

Solis Soto, Saiama N.Waqar, Ignacio I.Wistuba, and

Roy S. Herbst

81 Malignant pleural mesothelioma 1029

Michele Carbone, Daniel R. Gomez, Anne S. Tsao,

Haining Yang, and Harvey I. Pass

82 Thymomas and thymic tumors 1043

Mayur D. Mody,Gabriel L. Sica, Suresh S. Ramalingam,

and Dong M. Shin

83 Tumors of the heart and great vessels 1055

Moritz C.Wyler von Ballmoos and Michael J. Reardon

84 Primary germ cell tumors of the thorax 1061

John D. Hainsworth and Frank A. Greco

85 Neoplasms of the esophagus 1065

MaxW. Sung and Virginia R. Litle

86 Carcinoma of the stomach 1083

Carl Schmidt, Nour Daboul, Carly Likar, and JoshuaWeir

87 Primary neoplasms of the liver 1095

Hop S. Tran Cao, Junichi Shindoh, and Jean-Nicolas

Vauthey

88 Gallbladder and bile duct cancer 1109

Mariam F. Eskander, Christopher T. Aquina, and

Timothy M. Pawlik

89 Neoplasms of the exocrine pancreas 1123

Robert A. Wolff, Donghui Li, AnirbanMaitra, Susan

Tsai, Eugene Koay, and Douglas B. Evans

90 Neoplasms of the appendix and peritoneum 1139

Annie Liu, Diana Cardona, and Dan Blazer

91 Carcinoma of the colon and rectum 1147

Yota Suzuki, Douglas S. Tyler, and Uma R. Phatak

92 Neoplasms of the anus 1169

Alexandre A. A. Jácome and Cathy Eng

93 Renal cell carcinoma 1181

Claude M. Grigg, Earle F. Burgess, Stephen B. Riggs,

Jason Zhu, and Derek Raghavan

94 Urothelial cancer 1191

Derek Raghavan, Richard Cote, Earle F. Burgess, Derek

McHaffie, and Peter E. Clark

95 Neoplasms of the prostate 1201

Ana Aparicio, Patrick Pilie, Devaki S. Surasi, Seungtaek

Choi, Brian F. Chapin, Christopher J. Logothetis, and

Paul G. Corn

96 Tumors of the penis and the urethra 1239

Jad Chahoud, Andrea Necchi, and Philippe E. Spiess

97 Testis cancer 1245

Michael Hawking, Gladell Paner, Scott Eggener, and

Walter M. Stadler

98 Neoplasms of the vulva and vagina 1261

Michael Frumovitz and Summer B. Dewdney

99 Neoplasms of the cervix 1275

Anuja Jhingran

100 Endometrial cancer 1299

Shannon N.Westin, Karen Lu, and Jamal Rahaman

101 Epithelial ovarian, fallopian tube, and peritoneal

cancer 1311

Jonathan S. Berek, Malte Renz, Michael L. Friedlander,

and Robert C. Bast, Jr.

102 Nonepithelial ovarian malignancies 1329

Jonathan S. Berek, Malte Renz, Michael L. Friedlander,

and Robert C. Bast, Jr.

103 Molar pregnancy and gestational trophoblastic

neoplasia 1343

Neil S. Horowitz, Donald P. Goldstein, and Ross S. Berkowitz

104 Gynecologic sarcomas 1351

Jamal Rahaman and Carmel J. Cohen

105 Neoplasms of the breast 1361

Debu Tripathy, Sukh Makhnoon, Banu Arun, Aysegul

Sahin, Nicole M. Kettner, Senthil Damodaran, Khandan

Keyomarsi,Wei Yang, Kelly K. Hunt, Mark Clemens,

Wendy A. Woodward, Melissa P.Mitchell, Rachel

Layman, Evthokia A. Hobbs, Bora Lim, MeganDupuis,

Rashmi Murthy, Omar Alhalabi, Nuhad Ibrahim,

Ishwaria M. Subbiah, and Carlos Barcenas

106 Malignant melanoma 1413

Michael J. Carr, JustinM. Ko, SusanM. Swetter, Scott E.

Woodman, Vernon K. Sondak, Kim A. Margolin, and

Jonathan S. Zager

107 Other skin cancers 1437

Stacy L. McMurray,William G. Stebbins, Eric A.

Millican, and Victor A. Neel

108 Bone tumors 1451

Timothy A. Damron

109 Soft tissue sarcomas 1477

Katherine A.Thornton, Elizabeth H. Baldini, Robert G.

Maki, Brian O’Sullivan, Yan Leyfman, and Chandrajit P. Raut

110 Myelodysplastic syndromes 1501

Uma M. Borate

111 Acute myeloid leukemia in adults: mast cell

leukemia and other mast cell neoplasms 1517

RichardM. Stone, Charles A. Schiffer, and Daniel J. DeAngelo

112 Chronic myeloid leukemia 1537

Jorge Cortes, Richard T. Silver, and Hagop Kantarjian

113 Acute lymphoblastic leukemia 1547

Elias Jabbour, Nitin Jain, Hagop Kantarjian, and Susan

O’Brien

114 Chronic lymphocytic leukemia 1559

Jacqueline C. Barrientos, Kanti R. Rai, and Joanna M. Rhodes

115 Hodgkin lymphoma 1569

David J. Straus and Anita Kumar

116 Clonal hematopoiesis in cancer 1579

Philipp J. Rauch and David P. Steensma

117 Non-Hodgkin’s lymphoma 1587

Arnold S. Freedman and Ann S. LaCasce

118 Mycosis fungoides and Sézary syndrome 1603

Walter Hanel, Catherine Chung, and John C. Reneau

119 Plasma cell disorders 1611

Andrew J. Yee, Teru Hideshima, Noopur Raje, and

Kenneth C. Anderson

120 Myeloproliferative disorders 1633

Jeanne Palmer and Ruben Mesa

Part 12: MANAGEMENT OF CANCER

COMPLICATIONS

121 Neoplasms of unknown primary site 1647

John D. Hainsworth and Frank A. Greco

122 Cancer cachexia 1659

Assaad A. Eid, Rachel Njeim, Fadlo R. Khuri, and

David K.Thomas

123 Antiemetic therapy 1673

Michael J. Berger andDavid S. Ettinger

124 Neurologic complications of cancer 1683

Luis Nicolas Gonzalez Castro, Tracy T. Batchelor, and

Lisa M. DeAngelis

125 Dermatologic complications of cancer

chemotherapy 1701

Anisha B. Patel, Padmavathi V. Karri, and Madeleine Duvic

126 Skeletal complications 1715

Michael A. Via, Ilya Iofin, Jerry Liu, and Jeffrey I. Mechanick

127 Hematologic complications and blood bank

support 1729

Roger Belizaire and Kenneth C. Anderson

128 Coagulation complications of cancer patients 1739

Tzu-FeiWang and Kristin Sanfilippo

129 Urologic complications related to cancer and its

treatment 1747

Omar Alhalabi, Ala Abudayyeh, and Nizar M. Tannir

130 Cardiac complications 1757

Michael S. Ewer, Steven M. Ewer, andThomas M. Suter

131 Respiratory complications 1779

Vickie R. Shannon, George A. Eapen, Carlos A. Jimenez,

Horiana B. Grosu, Rodolfo C. Morice, Lara Bashoura,

Ajay Sheshadre, Scott E. Evans, Roberto Adachi,

Michael Kroll, Saadia A. Faiz, Diwakar

D. Balachandran, Selvaraj E. Pravinkumar,

and Burton F. Dickey

132 Gastrointestinal and hepatic complications in

cancer patients 1811

Robert S. Bresalier, Emmanuel S. Coronel, and Hao Chi Zhang

133 Oral complications of cancer and their treatment 1827

Stephen T. Sonis, Anna Yuan, and Alessandro Villa

134 Gonadal complications 1839

RobertW. Lentz and Catherine E. Klein

135 Sexual dysfunction 1849

Leslie R. Schover

136 Endocrine complications and paraneoplastic

syndromes 1855

Sai-Ching J. Yeung and Robert F. Gagel

137 Infections in patients with cancer 1869

Harrys A. Torres, Dimitrios P. Kontoyiannis, and

Kenneth V.I. Rolston

138 Oncologic emergencies 1883

Sai-Ching J. Yeung and Carmen P. Escalante

Part 13: THE FUTURE OF ONCOLOGY

139 A vision for twenty-first century healthcare 1907

Leroy Hood, Nathan D. Price, and James T. Yurkovich

Index 1915

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