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Holland-Frei Cancer Medicine Cloth


The original reference resource for medical oncologists, radiation oncologists, internists, and allied specialties involved in the treatment of cancer patients, Holland-Frei Cancer Medicine covers the ever-expanding field of current cancer science and clinical oncology practice. In this new ninth edition an outstanding editorial team from world-renowned medical centers continue to hone the leading edge forged in previous editions, with timely information on biology, immunology, etiology, epidemiology, prevention, screening, pathology, imaging, and therapy.

Holland-Frei Cancer Medicine, Ninth Edition, brings scientific principles into clinical practice and is a testament to the ethos that innovative, comprehensive, multidisciplinary treatment of cancer patients must be grounded in a fundamental understanding of cancer biology.

This ninth edition features hundreds of full color illustrations, photographs, tables, graphs and algorithms that enhance understanding of complex topics and make this text an invaluable clinical tool. Over 15 brand new chapters covering the latest advances, including chapters Cancer Metabolism, Bioinformatics, Biomarker Based Clinical Trial Design, Health Services Research and Survivorship bring this comprehensive resource up-to-date. Each chapter contains overview boxes, select references and other pedagogic features, designed to make the content easy to access and absorb. The full list of references for each chapter are available on the free Wiley Companion Digital Edition.

Inside this completely updated Ninth Edition you’ll find:

  • A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease
  • An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies
  • Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics
  • Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs
  • Free access to the Wiley Companion Digital Edition providing search across the book, full reference list with web links, downloadable illustrations and photographs, and post publication updates to key chapters  

Edited and authored by an international group of some of the best-known oncologists, cancer researchers, surgeons, pathologists, and other associated specialists in the world, and endorsed by the American Association of Cancer Research Holland-Frei Cancer Medicine offers a genuinely international view of cancer research and clinical oncology practice.

Endorsed by the American Association of Cancer Research

List of contributors xi

Preface xxvii

Acknowledgments xxix


1 Cardinal manifestations of cancer 3
James F. Holland, Waun Ki Hong,DonaldW. Kufe, Robert C. Bast Jr.,William N. Hait, Raphael E. Pollock, and Ralph R.Weichselbaum

2 Biological hallmarks of cancer 7
Douglas Hanahan and Robert A.Weinberg


3 Molecular biology, genomics, proteomics, and mouse models of human cancer 19
Srinivas R. Viswanathan,David A. Tuveson, and Matthew Meyerson

4 Oncogenes 47
Marco A. Pierotti, Milo Frattini, Francesca Molinari, Gabriella Sozzi, and Carlo M. Croce

5 Tumor suppressor genes 67
David Cosgrove, Ben Ho Park, and Bert Vogelstein

6 Epigenetic contributions to human cancer 85
James G. Herman and Stephen B. Baylin

7 Cancer genomics and evolution 93
William P. D. Hendricks, Aleksandar Sekulic, Alan H. Bryce, Muhammed Murtaza, Pilar Ramos, and Jeffrey M. Trent

8 Chromosomal aberrations in cancer 115
David J. VanderWeele, Megan E. McNerney, and Michelle M. Le Beau

9 MicroRNA expression in cancer 131
Serge Patrick Nana-Sinkam, Mario Acunzo, and Carlo M. Croce

10 Aberrant signaling pathways in cancer 137
Luca Grumolato and Stuart A. Aaronson

11 Differentiation therapy 147
Sai-Juan Chen, Xiao-Jing Yan, Guang-Biao Zhou, and Zhu Chen

12 Cancer stem cells 159
Yadwinder S. Deol, Jill Granger, and Max S.Wicha

13 Cancer and cell death 167
John C. Reed

14 Cancer cell immortality: targeting telomerase 179
Ilgen Mender, Zeliha Gunnur Dikmen,Woodring E. Wright, and JerryW. Shay

15 Cancer metabolism 187
Natalya N. Pavlova and Craig B.Thompson

16 Modeling therapy of late or early-stage metastatic disease in mice 199
Robert S. Kerbel, Marta Paez-Ribes, ShanMan, Ping Xu, Eric Guerin,William Cruz-Munoz, and John M. L. Ebos

17 Tumor angiogenesis 207
John V. Heymach, Amado Zurita-Saavedra, Scott Kopetz, Tina Cascone, and Monique Nilsson


18 Cancer bioinformatics 233
John N.Weinstein

19 Systems biology and genomics 247
Saima Hassan, Laura M. Heiser, and JoeW. Gray

20 Statistical innovations in cancer research 255
J. Jack Lee and Donald A. Berry

21 Biomarker-based clinical trial design in the era of genomic medicine 271
Richard Simon and Martine Piccart-Gebhart

22 Clinical informatics 277
Edward P. Ambinder


23 Chemical carcinogenesis 287
Lorne J. Hofseth, AinsleyWeston, and Curtis C. Harris

24 Endocrine and genetic bases of hormone-related cancers 307
Leslie Bernstein, Xia Pu, and Jian Gu

25 Ionizing radiation 321
David J. Grdina

26 Ultraviolet radiation carcinogenesis 327
James E. Cleaver, Susana Ortiz-Urda, Radhika Gulhar, Sarah T. Arron, Lionel Brookes 3rd, and David L.Mitchell

27 Inflammation and cancer 333
Jelena Todoric, Atsushi Umemura, Koji Taniguchi, and Michael Karin

28 RNA tumor viruses 341
Robert C. Gallo and Marvin S. Reitz

29 Herpesviruses 353
Jeffrey I. Cohen

30 Papillomaviruses and cervical neoplasia 361
Michael F. Herfs, Martin C. Chang, and Christopher P. Crum

31 Hepatitis viruses and hepatoma 367
HongyangWang, Guangwen Cao, Jing Fu, and Guishuai Lv

32 Parasites 373
Mervat Z. El Azzouni and Radwa G. Diab


33 The burden of cancer worldwide: current and future perspectives 383
Jacques Ferlay, Christopher P.Wild, and Freddie Bray

34 Cancer epidemiology 399
XifengWu, Xia Pu, Stephanie C. Melkonian, and Margaret R. Spitz

35 Behavioral approaches to cancer prevention 407
Errol J. Philip and Jamie S. Ostroff

36 Diet and nutrition in the etiology and prevention of cancer 415
Steven K. Clinton, Elizabeth M. Grainger, and Edward L. Giovannucci

37 Chemoprevention of cancer 433
William N.William Jr.,Waun Ki Hong, and Scott M. Lippman

38 Cancer screening and early detection 439
OtisW. Brawley


39 Nexgen pathology: predicting clinical course and targeting disease causation 459
Carlos Cordon-Cardo and Adolfo Firpo-Betancourt

40 Molecular diagnostics in cancer 469
Roshni D. Kalachand, Bryan T. Hennessy, Robert C. Bast Jr., and Gordon B. Mills

41 Principles of imaging 481
Lawrence H. Schwartz

42 Interventional radiology for the cancer patient 483
JudyU. Ahrar, Michael J. Wallace, and Rony Avritscher

43 Principles of surgical oncology 491
Mark Bloomston, Kenneth K. Tanabe, Raphael E. Pollock, and Donald L. Morton (deceased)

44 Principles of radiation oncology 503
Philip P. Connell and Ralph R.Weichselbaum

45 Principles of medical oncology 511
WilliamN. Hait, James F. Holland, Emil Frei III (deceased), DonaldW. Kufe, Robert C. Bast Jr., and Waun Ki Hong

46 Palliative care and pain management 521
Cardinale B. Smith

47 Principles of psycho-oncology 531
Jimmie C. Holland and TaliaW.Wiesel

48 Principles of cancer rehabilitation medicine 537
Michael D. Stubblefield, David C. Thomas, and Kristjan T. Ragnarsson

49 Integrative oncology in cancer care 543
Gabriel Lopez, Richard T. Lee, Alejandro Chaoul, M. Kay Garcia, and Lorenzo Cohen

50 Health services research 549
Michaela A. Dinan, Bradford R. Hirsch, and Amy Abernethy


51 Personalized medicine in oncology drug development 561
Nicholas C. Dracopoli, Iqbal Grewal, Chris H. Takimoto, and Peter F. Lebowitz


52 Preclinical and early clinical development of chemotherapeutic drugs, mechanism-based agents and biologics 573
Axel-R. Hanauske and Daniel D. Von Hoff

53 Tumor growth kinetics 589
Elizabeth Comen, Teresa A. Gilewski, and Larry Norton

54 Principles of dose, schedule, and combination therapy 601
William N. Hait and Joseph P. Eder

55 Pharmacology 613
Manish R. Sharma and Mark J. Ratain

56 Folate antagonists 625
Peter D. Cole, Lisa Figueiredo, and Joseph R. Bertino

57 Pyrimidine and purine antimetabolites 637
Robert B. Diasio

58 Alkylating agents and platinum antitumor compounds 649
Zahid H. Siddik

59 DNA topoisomerase targeting drugs 665
AnishThomas, Susan Bates,WilliamD. Figg Sr, and Yves Pommier

60 Agents targeting microtubules and mitotic processes 679
Eric K. Rowinsky

61 Endocrine therapy for hormone receptor-positive breast cancer 713
Aman U. Buzdar, Shaheenah Dawood, Harold A. Harvey, and Virgil Craig Jordan

62 Drug resistance and its clinical circumvention 733
Jeffrey A.Moscow, KennethH. Cowan, and Branimir I. Sikic


63 Cytokines, interferons, and hematopoietic growth factors 743
Suhendan Ekmekcioglu and Elizabeth A. Grimm

64 Monoclonal serotherapy 757
Robert C. Bast Jr., Michael R. Zalutsky, and Arthur E. Frankel

65 Vaccines and immunostimulants 777
Jeffery Schlom, James L. Gulley, and JamesW. Hodge

66 Cell-based cancer immunotherapy 793
Krina K. Patel, Judy S. Moyes, and Laurence J. Cooper

67 Cancer immunotherapy 801
Padmanee Sharma, Sumit K. Subudhi, Karl Peggs, Sangeeta Goswami, Jianjun Gao, Sergio Quezada, and James P. Allison

68 Cancer gene therapy 817
Haruko Tashiro and Malcolm Brenner

69 Cancer nanotechnology 825
Yanlan Liu, Danny Liu, Jinjun Shi, and Robert S. Langer

70 Hematopoietic cell transplantation 831
Roy Jones, Elizabeth Shpall, and Richard Champlin


71 Principles of pediatric oncology 845
Teena Bhatla andWilliam L. Carroll

72 Cancer and pregnancy 865
Jennifer K. Litton

73 Cancer and aging 875
ArtiHurria,Hyman B. Muss, and Harvey J. Cohen

74 Disparities in cancer care 883
OtisW. Brawley

75 Neoplasms in acquired immunodeficiency syndrome 891
Jeremy S. Abramson and David T. Scadden

76 Cancer survivorship: new challenge in cancer medicine 909
Julia H. Rowland


77 Primary and metastatic neoplasms of the brain in adults 919
Lisa M. DeAngelis

78 Neoplasms of the eye 935
Jasmine H. Francis, Amy C. Schefler, and David H. Abramson

79 Neoplasms of the endocrine glands: pituitary neoplasms 949
Chirag D. Gandhi, Margaret Pain, and Kalmon D. Post

80 Neoplasms of the thyroid 959
Steven I. Sherman, Maria E. Cabanillas, and Stephen Y. Lai

81 Neoplasms of the adrenal cortex 967
Tito Fojo

82 Tumors of the diffuse neuroendocrine and gastroenteropancreatic system 971
Evan Vosburgh

83 Neoplasms of the head and neck 981
Renata Ferrarotto, Merrill S. Kies, Adam S. Garden, and Michael E. Kupferman

84 Cancer of the lung 1011
Charles Lu, Daniel Morgensztern, Anne Chiang, Amir Onn, Boris Sepesi, Ara A. Vaporciyan, Joe Y. Chang, Ritsuko K. Komaki, Ignacio I. Wistuba, and Roy S. Herbst

85 Malignant pleural mesothelioma 1037
Daniel R. Gomez, Anne S. Tsao, Haining Yang, and Harvey I. Pass

86 Thymomas and thymic tumors 1051
Ronan J. Kelly and AlbertoM.Marchevsky

87 Tumors of the heart and great vessels 1063
Anthony F. Yu, Sai-Ching Jim Yeung, Carmen P. Escalante, Sarina van der Zee, A. P. Chahinian, and Valentin Fuster

88 Primary germ cell tumors of the thorax 1069
John D. Hainsworth and F. Anthony Greco

89 Neoplasms of the esophagus 1075
MaxW. Sung, Virginia R. Litle, Steven J. Chmura, Stephen G. Swisher, David C. Rice, Jaffer A. Ajani, Ritsuko K. Komaki, andMark K. Ferguson

90 Carcinoma of the stomach 1091
Carl Schmidt, Mariela Blum Murphy, James C. Yao, and Christopher H. Crane

91 Primary neoplasms of the liver 1103
Junichi Shindoh, KristofferW. Brudvik, and Jean-Nicolas Vauthey

92 Gallbladder and bile duct cancer 1115
Ahmed O. Kaseb, Marc Uemura,Melanie B. Thomas, and Steven A. Curley

93 Neoplasms of the exocrine pancreas 1129
Robert A.Wolff, Christopher H. Crane, Donghui Li, Douglas B. Evans, AnirbanMaitra, and Susan Tsai

94 Neoplasms of the small intestine, vermiform appendix, and peritoneum, and carcinoma of the colon and rectum 1151
Georgia M. Beasley, Zhifei Sun, Daniel P. Nussbaum, and Douglas S. Tyler

95 Neoplasms of the anus 1177
Bruce D. Minsky and Jose G. Guillem

96 Renal cell carcinoma 1187
Earle F. Burgess, Stephen B. Riggs, Brian I. Rini, and Derek Raghavan

97 Urothelial cancer 1195
Derek Raghavan, Richard Cote, Earle F. Burgess, Stephen B. Riggs, and Michael Haake

98 Neoplasms of the prostate 1205
Christopher J. Logothetis, Jeri Kim, JohnW. Davis, Brian F. Chapin, Deborah Kuban, Eleni Efstathiou, and Ana Aparicio

99 Tumors of the penis and the urethra 1237
James F. Holland, Raymond S. Lance, Donald F. Lynch Jr.

100 Testis cancer 1243
Christian Kollmannsberger, Craig R. Nichols, Siamak Daneshmand, Eric K. Hansen, Christopher L. Corless, Bruce J. Roth, and Lawrence Einhorn

101 Neoplasms of the vulva and vagina 1269
Summer B. Dewdney and Jacob Rotmensch

102 Neoplasms of the cervix 1281
Anuja Jhingran and Ana M. Rodriguez

103 Endometrial cancer 1305
Jamal Rahaman, Karen Lu, and Carmel J. Cohen

104 Epithelial ovarian, fallopian tube, and peritoneal cancer 1317
Jonathan S. Berek, Michael L. Friedlander, and Robert C. Bast Jr.

105 Nonepithelial ovarian malignancies 1339
Jonathan S. Berek, Michael L. Friedlander, and Robert C. Bast Jr.

106 Molar pregnancy and gestational trophoblastic neoplasia 1353
Donald P. Goldstein, Ross S. Berkowitz, and Neil S. Horowitz

107 Gynecologic sarcomas 1361
Jamal Rahaman and Carmel J. Cohen

108 Neoplasms of the breast 1369
Hope S. Rugo, Melanie Majure, Anthony Dragun, Meredith Buxton, and Laura Esserman

109 Malignant melanoma 1441
Justin M. Ko, Susan M. Swetter, Jonathan S. Zager, Vernon K. Sondak, Scott E.Woodman, and Kim A. Margolin

110 Other skin cancers 1461
William G. Stebbins, Eric A. Millican, and Victor A. Neel

111 Bone tumors 1475
Timothy A. Damron

112 Soft tissue sarcomas 1499
Robert G. Maki, Chandrajit P. Raut, and Brian O’Sullivan

113 The myelodysplastic syndrome 1529
Lewis R. Silverman

114 Acute myeloid leukemia in adults: mast cell leukemia and other mast cell neoplasms 1545
Richard M. Stone and Charles A. Schiffer

115 Chronic myeloid leukemia 1571
Jorge Cortes, Richard T. Silver, and Hagop M. Kantarjian

116 Acute lymphoblastic leukemia 1581
Nitin Jain, Stefan Faderl, Hagop M. Kantarjian, and Susan O'Brien

117 Chronic lymphocytic leukemia 1595
Kanti R. Rai and Jacqueline C. Barrientos

118 Hodgkin lymphoma 1605
Carol S. Portlock, Anita Kumar, and James Armitage

119 Non-Hodgkin’s lymphoma 1615
Arnold S. Freedman and Ann S. LaCasce

120 Mycosis fungoides and Sézary syndrome 1629
Richard T. Hoppe, Youn H. Kim, and Ranjana H. Advani

121 Plasma cell tumors 1635
Noopur Raje, Teru Hideshima, Andrew J. Yee, and Kenneth C. Anderson

122 Myeloproliferative neoplasms: essential thrombocythemia, primary myelofibrosis, and polycythemia vera 1659
Ayalew Tefferi


123 Neoplasms of unknown primary site 1673
John D. Hainsworth and F. Anthony Greco

124 Anorexia and cachexia 1685
Takao Ohnuma

125 Antiemetic therapy 1693
Patrick M. Forde and David S. Ettinger

126 Neurologic complications of cancer 1701
Lisa M. DeAngelis

127 Dermatologic complications of cancer chemotherapy 1717
Anisha B. Patel and Madeleine M. Duvic

128 Skeletal complications 1727
Michael A. Via, Ilya Iofin, and Jeffrey I. Mechanick

129 Hematologic complications and blood bank support 1737
Richard M. Kaufman and Kenneth C. Anderson

130 Coagulopathic complications of cancer patients 1745
Maria T. De Sancho and Jacob H. Rand

131 Urologic complications 1755
Rachel A. Sanford, Ala Abudayyeh, Christopher J. Logothetis, andNizar M. Tannir

132 Cardiac complications 1763
Michael S. Ewer, Steven M. Ewer, andThomas Suter

133 Respiratory complications 1781
Vickie R. Shannon, George A. Eapen, Carlos A. Jimenez, Horiana B. Grosu, Rodolfo C. Morice, Lara Bashoura, Scott E. Evans, Roberto Adachi, Michael Kroll, Saadia A. Faiz, Diwakar D. Balachandran, Selvaraj E. Pravinkumar, and Burton F. Dickey

134 Gastrointestinal and hepatic complications in cancer patients 1807
Robert S. Bresalier, H. Franklin Herlong, and Boris Blechacz

135 Oral complications of cancer and their treatment 1821
Stephen T. Sonis and Anna Yuan

136 Gonadal complications 1833
Vignesh Narayanan and Catherine E. Klein

137 Sexual dysfunction 1843
Leslie R. Schover

138 Endocrine complications and paraneoplastic syndromes 1849
Sai-Ching Jim Yeung and Robert F. Gagel

139 Infections in patients with cancer 1865
Lior Nesher and Kenneth V. I. Rolston

140 Oncologic emergencies 1879
Sai-Ching Jim Yeung and Carmen P. Escalante


141 A vision for twenty-first century healthcare 1901
Leroy Hood, Kristin Brogaard, and Nathan D. Price

Index 1911