Table Of ContentABELOFF’S CLINICAL
ONCOLOGY
ABELOFF’S CLINICAL
ONCOLOGY
FIFTH EDITION
JOHN E. NIEDERHUBER, MD
Executive Vice President, Inova Health System
CEO and Director, Inova Comprehensive Cancer and Research Institute
CEO, Inova Translational Medicine Institute
Falls Church, Virginia;
Professor, Oncology and Surgery
The Johns Hopkins University School of Medicine
Deputy Director
Johns Hopkins Clinical Research Network
Baltimore, Maryland
James O. Armitage, MD Joel E. Tepper, MD
Joe Shapiro Professor of Medicine Hector MacLean Distinguished Professor of Cancer Research
University of Nebraska Medical Center Department of Radiation Oncology
Omaha, Nebraska UNC Lineberger Comprehensive Cancer Center
University of North Carolina School of Medicine
James H. Doroshow, MD Chapel Hill, North Carolina
Bethesda, Maryland
Michael B. Kastan, MD, PhD
Executive Director, Duke Cancer Institute
William W. Shingleton Professor, Pharmacology
and Cancer Biology
Duke University Medical Center
Durham, North Carolina
1600 John F. Kennedy Blvd.
Ste. 1800
Philadelphia, PA 19103-2899
ABELOFF’S CLINICAL ONCOLOGY, FIFTH EDITION ISBN: 978-1-4557-2865-7
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ISBN: 978-1-4557-2865-7
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To my son, Matthew, and my wife, Kathy, who have and continue to make sacrifices so that I might pursue my passions in
medicine and research. To my colleagues at the National Cancer Institute and across the country whose selfless dedication to cancer
research is truly an inspiration to all. To the many students who have trained with me over the years, to my patients, and to my
colleagues at the Inova Translational Medicine Institute who have given me the opportunity to have this tremendously rewarding
career. Lastly, to Tracey, and to Marty, who, in memory, inspire all who knew them to work a little harder each day toward the
elimination of the pain and suffering from this disease.
JOHN E. NIEDERHUBER, MD
To my wife, Nancy, for her love and support over the last four and a half decades, and to our four children and ten grandchildren.
JAMES O. ARMITAGE, MD
To my wife, Robin Winkler Doroshow, MD, my classmate and greatest supporter, for her love, dedication, and commitment and
for the remarkable joy and caring she brings to her patients and to all around her. To my loving daughter, Deborah Doroshow, MD,
PhD, who is about to begin a career in oncology; my fondest hope is that you will enjoy sharing with and learning from those you
help as much as I have. To my patients and colleagues at the City of Hope and the National Cancer Institute who have all
contributed so much of themselves to my continuing education as a physician and investigator, please accept my appreciation and
utmost gratitude.
JAMES H. DOROSHOW, MD
To my wife, Kathy, and my sons, Benjamin, Nathaniel, and Jonathan. You are the lights of my life. I also acknowledge all of my
mentors, colleagues, and patients, who have taught me so much. A special note of gratitude goes to Marty Abeloff, a mentor and an
inspiring role model for career and for life.
MICHAEL B. KASTAN, MD, PhD
To my wife, Laurie, who has been my soul mate for many years and has constantly reminded me of life’s priorities. To my family
including my daughters, Miriam and Abigail, my grandchildren, Zekariah, Zohar, Samuel, Marcello, Jonah, and Aurelio. They have
been an inspiration. To my many teachers through the years who have helped define and foster my professional career, but especially
Herman Suit and Eli Glatstein.
JOEL E. TEPPER, MD
Memoriam
Martin D. Abeloff, MD (1942-2007)
Martin D. Abeloff, a founding editor of Clinical Oncology, dedicated that would be as valuable to the practicing oncologist as to the
his life to caring for patients with cancer and to teaching his art to primary care physician and physicians-in-training. The first edition
fellows, residents, and students. He was a brilliant and caring clini- of Clinical Oncology was published in 1995 to a gratifying response.
cian, an extremely effective leader, and a beloved mentor to many It is now established as a cornerstone reference for those caring for
trainees and young faculty. patients with cancer.
Marty was born on April 4, 1942, in Shenandoah, Pennsylvania. In the fifth edition, we continue Marty’s vision for an ever better,
He received his BA from The Johns Hopkins University in 1963 and unique, and accessible text so that future generations of oncologists
his MD from The Johns Hopkins University School of Medicine in will remember his inspiration and leadership.
1966. He spent the next year as an intern at the University of Chicago The editors again dedicate this text, which is already a recognized
Hospitals and Clinics. His legacy in medicine was established on his tangible aspect of his legacy in medicine, as a living memorial to him.
return to Baltimore in 1971 as a fellow in clinical oncology. He would Abeloff’s Clinical Oncology will continue to serve as a reminder to all
spend the rest of his career at The Johns Hopkins Hospital, achieving its users of this extraordinary person and exemplary physician who
the rank of Professor of Medicine in 1990. At various times, he served went before them.
as the fellowship training program director, chief of medical oncology, John E. Niederhuber, MD
clinical director of the cancer center, oncologist in chief at The Johns James O. Armitage, MD
Hopkins Hospital, and in 1992, was appointed the second director James H. Doroshow, MD
of The Johns Hopkins Oncology Center, later renamed, thanks to Michael B. Kastan, MD, PhD
Marty’s efforts, the Sidney Kimmel Comprehensive Cancer Center. Joel E. Tepper, MD
It was during his time as cancer center director that Marty brought
to life the idea of a comprehensive, user-friendly textbook of oncology
vii
Preface
With an avalanche of new insights into whole genome sequence and thorough in presenting the principles of clinical oncology. It is
variations and the genomic structural alterations associated with meant to be equally useful to students and trainees, experts in the
cancer, including their downstream effects on protein structure and various disciplines of oncology, and as a reference text for physicians
function, we are defining the specific communication pathway from other medical disciplines and the various staff who regularly
changes that drive the cancer initiation and development process. care for patients with cancer. It is our hope that readers will find this
While in the fourth edition the early days of whole genome sequenc- scholarly textbook properly balanced between the disciplines of
ing of patient tumors was beginning to suggest the presence of science, clinical medicine, and humanism and that it will serve them
multiple tumor subtypes within each organ’s tumor, we are now well in their efforts to prevent, diagnose, and effectively treat their
learning, in fact, that each individual and their tumor may be quite patients suffering from cancer.
unique. Individual physiognomies in terms of path of progression The multidisciplinary nature of cancer care is, and will continue
and unique cellular communication pathway alterations are begin- to be, reflected in our editors. Specialists in surgical oncology, pedi-
ning to define and offer greater opportunities for highly prescriptive atric oncology, radiation oncology, medical oncology, and hemato-
intervention(s). logic malignancies directed the development of the book. Reflecting
We are also gaining a much greater understanding of the relation- the multispecialty approach necessary for optimal care of patients,
ship of the host’s tissues to the process of tumor growth, invasion, many chapters are the joint product of several of these disciplines.
and metastasis. This new knowledge of how the tumor’s microenvi- Engaging the very best subject matter authorities was a guiding prin-
ronment is altered in terms of gene expression to support disease ciple for the editors and we are deeply indebted to our outstanding
growth, invasion, and distant spread is again providing novel oppor- authors who, in a most diligent and thoughtful way, have brought
tunities for therapeutic intervention. There is exciting new evidence their knowledge and skills to the fifth edition of Abeloff’s Clinical
to support the presence of a special subclass of cells within the tumor Oncology.
that has properties of “stemness,” which places them in the key role
of maintaining tumor growth and tumor spread. The cumulative ACKNOWLEDGMENTS
effect of these advances – where certain cancers can be prevented and
where others will be detected earlier and controlled – promises to be This fifth edition represents a highly collaborative and dynamic effort
transformative in our effort to conquer cancer. between the editors and Elsevier. We are greatly indebted to Taylor
The fifth edition of Abeloff’s Clinical Oncology incorporates the Ball and Kathleen Schlom for their creative input and guidance and
exciting advances in basic, translational, clinical, and epidemiologic for turning the principles behind this text into a reality. Finally, we
oncology. Each chapter begins with a summary highlighting the key want to express our gratitude to our many contributing authors for
points and includes self-assessment questions available on Expert their dedication to this project, their generosity of time and of course
Consult that would, for example, allow one to be better prepared to their very valuable friendship.
pass a specialty board exam. In addition to a critical analysis of the
literature and updated clinical studies, authors present their own John E. Niederhuber, MD
opinions in specially identified boxes and algorithms. James O. Armitage, MD
Despite significant progress, the diagnosis of cancer remains dev- James H. Doroshow, MD
astating to our patients and their families. Our goal is to provide a Michael B. Kastan, MD, PhD
reference textbook that is the most useful, understandable, attractive, Joel E. Tepper, MD
ix
Contributors
James L. Abbruzzese, MD Steven R. Alberts, MD
Professor Professor of Oncology
Chair, Department of Gastrointestinal Medical Oncology Mayo Clinic College of Medicine
The University of Texas MD Anderson Cancer Center Consultant in Medical Oncology
Houston, Texas Mayo Clinic
Rochester, Minnesota
Ghassan K. Abou-Alfa, MD
Associate Attending Physician Michelle Alonso-Basanta, MD, PhD
Gastrointestinal Oncology Service Assistant Professor of Radiation Oncology
Division of Solid Tumor Oncology Perelman School of Medicine
Department of Medicine University of Pennsylvania
Memorial Sloan-Kettering Cancer Center Philadelphia, Pennsylvania
Associate Professor of Medicine
Department of Medicine Megan E. Anderson, MD
Weill Cornell Medical College Instructor of Orthopaedic Surgery
New York, New York Harvard Medical School
Attending Orthopaedic Surgeon, Department of Orthopaedic
Janet L. Abrahm, MD Surgery
Professor of Medicine Boston Children’s Hospital
Harvard Medical School Attending Orthopaedic Surgeon, Department of Orthopaedic
Chief, Division of Adult Palliative Care Surgery
Psychosocial Oncology and Palliative Care Beth Israel Deaconess Medical Center
Dana-Farber Cancer Institute Consultant in Surgery
Boston, Massachusetts Dana-Farber Cancer Institute
Boston, Massachusetts
Jeffrey S. Abrams, MD
Associate Director, Cancer Therapy Evaluation Program Emmanuel S. Antonarakis, MBBCh
Acting Director for Clinical Research Assistant Professor of Oncology
Division of Cancer Treatment and Diagnosis Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute The Johns Hopkins University School of Medicine
National Institutes of Health Baltimore, Maryland
Bethesda, Maryland
Frederick R. Appelbaum, MD
Dara L. Aisner, MD, PhD Member and Director, Clinical Research Division
Assistant Professor Fred Hutchinson Cancer Research Center
Department of Pathology Professor and Head, Division of Medical Oncology
University of Colorado Anschutz Medical Center University of Washington School of Medicine
Aurora, Colorado Seattle, Washington
Shaheen Alanee, MPH, MD Jonathan B. Ashman, MD, PhD
Fellow, Urologic Oncology Assistant Professor of Radiation Oncology
Department of Medicine Mayo Clinic in Arizona
Memorial Sloan-Kettering Cancer Center Scottsdale, Arizona
New York, New York
xi
xii Contributors
Juliet L. Aylward, MD Ross Stuart Berkowitz, MD
Associate Professor William H. Baker Professor of Gynecology
Department of Dermatology Harvard Medical School
University of Wisconsin Director of Gynecologic Oncology
Madison, Wisconsin Brigham and Women’s Hospital
Dana-Farber Cancer Institute
Ali A. Baaj, MD Boston, Massachusetts
Instructor
Department of Neurosurgery Donald A. Berry, PhD
Spine Center Professor
Johns Hopkins Hospital Department of Biostatistics
Baltimore, Maryland Division of Quantitative Sciences
The University of Texas MD Anderson Cancer Center
Arjun V. Balar, MD Houston, Texas
Assistant Professor
Department of Medicine Therese B. Bevers, MD
New York University Langone Medical Center Professor, Department of Clinical Cancer Prevention
New York, New York Division of Cancer Prevention and Population Sciences
Medical Director, Cancer Prevention Center
Lodovico Balducci, MD The University of Texas MD Anderson Cancer Center
Professor of Oncology and Medicine Houston, Texas
University of South Florida College of Medicine
Tampa, Florida John F. Boggess, MD
Associate Professor
Nancy L. Bartlett, MD Department of Obstetrics and Gynecology
Professor of Medicine Division of Gynecologic Oncology
Washington University School of Medicine University of North Carolina School of Medicine
St. Louis, Missouri Chapel Hill, North Carolina
Qaiser Bashir, MD Leif-Erik Bohman, MD
Assistant Professor Department of Neurosurgery
Department of Stem Cell Transplantation, Division of Cancer Perelman School of Medicine
Medicine University of Pennsylvania
The University of Texas MD Anderson Cancer Center Philadelphia, Pennsylvania
Houston, Texas
Michael J. Borowitz, MD
Lynda Kwon Beaupin, MD Professor of Pathology and Oncology
Assistant Professor of Pediatrics Johns Hopkins Medical Institutions
School of Medicine and Biomedical Science Director of Hematopathology and Flow Cytometry
State University of New York at Buffalo Johns Hopkins Hospital
Assistant Professor of Pediatric Oncology Baltimore, Maryland
Roswell Park Cancer Institute
Buffalo, New York Jeff Boyd, PhD
Senior Vice President
Al B. Benson III, MD, FACP Molecular Medicine
Associate Director for Clinical Investigations Fox Chase Cancer Center
Robert H. Lurie Comprehensive Cancer Center Philadelphia, Pennsylvania
Northwestern University
Chicago, Illinois Julie R. Brahmer, MD
Associate Professor of Oncology
Sidney Kimmel Comprehensive Cancer Center
The Johns Hopkins University School of Medicine
Baltimore, Maryland
Contributors xiii
Joanna M. Brell, MD Jorge J. Castillo, MD
Program Director/Medical Officer The Warren Alpert Medical School
Community Oncology and Prevention Trials Research Group Brown University
Division of Cancer Prevention Division of Hematology and Oncology
National Cancer Institute Rhode Island Hospital/The Miriam Hospital
National Institutes of Health Providence, Rhode Island
Bethesda, Maryland
Manpreet K. Chadha, MD
Karen Brown, MD, FSIR Palo Verde Cancer Specialists
Attending Phoenix, Arizona
Interventional Radiology Service
Memorial Sloan-Kettering Cancer Center Richard Champlin, MD
Professor of Clinical Radiology Professor and Chairman
Department of Radiology Department of Stem Cell Transplantation and Cellular Therapy
Weill Cornell Medical College The University of Texas MD Anderson Cancer Center
New York, New York Houston, Texas
Powel H. Brown, MD, PhD Alfred E. Chang, MD
Professor and Chairman Hugh Cabot Professor of Surgery
Department of Clinical Cancer Prevention Department of Surgery
Division of Cancer Prevention and Population Sciences University of Michigan Health System
The University of Texas MD Anderson Cancer Center Ann Arbor, Michigan
Houston, Texas
Stephen J. Chanock, MD
Paul A. Bunn, MD Chief, Laboratory of Translational Genomics
Professor, James Dudley Chair in Cancer Research Director, Cancer Genomics Research Laboratory
Division of Medical Oncology Division of Cancer Epidemiology and Genetics
University of Colorado Denver School of Medicine Acting Co-Director, Center for Cancer Genomics
University of Colorado Anschutz Medical Center Office of the Director
Aurora, Colorado National Cancer Institute
National Institutes of Health
John C. Byrd, MD Rockville, Maryland
Professor, College of Medicine
The Ohio State University Vikash P. Chauhan, PhD
Columbus, Ohio Research Fellow
Radiation Oncology
Dario Campana, MD, PhD Massachusetts General Hospital
Professor, Department of Paediatrics Boston, Massachusetts
Yong Loo Lin School of Medicine
National University of Singapore Herbert Chen, MD
Singapore Section of Endocrine Surgery
Department of Surgery
David P. Carbone, MD, PhD University of Wisconsin
Department of Medicine, Medical Oncology Madison, Wisconsin
The James Thoracic Center
The Ohio State University Ronald C. Chen, MD, MPH
Columbus, Ohio Assistant Professor
Department of Radiation Oncology
H. Ballentine Carter, MD University of North Carolina
Professor of Urology Chapel Hill, North Carolina
The Johns Hopkins University School of Medicine
Baltimore, Maryland
