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2015v1.0
Abeloff’s
CLINICAL
ONCOLOGY
This page intentionally left blank
Abeloff’s
CLINICAL
ONCOLOGY
SIXTH EDITION
JOHN E. NIEDERHUBER, MD
Executive Vice President, Inova Health System
President and CEO, Genomics and Bioinformatics Research Institute
Fairfax, Virginia;
Professor, Department of Public Health Sciences
Member, Center for Public Health Genomics
University of Virginia School of Medicine
Charlottesville, Virginia;
Adjunct Professor, Oncology and Surgery
The Johns Hopkins University School of Medicine
Deputy Director
Johns Hopkins Clinical Research Network
Baltimore, Maryland
JAMES O. ARMITAGE, MD JAMES H. DOROSHOW, MD

Joe Shapiro Professor of Medicine Bethesda, Maryland
University of Nebraska Medical Center
Omaha, Nebraska
MICHAEL B. KASTAN, MD, PhD JOEL E.TEPPER, MD

Executive Director, Duke Cancer Institute Hector MacLean Distinguished Professor of
William and Jane Shingleton Professor, Cancer Research
Pharmacology and Cancer Biology Department of Radiation Oncology
Professor of Pediatrics UNC Lineberger Comprehensive Cancer Center
Duke University School of Medicine University of North Carolina School of Medicine
Durham, North Carolina Chapel Hill, North Carolina
ABELOFF’S CLINICAL ONCOLOGY, SIXTH EDITION ISBN: 978-0-323-47674-4
Copyright © 2020 by Elsevier, Inc. All rights reserved.
No part of this publication may be reproduced or transmitted in any form or by any means, electronic or
mechanical, including photocopying, recording, or any information storage and retrieval system, without
permission in writing from the publisher. Details on how to seek permission, further information about the
Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance
Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions.
This book and the individual contributions contained in it are protected under copyright by the Publisher
(other than as may be noted herein).
Notices
Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our understanding, changes in research methods, professional practices, or medical treatment
may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating
and using any information, methods, compounds, or experiments described herein. In using such
information or methods they should be mindful of their own safety and the safety of others, including
parties for whom they have a professional responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check the
most current information provided (i) on procedures featured or (ii) by the manufacturer of each product
to be administered, to verify the recommended dose or formula, the method and duration of
administration, and contraindications. It is the responsibility of practitioners, relying on their own
experience and knowledge of their patients, to make diagnoses, to determine dosages and the best
treatment for each individual patient, and to take all appropriate safety precautions.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors,
assume any liability for any injury and/or damage to persons or property as a matter of products liability,
negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas
contained in the material herein.
Previous editions copyrighted 2014, 2008, 2004, 2000, and 1995.
Library of Congress Control Number: 2018953655
Executive Content Strategist: Robin Carter

Content Development Manager: Laura Schmidt
Publishing Services Manager: Catherine Jackson
Senior Project Manager: Amanda Mincher
Design Direction: Bridget Hoette
Printed in China
Last digit is the print number: 9 8 7 6 5 4 3 2 1
1600 John F. Kennedy Blvd.

Ste 1600
Philadelphia, PA 19103-2899
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, University of Virginia, Johns Hopkins, and across the
country, whose selfless dedication to patient care and 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 49 ½ years.

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 remarkable daughter, Deborah Doroshow,
MD, PhD, who is completing her training for a career in academic 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, and my grandchildren, Zekariah, Zohar, Samuel, Marcelo, 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 primary
his life to caring for patients with cancer and to teaching his art to care physician and physicians-in-training. The first edition of Clinical
fellows, residents, and students. He was a brilliant and caring clinician, Oncology was published in 1995 to a gratifying response. It is now
an extremely effective leader, and a beloved mentor to many trainees established as a cornerstone reference for those caring for patients
and young faculty. with cancer.
Marty was born on April 4, 1942, in Shenandoah, Pennsylvania. He In the sixth edition, we continue Marty’s vision for an ever better,
received his BA from The Johns Hopkins University in 1963 and his unique, and accessible text so that future generations of oncologists
MD from The Johns Hopkins University School of Medicine in 1966. will remember his inspiration and leadership.
He spent the next year as an intern at the University of Chicago Hospitals The editors again dedicate this text, which is already a recognized
and Clinics. His legacy in medicine was established on his return to tangible aspect of his legacy in medicine, as a living memorial to him.
Baltimore in 1971 as a fellow in clinical oncology. He would spend the Abeloff ’s Clinical Oncology will continue to serve as a reminder to all
rest of his career at The Johns Hopkins Hospital, achieving the rank of its users of this extraordinary person and exemplary physician who
Professor of Medicine in 1990. At various times, he served as the fel- went before them.
lowship training program director, chief of medical oncology, clinical
director of the cancer center, oncologist in chief at The Johns Hopkins John E. Niederhuber, MD
Hospital, and in 1992, was appointed the second director of The Johns James O. Armitage, MD
Hopkins Oncology Center, later renamed, thanks to Marty’s efforts, the James H. Doroshow, MD
Sidney Kimmel Comprehensive Cancer Center. Michael B. Kastan, MD, PhD
It was during his time as cancer center director that Marty brought Joel E. Tepper, MD
to life the idea of a comprehensive, user-friendly textbook of oncology
vii
Contributors
James L. Abbruzzese, MD, FACP, FASCO, DSc (hon) Dara L. Aisner, MD, PhD
Duke Cancer Institute Distinguished Professor of Medical Oncology Associate Professor of Pathology
Chief, Division of Medical Oncology, Department of Medicine CU Anschutz Medical Campus
Associate Director for Clinical Research, Duke Cancer Institute University of Colorado
Duke University Medical Center Aurora, Colorado
Durham, North Carolina
Michelle Alonso-Basanta, MD, PhD
Omar Abdel-Wahab, MD Helene Blum Assistant Professor
Associate Attending Department of Radiation Oncology
Department of Medicine University of Pennsylvania
Leukemia Service Philadelphia, Pennsylvania
Memorial Sloan Kettering Cancer Center
New York, New York Jesus Anampa, MD, MS
Assistant Professor
Ghassan K. Abou-Alfa, MD Department of Oncology
Attending Physician Montefiore Medical Center
Memorial Sloan Kettering Cancer Center Albert Einstein College of Medicine
Professor of Medicine Bronx, New York
Weill Cornell Medicine
New York, New York Megan E. Anderson, MD
Assistant Professor
Janet L. Abrahm, MD Department of Orthopaedic Surgery
Professor of Medicine Harvard Medical School
Harvard Medical School Attending Orthopedic Surgeon
Member, Division of Palliative Care Department of Orthopedic Surgery
Psychosocial Oncology and Palliative Care Boston Children’s Hospital
Dana-Farber Cancer Institute Attending Orthopedic Surgeon
Boston, Massachusetts Department of Orthopedic Surgery
Beth Israel Deaconess Medical Center
Jeffrey S. Abrams, MD Boston, Massachusetts
Associate Director, Cancer Therapy Evaluation Program
Division of Cancer Treatment and Diagnosis Emmanuel S. Antonarakis, MD
National Cancer Institute Associate Professor of Oncology
Rockville, Maryland Sidney Kimmel Comprehensive Cancer Center
Johns Hopkins University School of Medicine
Jeremy S. Abramson, MD, MMSc Baltimore, Maryland
Director, Center for Lymphoma
Hematology/Oncology Richard Aplenc, MD, PhD
Massachusetts General Hospital Department of Pediatrics
Assistant Professor Section Chief, Hematologic Malignancies
Department of Medicine Chief Clinical Research Officer
Harvard Medical School Children’s Hospital of Philadelphia
Boston, Massachusetts Philadelphia, Pennsylvania
ix
x Contributors
Frederick R. Appelbaum, MD Karen Basen-Engquist, PhD, MPH

Executive Vice President and Deputy Director Professor of Behavioral Science
Fred Hutchinson Cancer Research Center University of Texas MD Anderson Cancer Center
Professor Houston, Texas
Division of Medical Oncology
University of Washington Lynda Kwon Beaupin, MD
Seattle, Washington Director, Adolescent and Young Adult Program
Roswell Park Cancer Institute
Luiz H. Araujo, MD, PhD Buffalo, New York
Scientific Director
COI Institute for Research and Education Ross S. Berkowitz, MD
Brazilian National Cancer Institute William H. Baker Professor of Gynecology
Rio de Janeiro, Brazil Department of Obstetrics and Gynecology
Harvard Medical School
Ammar Asban, MD Director of Gynecologic Oncology
Surgical Resident Department of Obstetrics and Gynecology
Department of Surgery Brigham and Women’s Hospital
University of Alabama at Birmingham Boston, Massachusetts
Birmingham, Alabama
Donald A. Berry, PhD
Edward Ashwood, MD Professor of Biostatistics
President and CEO Department of Biostatistics
ARUP Laboratories The University of Texas MD Anderson Cancer Center
Professor of Pathology Houston, Texas
University of Utah
Salt Lake City, Utah Therese Bevers, MD
Professor of Clinical Cancer Prevention
Farrukh T. Awan, MD, MS Medical Director, Cancer Prevention Center
Associate Professor of Medicine The University of Texas MD Anderson Cancer Center
Hematology Houston, Texas
The Ohio State University
Columbus, Ohio John F. Boggess, MD
Professor of Obstetrics and Gynecology
Juliet L. Aylward, MD University of North Carolina
Associate Professor of Dermatology Chapel Hill, North Carolina
University of Wisconsin School of Medicine and Public Health
Madison, Wisconsin Julie R. Brahmer, MD, MSc
Professor of Oncology
Arjun V. Balar, MD Department of Oncology
Associate Professor of Medicine Johns Hopkins Kimmel Cancer Center
Division of Hematology/Oncology Baltimore, Maryland
Director, Genitourinary Cancers Program
New York University Perlmutter Cancer Center Janet Brown, MD, FRCP, MSc, MBBS, BSc
New York University Langone Medical Center Professor
New York, New York Academic Unit of Clinical Oncology, Oncology, and Metabolism
Weston Park Hospital
Courtney J. Balentine, MD University of Sheffield
Assistant Professor of Surgery Sheffield, United Kingdom
Dallas VA Hospital
University of Texas Southwestern Karen Brown, MD
Dallas, Texas Attending Physician
Stefan K. Barta, MD, MS, MRCP(UK) Professor of Clinical Radiology
Associate Professor Weill Medical College at Cornell University
Hematology and Oncology New York, New York
Fox Chase Cancer Center
Philadelphia, Pennsylvania Powel Brown, MD, PhD
Professor and Chairman
Nancy Bartlett, MD Clinical Cancer Prevention
Professor of Medical Oncology The University of Texas MD Anderson Cancer Center
Washington University School of Medicine Houston, Texas
St. Louis, Missouri
Contributors xi
Ilene Browner, MD Stephen J. Chanock, MD

Assistant Professor Director
Department of Oncology and Division of Geriatric Medicine Division of Cancer Epidemiology and Genetics
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins National Cancer Institute
and Johns Hopkins Bayview Bethesda, Maryland
The Johns Hopkins University
Baltimore, Maryland Claudia I. Chapuy, MD
St. Elizabeth’s Medical Center
Paul A. Bunn, MD Dana-Farber Cancer Institute
Distinguished Professor of Medical Oncology Boston, Massachusetts
CU Anschutz Medical Campus
University of Colorado Vikash P. Chauhan, PhD
Aurora, Colorado Massachusetts Institute of Technology
Boston, Massachusetts
William R. Burns, MD
Assistant Professor of Surgery Herbert Chen, MD, FACS
University of Michigan Health System Chairman and Fay Fletcher Kerner Endowed Chair
Ann Arbor, Michigan Department of Surgery
University of Alabama at Birmingham
John C. Byrd, MD Surgeon-in-Chief
Professor of Internal Medicine–Hematology University of Alabama at Birmingham Health System
The Ohio State University Birmingham, Alabama
Columbus, Ohio
Ronald C. Chen, MD, MPH
Karen Cadoo, MD Associate Professor
Attending Medical Oncologist Department of Radiation Oncology
Gynecologic Medical Oncology and Clinical Genetic Services University of North Carolina at Chapel Hill
Memorial Sloan Kettering Cancer Center Chapel Hill, North Carolina
Weill Cornell Medical College
New York, New York Nai-Kong V. Cheung, MD, PhD
Enid A. Haupt Endowed Chair in Pediatric Oncology
David P. Carbone, MD, PhD Department of Pediatrics
Professor of Medicine Memorial Sloan-Kettering Cancer Center
Director, James Thoracic Center New York, New York
James Cancer Center
The Ohio State University Medical Center Jennifer H. Choe, MD, PhD
Columbus, Ohio Medical Instructor
Division of Medical Oncology
H. Ballentine Carter, MD Duke Cancer Institute
Professor of Urology Durham, North Carolina
Baltimore, Maryland Michaele C. Christian, MD
Cancer Therapy Evaluation Program (Retired)
Jorge J. Castillo, MD National Cancer Institute
Physician Rockville, Maryland
Hematologic Malignancies
Dana-Farber Cancer Institute Paul M. Cinciripini, PhD
Assistant Professor Professor and Chair of Behavioral Science
Harvard Medical School The University of Texas MD Anderson Cancer Center
Boston, Massachusetts Houston, Texas
Alfred E. Chang, MD Michael F. Clarke, MD

Hugh Cabot Professor of Surgery Professor of Medicine
University of Michigan Health System Division of Oncology
Ann Arbor, Michigan Stanford School of Medicine
Palo Alto, California
Eric Chang, MD, FASTRO
Professor and Chair of Radiation Oncology Robert E. Coleman, MBBS, MD
Keck School of Medicine of USC Academic Unit of Clinical Oncology
Los Angeles, California Weston Park Hospital
University of Sheffield
Sheffield, United Kingdom
xii Contributors
Robert L. Coleman, MD Jeffrey Crawford, MD

Professor and Executive Director, Cancer Network Research Professor of Medicine
Department of Gynecologic Oncology and Reproductive Medicine Division of Medical Oncology
The University of Texas MD Anderson Cancer Center Duke Cancer Institute
Houston, Texas Durham, North Carolina
Adriana M. Coletta, PhD, RD Kristy Crooks, PhD

Department of Behavioral Science Assistant Professor of Pathology
Center for Energy Balance in Cancer Prevention and Survivorship CU Anschutz Medical Campus
The University of Texas MD Anderson Cancer Center University of Colorado
Houston, Texas Aurora, Colorado
Jerry M. Collins, PhD Daniel J. Culkin, MD

Associate Director Professor
Division of Cancer Treatment and Diagnosis Department of Urology
National Cancer Institute University of Oklahoma Health Sciences Center
Bethesda, Maryland Oklahoma City, Oklahoma
Jean M. Connors, MD Brian G. Czito, MD

Hematology Division Professor of Radiation Oncology
Brigham and Women’s Hospital Duke University Medical Center
Dana-Farber Cancer Institute Durham, North Carolina
Boston, Massachusetts Piero Dalerba, MD
Assistant Professor of Pathology and Cell Biology
Michael Cools, MD Assistant Professor of Medicine
Department of Neurosurgery Division of Digestive and Liver Diseases
University of North Carolina Columbia University College of Physicians and Surgeons
Chapel Hill, North Carolina New York, New York
Kevin R. Coombes, PhD Josep Dalmau, MD, PhD

Professor of Biomedical Informatics ICREA Research Professor
The Ohio State University Hospital Clínic/Institut d’Investigació Biomèdica August Pi i Sunyer
Columbus, Ohio (IDIBAPS)
Barcelona, Spain
Jorge Cortes, MD Adjunct Professor Neurology
The University of Texas MD Anderson Cancer Center University of Pennsylvania
Houston, Texas Philadelphia, Pennsylvania
Mauro W. Costa, MSc, PhD Mai Dang, MD, PhD

Research Scientist Instructor in Neurology
The Jackson Laboratory Children’s Hospital of Philadelphia
Bar Harbor, Maine Philadelphia, Pennsylvania
Anne Covey, MD Michael D’Angelica, MD

Attending Physician Attending Physician
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center
Professor of Radiology Professor of Surgery
Weill Medical College at Cornell University Weill Medical College at Cornell University
New York, New York New York, New York
Kenneth H. Cowan, MD, PhD Kurtis D. Davies, PhD

Director, Fred and Pamela Buffett Cancer Center Assistant Professor of Pathology
University of Nebraska Medical Center CU Anschutz Medical Campus
Omaha, Nebraska University of Colorado
Aurora, Colorado
Christopher H. Crane, MD
Vice Chairman
Attending Physician
New York, New York
Contributors xiii
Myrtle Davis, DVM, PhD James H. Doroshow, MD

Chief, Toxicology and Pharmacology Branch Bethesda, Maryland
Division of Drug Treatment and Diagnosis
National Cancer Institute Jay F. Dorsey, MD, PhD
National Institutes of Health Associate Professor of Radiation Oncology
Bethesda, Maryland University of Pennsylvania
Philadelphia, Pennsylvania
Nicolas Dea, MD, MSc, FRCSC
Spinal Neurosurgeon Marianne Dubard-Gault, MD, MS
Clinical Associate Professor Medical Genetics Fellow
Department of Surgery Department of Medicine
Vancouver General Hospital Memorial Sloan Kettering Cancer Center
University of British Columbia New York, New York
Vancouver, British-Columbia, Canada
Steven G. DuBois, MD, MS
Ana De Jesus-Acosta, MD Associate Professor
Assistant Professor of Oncology Department of Pediatrics
Sidney Kimmel Comprehensive Cancer Center Harvard Medical School
The Johns Hopkins University School of Medicine Attending Physician
Baltimore, Maryland Department of Pediatrics
Boston Children’s Hospital
Angelo M. DeMarzo, MD, PhD Dana Farber Cancer Institute
Professor of Pathology Boston, Massachusetts
Baltimore, Maryland Dan G. Duda, PhD, DMD
Associate Professor
Theodore L. DeWeese, MD Harvard Medical School
Professor and Director of Radiation Oncology and Molecular Boston, Massachusetts
Radiation Sciences
Johns Hopkins University School of Medicine Malcolm Dunlop, MD
Baltimore, Maryland MRC Institute of Genetics and Molecular Medicine
The University of Edinburgh
Maximilian Diehn, MD, PhD Western General Hospital
Associate Professor of Radiation Oncology Edinburgh, United Kingdom
Stanford University
Palo Alto, California Linda R. Duska, MD
University of Virginia Health System
Subba R. Digumarthy, MD Emily Couric Clinical Cancer Center
Massachusetts General Hospital Charlottesville, Virginia
Madeleine Duvic, MD
Angela Dispenzieri, MD Professor and Deputy Chairman
Professor of Medicine and Laboratory Medicine Department of Dermatology
Mayo Clinic The University of Texas MD Anderson Cancer Center
Rochester, Minnesota Houston, Texas
Khanh T. Do, MD Imane El Dika, MD

Assistant Professor of Medicine Assistant Attending Physician
Harvard Medical School Memorial Sloan Kettering Cancer Center
Medical Oncology Instructor of Medicine
Dana-Farber Cancer Institute Weill Medical College at Cornell University
Boston, Massachusetts New York, New York
Konstantin Dobrenkov, MD Hashem El-Serag, MD, MPH

Clinical Director, Oncology Margaret M. and Albert B. Alkek Chair of the Department
Merck & Company, Inc. of Medicine
Kenilworth, New Jersey Professor of Gastroenterology and Hepatology
Baylor College of Medicine
Jeffrey S. Dome, MD, PhD Houston, Texas
Vice President, Center for Cancer and Blood Disorders
Children’s National Medical Center
Washington, D.C.
xiv Contributors
Jeffrey M. Engelmann, PhD Debra L. Friedman, MD, MS

Assistant Professor of Psychiatry and Behavioral Medicine Vanderbilt-Ingram Cancer Center
Medical College of Wisconsin Nashville, Tennessee
Milwaukee, Wisconsin
Arian F. Fuller, Jr., MD
David S. Ettinger, MD, FACP, FCCP Winchester Hospital
Alex Grass Professor of Oncology North Reading Medical
The Sidney Kimmel Comprehensive Cancer Center at Johns North Reading, Massachusetts
Hopkins Hospital
The Johns Hopkins University Lorenzo Galluzzi, PhD
Baltimore, Maryland Assistant Professor of Cell Biology in Radiation Oncology
Weill Cornell Medical College
Lola A. Fashoyin-Aje, MD, MPH New York, New York
Medical Officer
Office of Hematology and Oncology Products Mark C. Gebhardt, MD
Center for Drug Evaluation and Research Frederick W. and Jane M. Ilfeld Professor of Orthopaedic Surgery
U.S. Food and Drug Administration Harvard Medical School
Silver Spring, Maryland Surgeon-in-Chief
Department of Orthopedic Surgery
Eric R. Fearon, MD, PhD Beth Israel Deaconess Medical Center
Maisel Professor of Oncology Orthopedic Surgeon
Professor of Internal Medicine Department of Orthopedics
University of Michigan Medical School Children’s Hospital
Ann Arbor, Michigan Boston, Massachusetts
James M. Ford, MD Daniel J. George, MD

Professor of Medicine, Pediatrics, and Genetics Professor of Medicine
Division of Oncology and Medical Genetics Duke University Medical Center
Stanford University School of Medicine Durham, North Carolina
Stanford, California
Mark B. Geyer, MD
Wilbur A. Franklin, MD Assistant Attending
Professor Emeritus of Pathology Department of Medicine
CU Anschutz Medical Campus Leukemia Service and Cellular Therapeutics Center
University of Colorado Memorial Sloan Kettering Cancer Center
Aurora, Colorado Instructor in Medicine
Joan and Sanford I. Weill Department of Medicine
Phoebe E. Freer, MD Weill Cornell Medical College
Associate Professor New York, New York
Radiology and Imaging Sciences
University of Utah Hospitals/Huntsman Cancer Institute Amato J. Giaccia, PhD
Salt Lake City, Utah Jack, Lulu, and Sam Willson Professor of Cancer Biology
Department of Radiation Oncology
Boris Freidlin, PhD Stanford University School of Medicine
Division of Cancer Treatment and Diagnosis Stanford, California
National Cancer Institute
Bethesda, Maryland Mark R. Gilbert, MD
Senior Investigator and Chief
Alison G. Freifeld, MD Neuro-Oncology Branch
Professor of Internal Medicine National Cancer Institute
Infectious Diseases Division Bethesda, Maryland
Omaha, Nebraska Whitney Goldner, MD
Associate Professor of Internal Medicine
Terence W. Friedlander, MD Division of Diabetes, Endocrinology, and Metabolism
Associate Clinical Professor University of Nebraska Medical Center
Medicine Omaha, Nebraska
UCSF Medical Center
San Francisco, California
Contributors xv
Donald P. Goldstein, MD Missak Haigentz, MD

Professor of Obstetrics, Gynecology, and Reproductive Biology Montefiore Medical Center
Harvard Medical School Bronx, New York
Senior Scientist
Department of Obstetrics and Gynecology John D. Hainsworth, MD
Brigham and Women’s Hospital Chief Scientific Officer
Boston, Massachusetts Sarah Cannon Research Institute
Nashville, Tennessee
Annekathryn Goodman, MD
Massachusetts General Hospital Benjamin E. Haithcock, MD
Boston, Massachusetts Associate Professor of Surgery
University of North Carolina at Chapel Hill
Karyn A. Goodman, MD, MS Chapel Hill, North Carolina
Professor of Radiation Oncology
Grohne Chair in Clinical Cancer Research Christopher L. Hallemeier, MD
University of Colorado School of Medicine Assistant Professor of Radiation Oncology
Aurora, Colorado Mayo Clinic
Rochester, Minnesota
Kathleen Gordon, MD
Medical Director of Ophthalmology Samir Hanash, MD, PhD
IQVIA Evelyn & Sol Rubenstein Distinguished Chair for Cancer Prevention
Co-Chair Professor of Clinical Cancer Prevention
IQIVA Ophthalmology Center of Excellence The University of Texas MD Anderson Cancer Center
Clinical Associate Professor of Ophthalmology Houston, Texas
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina Aphrothiti J. Hanrahan, PhD
Assistant Lab Member
Laura Graeff-Armas, MD, MS Human Oncology and Pathogenesis Program
Associate Professor of Internal Medicine Memorial Sloan Kettering Cancer Center
Division of Diabetes, Endocrine and Metabolism New York, New York
Omaha, Nebraska James Harding, MD
Assistant Attending Physician
Alexander J. Greenstein, MD, MPH Memorial Sloan Kettering Cancer Center
Associate Professor of Surgery Assistant Professor of Medicine
Icahn School of Medicine at Mount Sinai Weill Medical College at Cornell University
Stuart A. Grossman, MD Michael R. Harrison, MD

Professor of Oncology, Medicine, and Neurosurgery Assistant Professor of Medicine
The Sidney Kimmel Comprehensive Cancer Center at Johns Division of Medical Oncology
Hopkins Medicine Duke Cancer Institute
The Johns Hopkins University Durham, North Carolina
Baltimore, Maryland
Muneer G. Hasham, PhD
Stephan Grupp, MD, PhD Research Scientist
Section Chief, Cellular Therapy and Transplant The Jackson Laboratory
Director, Cancer Immunotherapy Frontier Program Bar Harbor, Maine
CCCR Director of Translational Research
Children’s Hospital of Philadelphia Ernest Hawk, MD, MPH
Philadelphia, Pennsylvania Boone Pickens Distinguished Chair for Early Prevention of Cancer
Vice President and Division Head
Arjun Gupta, MD Division of Cancer Prevention and Population Sciences
Assistant Instructor The University of Texas MD Anderson Cancer Center
Department of Internal Medicine Houston, Texas
University of Texas Southwestern Medical Center
Dallas, Texas Jonathan Hayman, MD
Department of Internal Medicine
Irfanullah Haider, MD, MBA Johns Hopkins Bayview Medical Center
Breast Imaging Baltimore, Maryland
Brigham and Women’s Hospital
Boston, Massachussetts
xvi Contributors
Jonathan E. Heinlen, MD Clifford A. Hudis, MD

Assistant Professor Chief Executive Officer
Department of Urology American Society of Clinical Oncology
University of Oklahoma Health Sciences Center Alexandria, Virginia
Oklahoma City, Oklahoma
Stephen P. Hunger, MD
N. Lynn Henry, MD, PhD Jeffrey E. Perelman Distinguished Chair
Associate Professor Department of Pediatrics
Internal Medicine Chief, Division of Oncology
University of Utah Pediatrics
Salt Lake City, Utah Children’s Hospital of Philadelphia
Joseph Herman, MD †
Professor and Division Head ad-interim Arti Hurria, MD
Department of Radiation Oncology Professor
The University of Texas MD Anderson Cancer Center Department of Medical Oncology and Therapeutics Research
Houston, Texas City of Hope Comprehensive Cancer Center
Duarte, California
Brian P. Hobbs, PhD
Associate Staff David H. Ilson, MD, PhD
Quantitative Health Sciences and The Taussig Cancer Institute Attending Physician
Cleveland Clinic Gastrointestinal Oncology Service
Cleveland, Ohio Department of Medicine
Memorial Sloan-Kettering Cancer Center
Ingunn Holen, BSc, MSc, PhD New York, New York
Oncology
University of Sheffield Annie Im, MD
Sheffield, United Kingdom Assistant Professor of Medicine
Department of Hematology and Oncology
Leora Horn, MD, MSc UPMC Hillman Cancer Center
Associate Professor of Medicine Pittsburgh, Pennsylvania
Medicine–Hematology Oncology
Vanderbilt University
Gopa Iyer, MD
Assistant Attending Physician, Genitourinary Oncology Service
Department of Medicine
Neil S. Horowitz, MD
New York, New York
Department of Obstetrics and Gynecology
Division of Gynecologic Oncology
Elizabeth M. Jaffee, MD
Brigham and Women’s Hospital
The Dana and Albert “Cubby” Broccoli Professor of Oncology
Dana Farber Cancer Institute
Deputy Director, Sidney Kimmel Comprehensive Cancer Center at
Johns Hopkins
Steven M. Horwitz, MD Baltimore, Maryland
Associate Attending
Department of Medicine, Lymphoma Service Reshma Jagsi, MD, DPhil
Memorial Sloan Kettering Cancer Center Professor and Deputy Chair
Assistant Professor of Clinical Medicine Radiation Oncology
Weill-Cornell Medical College University of Michigan
New York, New York Ann Arbor, Michigan
Odette Houghton, MD Rakesh K. Jain, PhD

Associate Professor A.W. Cook Professor of Tumor Biology
Department of Ophthalmology Department of Radiation Oncology
Mayo Clinic Harvard Medical School
Scottsdale, Arizona Director
E.L. Steele Laboratory for Tumor Biology
Scott C. Howard, MD, MSc Department of Radiation Oncology
Professor of Acute and Tertiary Care Massachusetts General Hospital
University of Tennessee Health Sciences Center Boston, Massachusetts
Memphis, Tennessee
†
Deceased.
Contributors xvii
William Jarnagin, MD, FACS Hagop Kantarjian, MD

Winchester Hospital The University of Texas MD Anderson Cancer Center
North Reading Medical Houston, Texas
North Reading, Massachusetts
Giorgos Karakousis, MD
Aminah Jatoi, MD Assistant Professor of Surgery
Professor of Oncology University of Pennsylvania
Mayo Clinic Philadelphia, Pennsylvania
Maher Karam-Hage, MD
Anuja Jhingran, MD Professor of Behavioral Science
The University of Texas MD Anderson Cancer Center The University of Texas MD Anderson Cancer Center
Houston, Texas Houston, Texas
David H. Johnson, MD Nadine M. Kaskas, MD

Chairman, Department of Internal Medicine Resident Physician
University of Texas Southwestern Medical School Department of Dermatology
Dallas, Texas The Warren Alpert Medical School of Brown University
Providence, Rhode Island
Brian Johnston, MD
Royal Victoria Hospital Michael B. Kastan, MD, PhD
Belfast, United Kingdom Executive Director, Duke Cancer Institute
Director, Cancer Immunotherapy Frontier Program
†
Patrick G. Johnston, MD William and Jane Shingleton Professor, Pharmacology and
Center for Cancer Research and Cell Biology Cancer Biology
School of Medicine, Dentistry, and Biomedical Sciences Professor of Pediatrics
Queen’s University Belfast Duke University School of Medicine
Belfast, United Kingdom Durham, North Carolina
Kevin D. Judy, MD Nora Katabi, MD

Professor of Neurosurgery Department of Pathology
Thomas Jefferson University Memorial Sloan-Kettering Cancer Center
Jefferson Medical College New York, New York
Daniel R. Kaul, MD
Lisa A. Kachnic, MD Associate Professor of Infectious Disease
Professor and Chair of Radiation Oncology University of Michigan
Vanderbilt University Medical Center Ann Arbor, Michigan
Scott R. Kelley, MD, FACS, FASCRS
Orit Kaidar-Person, MD Assistant Professor of Surgery
Ramban Medical Center Division of Colon and Rectal Surgery
Haifa, Israel Mayo Clinic
Sanjeeva Kalva, MD, RPVI, FSIR
Chief, Interventional Radiology Nancy Kemeny, MD
Associate Professor of Radiology Attending Physician
University of Texas Southwestern Medical Center Memorial Sloan Kettering Cancer Center
Dallas, Texas Professor of Medicine
Weill Medical College at Cornell University
Deborah Y. Kamin, RN, MS, PhD New York, New York
Vice President
Policy and Advocacy Erin E. Kent, PhD, MS
American Society of Clinical Oncology Scientific Advisor
Alexandria, Virginia Outcomes Research Branch
Healthcare Delivery Research Program
Division of Cancer Control and Population Sciences
Rockville, Maryland
ICF, Inc.
Fairfax, Virginia
†
Deceased.
xviii Contributors
Oliver Kepp, PhD Daniel A. Laheru, MD

Metabolomics and Cell Biology Platforms Ian T. MacMillan Professorship in Clinical Pancreatic Research
Gustave Roussy Cancer Campus Department of Medical Oncology
Villejuif, France The Johns Hopkins University School of Medicine
Baltimore, Maryland
Simon Khagi, MD
Assistant Professor Paul F. Lambert, PhD
University of North Carolina School of Medicine Professor of Oncology
Lineberger Comprehensive Cancer Center University of Wisconsin
Chapel Hill, North Carolina Madison, Wisconsin
Joshua E. Kilgore, MD Mark Lawler, PhD

Division of Gynecologic Oncology Chair in Translational Cancer Genomics
University of North Carolina School of Medicine Centre for Cancer Research and Cell Biology
Chapel Hill, North Carolina School of Medicine, Dentistry and Biomedical Sciences
Queen’s University Belfast
D. Nathan Kim, MD, PhD Belfast, United Kingdom
Associate Professor
Department of Radiation Oncology Jennifer G. Le-Rademacher, PhD
University of Texas Southwestern Medical Center Associate Professor of Biostatistics
Dallas, Texas Health Sciences Research
Associate Professor of Oncology
Bette K. Kleinschmidt-DeMasters, MD Mayo Clinic
Professor of Neurology, Neurosurgery, and Pathology Rochester, Minnesota
CU Anschutz Medical Campus
University of Colorado John Y.K. Lee, MD
Aurora, Colorado Associate Professor of Neurosurgery
University of Pennsylvania
Edward L. Korn, PhD Philadelphia, Pennsylvania
Biometric Research Program
National Cancer Institute Nancy Y. Lee, MD
Bethesda, Maryland Department of Radiation Oncology
Guido Kroemer, MD, PhD New York, New York
Team 11, Centre de Recherche des Cordeliers
Paris, France Susanna L. Lee, MD, PhD
Massachusetts General Hospital
Geoffrey Y. Ku, MD Boston, Massachusetts
Assistant Attending Physician
Gastrointestinal Oncology Service Jonathan E. Leeman, MD
Department of Medicine Department of Radiation Oncology
Memorial Sloan Kettering Cancer Center Memorial Sloan-Kettering Cancer Center
Shivaani Kummar, MD Andreas Linkermann, MD

Professor of Medicine Department of Internal Medicine III
Director, Phase 1 Clinical Research Program Division of Nephrology
Stanford University University Hospital Carl Gustav Carus at the Technische
Palo Alto, California Universität Dresden
Dresden, Germany
Bonnie Ky, MD, MSCE
Assistant Professor of Medicine and Epidemiology Jinsong Liu, MD, PhD
Division of Cardiovascular Medicine Professor of Pathology
Senior Scholar The University of Texas MD Anderson Cancer Center
Center for Clinical Epidemiology and Biostatistics Houston, Texas
University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania Simon Lo, MD, FACR
Professor and Vice Chair for Strategic Planning
Department of Radiation Oncology
Professor of Neurological Surgery
University of Washington School of Medicine
Seattle, Washington
Contributors xix
Jason W. Locasale, PhD Amit Maity, MD

Associate Professor University of Pennsylvania
Department of Pharmacology and Cancer Biology Philadelphia, Pennsylvania
Duke University School of Medicine
Durham, North Carolina Neil Majithia, MD
Mayo Clinic
Charles L. Loprinzi, MD Rochester, Minnesota
Regis Professor of Breast Cancer Research
Department of Oncology Marcos Malumbres, PhD
Mayo Clinic Group Leader
Rochester, Minnesota Cell Division and Cancer
Spanish National Cancer Research Center (CNIO)
Maeve Lowery, MD Madrid, Spain
Professor of Translational Cancer Medicine
Trinity College Karen Colbert Maresso, MPH
Dublin, Ireland Program Director
Division of Cancer Prevention and Population Sciences
Emmy Ludwig, MD The University of Texas MD Anderson Cancer Center
Associate Attending Physician Houston, Texas
Associate Professor of Medicine John D. Martin, PhD
Weill Medical College at Cornell University The University of Tokyo
New York, New York Tokyo, Japan
Matthew A. Lunning, DO Koji Matsuo, MD, PhD

Associate Professor of Internal Medicine Assistant Professor of Obstetrics and Gynecology
University of Nebraska Medical Center University of Southern California
Omaha, Nebraska Los Angeles, California
Robert A. Lustig, MD Natalie H. Matthews, MD

Professor of Clinical Radiation Oncology Department of Dermatology
University of Pennsylvania The Warren Alpert Medical School of Brown University
Philadelphia, Pennsylvania Providence, Rhode Island
Mitchell Machtay, MD Lauren Mauro, MD

University Hospitals Cleveland Medical Center Assistant Professor of Medicine
Case-Western Reserve University School of Medicine George Washington University School of Medicine
Cleveland, Ohio Washington, D.C.
Crystal Mackall, MD R. Samuel Mayer, MD, MEHP

Endowed Professor of Pediatrics and Medicine Associate Professor and Vice Chair for Education
Stanford University Physical Medicine and Rehabilitation
Director The Johns Hopkins University School of Medicine
Stanford Center for Cancer Cell Therapy Medical Director, Cancer Rehabilitation Program
Director Physical Medicine and Rehabilitation
Parker Institute for Cancer Immunotherapy at Stanford The Johns Hopkins Hospital
Associate Director Baltimore, Maryland
Stanford Cancer Institute
Stanford, California Worta McCaskill-Stevens, MD
Chief, Community Oncology and Prevention Trials Research Group
David A. Mahvi, MD Division of Cancer Prevention
General Surgery Resident National Cancer Institute
Brigham and Women’s Hospital Rockville, Maryland
Megan A. McNamara, MD
David M. Mahvi, MD Assistant Professor of Medicine
Professor of Surgery Department of Medical Oncology
Chief, Surgical Oncology Duke University Medical Center
Medical University of South Carolina Durham, North Carolina
Charleston, South Carolina
xx Contributors
Neha Mehta-Shah, MD Jarushka Naidoo, MB, BCH

Assistant Professor Assistant Professor of Oncology
Washington University The Sidney Kimmel Comprehensive Cancer Center at Johns
St. Louis, Missouri Hopkins Hospital
Baltimore, Maryland
Robert E. Merritt, MD
Director, Thoracic Surgery Amol Narang, MD
James Cancer Center Assistant Professor of Radiation Oncology
The Ohio State University Medical Johns Hopkins University School of Medicine
Columbus, Ohio Baltimore, Maryland
Matthew I. Milowsky, MD Heidi Nelson, MD, FACS, FASCRS

Professor of Medicine Professor of Surgery
Division of Hematology/Oncology Division of Colon and Rectal Surgery
UNC Lineberger Comprehensive Cancer Center Mayo Clinic
Chapel Hill, North Carolina Rochester, Minnesota
Lori M. Minasian, MD William G. Nelson, MD, PhD

Deputy Director Professor and Director
Division of Cancer Prevention Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute Johns Hopkins University School of Medicine
National Institutes of Health Baltimore, Maryland
Bethesda, Maryland
Suzanne Nesbit, PharmD, BCPS, CPE
Tara C. Mitchell, MD Clinical Pharmacy Specialist, Pain Management
Assistant Professor of Medicine Research Associate, Department of Oncology
University of Pennsylvania The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Philadelphia, Pennsylvania The Johns Hopkins Hospital
Baltimore, Maryland
Demytra Mitsis, MD
Medical Oncology and Hematology Fellow Mark Niglas, MD, FRCPC
Department of Medicine Clinical Fellow
Roswell Park Cancer Institute Department of Radiation Oncology
Buffalo, New York Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
Michelle Mollica, PhD, MPH, RN
Program Director Tracey O’Connor, MD
Division of Cancer Control and Population Sciences Associate Professor of Oncology
Healthcare Delivery Research Program Department of Medicine
National Cancer Institute Roswell Park Cancer Institute
Bethesda, Maryland Buffalo, New York
Margaret Mooney, MD Kenneth Offit, MD, MPH

Branch Chief, Clinical Investigations Branch Chief, Clinical Genetics Service
Cancer Therapy Evaluation Program Robert and Kate Niehaus Chair in Inherited Cancer Genomics
Division of Cancer Treatment and Diagnosis Memorial Sloan Kettering Cancer Center
National Cancer Institute New York, New York
Rockville, Maryland
Mihaela Onciu, MD
Farah Moustafa, MD Medical Director
Department of Dermatology OncoMetrix Laboratories
The Warren Alpert Medical School of Brown University Poplar Healthcare
Providence, Rhode Island Memphis, Tennessee
Lida Nabati, MD
Instructor in Medicine
Senior Physician
Dana-Farber Cancer Institute
Contributors xxi
Eileen M. O’Reilly, MD Steven Z. Pavletic, MD, MS

Winthrop Rockefeller Chair in Medical Oncology Head, Graft-Versus-Host Disease and Autoimmunity Section
Section Head Hepatopancreaticobiliary & Neuroendocrine Cancers Experimental Transplantation and Immunology Branch
Gastrointestinal Oncology Service National Cancer Institute
Associate Director Bethesda, Maryland
David M. Rubenstein Center for Pancreatic Cancer Research
Attending Physician, Member Peter C. Phillips, MD
Memorial Sloan Kettering Cancer Center Professor of Neurology and Oncology
Professor of Medicine The Children’s Hospital of Philadelphia
Weill Medical College at Cornell University Philadelphia, Pennsylvania
New York, New York
Miriam D. Post, MD
Elaine A. Ostrander, PhD Associate Professor of Pathology
Chief and Distinguished Investigator CU Anschutz Medical Campus
Cancer Genetics and Comparative Genomics Branch University of Colorado
National Human Genome Research Institute Aurora, Colorado
Bethesda, Maryland
Amy A. Pruitt, MD
Lisa Pappas-Taffer, MD University of Pennsylvania
Assistant Professor of Clinical Dermatology Philadelphia, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania Christiane Querfeld, MD, PhD
Chief, Division of Dermatology
Drew Pardoll, MD, PhD Director, Cutaneous Lymphoma Program
Director, Bloomberg~Kimmel Institute for Cancer Immunotherapy Assistant Professor of Dermatology
Sidney Kimmel Comprehensive Cancer Center City of Hope
Johns Hopkins School of Medicine Duarte, California
Baltimore, Maryland
Vance A. Rabius, PhD
Jae H. Park, MD Research Director, Tobacco Treatment Program
Assistant Attending The University of Texas MD Anderson Cancer Center
Department of Medicine Houston, Texas
Leukemia Service and Cellular Therapeutics Center
Memorial Sloan Kettering Cancer Center S. Vincent Rajkumar, MD
Assistant Professor of Medicine Edward W. and Betty Knight Scripps Professor of Medicine
Joan and Sanford I. Weill Department of Medicine Division of Hematology
Weill Cornell Medical College Mayo Clinic
New York, New York Rochester, Minnesota
Anery Patel, MD Mohammad O. Ramadan, MD

Clinical Instructor Assistant Professor
Department of Internal Medicine Department of Urology
Division of Diabetes, Endocrine, and Metabolism University of Oklahoma Health Sciences Center
University of Nebraska Medical Center Oklahoma City, Oklahoma
Omaha, Nebraska
Erinn B. Rankin, PhD
Anish J. Patel, MD Assistant Professor of Radiation Oncology, Obstetrics,
Assistant Professor of Endocrinology and Gynecology
Department of Endocrinology Stanford University School of Medicine
University of Alabama at Birmingham Stanford, California
Birmingham, Alabama
Sushanth Reddy, MD
Steven R. Patierno, PhD Assistant Professor of Surgery
Deputy Director Department of Surgery
Duke Cancer Institute University of Alabama at Birmingham
Professor of Medicine Birmingham, Alabama
Professor of Pharmacology and Cancer Biology
Professor of Community and Family Medicine
Duke University Medical Center
Durham, North Carolina
xxii Contributors
Michael A. Reid, PhD Nadia Rosenthal, PhD

Postdoctoral Fellow Scientific Director
Department of Pharmacology and Cancer Biology The Jackson Laboratory
Duke University School of Medicine Bar Harbor, Maine
Durham, North Carolina Chair, Cardiovascular Science
National Heart and Lung Institute
Scott Reznik, MD Imperial College London
Associate Professor London, United Kingdom
Department of Cardiothoracic Surgery
University of Texas Southwestern Medical Center Meredith Ross, MD
Dallas, Texas Fellow
Department of Internal Medicine
Tina Rizack, MD, MPH Division of Diabetes, Endocrinology, and Metabolism
Hematologist/Oncologist University of Nebraska Medical Center
South County Health Omaha, Nebraska
Clinical Assistant Professor of Internal Medicine and Obstetrics
& Gynecology Julia H. Rowland, PhD
Alpert Medical School of Brown University Director, Office of Cancer Survivorship
Providence, Rhode Island Division of Cancer Control and Population Sciences
Jason D. Robinson, PhD Rockville, Maryland
Associate Professor of Behavioral Science
The University of Texas MD Anderson Cancer Center Anthony H. Russell, MD
Houston, Texas Massachusetts General Hospital
Leslie Robinson-Bostom, MD
Senior Attending Michael S. Sabel, MD, FACS
Department of Dermatology Associate Professor
The Warren Alpert Medical School of Brown University Surgery
Providence, Rhode Island University of Michigan
Ann Arbor, Michigan
Carlos Rodriguez-Galindo, MD
Departments of Global Pediatric Medicine and Oncology Arjun Sahgal, MD, FRCPC
St. Jude Children’s Research Hospital Professor of Radiation Oncology and Surgery
Memphis, Tennessee Deputy Chief, Department of Radiation Oncology
Sunnybrook Health Sciences Center
Paul B. Romesser, MD University of Toronto Faculty of Medicine
Department of Radiation Oncology Toronto, Ontario
New York, New York Ryan D. Salinas, MD
Resident Physician
Steven T. Rosen, MD Department of Neurosurgery
Provost & Chief Scientific Officer University of Pennsylvania
Director, Comprehensive Cancer Center and Beckman Philadelphia, Pennsylvania
Research Institute
Irell & Manella Cancer Center Director’s Distinguished Chair Erin E. Salo-Mullen, MS, MPH, CGC
Helen & Morgan Chu Director’s Chair, Beckman Research Institute Senior Genetic Counselor
City of Hope Clinical Genetics Service
Duarte, California Department of Medicine
Myrna R. Rosenfeld, MD, PhD New York, New York
Senior Investigator, Neuroimmunology
Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS) Manuel Salto-Tellez, MD
Barcelona, Spain Center for Cancer Research and Cell Biology
Adjunct Professor Neurology School of Medicine, Dentistry, and Biomedical Sciences
University of Pennsylvania Queen’s University Belfast
Philadelphia, Pennsylvania Belfast, United Kingdom
Contributors xxiii
Sydney M. Sanderson, BS Konstantin Shilo, MD

PhD Candidate Department of Pathology
Department of Pharmacology and Cancer Biology James Cancer Center
Duke University School of Medicine The Ohio State University Medical
Durham, North Carolina Columbus, Ohio
John T. Sandlund, MD Eric Small, MD

Member Professor of Medicine
Department of Oncology University of California, San Francisco
St. Jude Children’s Research Hospital San Francisco, California
Professor of Pediatrics
University of Tennessee College of Medicine Angela B. Smith, MD, MS, FACS
Memphis, Tennessee Associate Professor of Urology
Department of Urology
Victor M. Santana, MD University of North Carolina
Department of Oncology Chapel Hill, North Carolina
St. Jude Children’s Research Hospital
Memphis, Tennessee Stephen N. Snow, MD
Professor of Dermatology
Michelle Savage, MD Northwest Permanente
Department of Clinical Cancer Prevention Portland, Oregon
The University of Texas MD Anderson Cancer Center
Houston, Texas David B. Solit, MD
Geoffrey Beene Chair
Eric C. Schreiber, PhD Director, Center for Molecular Oncology
Associate Professor Member, Human Oncology and Pathogenesis Program
Department of Radiation Oncology Attending Physician, Genitourinary Oncology Service, Department
University of North Carolina School of Medicine of Medicine
Chapel Hill, North Carolina Memorial Sloan Kettering Cancer Center
New York, New York
Lynn Schuchter, MD
C. Willard Robinson Professor of Hematology and Oncology Anil K. Sood, MD
Professor of Medicine Professor and Vice Chair
University of Pennsylvania Department of Gynecologic Oncology and Reproductive Medicine
Philadelphia, Pennsylvania The University of Texas MD Anderson Cancer Center
Houston, Texas
Liora Schultz, MD
Department of Pediatric Oncology, Division of Oncology Enrique Soto-Perez-de-Celis, MD
Stanford University International Fellow
Stanford, California Department of Medical Oncology and Therapeutics Research
City of Hope
Michael V. Seiden, MD, PhD Duarte, California
Texas Oncology Researcher in Medical Science
The Woodlands, Texas Cancer Care in the Elderly Clinic
Department of Geriatrics
Morgan M. Sellers, MD, MS Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Icahn School of Medicine at Mount Sinai Mexico City, Mexico
New York, New York
Joseph A. Sparano, MD
Payal D. Shah, MD Associate Chairman
Assistant Professor Department of Oncology
Medicine Montefiore Medical Center
University of Pennsylvania Professor of Medicine and Women’s Health
Philadelphia, Pennsylvania Department of Medicine and Oncology
Albert Einstein College of Medicine
Jinru Shia, MD Bronx, New York
Member and Attending Pathologist
Memorial Sloan Kettering Cancer Center Vladimir S. Spiegelman, MD, PhD
Professor of Pathology and Laboratory Medicine Professor of Pediatrics and Pharmacology
Weill Medical College at Cornell University Department of Pediatrics
New York, New York Pennsylvania State University College of Medicine
Hershey, Pennsylvania
xxiv Contributors
Sheri L. Spunt, MD, MBA James E. Talmadge, PhD

Endowed Professor of Pediatric Cancer Professor of Pathology and Microbiology
Department of Pediatrics University of Nebraska Medical Center
Division of Hematology/Oncology Omaha, Nebraska
Stanford University School of Medicine
Stanford, California David T. Teachey, MD
Department of Pediatrics
Zsofia K. Stadler, MD Divisions of Hematology and Oncology
Assistant Attending Physician Children’s Hospital of Philadelphia
Department of Medicine Philadelphia, Pennsylvania
Assistant Professor of Medicine Catalina V. Teba, MD
Weill Cornell Medical College University Hospitals Cleveland Medical Center
New York, New York Case-Western Reserve University School of Medicine
Cleveland, Ohio
David P. Steensma, MD
Institute Physician Ayalew Tefferi, MD
Department of Medical Oncology Department of Hematology
Dana-Farber Cancer Institute Mayo Clinic
Associate Professor of Medicine Rochester, Minnesota
Boston, Massachusetts Bin Tean Teh, MD, PhD
Professor
Richard M. Stone, MD Division of Medical Sciences
Professor of Medicine National Cancer Centre Singapore
Harvard Medical School Professor, Cancer and Stem Cell Biology Program
Chief of Staff Duke–NUS Medical School
Department of Medical Oncology Singapore
Dana-Farber Cancer Institute
Boston, Massachusetts Joyce M.C. Teng, MD, PhD
Associate Professor of Dermatology and Pediatrics
Steven Kent Stranne, MD, JD Stanford of Medicine
Polsinelli PC Stanford University
Washington, D.C. Palo Alto, California
Kelly Stratton, MD Joel E. Tepper, MD

Assistant Professor Hector MacLean Distinguished Professor of Cancer Research
Department of Urology Department of Radiation Oncology
University of Oklahoma Health Sciences Center University of North Carolina School of Medicine
Oklahoma City, Oklahoma University of North Carolina Lineberger Comprehensive
Cancer Center
Bill Sugden, PhD Chapel Hill, North Carolina
Professor of Oncology
University of Wisconsin Premal H. Thaker, MD
Madison, Wisconsin Professor in Gynecologic Oncology
Division of Obstetrics and Gynecology
Andrew M. Swanson, MD Washington University School of Medicine
Assistant Professor of Dermatology St. Louis, Missouri
University of Wisconsin School of Medicine and Public Health
Madison, Wisconsin Aaron P. Thrift, PhD
Assistant Professor
Martin S. Tallman, MD Dan L. Duncan Comprehensive Cancer Center
Chief, Leukemia Service Department of Medicine, Gastroenterology Section
Memorial Sloan-Kettering Cancer Center Baylor College of Medicine
Professor of Medicine Houston, Texas
Joan and Sanford I. Weill Department of Medicine
Weill Cornell Medical College Arthur-Quan Tran, MD
New York, New York Division of Gynecologic Oncology
University of North Carolina School of Medicine
Chapel Hill, North Carolina
Contributors xxv
Grace Triska, MS Richard L. Wahl, MD

Washington University School of Medicine Elizabeth Mallinckrodt Professor and Director
St. Louis, Missouri Mallinckrodt Institute of Radiology
Washington University School of Medicine
Donald Trump, MD, FACP St. Louis, Missouri
Chief Executive Officer and Executive Director
Inova Schar Cancer Institute Michael F. Walsh, MD, FAAP, FACMG, DABMG
Falls Church, Virginia Assistant Member
Department of Pediatrics and Medicine
Kenneth Tsai, MD, PhD Divisions of Solid Tumor and Clinical Genetics
Associate Member Memorial Sloan Kettering Cancer Center
Anatomic Pathology and Tumor Biology New York City, New York
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida Thomas Wang, MD
Professor of Surgery
Chia-Lin Tseng, MD, FRCPC Department of Surgery
Assistant Professor University of Alabama at Birmingham
Radiation Oncologist Birmingham, Alabama
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada Jared Weiss, MD
Associate Professor of Medicine
Diane Tseng, MD, PhD Section Chief of Thoracic and Head/Neck Oncology
Department of Medicine Division of Hematology and Oncology
Division of Oncology University of North Carolina at Chapel Hill
Stanford University Chapel Hill, North Carolina
Stanford, California
Irving L. Weissman, MD
Sandra Van Schaeybroeck, MD Director, Institute for Stem Cell Biology and Regenerative Medicine
Center for Cancer Research and Cell Biology Director, Stanford Ludwig Center for Cancer Stem Cell Research
School of Medicine, Dentistry, and Biomedical Sciences and Medicine
Queen’s University Belfast Stanford University
Belfast, United Kingdom Palo Alto, California
Brian A. Van Tine, MD, PhD Shannon N. Westin, MD, MPH

Associate Professor Associate Professor of Gynecologic Oncology and
Internal Medicine Reproductive Medicine
Washington University in Saint Louis The University of Texas MD Anderson Cancer Center
St. Louis, Missouri Houston, Texas
Erin R. Vanness, MD Jeffrey D. White, MD

Associate Professor of Dermatology Associate Director, Office of Cancer Complementary and
University of Wisconsin School of Medicine and Public Health Alternative Medicine
Madison, Wisconsin Division of Cancer Treatment and Diagnosis
Gauri Varadhachary, MD Bethesda, Maryland
Professor
Medical Director, Gastrointestinal Center Richard Wilson, MD
Executive Medical Director, Ambulatory Operations Center for Cancer Research and Cell Biology
Department of Gastrointestinal Medical Oncology School of Medicine, Dentistry, and Biomedical Sciences
The University of Texas MD Anderson Cancer Center Queen’s University Belfast
Houston, Texas Belfast, United Kingdom
Marileila Varella-Garcia, PhD Richard J. Wong, MD

Professor of Medicine and Medical Oncology Department of Surgery
CU Anschutz Medical Campus Memorial Sloan-Kettering Cancer Center
University of Colorado New York, New York
Aurora, Colorado
xxvi Contributors
Gary S. Wood, MD Timothy Zagar, MD

Professor and Chair of Dermatology Northeastern Radiation Oncology
University of Wisconsin School of Medicine and Public Health Glens Falls, New York
Middleton VA Medical Center
Madison, Wisconsin Elaine M. Zeman, PhD
Associate Professor
Yaohui G. Xu, MD, PhD Department of Radiation Oncology
Associate Professor of Dermatology University of North Carolina School of Medicine
University of Wisconsin School of Medicine and Public Health Chapel Hill, North Carolina
Madison, Wisconsin
Tian Zhang, MD
Meng Xu-Welliver, MD, PhD Assistant Professor of Medicine
Associate Professor of Radiation Oncology Duke University Medical Center
James Cancer Center Durham, North Carolina
The Ohio State University Medical Center
Columbus, Ohio James A. Zwiebel, MD
Cancer Therapy Evaluation Program (Retired)
Shlomit Yust-Katz, MD National Cancer Institute
Professor Rockville, Maryland
Davidoff Cancer Center
Rabin Medical Center
Petah Tikva, Israel
Preface
New insights into whole genome sequence variations and the genomic useful to students and trainees, experts in the various disciplines of
structural alterations associated with cancer, including their downstream oncology, and as a reference text for physicians from other medical
effects on protein structure and function, are helping us to define specific disciplines and the various staff who regularly care for patients with
communication pathway changes that drive cancer initiation, progression, cancer. It is our hope that readers will find this scholarly textbook
metastasis, and resistance. We have learned that each individual and properly balanced between the disciplines of science, clinical medicine,
each tumor may be unique. Individual physiognomies in terms of path and humanism and that it will serve them well in their efforts to prevent,
of progression and unique cellular communication pathway alterations diagnose, and effectively treat their patients suffering from cancer.
are continuing to define the nature of specific cancers and offer greater The multidisciplinary nature of cancer care is, and will continue to
opportunities for the development of highly prescriptive intervention(s). be, reflected in our editors. Experts in cancer biology, surgical oncology,
In addition, we have a much greater understanding of the relationship pediatric oncology, radiation oncology, medical oncology, and hema-
of the host’s tissues, the patient’s immune system, and the broad tumor tologic malignancies directed the development of the content. Reflecting
microenvironment, to the process of tumor development and progression the multispecialty approach necessary for optimal care of patients, the
and their impact on tumor control. This new body of knowledge on majority of chapters are the joint product of several of these disciplines.
how the body’s immune system and the tumor’s microenvironment Engaging the very best subject matter authorities was a guiding principle
are altered to support disease growth, invasion, and distant spread is for the editors and we are deeply indebted to our outstanding authors
providing opportunities for the development of novel therapeutic who, in a most diligent and thoughtful way, have brought their knowledge
interventions. There is exciting new evidence to support the presence and skills to the sixth edition of Abeloff ’s Clinical Oncology.
of a special subclass of cells within the tumor that has properties of
“stemness,” which places them in the key role of maintaining tumor
ACKNOWLEDGMENTS
growth and tumor spread. The cumulative effect of these advances—
where certain cancers can be prevented and where others will be detected This sixth edition represents a highly collaborative and dynamic effort
earlier and controlled—promises to be transformative in our effort to between the editors and Elsevier. We are greatly indebted to Laura
conquer cancer. Schmidt, Kathleen Schlom, and Kristi Batchelor for their creative input
The sixth edition of Abeloff ’s Clinical Oncology incorporates the and guidance and for turning the principles behind this text into a
exciting advances in basic, translational, clinical, and epidemiologic reality. Finally, we want to express our gratitude to our many contributing
oncology. Each chapter begins with a summary highlighting the key authors for their dedication to this project, their generosity of time,
points and comprises a critical analysis of the literature and updated and, of course, their very valuable friendship.
clinical studies—authors present their own opinions in specially identified
boxes and algorithms. John E. Niederhuber, MD
Despite significant progress, the diagnosis of cancer remains devastat- James O. Armitage, MD
ing to patients and their families. Our goal is to provide a reference James H. Doroshow, MD
textbook that is the most useful, understandable, attractive, and thorough Michael B. Kastan, MD, PhD
in presenting the principles of clinical oncology. It is meant to be equally Joel E. Tepper, MD
xxvii
Another random document with
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animals and plants in order to live, so that we can further extend our
altruism at most to a moderate protection of other animals, if we are
to avoid injury to our own race. We may remark in passing that the
altruism of many lovers of animals, who prefer their favourite pets to
human beings and to the social welfare, is typical of the
exclusiveness and stupidity of misdirected impulses of sympathy.
Morality must therefore in the future consist of a common social
impulse—it must itself become social. This impulse must overthrow
not only egotism, but also the exclusiveness of individual
sympathies. We are still, alas, far from this goal! The family is often a
thieves’ kitchen; patriotism is a prolific parent of wars; while
communities and societies, however noble their objects may be,
readily degenerate into petty sects and cliques.
And now comes yet another difficulty, namely, the frequent lack of
harmony between the ethical motives which inspire an action and its
real moral value.
“Ich bin
Ein Theil von jener Kraft
Die stets das Böse will
Und stets das Gute schafft,”
says Mephistopheles in Goethe’s Faust.[B] Let us say often instead of

always, and mention also that other Power which often wills the good
and yet does the evil, and we have the well-known picture of the
intelligent, ambitious egotist, who, without any sense of duty,
achieves great and good results; and that of the foolish, infatuated
altruist, who devotes the whole might of his zeal for duty to the
service of socially pernicious forces!
[B] “I am a part of that power which always wills the evil and
always does the good.”
As a result of exaggerating the above-mentioned phenomena

certain theorists have imagined that ethics can be founded upon
pure egotism. But this is a mistake. Without the altruistic impulses of
sympathy and duty among its individual members no common social
existence can thrive; on the contrary, it must degenerate.
The power of the emotions in man is much too strong to allow of
any other result. Any one who imagines that he is completely master
of his emotions makes, if possible, a still greater mistake than one
who avows that he has never lied, or that his actions are governed
by free-will. All human morality is bound up with these impulses and
emotions. Socialism, for instance, will become moral, or else it will
not come to pass. Without the support of the social conscience of
mankind it cannot become moral. Every effort must therefore be
directed towards strengthening the social conscience.
The falsity of the theory of absolute good and evil is demonstrated
by the whole disposition of a world in which living creatures are
designed to prey upon one another. When a spider devours a fly it is
good for the spider and bad for the fly. The ethical value of the act
itself is therefore purely relative.
It is just the same with human ethics. To attempt to explain all the
evil in the world by the sin of Adam is to attribute a miserable
incapacity to God. The same holds true of the attempts of certain
modern Protestants to set up the dogma of a progressive revelation,
in order to bring the older dogmas into harmony with the theory of
evolution and descent. All these halting exegeses are only new
models of the artificial drags which theology seeks to impose upon
the free research of science.
Altruism and egotism stand only in relative opposition. Among ants
and bees they are instinctively adjusted to one another with
wonderful harmony, and are rarely, if ever, found in conflict. This
result can and must be striven after by mankind, however great may
be the difficulties presented by our hereditary nature. For its
achievement a harmonious co-operation of the hereditary social
conscience with reason and knowledge is absolutely necessary.
I must briefly mention two other points. Firstly, morality and social
or race hygiene become one and the same thing directly we include
in our conception of hygiene a healthy condition of the brain or soul,
and subordinate the individual hygiene to that of society in general.
Then everything socially unhygienic is immoral, and everything
immoral socially unhygienic. If, for instance, I ruin a healthy, active
member of society, in order possibly to achieve the salvation of an
incurably diseased criminal, I am committing, although from altruistic
motives, an act which is injurious from the point of view both of
ethics and social hygiene, and therefore evil and immoral.
Secondly, the boundaries of jurisprudence and of ethics are by no
means clear. Jurisprudence is more narrowly confined. It has no right
to lay claim to or to pass a verdict upon everything which ethics may
discover or attain. Laws and the constraint they imply are a
necessary evil, a crutch for the lame and defective social
conscience. They must be reduced to an indispensable minimum.
The ethical and social instincts, on the other hand, can never be too
highly developed. Humanity must gradually develop in the future to
such a point that jurisprudence may be completely replaced by an
instinctive and inculcated social impulse.
“Es erben sich Gesetz und Rechte

Wie eine ew’ge Krankheit fort.”[C]
[C] “Laws and statutes pass on in heritage, like an eternal

disease.”—Goethe, Faust.
In order now properly to understand our actual subject, viz. sexual
ethics, we must state the fact that an action, as well as the motives
which inspire it, may be either (1) ethically positive, i.e. good; (2)
ethically negative, i.e. evil; or (3) ethically indifferent, i.e. without any
relation to morals.
In their relationship to morals an action and its motive may be
completely independent of one another, as we have already seen.
We must further note that there are various degrees of duty, and
that from this cause conflicts may arise. There are duties towards
one’s self, which serve to increase the worth, and particularly the
social worth, of the individual by self-culture and education. In these
days of effeminate culture it is too often forgotten that self-discipline
and restraint, and even a certain degree of asceticism, fit the
individual for freedom and happiness, while the craving for pleasure
makes him useless and dependent.
Then there are duties towards the family and those nearer to us,
towards the State, towards existing Humanity, and towards posterity.
This last duty is the highest of all. Everything that we enjoy to-day in
culture and knowledge we owe to the toil, the suffering, and often the
martyrdom of our forefathers. Our most sacred duty is, therefore, to
secure for our descendants a loftier, happier and worthier existence
than our own.
Speaking generally, a rational system of morals must subordinate
the welfare of the individual to that of the community at large. A man
who is unprejudiced and possesses the ethical and social instinct will
therefore hold it as a principle first of all to do no man any injury;
then to develop his own individuality as highly as possible, which will
be both for his own good and that of the community; and as far as in
him lies to be of service to others and to Humanity.
From this we may derive the following commandment of sexual
ethics:—
Thou shalt take heed in thy sexual desire, in its manifestations in
thy soul, and chiefly in thy sexual acts, that thou do no hurt to thyself
nor another, nor, above all, to the race of men; but shalt strive with
thy might to increase the worth of each and all.
II. Sexual Ethics
Everything that we have up to the present said of ethics and the
social sense in general applies also to sexual ethics in particular.
The only essential thing is to discuss the matter without prejudice,
and to put aside the ancient traditions of mystagogy, dogma, and
custom. This should be comparatively easy when we consider our
present-day conventions, hypocritical as they are to the point of
nausea, and the manner in which they support the right of the
stronger and other rank abuses under the false cloak of morality.
In itself the sexual desire is neither moral nor immoral. It is simply
an instinct adapted to the reproduction of the species. The common
confusion of sexuality with immorality is, I repeat, entirely erroneous.
A man without sexual feeling must of course be extraordinarily
“moral” in his sex relationships, and yet he can be the greatest
scoundrel imaginable. His sexual coldness and indifference have not
the smallest ethical value.
According to the definition given above, we may classify every
sexual desire as ethically positive if it is of benefit to individuals, to
society, and especially to the race (that is, to posterity); as ethically
negative if it does injury to any or all of these; and as ethically
indifferent if it neither does injury nor is of any service. At the same
time we must observe the ethical gradation: (1) the race, (2) society,
(3) the more intimate surroundings or family, and (4) the individual
self.
When we come to examine the concrete cases more closely we
find that the circumstances attendant upon the gratification of the
sexual desire, and the consequences of this gratification, lead to
conflicts with morality far more frequently than does the sexual act
itself.
In the first place even the normal reproduction of human beings
may become immoral, in that it may do injury to the race or to
individuals. Malthus pointed out this fact. Habitable space upon the
earth is limited, while, on the other hand, the procreative capacity of
mankind is unlimited. If unlimited reproduction is permitted, it is
possible that the existing space may be insufficient to meet the
needs of the enormous multitudes of men which must result. The
latter may then fall victims to famine and distress, as in the case of
the Chinese, or the rabbits of Australia; and only disease, starvation,
or slaughter can bring about a return to the normal condition. It must
be obvious to every unbiassed person that this is not moral. And as
there are harmless methods of regulating the number of births and to
some extent the quality of the offspring, the just and proper use of
these methods must be described as ethically positive. Everything is
moral which makes for the happiness and well-being of society;
everything immoral which prejudices or endangers it.
There can, however, be too few people in the world; and there is
everywhere a great dearth of men and women wholly sound in mind
and body, light-hearted, unselfish, industrious, persevering,
intelligent, able and yet well-intentioned, peaceable, and honest.
On the other hand, we have a monstrous superabundance of
feeble, sickly, mentally perverted, criminally disposed, idle,
treacherous, vain, crafty, covetous, passionate, capricious, and
untrustworthy individuals, whose claims upon others are
inexhaustible, while their own services to society are either valueless
or actually harmful.
While the first-mentioned class produce far more than they
consume, it is appalling to think of the vast store of human energy
and human life which goes to waste in sick-rooms, lunatic asylums,
hospitals, and prisons. And if we look more closely we find outside
these institutions, and under no restraint, a still vaster army of
human sharks, who prey physically and mentally upon society, and
are a burden upon the industrious community. The greater number of
these useless pests owe their faults to an hereditarily defective
constitution of the protoplasmic germs which brought them into
being; and therefore a sound system of racial ethics demands
rational selection in breeding.
Equally destructive, however, are external conditions and habits of
life, such as the use of alcohol, resulting as they do in paralysis of
energy, confusion of the mind, and degeneration of the cells
(blastophthory).
The libido sexualis, or sexual desire in mankind is infinitely

stronger than is necessary for the reproduction of the race. Man has
no breeding season; he is always ready for sexual intercourse.
Although the number of women in the aggregate only slightly
exceeds that of men, the male has usually an instinctive inclination
to polygamy. Luther accurately estimated the normal requirements of
a healthy man in the prime of life at on the average two to three
sexual connections in each week; and yet this is far in excess of
what is necessary for the procreation of children in a monogamous
marriage. It is, moreover, well known that a man can even
considerably exceed the above number without injury to his health,
and there are women whose needs in this respect are actually
greater than those of men.
It therefore follows that the widespread artificial excitement of the
sexual desire from motives of sensuality is harmful from the
standpoint both of ethics and of social hygiene.
We cannot, it is true, be held responsible for a natural instinct
inherited from our ancestors. But we must seek to subdue this
instinct as far as possible, not to excite and stimulate it by artificial
means. Already there is more than enough purposeless, and
therefore ethically indifferent, sexual intercourse.
And yet Tolstoy is wrong in wishing to forbid this. As long as it
does no actual harm we must tolerate it, the more so because the
happiness of the individual and the cheerfulness with which he
labours are so often dependent upon the normal satisfaction of his
instincts.
Within the limits indicated above, the gratification of the sexual
instinct, whether in the case of man or woman, is in itself ethically
indifferent, provided it does not result in the procreation of children.
We have already dealt with the ethical value of procreation, which
depends upon the nature of the results expected. And we are
therefore bold enough to declare that every sexual connection which
does not injure either of the two persons who take part in it, or any
third person, and which, moreover, can do no injury to the child
which may be engendered by it, is in itself ethically indifferent, and
cannot therefore be immoral.
We have certainly imposed considerable modifications in this
sentence, for it is possible for a perfectly normal sexual connection
to do untold injury, especially to the woman and the child she bears;
so that an act which is in theory not immoral may become so in
practice, or may give rise to grave moral conflicts. This often
happens at the present time as the result of our prejudices,
established customs, and unjust laws.
From the standpoint of sexual ethics the ideal marriage is
undoubtedly a monogamous union, resting upon mutual and
enduring affection and loyalty, and consummated by the birth of
several children; a union in which the husband may be from six to
twelve years older than the wife, and both must be robust in mind
and body.
This ideal state of things is not as rare as our modern pessimists
would have us believe, but neither is it especially common.
Moreover, if this marriage is to reach that perfection which it can and
must attain, it must be completely free, that is to say, both parties
must be absolutely equal before the law, and no external compulsion
other than that of common obligations towards the children must
bind them to one another. To this end a complete separation of
property, and a just and proper valuation of every service performed
by the wife as well as the husband are of the first importance.
From the aforesaid it must by no means be inferred that every
person is to yield without restraint to his sexual desires.
Unfortunately this fundamentally false conception of free marriage
and free love is at the present time widespread, and it cannot be too
vigorously combated. In the first place, two persons are concerned in
the sexual act, and any exercise of constraint by one upon the other
is immoral and even criminal. The same holds true of every
seduction.
Moreover, the highest freedom of man lies in his mastery of self.
The only man who is truly free is the man who is able to control his
lower instincts. The compulsion which must be exercised in a
mutually happy sex relationship conformable to ethical principle
must, however, be no external legal compulsion, but an inward self-
repression. Fidelity in marriage must be a matter of mutual trust and
yet a matter of honour. The State and the laws cannot compel it, and
have never been able to do so; external constraint begets only
hypocrisy, strife, and treachery. On the other hand the State and the
law must, as time goes on, become more and more adapted to the
protection of the helpless offspring of sex unions.
Both parents, in proportion to their fitness and ability, must be
made responsible for the support of their children. It is in the highest
degree immoral to make a distinction between legitimate and
illegitimate children, and so to expose them and their mothers to
public disgrace because of the fulfilment of a natural function. Is it
not senseless, from the standpoint both of ethics and of law, to
declare the existence of a child, and therefore of a human being, to
be legal or illegal, or to speak of “natural children,” as if the others
were unnatural! In what bureaucratic brain can such an idea have
first arisen? It is only a remnant of a barbarous code of morals,
based upon the grossest prejudice. Antiquity, alas, justifies
everything—even crime!
Every woman who is healthy and strong should be proud of

becoming a mother. If sexual intercourse were frankly and naturally
treated as one of the most important acts in human life, the paternity
of the child would be easily ascertainable. A woman should not wait
until the birth of the child before speaking of it, but should promptly
make a formal declaration as to its parentage to the registrar of
births as soon as she becomes aware of her pregnancy. This would
be easily practicable if all girls received proper instruction regarding
the most important function of their lives. Instead of this, everything
is now concealed from them, and they are brought up in gross
ignorance of their sexual nature and duties.
If every pregnancy were at once legally recognised in this way,
and if the law would determine the responsibilities of both parents
towards their offspring, untrammelled by marriage laws and with the
well-being of society as its only aim, the most pressing need of our
time, from the standpoint of sexual ethics, would be satisfied. A
complete equality can only be attained by naming all children after
the mother. This is, moreover, the only rational and just system. It
was formerly the custom among many primitive peoples.
None of these reforms, however, need in any way debar the
formation of voluntary marriage contracts. Such contracts are,
indeed, distinctly advisable, for the voluntary resolve of two people to
remain faithful to one another, and to build up a permanent home for
their children, is at once the best, truest, and most natural foundation
of marriage.
But no one can foresee the future, and therefore simple facilities
for divorce must be provided in case it becomes intolerable or
inexpedient for the two persons to live together any longer. A divorce
must take place if one or both of the parties wish for it. The State and
the Law must only have the right to demand the fulfilment by the
parents of all obligations towards their children. Marriage contracts
for a fixed period are therefore as such not immoral. Such
agreements have even been recommended by the Christian
philosopher Charles Secrétan, in his book Le Droit de la Femme.
Sterile marriages, or other sex relationships, must be free. The law
has no concern with them as long as they do not involve injury to any
one’s property, health, or personal will. They are in themselves
ethically indifferent.
On the other hand, all sexual intercourse which is bought or sold,
such as marriage for money, the keeping of paid mistresses, and the
whole system of prostitution, is immoral, because it is corrupting and
devoid of love, and amounts simply to plunder by the aid of money.
Prostitution is a hotbed of sexual vices and abnormal practices. By
its means the sexual instinct is perverted and led astray into every
imaginable bypath, while women are degraded in the basest of all
slaveries.
Most repulsive of all, from the point of view of ethics, is the trade in
prostitutes known as the “white slave traffic,” with its criminal devices
for the enticement, intimidation, and seduction of young girls. The
traffic in waitresses for cafés and beer-gardens is often little better. It
is sad enough to reflect that these loathsome outgrowths of sexual
immorality often still enjoy the protection of the State, and that many
medical men defend their continuance under the pretext of hygiene.
It is just in this very respect that we see that social hygiene and
ethics are one and the same thing. Only the idiotic one-sidedness of
your specialist could declare such a monstrosity as State-established
prostitution to be hygienic. A system which makes for the mental and
physical ruin of the race cannot be hygienic, and the delusion that by
its aid men are protected from venereal disease is in direct conflict
with the actual facts.
Moreover, sexual intercourse which is bought and sold has no
relation to love. As a mode of gratifying the sex instinct it stands
even lower in the moral scale than the habit of self-abuse. And any
man who makes use of prostitution becomes an accomplice in
creating this miserable class of outcasts whom we speak of as
“unfortunates.” In short, whoremongery and prostitution are a social
cancer, and therefore in the highest degree immoral. They furnish an
instance of the manner in which money corrupts our whole
civilisation. This corrupting influence, with its robbery of one man by
another, makes itself felt in every department of life, and is exercised
by every form of private capital.
The climax of immorality in the cult of Mammon is reached,
however, by the capital employed in maintaining the two great evils
of alcohol and prostitution, both of which act as bloodsuckers upon
the vitality of the individual, the race, and all that is holiest in men.
These two forms of capital work hand in hand, fashioning the
goddess of love in the likeness of a lewd, sordid harlot, with the man
as at once her ravisher and her victim. They are also the worst
enemies of our descendants, whose procreation is often undertaken
in a moment of intoxication, and whose lives are exposed to the risk
of alcoholic degeneration or venereal disease!
These, therefore, are the chief foes of sexual morality: the struggle
for wealth (as exemplified in the domination of private capital) and
the use of alcohol. Let us combat both in the name of ethics. “In hoc
signo vincemus!”
The following will, I hope, make my meaning still clearer.

In sexual ethics many diseases and abnormalities play, of course,
a great part. First of all there are the venereal diseases, and
particularly syphilis and gonorrhœa, which often destroy family
happiness and endanger the offspring. It is too often forgotten that
chronic gonorrhœa can poison marriage, and that decay of the
spinal marrow (locomotor ataxia) and the so-called softening of the
brain (progressive or general paralysis) are nothing else than a very
late result of syphilis, appearing from ten to twenty years after
infection.
In a brief statistical discussion of the question, based upon
medical information, I have shown that seventy-five per cent of
venereal infections are acquired while in a state of alcoholic
excitement. In the vast majority of these cases the infection is
communicated by means of prostitution, which, as the result of the
incredibly numerous and varied sex relationships of the women,
serves simply as a vast manufactory of venereal diseases.
It is true that married women are often infected by their husbands
or lovers, but this is only a result of the previous visits of the latter to
houses of ill-fame. Hygiene and morals both suffer serious injury in
this way. Any one who is infected, and nevertheless has sexual
connection with a person not infected in the same way, commits a
basely immoral act, if not a crime. This is done, however, daily, when
the infection is concealed. Nay, more, the medical men who officially
visit and examine prostitutes are well aware that they can at most
only temporarily remedy a few of the worst symptoms, and that they
are powerless to cure the disease itself. In spite of this such women
are set at liberty once more to carry on their disastrous trade! And
very few prostitutes ever completely escape venereal infection.
These are the fruits of paid “love,” maintained chiefly by the
drinking habits of the present day. It is plain that the chief task of
sexual ethics must be the cleansing of this Augean stable. There are,
however, a host of other social evils of a similar kind, such as the
seduction and exploitation of waitresses, women factory workers,
and so forth. These abuses belong to the same domain and present
the same opportunities of infection.
The various perversions of the sexual instinct constitute another

prolific source of disaster. Most of these are hereditary, and therefore
inborn. We will only briefly mention sadism (the combination of acts
of cruelty and violence with sexual gratification), masochism (sexual
gratification combined with the passive endurance of similar cruelty
and violence), inverted sexual feeling (homosexuality), fetishism
(sexual attraction for inanimate objects), exhibitionism, sodomy, etc.
The unfortunate people who suffer from these perversions are
treated unjustly and, for the most part, far too harshly. Perverse
instincts which injure no one when carried into practice (fetishism, for
example), are ethically indifferent and harmless, in that their
possessors, generally speaking, do not multiply. It is, however,
immoral for such persons to marry. Any one who suffers from an
hereditary perversion of the sex instinct should avoid marriage and
all procreation of children.
But if the pervert can only gratify his instinct by injuring other
people, he must be regarded as a dangerous lunatic, and placed
under curative treatment. There must, however, be no question of
legal punishment. The foregoing treatment is above all necessary in
the case of sadists (who frequently commit murder) and in that of
persons of unsound mind who violate children. Homosexual persons
(i.e. men or women whose sexual inclination is for their own sex)
are, on the other hand, comparatively harmless as long as they
direct their attentions to adults, and provided there is no seduction or
use of compulsion. The same holds good in the case of other
perversions such as inclination for animals. Our laws are still entirely
at fault in these matters, and inflict punishment upon the basis of
ancient theological dogmas.
The case of perversions acquired by suggestion, evil example, or
frequent repetition is somewhat different. These latter are much
more readily curable.
Perverted sexual habits often arise from a craving for variety, or as
makeshifts adopted when the opportunity for normal sex intercourse
is denied. Our efforts must be directed towards removing these
causes by raising the general standard of social morals.
Religious morality has been the cause of untold mischief in this
matter of sexual perversions by representing as great sins and
crimes actions which are in reality the result of a diseased mental
state.
The habit of self-abuse is also extremely variable in its origin. It
arises usually as a makeshift, but often as the result of evil example.
It may also (although less frequently) be inherited, or originate from
nervous trouble, while in other cases it is prompted by mechanical
causes (phimosis, worms, or gymnastic exercises). There is no
greater blunder than that of exaggerating its importance by
representing it as a horrible and extremely dangerous vice. It must
be cured by pacification and soothing, by strengthening of the will,
and in some cases by providing the means of normal sexual
intercourse (not, however, by means of prostitution). This is the only
proper treatment of self-abuse, which is not as dangerous as is
commonly maintained. In this, as in all other cases, our conception
of sexual ethics will point out the right path.
Abnormalities of the brain or mind, especially constitutional

(hereditary) mental inferiorities, such as weakness of will-power,
moral idiocy (inherent lack of conscience), epilepsy, hysteria,
hypochondria, kleptomania, etc., together with all acquired mental
troubles, are the cause of innumerable sexual disorders and
perversions; of vices, crimes, and misdeeds of every description; of
rapine and seduction; of unhappy marriages, or rather hells upon
earth; and of the birth of countless doomed and wretched children.
Here we may see once again that ethics and social hygiene are at
one. Until now the theologians and the lawyers have treated these
mental conditions by denouncing them as deadly sins and
imprisoning the unhappy victims. This is disastrous to morality, to the
unfortunate persons themselves, and to society at large. Expert
mental treatment with a view to a fundamental cure is the first
necessity.
Here, again, alcohol and narcotics in general are the stone which
sets the whole avalanche in motion. The use of alcohol produces
mental inferiorities by its corrupting influence upon the cells
(blastophthory), and many people whose weakness of mind is
traceable to this cause cannot resist its use, and so become
dangerous inebriates.
Once more, it is the source and fountain of the evil that must be
stopped.
But there are other hereditary diseases and degeneracies of every
kind, not only of the brain, but of the whole body, such as the
disposition to tuberculosis, rickets, short-sightedness, and diseases
of the blood, all of which are related to sexual life and morals,
because they are all more or less injurious to the individual and to
society.
If persons suffering from such diseases have children at all they
must proceed with the greatest caution, and they should always be
instructed as to the hereditary nature of their maladies and the risk of
their transmission.
And now can we not hear the dictates of a truly human moral
code, based upon the facts that we have just considered?
It is true that we cannot change the present hereditary nature of
man, but it is none the less our duty, now that Science has revealed
this nature to us, to prepare for our posterity a greater degree of
happiness and a higher standard of social life than we now possess.
To this end we must first strive with all our might to destroy the all-
corrupting supremacy of private capital and wealth, with its
exploitation of human life and energy; and we must further combat
the use of all narcotic poisons, especially that of alcohol.
We must not rest until these two deadly monsters are overthrown.
In the sphere of sexual life we must endeavour to replace by truth
and justice the present-day hypocrisy which parades under the false
banner of “morality.” We must also restore to woman the same
natural and equal rights possessed by man.
Moreover, we must no longer be content to remain indifferent and
idle witnesses of the senseless and unthinking procreation of
countless wretched children, whose parents are diseased and
vicious, and whose lives are for the most part destined to be a curse
both to themselves and their fellow-men.
We must therefore recommend to all persons who are sickly or
infirm in body or mind, and especially to all suffering from hereditary
ailments, the use of means for the prevention or regulation of
conceptions,[D] so that they may not, out of pure stupidity and
ignorance, bring into the world creatures doomed to misery and
misfortune, and predisposed to disease, insanity, and crime.
[D] We refer, of course, to such preventive methods as are
completely harmless to the persons making use of them. Methods
for the prevention of conception, in general fulfil this condition.
We must endeavour in this way to bring about a vast and universal
sterilisation of all worthless, incapable or diseased people, without
attempting to prohibit in an ascetic and impracticable manner the
gratification of their normal sexual instinct and their desire for
affection.
The qualification for parentage must not be the possession of a
certain amount of money or property, but solely the social worth and
intrinsic hereditary qualities of the two individuals.
The multiplication of all who are healthy, capable, and ethically fit
must be encouraged as far as possible.
An excessive frequency of childbirths in the case of one woman
must be prevented and regulated by the use of the means
mentioned above.
In this way we shall carry out a true racial selection and prepare
the way for a better and happier Humanity. And so at last we shall
have brought our true sexual ethics into living being and reality.
Royal 8vo, 550 pp.
Just Ready.
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THE SEXUAL QUESTION.

A SCIENTIFIC, PSYCHOLOGICAL, HYGIENIC, and
SOCIOLOGICAL STUDY for the CULTURED CLASSES.
By AUGUST FOREL, M.D., Ph.D., LL.D.

Formerly Professor of Psychiatry and Director of the Provincial
Lunatic Asylum, Zürich.
English adaptation by C. F. Marshall, M.D., F.R.C.S. (London).
With 23 Illustrations, 17 of which are printed in colours.
This book is the fruit of long experience and reflection. It has two
fundamental ideas—the study of nature, and the study of the
psychology of man in health and in disease.
“It is imperative that every man and woman shall know (1) the
complete facts of normal sexual life, i.e. the physical conditions of
reproduction; and (2) so much of sex pathology as is necessary in
order to avoid the many pitfalls existing round them. The highest
praise we can give Prof. Forel’s book is to say that it meets this
need. It is ‘a scientific, psychological, hygienic, and sociological
study’ of the sexual question.”—The New Age.
MARRIAGE AND DISEASE.

Cloth. Price 10s. 6d. net.
Being an Abridged Edition of “Health and Disease in Relation to
Marriage and the Married State.” (2 vols., 30s. net.)
By many Authors. Edited by Prof. H. SENATOR and Dr. S.
KAMINER.
Translated by J. DULBERG, M.D., J.P. (Manchester). Demy 8vo.
452 pp.
To give an idea of the scope of the work, it may be stated that it
contains chapters on such subjects as:—The Hygienic Significance
of Marriage, Congenital and Inherited Diseases and Predispositions
to Disease, Consanguinity and Marriage, Climate, Race and
Nationality in Relation to Marriage, Sexual Hygiene in Married Life,
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containing, as The British Medical Journal states, “a vast amount of
trustworthy information well arranged in a clear and plain style.” By
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MONISM? An Antidote to Prof.

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To my wife, Nancy, for her love and support over 49 ½ years.

Martin D. Abeloff, MD (1942-2007)

Frederick R. Appelbaum, MD Karen Basen-Engquist, PhD, MPH

Ilene Browner, MD Stephen J. Chanock, MD

Alfred E. Chang, MD Michael F. Clarke, MD

Robert L. Coleman, MD Jeffrey Crawford, MD

Adriana M. Coletta, PhD, RD Kristy Crooks, PhD

Jerry M. Collins, PhD Daniel J. Culkin, MD

Jean M. Connors, MD Brian G. Czito, MD

Kevin R. Coombes, PhD Josep Dalmau, MD, PhD

Mauro W. Costa, MSc, PhD Mai Dang, MD, PhD

Anne Covey, MD Michael D’Angelica, MD

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Myrtle Davis, DVM, PhD James H. Doroshow, MD

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Jeffrey M. Engelmann, PhD Debra L. Friedman, MD, MS

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Stuart A. Grossman, MD Michael R. Harrison, MD

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William Jarnagin, MD, FACS Hagop Kantarjian, MD

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Oliver Kepp, PhD Daniel A. Laheru, MD

Joshua E. Kilgore, MD Mark Lawler, PhD

Shivaani Kummar, MD Andreas Linkermann, MD

Jason W. Locasale, PhD Amit Maity, MD

Matthew A. Lunning, DO Koji Matsuo, MD, PhD

Robert A. Lustig, MD Natalie H. Matthews, MD

Mitchell Machtay, MD Lauren Mauro, MD

Crystal Mackall, MD R. Samuel Mayer, MD, MEHP

Neha Mehta-Shah, MD Jarushka Naidoo, MB, BCH

Matthew I. Milowsky, MD Heidi Nelson, MD, FACS, FASCRS

Lori M. Minasian, MD William G. Nelson, MD, PhD

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Eileen M. O’Reilly, MD Steven Z. Pavletic, MD, MS

Anery Patel, MD Mohammad O. Ramadan, MD

Michael A. Reid, PhD Nadia Rosenthal, PhD