Cover Page

CANCER

Prevention, Early Detection, Treatment and Recovery

SECOND EDITION



Edited by



Gary S. Stein
Kimberly P. Luebbers

University of Vermont Larner College of Medicine
149 Beaumont Avenue, HSRF 326
Burlington, VT 05405, USA






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LIST OF CONTRIBUTORS

Thomas P. Ahern Assistant Professor, Department of Biochemistry and Department of Surgery, Larner College of Medicine, University of Vermont, Burlington, VT, USA

Christopher B. Allard Massachusetts General Hospital, Boston, MA, USA

Sarah R. Amend The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Ogheneruona Apoe University of Vermont Medical Center, Burlington, VT, USA

Jesse N. Aronowitz Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

Elizabeth Bannon Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

Anant Bhave Larner College of Medicine, University of Vermont, Burlington, VT, USA

Maryann Bishop‐Jodoin Department of Radiation Oncology, University of Massachusetts Medical School, Worcester, MA, USA. IROC Rhode Island, Lincoln, RI, USA

Michael L. Blute Massachusetts General Hospital, Boston, MA, USA

Bruce A. Bornstein Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

Carla D. Bradford Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

Leslie Bradford Maine Medical Center, Scarborough, ME, USA

Harry Bushe Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

Frances E. Carr Professor, University of Vermont Cancer Center, Department of Pharmacology, Cancer Center, University of Vermont College of Medicine, Burlington, VT, USA

Maria G. Cicchetti Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA. IROC Rhode Island, Lincoln, RI, USA

Eric M. Clark Department of Surgery, University of Vermont, Burlington, VT, USA

Bernard F. Cole Professor, Department of Mathematics and Statistics, College of Engineering and Mathematical Sciences, University of Vermont, Burlington, VT, USA

Marion Couch Richard T. Miyamoto Professor and Chair, Department of Otolaryngology–Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, USA

David Cranmer President, Vermont Cancer Survivor Network, Montpelier, VT, USA

W. Christian Crannell Department of Surgery, University of Vermont, Burlington, VT, USA

Kristin DeStigter Larner College of Medicine, University of Vermont, Burlington, VT, USA

Linda Ding Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

Liang Dong The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Department of Urology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China

Mai K. ElMallah Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA. Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, USA

Mark F. Evans Assistant Professor, Department of Pathology & Laboratory Medicine, University of Vermont, Burlington, VT, USA

Thomas J. FitzGerald Department Chair & Professor, Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare, Worcester, MA, USA. Principal Investigator, IROC Rhode Island, Lincoln, RI, USA

Terence R. Flotte Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA. Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, USA. Microbiology & Physiologic Systems, University of Massachusetts Medical School, Worcester, MA, USA

Garth Garrison Division of Pulmonary and Critical Care Medicine, University of Vermont Medical Center, Burlington, VT, USA

Robert H. Getzenberg Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA

Jonathan M. Glanzman Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

David J. Goff Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

Solomon A. Graf Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Department of Medicine, University of Washington, Seattle, WA, USA. Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA

Kristina Guyton Department of Surgery, University of Chicago Medicine, Chicago, IL, USA

Jean R. Harvey Associate Dean for Research, College of Agriculture and Life Sciences, Robert L. Bickford, Jr. Endowed Professor, Chair, Department of Nutrition and Food Sciences, University of Vermont, Vermont, VT, USA

Jessica L. Heath Assistant Professor of Pediatrics and Biochemistry, Pediatric Hematology‐Oncology, University of Vermont, Burlington, VT, USA

Beth B. Herrick Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

Sally Herschorn Larner College of Medicine, University of Vermont, Burlington, VT, USA

Jessica R. Hiatt Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

Neil Hyman Department of Surgery, University of Chicago Medicine, Chicago, IL, USA

Ted James Department of Surgery, University of Vermont Medical Center, Burlington, VT, USA

Chris A. Jones Department of Surgery, University of Vermont, Burlington, VT, USA

Michael Kalfopolous Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA

Farrah B. Khan Division of Hematology and Oncology, University of Vermont Medical Center, Burlington, VT, USA

Sahn‐Ho Kim Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, USA

C. Matthew Kinsey Division of Pulmonary and Critical Care Medicine, University of Vermont Medical Center, Burlington, VT, USA

I‐Lin Kuo Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

Jennifer LaFemina Division of Surgical, UMass Memorial Health Center, University of Massachusetts Medical School, Worcester, MA, USA

Benjamin Lange Larner College of Medicine, University of Vermont, Burlington, VT, USA

Fran Laurie Department of Radiation Oncology, University of Massachusetts Medical School, Worcester, MA, USA. IROC Rhode Island, Lincoln, RI, USA

Yuan‐Chyuan Lo Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

Kimberly P. Luebbers Assistant Dean for Clinical Research, Direct for the Office of Clinical Trials Research, University of Vermont Larner College of Medicine Office of Clinical Trials, Burlington, VT, USA

Jennifer L. May Outpatient Oncology Dietitian, The University of Vermont Cancer Center, VT, USA

Kathleen McBeth University of Vermont Medical Center, Burlington, VT, USA

Wendy McKinnon Certified Genetic Counselor, University of Vermont Cancer Center, Burlington, VT, USA

Janaki Moni, MD Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA. IROC Rhode Island, Lincoln, RI, USA

Jesse Moore Department of Surgery, University of Vermont, Burlington, VT, USA

Michael Moore Arilla Spence DeVault Professor of Otolaryngology–Head and Neck Surgery, Chief, Division of Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, USA

David C. Nalepinski Assistant Vice President for Community Oncology, Duke Cancer Institute, Durham, NC, USA

Mitchell Norotsky Department of Surgery, University of Vermont, Burlington, VT, USA

Amrita Pandit University of Vermont Medical Center, Burlington, VT, USA

Scott Perrapato University of Vermont Larner College of Medicine, Burlington, VT, USA

Kenneth J. Pienta The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Richard S. Pieters Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

Carlos A. Pino Professor of Anesthesiology and Pain Medicine, Director, Center for Pain Medicine, The Robert Larner, MD College of Medicine, The University of Vermont, Burlington, VT, USA

Mark K. Plante Division of Urology, Department of Surgery, University of Vermont Medical Center, Burlington, VT, USA

Kumar G. Prasad Clinical Instructor, Department of Otolaryngology–Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. Department of Otolaryngology–Head and Neck Surgery, Meritas Health, North Kansas City, MO, USA

G. Premveer Reddy Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, USA

Paul S. Rava Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

Michaela Reagan Assistant Professor, Tufts University School of Medicine, Boston, MA, USA. Faculty Scientist I, Maine Medical Center Research Institute, Scarborough, ME, USA

Lawrence Recht Department of Neurology & Clinical Neurosciences, Stanford University School of Medicine, Stanford, CA, USA

Lekkala V. Reddy Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, USA

Judy R. Rees Associate Professor, Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA. Norris Cotton Cancer Center, Lebanon, NH, USA

Sean Reynolds Larner College of Medicine, University of Vermont, Burlington, VT, USA

Christopher Riberdy Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

Alan Rosmarin Wolters Kluwer Health, Waltham, MA, USA

Allison Sacher Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

Jonathan Saleeby Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

Baddr Shakhsheer Department of Surgery, University of Chicago Medicine, Chicago, IL, USA

Shirin Sioshansi Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

David W. Sobel Division of Urology, Department of Surgery, University of Vermont Medical Center, Burlington, VT, USA

Brian L. Sprague Departments of Biochemistry and Department of Surgery, Larner College of Medicine, University of Vermont, Burlington, VT, USA

Gary S. Stein Director, University of Vermont Cancer Center, Perelman Professor and Chair, Department of Biochemistry, Professor, Department of Surgery, University of Vermont Larner College of Medicine, Burlington, VT, USA

F. Marc Stewart Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Department of Medicine, University of Washington, Seattle, WA, USA

Celeste Straight UMass Memorial Health Care, Central Mass Ob/Gyn, Shrewsbury, MA, USA

Jill Sudhoff‐Guerin Health Policy and Advocacy Consultant, The Vermont Medical Society, Montpelier, VT, USA

Bradley Switzer Division of Medical Oncology, UMass Memorial Health Center, University of Massachusetts Medical School, Worcester, MA, USA

Gabriella Szalayova University of Vermont Medical Center, Burlington, VT, USA

Phil Trabulsy University of Vermont, Burlington, VT, USA

Kenneth Ulin Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

John M. Varlotto Department of Radiation Oncology, University of Massachusetts Medical School; UMass Memorial Healthcare Systems, Worcester, MA, USA

Harold James Wallace, III Division of Radiation Oncology, Larner College of Medicine, University of Vermont, Burlington, VT, USA

Tao Wang Department of Radiation Oncology, University of Massachusetts Medical School, Worcester, MA, USA

George J. Weiner Director, C.E. Block Chair of Cancer Research, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA, USA. Professor, Department of Internal Medicine, Carver College of Medicine, Iowa City, IA, USA. Professor, Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, Iowa City, IA, USA

Giles F. Whalen Division of Surgical, UMass Memorial Health Center, University of Massachusetts Medical School, Worcester, MA, USA

Marie E. Wood University of Vermont Medical Center, Burlington, VT, USA

Richard C. Zieren The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Department of Urology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Susan Zweizig University of Massachusetts, UMass Memorial Health Care, Worcester, MA, USA

PREFACE

Cancer is a leading cause of death globally. The social and economic burdens are profound. Making a difference in cancer prevention, early detection, treatment, and survivorship is not an option but a requirement and obligation. This responsibility is shared by cancer scientists, physicians, and a broad spectrum of healthcare professionals as well as by cancer advocates, educators, thought leaders, and lawmakers who are committed to making cancer preventable and treatable. Every life lost to cancer is a powerful motivation to accelerate progress toward bringing cancer under control. We are moving forward with confidence that more than half of the people who encounter cancer are cured. Reinforcing progress, an increasing number of people are living with cancer, undergoing long‐term treatments, and experiencing quality lives.

Collaborative, multidisciplinary partnerships of dedicated scientists and physician‐investigators are providing unique opportunities to reduce the burden of cancer. There is increasing capacity and capability to abbreviate the translation of discoveries in laboratories to advances in cancer prevention, early detection, treatment with clinical trials, and survivorship. There is recognition for the necessity to rectify disparities that result from restrictive healthcare access in many rural and urban communities. Initiatives to expand treatment options and opportunities for cancer patients irrespective of social or economic limitations must be a priority. An investment that enhances capabilities in cancer prevention, early detection, targeted treatment, and survivorship should be obligatory. The return on the investment will be immediate, progressively increase, and make a sustainable difference in quality of life.

“Cancer: Prevention, Early Detection, Treatment and Recover” was developed to provide a patient‐centric book that synthesizes current understanding of the biology and treatment of cancer. We have responded to the importance of readily accessible explanations that accurately, directly, and comprehensively explain the biomedical parameters of cancer. We were guided by the necessity for facts, perspectives, and resources to enable cancer patients and caregivers to responsibly access options for “informed” and “comfortable” decisions.

This book provides a unique and valued resource, presenting an overview of cancer with emphasis on navigating the emerging “roadmap” from cancer prevention to early detection, treatment, and recovery. There are comprehensive books focused on the mechanistic and clinical facets of cancer. “Cancer: Prevention, Early Detection, Treatment and Recovery” authoritatively outlines the challenges and opportunities associated with cancer biology, cancer research, and the spectrum of clinical considerations that are central to “experiencing cancer” as well as to studying, investigating, and treating cancer.

“Cancer: Prevention, Early Detection, Treatment and Recovery” is dedicated to Dr. Arthur B. Pardee, who has been instrumental in establishing the foundation for progress in the prevention and treatment of cancer. Arthur Pardee has, for many years, been making visionary and far reaching discoveries in cancer‐compromised biological control that translate molecular and cellular changes during the onset and progression of cancer to novel strategies for cancer diagnosis and therapy. His contributions include the mechanistic understanding for control of gene expression, regulation of the cell cycle, and the coordinate control of genes that are responsible for physiological responsiveness and compromises associated with cancer onset and progression. Until his death on February 24, 2019, Arthur Pardee’s discoveries consistently accelerated progress toward making cancer preventable and treatable. He will continue to be an inspirational role model for scientists and physician investigators throughout the international cancer research community.

Gary S. Stein
Kimberly P. Luebbers

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CANCER AND THE CANCER EXPERIENCE