2020 ASTRO RADIATION/CANCER BIOLOGY STUDY GUIDE Produced by the Radiation/Cancer Biology Study Guide Taskforce of American Society for Radiation Oncology Copyright © 2020 American Society for Radiation Oncology If you notice and errors or have feedback about this document, please contact: Gayle Woloschak, PhD, Professor Departments of Radiation Oncology and Radiology Robert E. Lurie Comprehensive Cancer Center Feinberg School of Medicine Northwestern University 303 E. Chicago Avenue, Ward 13-002 Chicago, IL 60611 Tel: 312-503-4312 Email: [email protected] Kathryn Huber, MD, PhD Tufts Medical Center 800 Washington St. Box 359 Boston, MA 0211 Email: [email protected] 1 Editors-in-Chief (2020) Gayle E. Woloschak, Ph.D. Northwestern University Medical School Kathryn Huber, MD, PhD Tufts Medical Center Editors-in-Chief (2014) Gayle E. Woloschak, Ph.D. Northwestern University Medical School Christopher Barker, M.D. Memorial Sloan Kettering Cancer Center Editor-in-Chief (2006-2012) Barry S. Rosenstein, Ph.D. Mount Sinai School of Medicine NYU School of Medicine Associate Editors 2020 Bryan Allen, MD, PhD Sunil Krishnan, MD, FASTRO University of Iowa Mayo Clinic, Florida David Mayhew, MD, PhD Dorthe Schaue, PhD Tufts Medical Center University of California, Los Angeles Douglas Spitz, PhD Ranjit Bindra, MD, PhD University of Iowa Yale University Yaacov Lawrence, MD, MRCP Zhiyuan Shen, PhD Sheba Medical Center Rutgers Cancer Institute of New Jersey Naoyuki Saito, MD, PhD Indiana University School of Medicine Associate Editors (2013) Elizabeth Balcer-Kubiczek, Ph.D. David Gius, M. D., Ph. D. University of Maryland School of Medicine Northwestern University Medical School Beth Beadle, M. D., Ph.D. Martin Hauer-Jensen, Ph. D. Univ. Texas M. D. Anderson Cancer Center Univ. Arkansas School of Medicine Eleanor Blakely, Ph. D. Michael Joiner, Ph. D. Wayne State Lawrence Berkely National Laboratory University 2 Juong G. Rhee, Ph.D. Michael D. Story, Ph.D. University of Texas University of Maryland School of Medicine Southwestern Medical Center Navesh K. Sharma, Ph.D., D.O. Phuoc Tran, M. D., Ph. D. University of Maryland School of Johns Hopkins School of Medicine Medicine Brian Marples, Ph. D. Zhiyuan Shen, M.D., Ph.D. UMDNJ-Robert William Beaumont Hospital Wood Johnson Medical School Associate Editors (2011-2012) Elizabeth Balcer-Kubiczek, Ph.D. Brad G. Wouters, Ph.D. University of Maryland School of Medicine Ontario Institute for Cancer Research Christopher Barker, M.D. Michael E.C. Robbins, Ph.D. Memorial Sloan Kettering Cancer Center Wake Forest University School of Medicine Michael C. Joiner, Ph.D. Juong G. Rhee Ph.D. Karmanos Cancer Institute, Wayne State University of Maryland School of Medicine University School of Medicine Navesh K. Sharma, Ph.D., D.O. David G. Kirsch, M.D., Ph.D. University of Maryland School of Medicine Duke University Medical Center Zhiyuan Shen, M.D., Ph.D. Brian Marples, PhD UMDNJ-Robert Wood Johnson Medical School William Beaumont Hospital Michael D. Story, Ph.D. University of Texas Southwestern Medical Center Associate Editors (2006-2011) Kathryn D. Held, Ph.D. Jacqueline Williams, Ph.D. Harvard Medical School Massachusetts General University of Rochester Medical Center Hospital Elaine M. Zeman, Ph.D. Sara Rockwell, Ph.D. University of North Carolina School of Medicine Yale University School of Medicine Contributors Joan Allalunis-Turner, Ph.D. Elizabeth K. Balcer-Kubiczek, Ph.D. University Cross Cancer Institute of Maryland School of Medicine Sally A. Amundson, Ph.D. Kevin A. Camphausen, M.D. National Columbia University Cancer Institute/NIH 3 Theodore L. DeWeese, M.D. Johns Hopkins David Kirsch, M.D., Ph.D. University School of Medicine Duke University School of Medicine Evan B. Douple, Ph.D. The National Academies Amy Kronenberg, Sc.D. Nuclear and Radiation Studies Board Lawrence Berkeley National Laboratory Adriana Haimovitz-Friedman, Ph.D. Memorial Sloan- William F. Morgan, Ph.D. Kettering Cancer Center Pacific Notrhwest National Laboratory Dennis E. Hallahan, M.D. John P. Murnane, Ph.D. Vanderbilt University University of California, San Francisco Martin Hauer-Jensen, M.D., Ph.D. Peggy L. Olive, Ph.D. University of Arkansas for Medical Sciences British Columbia Cancer Research Centre Kathryn D. Held, Ph.D. Martin Pruschy, Ph.D. Harvard Medical School Massachusetts General University Hospital Zurich Hospital Sara Rockwell, Ph.D. Richard P. Hill, Ph.D. Yale University School of Medicine Ontario Cancer Institute Michael E.C. Robbins, Ph.D. Rakesh K. Jain, Ph.D. Harvard Medical School Wake Forest University School of Medicine Massachusetts General Hospital Joseph L. Roti Roti, Ph.D. Henning Willers, M.D. Washington University School of Medicine Harvard Medical School Massachusetts General Hospital Carolyn I. Sartor, M.D. University of North Carolina School of Medicine Jacqueline Williams, Ph.D. University of Rochester Medical Center Joann Sweasy, Ph.D. Yale University School of Medicine Elaine M. Zeman, Ph.D. University of North Carolina School of Medicine Marie-Catherine Vozenin-Brotons Ph.D. Institut Gustave Roussy Daniel Zips, Ph.D. Technical University Dresde Gayle E. Woloschak, Ph.D. Northwestern University Medical School 4 Table of Contents Contents Table of Contents ................................................................................................................................................. 5 Radiation-Matter Interactions .............................................................................................................................. 7 DNA Damage Mechanisms ................................................................................................................................... 9 DNA Repair Mechanisms .................................................................................................................................... 10 Chromosome Damage ........................................................................................................................................ 14 Cell Death Mechanisms ...................................................................................................................................... 16 Survival Assay ..................................................................................................................................................... 19 Cell Survival Models ........................................................................................................................................... 21 Linear Energy Transfer ....................................................................................................................................... 24 Oxygen Effect ..................................................................................................................................................... 26 Cellular Repair .................................................................................................................................................... 28 Tumor Assay Systems ......................................................................................................................................... 30 Tumor Biology and Microenvironment .............................................................................................................. 32 Cell and Tissue Kinetics ...................................................................................................................................... 38 Molecular Signaling ............................................................................................................................................ 42 Cancer ................................................................................................................................................................ 44 Total Body Irradiation......................................................................................................................................... 50 Normal Tissue Response .................................................................................................................................... 52 Therapeutic Ratio ............................................................................................................................................... 58 Time, Dose, Fractionation .................................................................................................................................. 60 Brachytherapy .................................................................................................................................................... 62 Alternative Delivery Systems .............................................................................................................................. 63 Chemotherapy.................................................................................................................................................... 65 Radiation Modifying Drugs ................................................................................................................................. 68 Hyperthermia ..................................................................................................................................................... 71 Radiation Carcinogenesis ................................................................................................................................... 72 Heritable Effects ................................................................................................................................................