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Low Dose and Low Dose-Rate Radiation Effects and Models

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Forty-Fourth Annual Meeting Program Low Dose and Low Dose-Rate Radiation Effects and Models April 14–15, 2008 Bethesda North Marriott Hotel & Conference Center 5701 Marinelli Road North Bethesda, MD 20852 On the cover: • top: Two nuclei have each been “hit” by three alpha particles from a microbeam and show activated γH2AX foci at the site of the traversal. • center: Chromosome painting technology makes it possible to identify each human chromosome and characterize the number, location and types of aberrations produced by ionizing radiation. • bottom: Measuring the frequency of micronuclei provides a rapid measure of cytogenetic damage, which increases as a function of radiation dose. Introduction Low Dose and Low Dose-Rate Radiation Effects and Models Forty-Fourth Annual Meeting of the National Council on Radiation Protection and Measurements (NCRP) Potential human health effects of low doses of ionizing models of the biological responses and human health radiation such as those experienced in occupational impacts of exposure to low doses of radiation. The and medical exposures are of great contemporary meeting will feature presentations by international interest. Considerable debate exists over the applica- experts on the topics of (1) molecular, cellular, tissue, bility of a linear-nonthreshold model for characterizing and laboratory animal studies on the effects of expo- the biological responses and health effects of expo- sure to low dose and low dose-rate radiation, (2) sure to low radiation doses, and alternative models results of epidemiological studies on human health have been proposed. A related subject of interest and effects of low radiation doses in occupational, medical debate is the effect of the rate of delivery of radiation and other exposure scenarios, (3) potential impacts of doses on the biological and health outcomes of expo- these findings on future regulatory guidance and pub- sure. The primary goal of the 2008 NCRP Annual lic health policy. The perspectives of research scien- Meeting will be to bring these issues into the perspec- tists, public health officials, and regulatory agencies tive of currently available data and will be presented. 1 Program Summary Monday, April 14, 2008 10:30 am DNA Damage and Repair as a Factor Contributing to Risk from Opening Session Radiation Penny A. Jeggo 8:00 am Welcome University of Sussex, Thomas S. Tenforde United Kingdom President 11:00 am Low-Dose Gene Expression National Council on Radiation Phenotyping – Molecular Protection and Measurements Pathways for Radioprotection Against DNA Damage and 8:15 am Fifth Annual Warren K. Sinclair Chromosomal Abnormalities in Keynote Address Tissues Issues in Quantifying the Effects of Andrew J. Wyrobek Low-Level Radiation Lawrence Berkeley National Dudley T. Goodhead Laboratory Medical Research Council, United Kingdom 11:30 am Radiation Protection and Nontargeted Cellular and Tissue 9:15 am Overview of Goals of the Meeting Responses at Low Radiation Antone L. Brooks Doses Washington State University at Tri- William F. Morgan Cities University of Maryland School of 9:35 am Low-Dose Extrapolation of Medicine Radiation-Related Health Risks: Status of Human Studies and 12:00 pm Lunch State of the Art Charles E. Land 1:15 pm Low-Dose Radiation Responses in National Cancer Institute Cells, Tissues and Animals: Introductory Remarks 10:05 am Break Gayle E. Woloschak Molecular, Cellular, Tissue Northwestern University and Animal Radiation 1:20 pm Chromosome Aberrations as a Responses of Relevance to Function of Dose, Dose Rate, and Linear Energy Transfer: Radiation Protection Implications for Radiation Risk Gayle E. Woloschak and Amy Michael N. Cornforth Kronenberg, Session Co-Chairs University of Texas Medical Branch 10:25 am Molecular Responses: 1:50 pm Factors that Modify Radiation- Introductory Remarks Induced Carcinogenesis Amy Kronenberg Ann R. Kennedy Lawrence Berkeley National University of Pennsylvania School of Laboratory Medicine 2 Program Summary 2:20 pm Role of Tissue Responses in Modification of Radiation Effects Tuesday, April 15 Mary Helen Barcellos-Hoff 8:10 am NCRP Annual Business Meeting Lawrence Berkeley National Laboratory 9:10 am Break 2:50 pm Break Human Epidemiology 3:10 pm Influence of Low Linear Energy Transfer Radiation Dose and Dose Studies Rate on Radiation Risk: Life-Span John D. Boice, Jr., Session Chair Dog Studies Antone L. Brooks 9:30 am Human Epidemiology Studies as a Washington State University at Tri- Basis for Current Radiation Risk Cities Estimates: Introductory Remarks 3:40 pm Variations in Radiation Sensitivity John D. Boice, Jr. Among Individuals—The Potential Impact on Risk Assessment International Epidemiology Institute Joel S. Bedford 9:35 am Low-Dose Radiation Epidemiology Colorado State University Studies: Status and Issues Roy E. Shore 4:10 pm Biophysical Modelling and Systems Biology Approaches Radiation Effects Research to Understanding Low-Dose Foundation, Japan Radiation Effects 10:05 am Impact of Dosimetry Uncertainties Herwig G. Paretzke on Dose-Response Analyses GSF-Institut fur Strahlenschutz, Ethel S. Gilbert Germany National Cancer Institute 4:40 pm Break 10:35 am Break Thirty-Second Lauriston S. 10:55 am Debate on the Topic “Does Taylor Lecture on Scientific Evidence Support a Change from the LNT Model for Radiation Protection and Low-Dose Radiation Risk Measurements Extrapolation?”: Moderator’s Introductory Remarks 5:00 pm Introduction of the Lecturer Eric J. Hall Michael T. Ryan Columbia University Radiation Standards, Dose/Risk 11:00 am Affirmative Response Assessments, Public Interactions, and Yucca Mountain: Thinking Dietrich Averbeck Outside the Box Institut Curie, France Dade W. Moeller 11:15 am Negative Response Dade Moeller & Associates, Inc. David J. Brenner 6:00 pm Reception in Honor of the Lecturer Columbia University 3 Program Summary 11:30 am Reply to Dietrich Averbeck 1:55 pm U.S. Environmental Protection David J. Brenner Agency's Perspective on What it Would Take to Promote or Require 11:35 am Reply to David J. Brenner a Change in Radiation Protection Dietrich Averbeck Regulations Juan Reyes 11:40 am Questions and Discussion 2:05 pm Questions and Discussion 12:00 pm Lunch Paul A. Locke, Moderator Low-Dose Radiation 2:20 pm Break Effects, Regulatory Policy 2:40 pm Public Perception and Policy: and Impacts on the Public Introductory Remarks Susan D. Wiltshire, Session Chair Susan D. Wiltshire 1:00 pm What Would It Take to Promote or JK Research Associates Require a Change in Regulations?: 2:45 pm Beliefs About Radiation: Introductory Remarks Scientists, the Public, and Public Jill A. Lipoti Policy New Jersey Department of Hank C. Jenkins-Smith Environmental Protection University of Oklahoma 1:05 pm Low-Dose Effects and Modeling in 3:15 pm Federal Programs to Reimburse Public Health Decision Making: the Public for Environmental and Examining the Past, Explaining the Occupational Exposures Present, and Exploring the Future Paul L. Ziemer Paul A. Locke Purdue University Johns Hopkins Bloomberg School of Public Health 3:45 pm How Do We Combine Science and Regulations for Decision Making 1:35 pm Low-Dose Radiation Effects, Following Radiological Accidents Regulatory Policy, and Impact on and Incidents? the Public: U.S. Nuclear John W. Poston, Sr. Regulatory Commission Perspective Texas A&M University Martin J. Virgilio 4:15 pm Closing Remarks 1:45 pm U.S. Department of Energy Thomas S. Tenforde Perspective: Supporting Research President, NCRP to Inform Regulatory Policy 4:25 pm Adjourn Noelle F. Metting 4 Abstracts Monday, April 14, 2008 Opening Session 8:00 am Welcome Thomas S. Tenforde President, National Council on Radiation Protection and Measurements 8:15 am Fifth Annual Warren K. Sinclair Keynote Address Issues in Quantifying the Effects of Low-Level Radiation Dudley T. Goodhead Medical Research Council, United Kingdom Much is known about health risks of ioniz- These approaches have had considerable ing radiation. Quantification of risks is far success in protecting humans. But do more advanced than for many other tox- they go far enough? Or, conversely, are ins. Acute tissue effects, and then can- they overprotective, thereby distorting the cers, became apparent remarkably soon allocation of resources and impeding after the discovery of x rays and radioac- medical and industrial progress? There is tivity, more than 110 y ago. Experimental a continuing need for quantification, with systems soon showed that heritable improved accuracy and confidence. Epi- genetic risks were also possible, but these demiology is the essential starting point, have remained elusive in humans. Studies but is fundamentally limited in what it can on the survivors of the atomic bombs in achieve. Support for the current Japan shifted the emphasis back to carci- approaches may be sought from basic nogenic risk; successive follow-ups have studies of the critical molecules, cells, tis- tended to yield increased risk factors and sues, animals and humans. Historical par- reveal direct risks at successively lower adigms of radiation carcinogenesis have doses. Given the inevitable statistical limi- arisen from such studies and driven the tations of epidemiology, direct estimates thinking of those who develop protection are unobtainable at the low doses of pri- policy. Notions of single-hit kinetics at low mary relevance in radiation protection. doses, quadratic responses at higher These low-dose estimates must be doses due to interacting events, reduction obtained by purely mathematical
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  • Thesis to My Family, for the Joy in Everyday Life

    Thesis to My Family, for the Joy in Everyday Life

    From DEPARTMENT OF ONCOLOGY AND PATHOLOGY Karolinska Institutet, Stockholm, Sweden STEREOTACTIC BODY RADIATION THERAPY OF PRIMARY LUNG CANCER AND METASTASES Karin Lindberg Stockholm 2015 All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. Printed by AJ E-print AB © Karin Lindberg, 2015 ISBN 978-91-7549-942-0 Institutionen för Onkologi-Patologi Stereotactic Body Radiation Therapy of Primary Lung cancer and Metastases AKADEMISK AVHANDLING som för avläggande av medicine doktorsexamen vid Karolinska Institutet offentligen försvaras i Radiumhemmets föreläsningssal, plan 01 (P1:01), Karolinska Universitetssjukhuset Solna Fredagen den 29:e maj 2015, kl 10.00 Av Karin Lindberg Leg läkare Huvudhandledare: Fakultetsopponent: Rolf Lewensohn, MD, PhD, Professor Matthias Guckenberger, MD, PhD, Professor Karolinska Institutet University Hospital Zürich (USZ) Department of Radiation Oncology Institutionen för Onkologi-Patologi Bihandledare: Betygsnämnd: Peter Wersäll, MD, PhD, Docent Magnus Sköld, MD, PhD, Professor Karolinska Institutet Karolinska Institutet Institutionen för Onkologi-Patologi Institutionen för Medicin Solna Signe Friesland, MD, PhD Thomas Asklund, MD, PhD, Docent Karolinska Institutet Umeå Universitet Institutionen för Onkologi-Patologi Institutionen för strålningsvetenskaper Anders Montelius, PhD, Docent Uppsala Universitet Institutionen för Immunologi, Genetik och Patologi I dedicate this thesis to my family, for the joy in everyday life. ...”Kärlek som är att vakna tillsammans och möta den blåögda morgonen att utbyta leenden som värmer och värnar och den nya dagens framtid att på resan genom dagen vila tillsammans på klockslagens små väntstationer och intaga gemensamma måltider upplysta av lingonsyltens röda glädje”... Ur Den dagliga kärleken av Maria Wine ABSTRACT Stereotactic body radiation therapy (SBRT) has been assessed by both retrospective and prospective studies showing excellent treatment outcome with acceptable toxicity and high grade of local control.