Linear-Nonthreshold Dose-Response Model Research Articles

Risks Associated with Low Doses and Low Dose Rates of Ionizing Radiation: Why Linearity May Be (Almost) the Best We Can Do

Deterministic and stochastic effects associated with high-dose ionizing radiation (x-ray) exposure have been known for almost as long as ionizing radiation itself (1–3). At lower doses, radiation risks are primarily stochastic effects, in particular, somatic effects (cancer) rather than the deterministic effects characteristic of higher-dose exposure (4–6). In contrast to deterministic effects, for stochastic effects, scientific committees generally assume that at sufficiently low doses there is a positive linear component to the dose response—that is, that there is no threshold (4–6). This does not preclude there being higher-order (eg, quadratic) powers of dose in the dose response that may be of importance at higher doses. It is on this basis that models linear (or linear-quadratic) in dose are often used to extrapolate the experience of the Japanese atomic bomb survivors (who were typically exposed at a high dose rate to moderate doses [average, 0.1 Sv]) to estimate risks from low doses and low dose rates (4–6). Most population-based cancer risk estimates are based primarily on the Japanese atomic bomb survivor Life Span Study (LSS) cohort data (4–6). However, evidence of excess risks comes from a large number of other studies as well. In the parallel editorial (7), evidence is presented for possible real (or at least “practical”) thresholds or “hormetic” (beneficial) effects of low doses of ionizing radiation. As we summarize here, and in contrast to the arguments of Tubiana et al (7), we judge that there is little epidemiologic or biologic evidence for these for cancer. The arguments are of three forms: (a) assessment of the degree of curvature in the cancer dose response within the Japanese atomic bomb survivors and other exposed groups (in particular, departure from linear or linear-quadratic curvature), (b) consistency of risks between the Japanese and other moderate- and low-dose cohorts, and (c) assessment of biologic data on mechanisms. Most of the information on radiation-induced cancer risk comes from (a) the Japanese atomic bomb survivors, (b) medically exposed populations, (c) occupationally exposed groups, and (d) environmentally exposed groups (6). In the higher-dose radiation therapy studies, where doses received are very much higher than in the LSS, sometimes in the range at which cell sterilization occurs, excess cancer risks per unit dose tend to be less than in comparable subsets of the LSS (8,9). However, as we show, risks in moderate- and low-dose medically and occupationally exposed groups are generally consistent with those in the LSS.

TH-D-AUD A-07: Risk of Secondary Fatal Malignancies From Cyberknife Radiosurgery

Purpose: This work measures peripheral doses and estimates the risk of secondary fatal malignancies associated with pediatric brain and adult prostate treatments delivered with a Cyberknife and a conventional, gantry-based accelerator. Method and Materials: Comparable Cyberknife and IMRT brain treatment plans were developed for a pediatric anthropomorphic Rando phantom using the Cyberknife Multiplan and Phillips Pinnacle treatment planning system, respectively. Similarly, adult prostate treatment plans were generated using the Multiplan and Pinnacle planning systems for an adult Rando phantom. Target and organs at risk were contoured for each phantom and equivalent, clinically appropriate normal tissue constraints were utilized for each treatment modality. TLD were positioned in specific organ locations within each anthropomorphic phantom and were irradiated three times per plan. The average dose was determined for each out-of-field organ site and was compared between the two different treatment delivery devices. Organ weighted, linear non-threshold dose response model risk factors were then used to estimate the risk of secondary fatal malignancies. Results: Doses calculated from the adult TLD data were equal to or lower for all organs with the IMRT treatment, and hence, the overall risk was lower. The pediatric TLD dose findings were mixed between the IMRT and Cyberknife treatments. TLD located in cranial organ sites, proximal to the treatment field, exhibited higher readings for the IMRT treatment. However, the Cyberknife treatment consistently resulted in higher average doses at all distant organ sites. Conclusion: The overall risk of secondary fatal malignancies was higher for the Cyberknife compared to the IMRT adult and pediatric treatments, with the exception of critical organs adjacent to the treatment field for the pediatric case. This appears to be due to higher out-of-field secondary radiation doses resulting from the greater number of monitor units and longer treatment times associated with Cyberknife treatments.

Legitimating a Nuclear Critic: John Gofman, Radiation Safety, and Cancer Risks

Whether low-level ionizing radiation has an effect on humans has been a polarizing issue for the last fifty years. The epicenter of this controversy has been the validity of the linear non-threshold dose-response model, according to which any amount of radiation, however small, causes damage to human genes and health. In the late 1960s and early 1970s, the nuclear scientist and medical researcher John Gofman (1918-2007) played a pivotal role in the debate. Historical accounts have treated Gofman as a radical antinuclear scientist whose unscientific arguments put enormous political pressure on the nuclear power industry and regulatory agencies. Gofman's bitter struggle with the Atomic Energy Commission, which funded his research at Lawrence Livermore National Laboratory, partly accounts for this view. However, my analysis of Gofman's involvement in the low-level radiation debate shows how he also helped shift the focus in radiation safety from the risks of genetic damage or leukemia to somatic or cancer risks. His arguments led to the introduction of the linear non-threshold radiation model as a means of numerically estimating cancer risks. This was a watershed event in radiation-safety science and politics. Gofman's case sheds light on the process by which a scientist could secure legitimation even when his technical arguments threatened the government's interests. I conclude that it also points to an open issue in the history of antinuclear scientists, or of other politically active scientists or technology critics: treating them as critics should not preclude historians from treating them as scientists.

Mammography: Better, Safer, and More Effective?

HomeRadiologyVol. 240, No. 1 PreviousNext Reviews and CommentaryEditorialsMammography: Better, Safer, and More Effective?Otha W. Linton, David A. SchauerOtha W. Linton, David A. SchauerAuthor Affiliations1From the International Society of Radiology (O.W.L.) and National Council on Radiation Protection and Measurements (D.A.S.), 7910 Woodmont Ave, Suite 400, Bethesda, MD 20814. Received August 17, 2005; final version accepted September 2.Address correspondence to O.W.L.Otha W. LintonDavid A. SchauerPublished Online:Jul 1 2006https://doi.org/10.1148/radiol.2401051399MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In References1 National Council on Radiation Protection and Measurements. A guide to mammography and other breast imaging procedures. NCRP report no. 149. Bethesda, Md: National Council on Radiation Protection and Measurements, 2004. Google Scholar2 National Council on Radiation Protection and Measurements. Mammography: a user's guide. NCRP report no. 85. Bethesda, Md: National Council on Radiation Protection and Measurements, 1986. Google Scholar3 Egan RL. Experience with mammography in a tumor institution: evaluation of 1,000 studies. Radiology 1960; 75: 894–900. Link, Google Scholar4 Strax P, Venet L, Shapiro S. Value of mammography in reduction of mortality from breast cancer in mass screening. Am J Roentgenol Radium Ther Nucl Med 1973; 117: 686–689. Crossref, Medline, Google Scholar5 Breast cancer screening. NIH Consensus Statement 1977; 1(1): 5–8. Google Scholar6 Hendrick RE, Smith RA, Rutledge JH, Smart CR. Benefit of screening mammography in women ages 40–49: a new meta-analysis of randomized controlled trials. J Natl Cancer Inst Monogr 1997; 22: 87–92. Medline, Google Scholar7 Jemal A, Clegg LX, Ward E, et al. Annual report to the nation on the status of cancer, 1975–2001, with a special feature regarding survival. Cancer 2004; 101: 3–26. Crossref, Medline, Google Scholar8 Houn F, Elliott ML, McCrohan JL. The Mammography Quality Standards Act of 1992: history and philosophy. Radiol Clin North Am 1995; 33: 1059–1065. Medline, Google Scholar9 National Institutes of Health Consensus Developmental Panel. National Institutes of Health Consensus Development Conference Statement: breast cancer screening for women ages 40–49, January 21–23, 1997. J Natl Cancer Inst Monogr 1997; 22: vii–xviii. Google Scholar10 Kolata G. Stand on mammograms greeted by outrage. New York Times. January 28, 1997: C1. Google Scholar11 National Council on Radiation Protection and Measurements. Evaluation of the linear-nonthreshold dose-response model for ionizing radiation. NCRP report no. 136. Bethesda, Md: National Council on Radiation Protection and Measurements, 2001. Google ScholarArticle HistoryPublished in print: July 2006 FiguresReferencesRelatedDetailsCited ByAnnals of Surgical Oncology, Vol. 17, No. S3Recommended Articles Digital Mammography and Breast Tomosynthesis Performance in Women with a Personal History of Breast Cancer, 2007–2016Radiology2021Volume: 300Issue: 2pp. 290-300Digital Breast Tomosynthesis Screening for Breast Cancer: It Is Cost-effective!Radiology2020Volume: 297Issue: 1pp. 49-50An Evidence-based and Inclusive Breast Cancer Screening Strategy: Summary of Current Guidelines from the American College of Radiology and Society of Breast ImagingRadiology: Imaging Cancer2022Volume: 4Issue: 2Benefit to Radiation Risk of Breast-specific Gamma Imaging Compared with Mammography in Screening Asymptomatic Women with Dense BreastsRadiology2016Volume: 281Issue: 2pp. 583-588City Patterns of Screening Mammography Uptake and Disparity across the United StatesRadiology2019Volume: 293Issue: 1pp. 151-157See More RSNA Education Exhibits Breast Health in the Elderly: Implications for ImagingDigital Posters2020High Risk Breast Cancer Screening  Digital Posters2020Let’s Talk about Next-Generation Breast Cancer Screening Programs: How Should We Do? What Should We Use?Digital Posters2020 RSNA Case Collection Fibroadenoma of the breastRSNA Case Collection2020Invasive ductal carcinoma as developing asymmetryRSNA Case Collection2021Hyperplastic Residual Breast TissueRSNA Case Collection2022 Vol. 240, No. 1 Metrics Altmetric Score PDF download

Abandoning linear no threshold

CorrespondenceAbandoning linear no thresholdA Edwards and S BoufflerA EdwardsNational Radiological Protection Board, Chilton, Didcot, Oxon OX11 0RQ, UKSearch for more papers by this author and S BoufflerNational Radiological Protection Board, Chilton, Didcot, Oxon OX11 0RQ, UKSearch for more papers by this authorPublished Online:28 Jan 2014https://doi.org/10.1259/bjr/23751379SectionsPDF/EPUBFull Text ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail About"Abandoning linear no threshold." The British Journal of Radiology, 78(932), pp. 770–771 References 1 Feinendegen LE. Evidence for beneficial low level level radiation effects and radiation hormesis. Br J Radiol 2005;78:3–7. Link ISI, Google Scholar2 UNSCEAR. United Nations Scientific Committee on the Effects of Atomic Radiation. Report to the General Assembly, Annex G. United Nations, New York, 2000. Google Scholar3 National Council on Radiation Protection and Measurements. Report 136, Evaluation of the linear-nonthreshold dose-response model for ionising radiation. Bethesda, MD: NCRP, 2001. Google Scholar4 Rothkamm K, Lobrich M. Evidence for a lack of DNA double strand break repair in human cells exposed to very low x-ray doses. Proc Natl Acad Sci USA 2003;100:5057–62. Crossref Medline ISI, Google Scholar5 Enns L, Bogen KT, Wizniak J, Murtha AD, Weinfeld M. Low-dose radiation hypersensitivity is associated with p53-dependent apoptosis. Mol Cancer Res 2004;2:557–66. Medline ISI, Google Scholar Previous article Next article FiguresReferencesRelatedDetailsCited byBJR Review of the Year – 20055 March 2014 | The British Journal of Radiology, Vol. 79, No. 939 Volume 78, Issue 932August 2005Pages: 681-772 © The British Institute of Radiology History ReceivedMarch 08,2005AcceptedMarch 22,2005Published onlineJanuary 28,2014 Metrics Download PDF

Nonlinear Response for Neoplastic Transformation following Low Doses of Low Let Radiation

There are now several independent studies that indicate that the dose-response for the endpoint of radiation-induced neoplastic transformation in vitro is non-linear for low linear energy transfer (LET) radiation. At low doses (<10 cGy) the transformation frequency drops below that seen spontaneously. Importantly, this observation has been made using fluoroscopic energy x-rays, a commonly used modality in diagnostic radiology, the practice of which is responsible for the majority of radiation exposure to the general public. Since the transformation frequency is reduced over a large dose range (0.1 to 10cGy) it is likely that multiple mechanisms are involved and that the relative contribution of these may vary with dose. These include the killing of a subpopulation of cells prone to spontaneous transformation at the lowest doses, and the induction of DNA repair at somewhat higher doses. Protective effects of low doses of low LET radiation on other cancer-relevant endpoints in vitro and in vivo have also been observed by several independent laboratories. These observations strongly suggest that the linear-nonthreshold dose-response model is unlikely to apply to the induction of cancer by low doses of low LET radiation in humans.

Exposure to residential radon causes lung cancer. For the proposition.

Exposure to residential radon causes lung cancer. For the proposition.

Evaluation of the Linear-Nonthreshold Dose-Response Model for Ionizing Radiation

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Pathway to a paradigm: the linear nonthreshold dose-response model in historical context. The American Academy of Health Physics 1995 Radiology Centennial Hartman Oration.

This paper traces the evolution of the linear nonthreshold dose-response model and its acceptance as a paradigm in radiation protection practice and risk analysis. Deterministic effects such as skin burns and even deep tissue trauma were associated with excessive exposure to x rays shortly after their discovery, and carcinogenicity was observed as early as 1902. Still, it was not until 1925 that the first protective limits were suggested. For three decades these limits were based on the concept of a tolerance dose which, if not exceeded, would result in no demonstrable harm to the individual and implicitly assumed a threshold dose below which radiation effects would be absent. After World War II, largely because of genetic concerns related to atmospheric weapons testing, radiation protection dose limits were expressed in terms of a risk based maximum permissible dose which clearly implied no threshold. The 1927 discovery by Muller of x-ray induced genetic mutations in fruit flies, linear with dose and with no apparent threshold, was an important underpinning of the standards. The linear nonthreshold dose-response model was originally used to provide an upper limit estimate of the risk, with zero being the lower limit, of low level irradiation since the dose-response curve could not be determined at low dose levels. Evidence to the contrary such as hormesis and the classic studies of the radium dial painters notwithstanding, the linear nonthreshold model gained greater acceptance and in the centennial year of the discovery of x rays stands as a paradigm although serious questions are beginning to be raised regarding its general applicability. The work includes a brief digression describing the work of x-ray protection pioneer William Rollins and concludes with a recommendation for application of a de minimis dose level in radiation protection.