Radiation Dose and Stochastic Risk From Exposure to Medical Imaging

Abstract

The inscription on a medal given to me on behalf of the Cellular and Molecular Toxicology Division of Japan's National Institutes of Health Sciences 3 weeks before the September 11, 2001 terrorist attacks on the United States quotes Paracelsus (1493–1541): “All things are poisons, for there is nothing without poisonous qualities. It is only the dose which makes a thing a poison.” Our ability to harness energy from radionuclides has resulted in enormous benefits, ranging from the generation of electrical power to the development of three-dimensional images of an organ. And yet these remarkable technologies have the potential for poisonous consequences. Exposure to a radiation dose of sufficient quantity leads to predictable cellular toxicities (ie, deterministic effects) such as apoptosis and necrosis, as well as to random events in cells that predispose to genetic mutations and malignant transformation (ie, stochastic events). Radiation doses are measured as an absorbed dose (gray or Gy) in a material, or a dose equivalence (sievert or Sv) in a biologic tissue. One Gy is roughly equal to 1 Sv. Common prefixes include milli (10−3) and micro (10−6). For example, a milligray (mGy) is equal to 10−3 Gy, and a microsievert (µSv) is equal to 10−6 Sv. Doses from the 2011 Fukushima incident were extremely low and were, therefore, measured in µSv. The dose at which one-half of people die (lethal dose 50) at 60 days after exposure (lethal dose 50/60) for adults receiving supportive care plus antibiotics is 6.0 to 7.0 Gy (Sv). Aside from the psychologic and psychosocial impacts, the primary effect of low-dose exposure (generally considered to be < 1 Gy or < 1 Sv) is the induction of cancer. The probability of cancer induction is related to radiation dose in a linear (for solid cancers) or curvilinear (for leukemia) fashion. Based on the evidence in the Life Span Study of Japanese atomic bomb survivors, such cancers will occur when the exposed individual reaches the age at which he/she is at risk of cancer at the site in question (ie, for breast cancer, it is after the age of 60 years old). Although the development of cancer is the most serious somatic effect of radiation at a dose of < 1 Gy (< 1 Sv), virtually all observational data have been derived from exposures to a dose of > 0.1 Gy (100 mGy or 100 mSv).1Mettler Jr, FA Upton AC Medical Effects of Ionizing Radiation. 3rd ed. Saunders/Elsevier, Philadelphia, PA2008: 71Crossref Google Scholar It is assumed that cancer risk at doses < 100 mGy (< 100 mSv) are also linear with dose, and that this risk declines as the dose reaches zero, without a threshold (ie, the linear, no threshold [LNT] model). Controversy exists regarding cancer risk at < 100 mGy.2Feinendegen LE Brooks AL Morgan WF Radiation-induced acute illness. Introduction.Health Phys. 2011; 100: 244-246Crossref PubMed Scopus (1) Google Scholar Results of laboratory studies often show minimal or no biologic effects at a dose of < 100 mGy. Moreover, the LNT model for stochastic effects contrasts with the dose-effect relationship for deterministic effects in humans in which a threshold dose must be reached for deterministic injuries such as bone marrow depression, desquamation, mucositis, pneumonitis, pulmonary fibrosis, pericardial effusion and tamponade, esophagitis and stricture, hepatic fibrosis, venoocclussive disease, proctitis, cystitis, nephritis, and so forth. Therefore, the LNT hypothesis has not been validated by either experimental data generated in laboratory studies or observational data generated in epidemiologic studies. In fact, a dose threshold model (with a threshold value of 40 mGy, 95% CI, < 0–85 mGy) for cancer incidence may fit the data as well as but no better than the LNT model.3Shore RE Implications of radiation epidemiologic data for risk assessment and radiation protection.Health Phys. 2011; 100: 306-308Crossref PubMed Google Scholar, 4Preston DL Ron E Tokuoka S et al.Solid cancer incidence in atomic bomb survivors: 1958–1998.Radiat Res. 2007; 168: 1-64Crossref PubMed Scopus (1325) Google Scholar If this threshold is applied, exposure to doses of < 40 mGy would not result in a higher cancer risk. To safeguard against radiation injury, the National Council on Radiation Protection and Measurements and the International Commission on Radiation Protection have developed recommendations for maximal permissible doses (MPDs) and dose limits based on the LNT model.5Seed TM Radiation protectants: current status and future prospects.Health Phys. 2005; 89: 531-545Crossref PubMed Scopus (73) Google Scholar Table 11Mettler Jr, FA Upton AC Medical Effects of Ionizing Radiation. 3rd ed. Saunders/Elsevier, Philadelphia, PA2008: 71Crossref Google Scholar, 6International Commission of Radiological Protection website.http://www.icrp.orgGoogle Scholar provides a summary of the MPDs that are generally accepted by governments as maximal limits that are permitted by law. Both organizations recommend that radiation dose be kept as low as reasonably achievable (ALARA), “taking into account the state of technology and economics of improvement in relation to benefits to the public health and safety as well as inclusion of other societal and socioeconomic considerations.”7Preston RJ Radiation biology: concepts for radiation protection.Health Phys. 2005; 88: 545-556Crossref PubMed Scopus (36) Google Scholar The ALARA recommendation represents a conceptual approach that is based on continually evolving technology and economics.Table 1Recommendations for Maximal Permissible DosePopulationNCRP, mSvICRP, mSvGeneral public Annual MPD11Radiation workers Annual MPD5020 Cumulative MPD10 × age (y)NA MPD during pregnancy52Modified from Mettler et al1Mettler Jr, FA Upton AC Medical Effects of Ionizing Radiation. 3rd ed. Saunders/Elsevier, Philadelphia, PA2008: 71Crossref Google Scholar and the ICRP.6International Commission of Radiological Protection website.http://www.icrp.orgGoogle Scholar Note: Government standards include maximal doses that are higher for occupational workers than for the general public, because radiation workers presumably accept a higher risk in exchange for the benefits of their employment. ICRP = International Commission on Radiological Protection; MDP = maximal permissible dose (effective dose limits for external exposure, exclusive of background radiation and medical radiation); NA = not applicable; NCRP = National Council on Radiation Protection and Measurements. Open table in a new tab Modified from Mettler et al1Mettler Jr, FA Upton AC Medical Effects of Ionizing Radiation. 3rd ed. Saunders/Elsevier, Philadelphia, PA2008: 71Crossref Google Scholar and the ICRP.6International Commission of Radiological Protection website.http://www.icrp.orgGoogle Scholar Note: Government standards include maximal doses that are higher for occupational workers than for the general public, because radiation workers presumably accept a higher risk in exchange for the benefits of their employment. ICRP = International Commission on Radiological Protection; MDP = maximal permissible dose (effective dose limits for external exposure, exclusive of background radiation and medical radiation); NA = not applicable; NCRP = National Council on Radiation Protection and Measurements. In no other way has the recent change in average radiation dose to humans been affected more than by the development of body imaging. Although natural sources of radiation compose the major source of exposure in most countries, medical exposure has emerged as the primary source of exposure in the United States.8Mettler Jr, FA Bhargavan M Faulkner K et al.Radiologic and nuclear medicine studies in the United States and worldwide: frequency, radiation dose, and comparison with other radiation sources—1950–2007.Radiology. 2009; 253: 520-531Crossref PubMed Scopus (634) Google Scholar Diagnostic radiology and nuclear medicine examinations contribute 2.4 m Sv and 0.8 mSv, respectively, to the average annual exposure of 6.2 mSv. The largest contribution to exposure per study is the CT scan, with average effective doses of 14.0 mSv and 7.0 mSv for abdomen/pelvis and chest examinations, respectively. These doses may vary by up to 20-fold among patients receiving the same type of study, even within the same institution.9Smith-Bindman R Lipson J Marcus R et al.Radiation dose associated with common computed tomography examinations and the associated lifetime attributable risk of cancer.Arch Intern Med. 2009; 169: 2078-2086Crossref PubMed Scopus (1832) Google Scholar Owing to the rapid increase in the clinical use of CT scanning (estimated at an annual growth rate of 10% between 1993 and 2007),8Mettler Jr, FA Bhargavan M Faulkner K et al.Radiologic and nuclear medicine studies in the United States and worldwide: frequency, radiation dose, and comparison with other radiation sources—1950–2007.Radiology. 2009; 253: 520-531Crossref PubMed Scopus (634) Google Scholar the potential impact of this technology on overall cancer burden (and, therefore, health-care costs) is formidable.9Smith-Bindman R Lipson J Marcus R et al.Radiation dose associated with common computed tomography examinations and the associated lifetime attributable risk of cancer.Arch Intern Med. 2009; 169: 2078-2086Crossref PubMed Scopus (1832) Google Scholar, 10Berrington de González A Mahesh M Kim K-P et al.Projected cancer risks from computed tomographic scans performed in the United States in 2007.Arch Intern Med. 2009; 169: 2071-2077Crossref PubMed Scopus (1511) Google Scholar The potential risk of radiation-associated cancer has led to calls for better regulation of the use of medical imaging technology so that the benefit-risk ratio is maximized.11Twombly R Federal oversight of medical radiation is on horizon as experts face off.J Natl Cancer Inst. 2010; 102: 514-515Crossref PubMed Scopus (5) Google Scholar, 12Hricak H Brenner DJ Adelstein SJ et al.Managing radiation use in medical imaging: a multifaceted challenge.Radiology. 2011; 258: 889-905Crossref PubMed Scopus (241) Google Scholar The report by Rohner et al13Rohner DJ Bennett S Samaratunga C et al.Cumulative total effective whole-body radiation dose in critically ill patients.Chest. 2013; 144: 1481-1486Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar in this issue of CHEST (see page 1481) addresses the radiation dose that occurs in a mixed-use, adult surgical ICU as a result of frequent diagnostic imaging. The authors calculated the effective dose for all diagnostic imaging studies performed on 74 consecutive patients. The effective dose takes into account the type (or quality) of radiation and the relative sensitivity of the exposed organ/tissue, as determined by the weighting factor for that organ/tissue. It is defined as the product of the equivalent dose in tissue and the tissue weighting factor summed over all tissues. It is useful for comparing studies and exposure types. For example, to compare the stochastic risk from a 4-mSv equivalent dose to the lung (whose weighting factor is 0.12) with a similar dose to the whole body, one multiplies 4 mSv by 0.12 to derive an effective dose of 0.48 mSv. Therefore, the risk from a lung dose of 4 mSv is about the same as a whole-body dose of 0.48 mSv. The authors found that, in 6.8% of patients, the effective dose exceeded not only the public but also the occupational recommended dose limit of 50 mSv (see Table 1). The majority of the dose was due to CT scans. Accordingly, 6.8% of the patients discharged from this unit are at an increased risk of developing leukemia and/or a solid tumor as their attained age approaches the age at which these malignancies develop in unexposed individuals. The risk of incident cancers from CT scans has been estimated by the Biological Effects of Ionizing Radiation Committee to be 1.5% to 2.0%.14Committee to Assess Health Risk from Exposure to Low Levels of Ionizing Radiation National Research Council, Health Risks for Exposure to Low Levels of Ionizing Radiation: BEIR VII – Phase 2. National Academics Press, Washington, DC2005Google Scholar Cancer risk is higher in a child because of the increased number of years of expected life and the rapid growth of developing organs. Pearce et al15Pearce MS Salotti JA Little MP et al.Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study.Lancet. 2012; 380: 499-505Abstract Full Text Full Text PDF PubMed Scopus (2603) Google Scholar recently reported that the excess risk of leukemia and brain cancers may be tripled among individuals younger than 22 years of age whose cumulative dose from CT scans was 50 mGy (approximately 50 mSv), with an excess relative risk of 0.36 per mGy for leukemia and 0.023 per mGy for brain tumors. Although this study lacked a contemporaneous comparator group of unexposed individuals and it did not consider the precision of (or variability in) dose estimates, it provides, to the best of our knowledge, the first evidence that cancer risk may be increased after CT scans. The “take home” message from the Rohner et al13Rohner DJ Bennett S Samaratunga C et al.Cumulative total effective whole-body radiation dose in critically ill patients.Chest. 2013; 144: 1481-1486Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar study is that critical care physicians should carefully assess both the benefits and the risks before ordering diagnostic radiology examinations. Questions such as “does this study meet the guidelines for this condition,” “how will this study improve patient care,” “are alternative diagnostic approaches of equal benefit,” and “is a radiology consultation indicated in this situation” should be answered before writing the order. These and other dose-reduction strategies have been reviewed by Sarma et al.16Sarma A Heilbrun ME Conner KE Stevens SM Woller SC Elliott CG Radiation and chest CT scan examinations: what do we know?.Chest. 2012; 142: 750-760Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar In summary, much needs to be done to improve our understanding of a “safe” radiation dose. Although extrapolation of high-dose effects to the low-dose region (< 100 m Gy or < 100 mSv) of the dose-response curve may overestimate stochastic risk, it may be better to err on the conservative side when making recommendations of MPD to patients and/or their families. Following the principle of ALARA takes this uncertainty into account and allows physicians to accommodate new technology and fluctuations in health-care finances. Enhanced dialogue and enriched working relationships among epidemiologists and experimentalists will be important to clarify that which makes radiation a poison: its dose.17Dainiak N Recommendations for assessment of consequences and health risks of low-level exposure to ionizing radiation.Health Phys. 2011; 100: 311-312Crossref PubMed Google Scholar