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Table 1.  
Characteristics of the Study Population
Characteristics of the Study Population
Table 2.  
Characteristics of Individuals Exposed to Diagnostic Low-Dose Ionizing Radiation Based on a 2-Year Lag Period
Characteristics of Individuals Exposed to Diagnostic Low-Dose Ionizing Radiation Based on a 2-Year Lag Period
Table 3.  
Outcomes of Individuals Exposed to Diagnostic Low-Dose Ionizing Radiation Group by Cancer Type Based on a 2-Year Lag Perioda
Outcomes of Individuals Exposed to Diagnostic Low-Dose Ionizing Radiation Group by Cancer Type Based on a 2-Year Lag Perioda
Table 4.  
Outcomes of Individuals Exposed to Computed Tomography by Cancer Type Based on a 2-Year Lag Perioda
Outcomes of Individuals Exposed to Computed Tomography by Cancer Type Based on a 2-Year Lag Perioda
Table 5.  
Number of Cancers and IRRs for Various Lag Periods Among Individuals Exposed to Diagnostic Low-Dose Ionizing Radiationa
Number of Cancers and IRRs for Various Lag Periods Among Individuals Exposed to Diagnostic Low-Dose Ionizing Radiationa
1.
Berrington de González  A, Mahesh  M, Kim  KP,  et al.  Projected cancer risks from computed tomographic scans performed in the United States in 2007.  Arch Intern Med. 2009;169(22):2071-2077. doi:10.1001/archinternmed.2009.440PubMedGoogle ScholarCrossref
2.
Einstein  AJ.  Beyond the bombs: cancer risks of low-dose medical radiation.  Lancet. 2012;380(9840):455-457. doi:10.1016/S0140-6736(12)60897-6PubMedGoogle ScholarCrossref
3.
Ahmed  BA, Connolly  BL, Shroff  P,  et al.  Cumulative effective doses from radiologic procedures for pediatric oncology patients.  Pediatrics. 2010;126(4):e851-e858. doi:10.1542/peds.2009-2675PubMedGoogle ScholarCrossref
4.
Brenner  D, Elliston  C, Hall  E, Berdon  W.  Estimated risks of radiation-induced fatal cancer from pediatric CT.  AJR Am J Roentgenol. 2001;176(2):289-296. doi:10.2214/ajr.176.2.1760289PubMedGoogle ScholarCrossref
5.
Brenner  DJ, Doll  R, Goodhead  DT,  et al.  Cancer risks attributable to low doses of ionizing radiation: assessing what we really know.  Proc Natl Acad Sci U S A. 2003;100(24):13761-13766. doi:10.1073/pnas.2235592100PubMedGoogle ScholarCrossref
6.
Brenner  DJ, Hall  EJ.  Computed tomography: an increasing source of radiation exposure.  N Engl J Med. 2007;357(22):2277-2284. doi:10.1056/NEJMra072149PubMedGoogle ScholarCrossref
7.
Frush  DP, Donnelly  LF, Rosen  NS.  Computed tomography and radiation risks: what pediatric health care providers should know.  Pediatrics. 2003;112(4):951-957. doi:10.1542/peds.112.4.951PubMedGoogle ScholarCrossref
8.
Rice  HE, Frush  DP, Farmer  D, Waldhausen  JH; APSA Education Committee.  Review of radiation risks from computed tomography: essentials for the pediatric surgeon.  J Pediatr Surg. 2007;42(4):603-607. doi:10.1016/j.jpedsurg.2006.12.009PubMedGoogle ScholarCrossref
9.
Parker  L.  Computed tomography scanning in children: radiation risks.  Pediatr Hematol Oncol. 2001;18(5):307-308. doi:10.1080/088800101300312564PubMedGoogle ScholarCrossref
10.
Budoff  M.  Cardiac CT: benefits outweigh the risks.  J Cardiovasc Comput Tomogr. 2011;5(4):275-276. doi:10.1016/j.jcct.2011.05.004PubMedGoogle ScholarCrossref
11.
Blettner  M, Schlehofer  B, Samkange-Zeeb  F, Berg  G, Schlaefer  K, Schüz  J.  Medical exposure to ionising radiation and the risk of brain tumours: Interphone study group, Germany.  Eur J Cancer. 2007;43(13):1990-1998. doi:10.1016/j.ejca.2007.06.020PubMedGoogle ScholarCrossref
12.
Linet  MS, Kim  KP, Rajaraman  P.  Children’s exposure to diagnostic medical radiation and cancer risk: epidemiologic and dosimetric considerations.  Pediatr Radiol. 2009;39(1):1008-1026.Google Scholar
13.
Fazel  R, Krumholz  HM, Wang  Y,  et al.  Exposure to low-dose ionizing radiation from medical imaging procedures.  N Engl J Med. 2009;361(9):849-857. doi:10.1056/NEJMoa0901249PubMedGoogle ScholarCrossref
14.
Rehani  MM, Berry  M.  Radiation doses in computed tomography: the increasing doses of radiation need to be controlled.  BMJ. 2000;320(7235):593-594. doi:10.1136/bmj.320.7235.593PubMedGoogle ScholarCrossref
15.
Hendee  WR, O’Connor  MK.  Radiation risks of medical imaging: separating fact from fantasy.  Radiology. 2012;264(2):312-321. doi:10.1148/radiol.12112678PubMedGoogle ScholarCrossref
16.
Thompson  DE, Mabuchi  K, Ron  E,  et al.  Cancer incidence in atomic bomb survivors: part II: solid tumors, 1958-1987.  Radiat Res. 1994;137(2)(suppl):S17-S67. doi:10.2307/3578892PubMedGoogle ScholarCrossref
17.
Preston  DL, Kusumi  S, Tomonaga  M,  et al.  Cancer incidence in atomic bomb survivors: part III: leukemia, lymphoma and multiple myeloma, 1950-1987.  Radiat Res. 1994;137(2)(suppl):S68-S97. doi:10.2307/3578893PubMedGoogle ScholarCrossref
18.
Preston  DL, Ron  E, Tokuoka  S,  et al.  Solid cancer incidence in atomic bomb survivors: 1958-1998.  Radiat Res. 2007;168(1):1-64. doi:10.1667/RR0763.1PubMedGoogle ScholarCrossref
19.
Pearce  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(9840):499-505. doi:10.1016/S0140-6736(12)60815-0PubMedGoogle ScholarCrossref
20.
Berrington de González  A, Darby  S.  Risk of cancer from diagnostic x-rays: estimates for the UK and 14 other countries.  Lancet. 2004;363(9406):345-351. doi:10.1016/S0140-6736(04)15433-0PubMedGoogle ScholarCrossref
21.
Mathews  JD, Forsythe  AV, Brady  Z,  et al.  Cancer risk in 680,000 people exposed to computed tomography scans in childhood or adolescence: data linkage study of 11 million Australians.  BMJ. 2013;346(346):f2360. doi:10.1136/bmj.f2360PubMedGoogle ScholarCrossref
22.
Lin  MC, Lee  CF, Lin  CL,  et al.  Dental diagnostic x-ray exposure and risk of benign and malignant brain tumors.  Ann Oncol. 2013;24(6):1675-1679. doi:10.1093/annonc/mdt016PubMedGoogle ScholarCrossref
23.
Cardis  E, Vrijheid  M, Blettner  M,  et al.  Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries.  BMJ. 2005;331(7508):77. doi:10.1136/bmj.38499.599861.E0PubMedGoogle ScholarCrossref
24.
World Medical Association.  World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.  JAMA. 2013;310(20):2191-2194. doi:10.1001/jama.2013.281053.Google ScholarCrossref
25.
World Health Organization.  International Statistical Classification of Diseases, Tenth Revision (ICD-10). Geneva, Switzerland: World Health Organization; 1992.
26.
United Nations Scientific Committee on the Effects of Atomic Radiation.  Effects of Ionizing Radiation: UNSCEAR 2006 Report to the General Assembly, with Scientific Annexes. New York, NY: United Nations; 2008.
27.
National Research Council.  Health Risks From Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2. Washington, DC: The National Academies Press; 2006.
28.
Miglioretti  DL, Johnson  E, Williams  A,  et al.  The use of computed tomography in pediatrics and the associated radiation exposure and estimated cancer risk.  JAMA Pediatr. 2013;167(8):700-707. doi:10.1001/jamapediatrics.2013.311PubMedGoogle ScholarCrossref
29.
 The 2007 Recommendations of the International Commission on Radiological Protection: ICRP publication 103.  Ann ICRP. 2007;37(2-4):1-332.PubMedGoogle Scholar
30.
Smith-Bindman  R, Miglioretti  DL, Larson  EB.  Rising use of diagnostic medical imaging in a large integrated health system.  Health Aff (Millwood). 2008;27(6):1491-1502. doi:10.1377/hlthaff.27.6.1491PubMedGoogle ScholarCrossref
31.
Brady  Z, Cain  TM, Johnston  PN.  Justifying referrals for paediatric CT.  Med J Aust. 2012;197(2):95-99. doi:10.5694/mja11.11124PubMedGoogle ScholarCrossref
32.
Chodick  G, Ronckers  CM, Shalev  V, Ron  E.  Excess lifetime cancer mortality risk attributable to radiation exposure from computed tomography examinations in children.  Isr Med Assoc J. 2007;9(8):584-587.PubMedGoogle Scholar
33.
Nikkilä  A, Erme  S, Arvela  H,  et al.  Background radiation and childhood leukemia: a nationwide register-based case-control study.  Int J Cancer. 2016;139(9):1975-1982. doi:10.1002/ijc.30264PubMedGoogle ScholarCrossref
34.
Song  SO, Jung  CH, Song  YD,  et al.  Background and data configuration process of a nationwide population-based study using the Korean National Health Insurance system.  Diabetes Metab J. 2014;38(5):395-403. doi:10.4093/dmj.2014.38.5.395PubMedGoogle ScholarCrossref
35.
Kim  NH, Lee  J, Kim  TJ,  et al.  Body mass index and mortality in the general population and in subjects with chronic disease in Korea: a nationwide cohort study (2002-2010).  PLoS One. 2015;10(10):e0139924. doi:10.1371/journal.pone.0139924PubMedGoogle ScholarCrossref
36.
Lee  YH, Han  K, Ko  SH, Ko  KS, Lee  KU; Taskforce Team of Diabetes Fact Sheet of the Korean Diabetes Association.  Data analytic process of a nationwide population-based study using national health information database established by National Health Insurance Service.  Diabetes Metab J. 2016;40(1):79-82. doi:10.4093/dmj.2016.40.1.79PubMedGoogle ScholarCrossref
37.
Arbogast  PG.  Performance of floating absolute risks.  Am J Epidemiol. 2005;162(5):487-490. doi:10.1093/aje/kwi221PubMedGoogle ScholarCrossref
38.
Walsh  L, Shore  R, Auvinen  A, Jung  T, Wakeford  R.  Risks from CT scans: what do recent studies tell us?  J Radiol Prot. 2014;34(1):E1-E5. doi:10.1088/0952-4746/34/1/E1PubMedGoogle ScholarCrossref
39.
Berrington de González  A, Salotti  JA, McHugh  K,  et al.  Relationship between paediatric CT scans and subsequent risk of leukaemia and brain tumours: assessment of the impact of underlying conditions.  Br J Cancer. 2016;114(4):388-394. doi:10.1038/bjc.2015.415PubMedGoogle ScholarCrossref
40.
Prasad  KN, Cole  WC, Haase  GM.  Radiation protection in humans: extending the concept of as low as reasonably achievable (ALARA) from dose to biological damage.  Br J Radiol. 2004;77(914):97-99. doi:10.1259/bjr/88081058PubMedGoogle ScholarCrossref
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    5 Comments for this article
    EXPAND ALL
    Reducing imaging
    Frederick Rivara, MD, MPH | University of Washington
    This study gives further impetus to reduce the use of ionizing radiation due to imaging, especially CT scan use. It seems it is all too easy to ordered, neck, chest, abdomen, pelvis CT scans for trauma patients, for example. Is there good data to show that such extensive use of imaging has reduced mortality?
    CONFLICT OF INTEREST: Editor in Chief, JAMA Network Open
    Egg or chicken?
    Giovanni Melandri, MD | Cardiovascular Ambulatory Care
    Maybe that patients are exposed because there are signs or symptoms of cancer already!
    CONFLICT OF INTEREST: None Reported
    MRI-exposed group as a possible control for the uncertainty for diagnostic testing?
    Joao Ramos, MD | Neuroradiology Department, Centro Hospitalar Lisboa Ocidental
    Though good evidence is provided pointing towards increased cancer incidence in patients exposed to low-dose radiation exposure at an early age, a strong limitation of possible reverse causation for the findings presented still remains - as mentioned in the discussion -, as there is no information of the clinical question to be answered by the radiation-based diagnostic test. Given the focus to further consolidate the hypothesis of a (real) causation, have the authors considered performing further analysis of this cohort between subjects exposed to radiation-based tests vs MRI-only? Though not perfectly matched and perhaps with only a limited number of patients - due to varying resource availability as well as per clinical guidelines indications -, similar uncertainties regarding the motive for performing the diagnostic test would apply in MRI-only patients and could serve as a pseudo-control group to further isolate radiation effects.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Fatally flawed
    Michael O'Connor, Ph.d. | Mayo Clinic
    This article is a prime example of reverse causation. The latency period for induction of leukemia is 5–7 years, and for solid tumors is at least 10 years, so cancers occurring earlier than this should be considered to be naturally occurring rather than induced by radiation exposure (see Health Risks for exposure to low levels of ionizing radiation, BEIR VII, National research council of the National Academies, 2006; Hall EJ. Radiobiology for the radiologist. 5th ed Philadelphia (PA): Lippincott Williams & Wilkins; 2000. p. 149).

    Hence none of the cancers reported in this article are due to ionizing
    radiation. The most probable explanation is that underlying cancers generated symptoms requiring diagnostic imaging. This is further confirmed by the fact that the increased incidence risk ratio diminished between year 1 and year 5.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Discrepancies with overall cancer incidence?
    Rebecca Marsh, Ph.D. |
    It is interesting that the authors do not address the fact that the overall cancer incidence in the exposed group (0.11%) is LOWER than the overall cancer incidence in the unexposed group (0.19%).


    -Rebecca M. Marsh
    CONFLICT OF INTEREST: None Reported
    Original Investigation
    Oncology
    September 4, 2019

    Association of Exposure to Diagnostic Low-Dose Ionizing Radiation With Risk of Cancer Among Youths in South Korea

    Author Affiliations
    • 1Division of Spinal Surgery, Department of Orthopedics, College of Medicine, Korea University, Seoul, South Korea
    • 2Department of Biostatistics, College of Medicine, Catholic University, Seoul, South Korea
    • 3Division of Hematology/Oncology, Department of Internal Medicine, College of Medicine, Korea University, Seoul, South Korea
    JAMA Netw Open. 2019;2(9):e1910584. doi:10.1001/jamanetworkopen.2019.10584
    Key Points español 中文 (chinese)

    Question  Is exposure to diagnostic low-dose ionizing radiation in youths associated with increased risk of cancer?

    Findings  In this population-based cohort study including more than 12 million South Korean youths, the overall cancer incidence was greater among individuals exposed to diagnostic low-dose ionizing radiation than among nonexposed individuals after adjusting for age and sex (incidence rate ratio, 1.64). The incidence of cancer increased significantly for many types of cancers after radiation exposure, particularly mouth and pharynx, breast, thyroid, lymphoid and hematopoietic, and myelodysplasia cancers.

    Meaning  The association of increased cancer risk with exposure to diagnostic low-dose ionizing radiation may be important to inform decisions about diagnostic use of low-dose ionizing radiation in Asian youth populations worldwide.

    Abstract

    Importance  Diagnostic low-dose ionizing radiation has great medical benefits; however, its increasing use has raised concerns about possible cancer risks.

    Objective  To examine the risk of cancer after diagnostic low-dose radiation exposure.

    Design, Setting, and Participants  This population-based cohort study included youths aged 0 to 19 years at baseline from South Korean National Health Insurance System claim records from January 1, 2006, to December 31, 2015. Exposure to diagnostic low-dose ionizing radiation was classified as any that occurred on or after the entry date, when the participant was aged 0 to 19 years, on or before the exit date, and at least 2 years before any cancer diagnosis. Cancer diagnoses were based on International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Data were analyzed from March 2018 to September 2018.

    Main Outcomes and Measures  The primary analysis assessed the incidence rate ratios (IRRs) for exposed vs nonexposed individuals using the number of person-years as an offset.

    Results  The cohort included a total of 12 068 821 individuals (6 339 782 [52.5%] boys). There were 2 309 841 individuals (19.1%) aged 0 to 4 years, 2 951 679 individuals (24.5%) aged 5 to 9 years, 3 489 709 individuals (28.9%) aged 10 to 14 years, and 3 317 593 individuals (27.5%) aged 15 to 19 years. Of these, 1 275 829 individuals (10.6%) were exposed to diagnostic low-dose ionizing radiation between 2006 and 2015, and 10 792 992 individuals (89.4%) were not exposed. By December 31, 2015, 21 912 cancers were recorded. Among individuals who had been exposed, 1444 individuals (0.1%) received a cancer diagnosis. The overall cancer incidence was greater among exposed individuals than among nonexposed individuals after adjusting for age and sex (IRR, 1.64 [95% CI, 1.56-1.73]; P < .001). Among individuals who had undergone computed tomography scans in particular, the overall cancer incidence was greater among exposed individuals than among nonexposed individuals after adjusting for age and sex (IRR, 1.54 [95% CI, 1.45-1.63]; P < .001). The incidence of cancer increased significantly for many types of lymphoid, hematopoietic, and solid cancers after exposure to diagnostic low-dose ionizing radiation. Among lymphoid and hematopoietic cancers, incidence of cancer increased the most for other myeloid leukemias (IRR, 2.14 [95% CI, 1.86-2.46]) and myelodysplasia (IRR, 2.48 [95% CI, 1.77-3.47]). Among solid cancers, incidence of cancer increased the most for breast (IRR, 2.32 [95% CI, 1.35-3.99]) and thyroid (IRR, 2.19 [95% CI, 1.97-2.20]) cancers.

    Conclusions and Relevance  This study found an association of increased incidence of cancer with exposure to diagnostic low-dose ionizing radiation in a large cohort. Given this risk, diagnostic low-dose ionizing radiation should be limited to situations in which there is a definite clinical indication.

    Introduction

    Diagnostic low-dose ionizing radiation has great medical benefits; however, its widespread use has also raised concerns about adverse effects of radiation. The largest concern with ionizing radiation is increased cancer risk, particularly after childhood exposures.1-15 The biological hazards of ionizing radiation have been well documented since the atomic bomb explosions in Hiroshima, Japan, and Nagasaki, Japan, which caused a high incidence of atomic bomb–induced health issues, including various types of cancer.16-18 A 2012 study of 180 000 young people who underwent computed tomography (CT) scans in the United Kingdom reported increased risk of leukemia and brain cancer, which was correlated with the dose of radiation.19 That study reported provisional risk estimates for these 2 cancers. Unfortunately, there are fewer studies that address cancer risk after exposure to diagnostic low- to medium-dose ionizing radiation, to our knowledge. Previously, it was thought to be impractical to directly estimate the risk of cancer after such low doses of radiation.19-23 This study used a representative sample of all South Korean National Health Insurance System (KNHIS) claims data to derive direct estimates of cancer risk associated with diagnostic low-dose ionizing radiation exposure in individuals aged 0 to 19 years by comparing their cancer incidence with that of a comparison cohort.

    Methods
    Database

    This study used cohort data released by the KNHIS in 2017. The data were derived from 49 570 064 nationally representative individuals who constitute the entire population in the KNHIS, and include all medical claims filed from 2002 to 2015. All exposures to diagnostic low-dose ionizing radiation funded by the KNHIS during 2002 to 2015 were identified for this cohort. The KNHIS has offered a special support system for rare and intractable disease, including cancers, since 2006. Consequently, more than 90% of medical payments for patients with confirmed cancer diagnoses are supported by insurance. We included individuals with confirmed diagnoses who were being supported by the KNHIS special support system. In addition, to exclude cancer survivors and disease recurrence, we excluded individuals who had received cancer diagnoses prior to the study entry date.

    This study adhered to the tenets of the Declaration of Helsinki.24 The KNHIS National Sample Cohort project was approved by the institutional review board of the KNHIS. This study design was also reviewed and approved by the institutional review board of Korea University Medical Center, Gyeonggi-do, South Korea. Written informed consent was waived because data were deidentified. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. Data were analyzed from March 2018 to September 2018.

    Study Design

    Participants entered the study on January 1, 2006, and remained in it until the exit date. The exit date was either December 31, 2015, the date of death, or the date of cancer diagnosis. Cancer diagnoses were based on International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes.25 Cancers that were diagnosed in cohort members through December 31, 2015, were assessed if there was at least a 2-year interval between diagnostic low-dose ionizing radiation exposure and diagnosis. Diagnostic low-dose ionizing radiation exposures were defined as any that occurred on or after the entry date, when the participant was aged 0 to 19 years, on or before the exit date, and at least 2 years (lag period) before any cancer diagnosis.21 The lag period was adopted given the possibility that the scan was part of a diagnostic evaluation for cancer. To minimize the bias according to lag period, we calculated the risks with 3 different lag periods (1, 2, and 5 years). We set the first exposure date as the start point of the lag period, and multiple exposures were calculated if additional exposures occurred during the lag period. To calculate person-years at risk, we assigned each individual to the nonexposed group from entry until transfer (date of the first exposure plus the lag period). For the exposed group, we assigned individuals from transfer until exit (eFigure 1 in the Supplement). We hypothesized a lag period of 0 to 2 years for hematopoietic cancers and 0 to 5 years for solid tumors.26,27 Repeated imaging is recommended for solid tumors, particularly in the early period after clinical symptoms appear or after a tumor is incidentally found on imaging performed for another reason.27

    Statistical Analysis

    The primary analysis assessed the incidence rate ratios (IRRs) for exposed vs nonexposed individuals using the number of person-years as an offset. We used likelihood ratio tests to assess the significance of IRR departures from unity. The IRRs were calculated using the Poisson regression model after adjusting for age and sex. Cox proportional hazard regression models were used to adjust the different duration and potential dropout. The risks of exposure were calculated with IRRs and the excess number of cancers. These risks were divided into the risks of each cancer according to categorized ICD-10 code, assuming a Poisson distribution with 95% CI. The floating 95% CI for the IRR categorized according to the number of diagnostic scans was calculated using the amount of information in each category. The procedures were programmed in SAS statistical software version 9.3 (SAS Institute) using 2-tailed P values, and statistical significance was set at P less than .05. The number of diagnostic low-dose ionizing radiation events provided the simplest measure of a person’s radiation exposure.

    Results
    Study Population and Overall Cancer Risk

    The cohort included a total of 12 068 821 individuals (6 339 782 [52.5%] boys) (eFigure 2 in the Supplement). At baseline, there were 2 309 841 individuals (19.1%) aged 0 to 4 years, 2 951 679 individuals (24.5%) aged 5 to 9 years, 3 489 709 individuals (28.9%) aged 10 to 14 years, and 3 317 593 individuals (27.5%) aged 15 to 19 years (Table 1). The distributions of age, sex, income, and place of residence were stratified for statistical analysis. Based on a 2-year lag period, 1 275 829 individuals (10.6%) were transferred into the diagnostic low-dose ionizing radiation exposed group before exit from the study. Of those in the exposed group, 178 518 individuals (14.0%) underwent more than 1 scan. Among the full cohort, 21 912 cancers were recorded by December 31, 2015, including 1444 cancers in 1 275 829 individuals (0.1%) exposed to diagnostic low-dose ionizing radiation at least 2 years before any cancer diagnosis (Table 2). The overall cancer incidence was greater for exposed individuals than it was for nonexposed individuals after adjusting for age and sex (IRR, 1.64 [95% CI, 1.56-1.73]; P < .001) (Table 3).

    Cancer Risk Associated With CT Scan

    Based on the 2-year lag period, a total of 1 179 021 individuals (9.8%) were transferred into the CT-exposed group before exit from the study. Among the full cohort, 21 912 cancers were recorded by December 31, 2015, including 1216 cancers in 1 179 021 individuals (0.1%) exposed to CT at least 2 years prior to any cancer diagnosis. The overall cancer incidence was greater for exposed individuals than it was for nonexposed individuals after adjusting for age and sex (IRR, 1.54 [95% CI, 1.45-1.63]; P < .001) (Table 4).

    IRRs for Various Lag Periods

    Incidence rate ratios decreased with longer lag period (Table 5), but the difference was not statistically significant. Consequently, we used IRRs with a 2-year lag period for further analysis.

    Risks of Specific Cancers

    There was an excess of 404.8 solid cancers and 159.1 lymphoid and hematopoietic cancers in individuals exposed to diagnostic low-dose ionizing radiation compared with in those who were nonexposed (Table 3). The incidence of cancer increased significantly for many types of lymphoid and hematopoietic cancers (IRR, 1.53 [95% CI, 1.39-1.69]), as well as for solid cancers (IRR, 1.70 [95% CI, 1.59-1.81]). Among lymphoid and hematopoietic cancers, myelodysplasia (IRR, 2.48 [95% CI, 1.77-3.47]) and other myeloid leukemias (IRR, 2.14 [95% CI, 1.86-2.46]) had the highest incidence, although the incidence was also increased in other cancers. Among solid cancers, breast (IRR, 2.32 [95% CI, 1.35-3.99]), thyroid (IRR, 2.19 [95% CI, 1.97-2.20]), and mouth and pharynx (IRR, 2.01 [95% CI, 1.38-2.92]) had the highest incidence, although the incidence was also increased in other solid cancers. We found similar results in the CT exposure group (Table 4).

    Cancer Risk According to Type of First Exposure

    Lymphoid and hematopoietic cancers consistently had higher IRRs with various amounts of irradiation. The IRR of the exposed group was higher than that of the nonexposed group not only in the target area of irradiation, eg, the IRR for brain cancer was higher among individuals who underwent head or brain CT than among the overall group exposed to any diagnostic low-dose ionizing radiation (1.65 [95% CI, 1.35-2.01] vs 1.57 [95% CI, 1.38-1.78]) but also for lymphoid and hematopoietic cancers when considered separately among individuals who underwent bone scans (3.25 [95% CI, 1.46-7.23]) (eTable 1 in the Supplement). In addition, compared with the total group exposed to diagnostic low-dose ionizing radiation, there was a higher IRR among individuals exposed to abdominal imaging for digestive (3.11 [95% CI, 2.10-4.59] vs 1.83 [95% CI, 1.22-2.74]), breast (3.35 [95% CI, 1.49-7.54] vs 2.32 [95% CI, 1.35-3.99]), and female genital (2.62 [95% CI, 1.85-3.72] vs 1.77 [95% CI, 1.41-2.24]) cancers. Chest CT was associated with significantly increased IRR for respiratory cancer compared with the full diagnostic low-dose ionizing radiation exposure group (5.68 [95% CI, 2.93-11.01] vs 1.95 [95% CI, 1.38-2.75]). Mouth and pharynx cancer had higher IRR with spine or neck CT than with other CT exposures (6.46 [95% CI, 3.45-12.11] vs 2.19 [95% CI, 1.50-3.20]) (eTable 1 in the Supplement).

    Cancer Risk According to Number of Exposures

    The incidence of cancer increased significantly with additional diagnostic low-dose radiation exposures (eTable 2 in the Supplement). We compared the different IRRs of 3 lag periods to minimize the reverse causation of certain cancers. Individuals with more than 3 CT scans had significantly increased IRRs in 3 various lag periods (1 year: 9.05 [95% CI 7.84-10.46]; 2 years: 5.98 [95% CI, 5.13-6.98]; 5 years: 2.90 [95% CI, 2.19-3.83]), although the number of individuals was insufficient to determine the associations of repeated scans.

    Discussion
    Overall Associations of Diagnostic Low-Dose Ionizing Radiation Exposure Among Young People

    The increased use of CT in general has resulted in many children receiving high-dose examinations.28 If the carcinogenic effect of diagnostic low-dose radiation is greater in a subset of people who are genetically susceptible, it would have important clinical implications for the standards of radiation protection.2,5,10,13-15,29-31 Various studies have used risk projection models to estimate the potential lifetime excess cancer risk from CT scans. These models are largely based on risk models from studies of survivors of the atomic bombs in Japan.16-18 Our study found an association of increased cancer incidence with exposure to ionizing radiation and with exposure to CT scans. Therefore, our findings raise concerns regarding the use and subsequent risks of diagnostic low-dose ionizing radiation exposure in youths.3,8,9,14,31,32 After adjusting for age and sex, the overall cancer incidence was greater in individuals exposed to radiation than it was in those who were nonexposed. However, risk analysis in the United States suggests that, for children, the lifetime excess risk of any incident cancer for a head CT scan is approximately 1 cancer per 1000 to 2000 scans.1,19 Therefore, the absolute excess lifetime cancer risk is small compared with the lifetime risk of developing cancer in the general population, which is approximately 1 in 3.19 Provided that imaging is clinically justified, it might be appropriate in a younger patient who needs correct diagnosis.

    Risks of Specific Cancers

    In a 2012 UK cohort study,19 significant associations were found between the estimated radiation doses to the red bone marrow and brain provided by CT scans and the incidence of leukemia and brain tumors. The study by Pearce et al19 reported that the cumulative ionizing radiation doses from 2 to 3 head CTs could increase the risk of brain tumors nearly 3-fold, while 5 to 10 head CTs could increase the risk of leukemia 3-fold. In a 2013 Australian cohort study,21 there were increased risks of several types of solid cancers and of leukemia, myelodysplasia, and other lymphoid cancers among individuals exposed to at least 1 CT scan compared with nonexposed young people. Our results are similar to those of these studies.19,21 There were 404.8 additional solid cancers and 159.1 additional lymphoid or hematopoietic cancers in individuals who had been exposed to diagnostic low-dose ionizing radiation compared with those nonexposed. This association was also true for solid cancers and lymphoid and hematopoietic cancers when considered separately. Among lymphoid and hematopoietic cancers and other lymphomas, myeloid leukemias and myelodysplasia had the largest IRRs. However, the incidence was also increased in other cancers. Among solid cancers, the largest IRRs were present in mouth and pharynx, breast, and thyroid cancers. These results were similar to the conclusions of the 2008 United Nations Scientific Committee on the Effects of Atomic Radiation study,26 which reported a positive association between mouth and pharynx, respiratory, breast, and thyroid cancers, as well as leukemias, after low-dose ionizing radiation exposure. A 2016 study33 reported that children exposed to low-dose diagnostic ionizing radiation had an increased likelihood of developing leukemia compared with those who were not exposed.

    Cancer Risk According to Radiation Type

    A study by Miglioretti et al28 evaluated trends of CT use in pediatrics, as well as the association of radiation exposure with cancer risk. They reported that attributable risk was higher in patients who underwent CT scans of the abdomen and pelvis or spine than in those who underwent other types of CT. In our study, lymphoid and hematopoietic cancers had consistently higher IRR values compared with other cancers. In addition, digestive, female genital, and breast cancers demonstrated higher IRR values with abdominal CT than with other types of CT. Similarly, mouth and pharynx cancers had a higher IRR associated with spine or neck CT than with other diagnostic radiation types. These trends are similar to those of previous studies,21,28 which emphasize dose reduction strategies with regard to specific types of radiation and populations. However, one should be cautious when interpreting these results given the lack of clinical information regarding the reasons for using diagnostic radiation. Although we observed a similarly increased pattern in the 5-year lag period with specific types of radiation, we cannot completely rule out reverse causation. In addition, a study by Nikkila et al33 reported that background low doses of ionizing radiation were associated with increased risk of childhood leukemia. In the study by Nikkila et al,33 collected survey data of background gamma radiation in Finland were used to assess the background exposure of these study individuals. If we consider other variables (reverse causation and background low-dose radiation), we cannot determine the true associations of certain kinds of diagnostic radiation.

    Comparison With Other Studies

    We recorded 21 912 cancers, including 1444 cancers in 1 275 829 individuals exposed to diagnostic low-dose radiation at least 2 years prior to any cancer diagnosis. The overall cancer incidence was greater in individuals who had been exposed to a CT scan than in nonexposed individuals after adjusting for age and sex. In a 2013 Australian study,21 60 674 cancers were recorded, including 3150 in 680 211 individuals who had been exposed to a CT scan at least 1 year before cancer diagnosis. The overall cancer incidence was greater in individuals who had been exposed than in nonexposed individuals after accounting for age, sex, and birth year. These results are similar to a 2012 study19 of young people exposed to CT scans in the United Kingdom. In our study, the overall cancer incidence was smaller than that in other studies. Although ethnic and regional differences should also be considered, this result suggests that the cancer diagnoses in this study were accurate, which could minimize overestimation or underestimation of the carcinogenic effect of radiation. Furthermore, our study found that exposure to other forms of diagnostic low-dose ionizing radiation, including intravenous urography, upper gastrointestinal tract series, bone scan, and others, were also associated with increased IRRs.4,19,21,32 It is important not to overestimate the effect of CT, and all forms of diagnostic low-dose ionizing radiation should be assessed. In addition, we calculated risks of 3 different lag periods to minimize reverse causation according to previous investigations.26,27 Although we adopted a 2-year lag period after comparison of the IRRs for different lag periods, 1-year and 5-year lag periods were associated with similar IRR increases, which supports the reliability of our study.

    Strengths and Limitations

    Our study had several strengths. To our knowledge, it was one of the largest population-based studies to date that evaluated diagnostic medical radiation exposure. The data were obtained from 49 570 064 nationally representative individuals.34-36 In South Korea, patients with KNHIS pay 30% of their total medical expenses, while the medical providers are required to submit claims for the remaining 70%. These claims are accompanied by the direct medical costs of both inpatient and outpatient care. A total of 97% of the South Korean population is covered by the Medical Assistance Program. Therefore, nearly all of the data in the health system are centralized in large databases. None of the patients’ health care records were duplicated or omitted, because all South Korean residents receive a unique identification number at birth. Public funding under the comprehensive health insurance system has allowed us to study the exposed cohort drawn from the general population.34-36 We believe that this sample is likely representative of the population of children and young adults in South Korea who have undergone diagnostic low-dose ionizing radiation. To our knowledge, this is the first study to explore the cancer risk associated with overall diagnostic low-dose ionizing radiation in an Asian cohort. Our results contribute to the literature for decision-making regarding the diagnostic use of low-dose ionizing radiation in young populations in Asia and worldwide.

    This study also has several limitations. It was not possible to collect protocols or machine parameters for all of the exposures; therefore, we were unable to estimate individual radiation doses. Consequently, we could not calculate a direct estimate of the excess rate ratio per gray, as did other studies from the United Kingdom19 and Australia.21 Our study would have missed exposures that took place outside of South Korea, before January 1, 2002, after December 31, 2015, and those in patients older than 19 years. We adopted floating CIs, which are sensitive and result in overly narrow interval estimates.37 A major weakness of our study was a lack of information regarding the reasons for obtaining a CT. We cannot assume that all of the excess cancers observed during the follow-up period were associated with low-dose ionizing radiation, as scanning decisions were based on medical indications.38 Some of these indications may confound the association if they were also associated with cancer. If these factors are available in the claims data, then they should be included for statistical adjustment. Therefore, we cannot rule out the possibility of reverse causation, in which the early symptoms of cancer prompted exposure to diagnostic low-dose radiation. A study by Walsh et al38 reported that the published reports of CT scan studies suggest that their findings should be interpreted with caution given the potential for reverse causation. They reported that it is difficult to extract conclusions regarding the risk of radiation exposure given the considerable number of extraneous factors related to the reasons for performing CT scan. We agree with the criticisms of our study design and recognize the possibility of reverse causation in our results. Another source of confounding may include geographic factors. Recently, several study designs have been adopted to overcome similar biases of previous study designs. A study by Berrington de González et al39 reanalyzed the original data and reviewed additional clinical information from radiology information systems databases, including the underlying cause of death and pathology reports. Interestingly, the study by Berrington de González et al found similar results after these additional analyses.39 Additionally, we could not completely adjust the possible extra-Poisson variation, but negative binomial models or Poisson with robust SEs can be used to handle it. Statistical adjustment with a different method may improve the accuracy of IRRs in a future study.

    Conclusions

    In conclusion, the associations we found of diagnostic low-dose ionizing radiation with increased incidence of cancer in youths suggest that there is incentive to limit radiation doses to as low as reasonably achievable and to only scan when justified.29,40 Medical professionals should weigh the benefits of diagnostic low-dose ionizing radiation with the associated risks to justify each decision.

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    Article Information

    Accepted for Publication: July 11, 2019.

    Published: September 4, 2019. doi:10.1001/jamanetworkopen.2019.10584

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2019 Hong J-Y et al. JAMA Network Open.

    Corresponding Author: Jae-Young Hong, MD, PhD, Division of Spinal Surgery, Department of Orthopedics, College of Medicine, Korea University, South Korea, 123, Jeokgeum-ro, Danwon-gu, Ansan-si, Gyeonggi-do, 15355, South Korea (osspine@korea.ac.kr).

    Author Contributions: Dr Hong had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Hong, Han, Kim.

    Acquisition, analysis, or interpretation of data: Hong, Han, Jung.

    Drafting of the manuscript: Hong, Jung, Kim.

    Critical revision of the manuscript for important intellectual content: Hong, Han.

    Statistical analysis: Hong, Han, Jung.

    Administrative, technical, or material support: Hong.

    Supervision: Hong, Kim.

    Conflict of Interest Disclosures: None reported.

    References
    1.
    Berrington de González  A, Mahesh  M, Kim  KP,  et al.  Projected cancer risks from computed tomographic scans performed in the United States in 2007.  Arch Intern Med. 2009;169(22):2071-2077. doi:10.1001/archinternmed.2009.440PubMedGoogle ScholarCrossref
    2.
    Einstein  AJ.  Beyond the bombs: cancer risks of low-dose medical radiation.  Lancet. 2012;380(9840):455-457. doi:10.1016/S0140-6736(12)60897-6PubMedGoogle ScholarCrossref
    3.
    Ahmed  BA, Connolly  BL, Shroff  P,  et al.  Cumulative effective doses from radiologic procedures for pediatric oncology patients.  Pediatrics. 2010;126(4):e851-e858. doi:10.1542/peds.2009-2675PubMedGoogle ScholarCrossref
    4.
    Brenner  D, Elliston  C, Hall  E, Berdon  W.  Estimated risks of radiation-induced fatal cancer from pediatric CT.  AJR Am J Roentgenol. 2001;176(2):289-296. doi:10.2214/ajr.176.2.1760289PubMedGoogle ScholarCrossref
    5.
    Brenner  DJ, Doll  R, Goodhead  DT,  et al.  Cancer risks attributable to low doses of ionizing radiation: assessing what we really know.  Proc Natl Acad Sci U S A. 2003;100(24):13761-13766. doi:10.1073/pnas.2235592100PubMedGoogle ScholarCrossref
    6.
    Brenner  DJ, Hall  EJ.  Computed tomography: an increasing source of radiation exposure.  N Engl J Med. 2007;357(22):2277-2284. doi:10.1056/NEJMra072149PubMedGoogle ScholarCrossref
    7.
    Frush  DP, Donnelly  LF, Rosen  NS.  Computed tomography and radiation risks: what pediatric health care providers should know.  Pediatrics. 2003;112(4):951-957. doi:10.1542/peds.112.4.951PubMedGoogle ScholarCrossref
    8.
    Rice  HE, Frush  DP, Farmer  D, Waldhausen  JH; APSA Education Committee.  Review of radiation risks from computed tomography: essentials for the pediatric surgeon.  J Pediatr Surg. 2007;42(4):603-607. doi:10.1016/j.jpedsurg.2006.12.009PubMedGoogle ScholarCrossref
    9.
    Parker  L.  Computed tomography scanning in children: radiation risks.  Pediatr Hematol Oncol. 2001;18(5):307-308. doi:10.1080/088800101300312564PubMedGoogle ScholarCrossref
    10.
    Budoff  M.  Cardiac CT: benefits outweigh the risks.  J Cardiovasc Comput Tomogr. 2011;5(4):275-276. doi:10.1016/j.jcct.2011.05.004PubMedGoogle ScholarCrossref
    11.
    Blettner  M, Schlehofer  B, Samkange-Zeeb  F, Berg  G, Schlaefer  K, Schüz  J.  Medical exposure to ionising radiation and the risk of brain tumours: Interphone study group, Germany.  Eur J Cancer. 2007;43(13):1990-1998. doi:10.1016/j.ejca.2007.06.020PubMedGoogle ScholarCrossref
    12.
    Linet  MS, Kim  KP, Rajaraman  P.  Children’s exposure to diagnostic medical radiation and cancer risk: epidemiologic and dosimetric considerations.  Pediatr Radiol. 2009;39(1):1008-1026.Google Scholar
    13.
    Fazel  R, Krumholz  HM, Wang  Y,  et al.  Exposure to low-dose ionizing radiation from medical imaging procedures.  N Engl J Med. 2009;361(9):849-857. doi:10.1056/NEJMoa0901249PubMedGoogle ScholarCrossref
    14.
    Rehani  MM, Berry  M.  Radiation doses in computed tomography: the increasing doses of radiation need to be controlled.  BMJ. 2000;320(7235):593-594. doi:10.1136/bmj.320.7235.593PubMedGoogle ScholarCrossref
    15.
    Hendee  WR, O’Connor  MK.  Radiation risks of medical imaging: separating fact from fantasy.  Radiology. 2012;264(2):312-321. doi:10.1148/radiol.12112678PubMedGoogle ScholarCrossref
    16.
    Thompson  DE, Mabuchi  K, Ron  E,  et al.  Cancer incidence in atomic bomb survivors: part II: solid tumors, 1958-1987.  Radiat Res. 1994;137(2)(suppl):S17-S67. doi:10.2307/3578892PubMedGoogle ScholarCrossref
    17.
    Preston  DL, Kusumi  S, Tomonaga  M,  et al.  Cancer incidence in atomic bomb survivors: part III: leukemia, lymphoma and multiple myeloma, 1950-1987.  Radiat Res. 1994;137(2)(suppl):S68-S97. doi:10.2307/3578893PubMedGoogle ScholarCrossref
    18.
    Preston  DL, Ron  E, Tokuoka  S,  et al.  Solid cancer incidence in atomic bomb survivors: 1958-1998.  Radiat Res. 2007;168(1):1-64. doi:10.1667/RR0763.1PubMedGoogle ScholarCrossref
    19.
    Pearce  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(9840):499-505. doi:10.1016/S0140-6736(12)60815-0PubMedGoogle ScholarCrossref
    20.
    Berrington de González  A, Darby  S.  Risk of cancer from diagnostic x-rays: estimates for the UK and 14 other countries.  Lancet. 2004;363(9406):345-351. doi:10.1016/S0140-6736(04)15433-0PubMedGoogle ScholarCrossref
    21.
    Mathews  JD, Forsythe  AV, Brady  Z,  et al.  Cancer risk in 680,000 people exposed to computed tomography scans in childhood or adolescence: data linkage study of 11 million Australians.  BMJ. 2013;346(346):f2360. doi:10.1136/bmj.f2360PubMedGoogle ScholarCrossref
    22.
    Lin  MC, Lee  CF, Lin  CL,  et al.  Dental diagnostic x-ray exposure and risk of benign and malignant brain tumors.  Ann Oncol. 2013;24(6):1675-1679. doi:10.1093/annonc/mdt016PubMedGoogle ScholarCrossref
    23.
    Cardis  E, Vrijheid  M, Blettner  M,  et al.  Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries.  BMJ. 2005;331(7508):77. doi:10.1136/bmj.38499.599861.E0PubMedGoogle ScholarCrossref
    24.
    World Medical Association.  World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.  JAMA. 2013;310(20):2191-2194. doi:10.1001/jama.2013.281053.Google ScholarCrossref
    25.
    World Health Organization.  International Statistical Classification of Diseases, Tenth Revision (ICD-10). Geneva, Switzerland: World Health Organization; 1992.
    26.
    United Nations Scientific Committee on the Effects of Atomic Radiation.  Effects of Ionizing Radiation: UNSCEAR 2006 Report to the General Assembly, with Scientific Annexes. New York, NY: United Nations; 2008.
    27.
    National Research Council.  Health Risks From Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2. Washington, DC: The National Academies Press; 2006.
    28.
    Miglioretti  DL, Johnson  E, Williams  A,  et al.  The use of computed tomography in pediatrics and the associated radiation exposure and estimated cancer risk.  JAMA Pediatr. 2013;167(8):700-707. doi:10.1001/jamapediatrics.2013.311PubMedGoogle ScholarCrossref
    29.
     The 2007 Recommendations of the International Commission on Radiological Protection: ICRP publication 103.  Ann ICRP. 2007;37(2-4):1-332.PubMedGoogle Scholar
    30.
    Smith-Bindman  R, Miglioretti  DL, Larson  EB.  Rising use of diagnostic medical imaging in a large integrated health system.  Health Aff (Millwood). 2008;27(6):1491-1502. doi:10.1377/hlthaff.27.6.1491PubMedGoogle ScholarCrossref
    31.
    Brady  Z, Cain  TM, Johnston  PN.  Justifying referrals for paediatric CT.  Med J Aust. 2012;197(2):95-99. doi:10.5694/mja11.11124PubMedGoogle ScholarCrossref
    32.
    Chodick  G, Ronckers  CM, Shalev  V, Ron  E.  Excess lifetime cancer mortality risk attributable to radiation exposure from computed tomography examinations in children.  Isr Med Assoc J. 2007;9(8):584-587.PubMedGoogle Scholar
    33.
    Nikkilä  A, Erme  S, Arvela  H,  et al.  Background radiation and childhood leukemia: a nationwide register-based case-control study.  Int J Cancer. 2016;139(9):1975-1982. doi:10.1002/ijc.30264PubMedGoogle ScholarCrossref
    34.
    Song  SO, Jung  CH, Song  YD,  et al.  Background and data configuration process of a nationwide population-based study using the Korean National Health Insurance system.  Diabetes Metab J. 2014;38(5):395-403. doi:10.4093/dmj.2014.38.5.395PubMedGoogle ScholarCrossref
    35.
    Kim  NH, Lee  J, Kim  TJ,  et al.  Body mass index and mortality in the general population and in subjects with chronic disease in Korea: a nationwide cohort study (2002-2010).  PLoS One. 2015;10(10):e0139924. doi:10.1371/journal.pone.0139924PubMedGoogle ScholarCrossref
    36.
    Lee  YH, Han  K, Ko  SH, Ko  KS, Lee  KU; Taskforce Team of Diabetes Fact Sheet of the Korean Diabetes Association.  Data analytic process of a nationwide population-based study using national health information database established by National Health Insurance Service.  Diabetes Metab J. 2016;40(1):79-82. doi:10.4093/dmj.2016.40.1.79PubMedGoogle ScholarCrossref
    37.
    Arbogast  PG.  Performance of floating absolute risks.  Am J Epidemiol. 2005;162(5):487-490. doi:10.1093/aje/kwi221PubMedGoogle ScholarCrossref
    38.
    Walsh  L, Shore  R, Auvinen  A, Jung  T, Wakeford  R.  Risks from CT scans: what do recent studies tell us?  J Radiol Prot. 2014;34(1):E1-E5. doi:10.1088/0952-4746/34/1/E1PubMedGoogle ScholarCrossref
    39.
    Berrington de González  A, Salotti  JA, McHugh  K,  et al.  Relationship between paediatric CT scans and subsequent risk of leukaemia and brain tumours: assessment of the impact of underlying conditions.  Br J Cancer. 2016;114(4):388-394. doi:10.1038/bjc.2015.415PubMedGoogle ScholarCrossref
    40.
    Prasad  KN, Cole  WC, Haase  GM.  Radiation protection in humans: extending the concept of as low as reasonably achievable (ALARA) from dose to biological damage.  Br J Radiol. 2004;77(914):97-99. doi:10.1259/bjr/88081058PubMedGoogle ScholarCrossref
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