The use of diagnostic medical imaging is becoming increasingly more commonplace in the pediatric setting. However, many medical imaging modalities expose pediatric patients to ionizing radiation, which has been shown to increase the risk of cancer development in later life. This review article provides a comprehensive overview of the available data regarding the risk of cancer development following exposure to ionizing radiation from diagnostic medical imaging. Attention is paid to modalities such as computed tomography scans and fluoroscopic procedures that can expose children to radiation doses orders of magnitude higher than standard diagnostic x-rays. Ongoing studies that seek to more precisely determine the relationship of diagnostic medical radiation in children and subsequent cancer development are discussed, as well as modern strategies to better quantify this risk. Finally, as cardiovascular imaging and intervention contribute substantially to medical radiation exposure, we discuss strategies to enhance radiation safety in these areas.
Introduction
Environmental factors have long been thought to play a role in the development of adult and pediatric malignancies. Studies involving long-term survivors of the atomic bombing of Hiroshima and Nagasaki as well as studies involving nuclear and radiation workers have provided compelling evidence correlating ionizing radiation with carcinogenesis . Furthermore, it is estimated that only 5% of pediatric cancers are directly attributable to an inherited genetic cause , and ionizing radiation has been shown to be causal in a large number of human malignancies . At times veiled within the context of health-care delivery, exposure to ionizing radiation from diagnostic medical imaging is increasing in the United States. In a report by the National Council on Radiation Protection and Measurements in 2009, it was stated that “in 2006 Americans were exposed to more than seven times as much ionizing radiation from medical procedures as was the case in the early 1980s” . The pediatric population is certainly not immune to the rising radiation exposure from medical imaging. For example, the increased use of computed tomography (CT) scanners in the diagnosis of pediatric conditions has grown steadily over the past decade , and according to some publications, the use of this diagnostic modality may be substantially higher in the United States than in other parts of the world . Recognizing that 40% of medical radiation exposure in the United States is a result of cardiovascular imaging and intervention, the American Heart Association has recently published a scientific statement that outlines practical approaches to improving radiation safety during cardiovascular imaging and interventional procedures . This statement includes recommendations based on the benefit of proposed procedure or treatment in conjunction with strength of scientific evidence of efficacy and concludes with an outline of core concepts of improving radiation safety in medical imaging that include education, justification, and optimization.
One of the most challenging aspects involving cancer risk assessment resulting from diagnostic imaging is the quantitation and standardization of radiation exposure and dose . Radiation dose to a patient varies considerably with the imaging modality being employed. At the lower end of the spectrum, a simple Posterior-Anterior (PA) chest radiograph may result in an effective dose of 0.013 mSv per study, whereas a CT scan of the abdomen or pelvis would result in an effective dose of 15 mSv per examination . Furthermore, in procedures such as catheterizations performed under fluoroscopy that require operator skill and are influenced heavily by patient characteristics, there can be tremendous variability in radiation dose . The earliest population-based studies examining cancer risk after exposure to ionizing radiation from diagnostic medical imaging used a number of procedures as a surrogate for total dose exposure . This resulted in a very crude stratification of results, with findings often difficult to interpret, as total radiation dose varies with patient age, weight, procedure type, and duration of procedure. There does not exist a simple, uniform method that allows for estimating (or calculating) accurate radiation dose absorbed by an individual patient. Therefore, a number of computed values are often employed in studies examining cancer risk from radiation exposure. Table 1 provides a list of commonly used radiation term and definitions.
TABLE 1
Radiation Measurement Terms and Definitions
Measurement Historical Name SI Name SI Unit Absorbed dose rad Gray (Gy) J⋅kg −1 Equivalent dose rem Sievert (Sv) J⋅kg −1 Effective dose Effective dose equivalent Sievert (Sv) J⋅kg −1
Term Definition Lifetime attributable risk Sum of each year’s excessive cancer probability after exposure Stochastic health risk Probability of developing cancer increases proportionally with dose Deterministic health risk Severity of the health risk effect increases with dose above a certain threshold
With the increased utilization of diagnostic medical imaging comes increased exposure to ionizing radiation and increased risk of unwanted effects. Pediatric patients are perhaps even more susceptible to these effects owing to the fact that their organ systems are still undergoing development and therefore more vulnerable to damage . Investigators have postulated a link between exposure to ionizing radiation from diagnostic medical imaging during childhood and the subsequent development of cancer. The concept of lifetime attributable risk (LAR) implies that with increasing exposure to radiation, patients have an increasing risk of developing cancer. The pediatric population is inherently more sensitive and susceptible to the effect of ionizing radiation. In addition, children with chronic diseases are initially scanned younger, and are subject to more imaging studies, therefore with increased probability of higher accumulated lifetime radiation doses . A number of studies have been published examining this connection, with enough evidence to raise concern and provide rationale for further investigation. A contextual understanding of published data is therefore a requisite in understanding and mitigating risk from diagnostic medical radiation.
Diagnostic X-rays
As far back as the 1950s, studies have attempted to correlate pediatric postnatal x-ray exposure with the subsequent development of malignancy. An early case-control study that included 1416 children who had died of cancer before age 10 in England and Wales between 1953 and 1955 found that the incidence of more than one diagnostic x-ray exposure was higher in the cohort of children who had died from cancer than in controls . As a likely result of these positive findings, a number of epidemiological studies have been conducted to determine the risk of cancer development following exposure to ionizing medical radiation. Many of these studies, as outlined in Table 2 , have failed to demonstrate any such association . However, other studies have yielded significant findings ( Table 3 ). Positive correlations have been demonstrated in a wide variety of cancers including Ewing disease , leukemia or lymphoma , brain tumors , and breast cancer .
TABLE 2
Negative Studies Involving Diagnostic X-rays
First Author Year Type of Study # of Cases # of Controls Type of Cancers Ager 1965 Case-control 112 Not stated Leukemia Shu 1988 Case-control 309 618 Leukemia Magnani 1990 Case-control 183 307 ALL; AnLL; NHL McCredie 1994 Case-control 82 164 Brain tumors Schüz 2001 Case-control 466 2458 CNS tumors Kuijten 1990 Case-control 163 163 Astrocytoma Bunin 1994 Case-control 322 321 Astrocytic glioma; PNET Gelberg 1997 Case-control 130 130 Osteosarcoma Hartley 1988 Case-control 555 1110 All childhood cancers
TABLE 3
Positive Studies Involving Diagnostic X-rays
First Author Year Type of Study # of Cases # of Controls Type of Cancers Stewart 1958 Case-control 1416 Not stated Leukemia; others Polhemus 1959 Case-control 251 Not stated Leukemia Graham 1966 Case-control 319 884 Leukemia Shu 1994 Case-control 642 642 Acute leukemia; lymphoma; brain tumors Shu 2002 Case-control 1842 1986 ALL Howe 1989 Case-control 74 138 Brain tumors Winn 1992 Case-control 204/191 204/191 Ewing sarcoma Preston-Martin 1980 Case-control 185 185 Female Preston-Martin 1982 Case-control 209 209 Meningioma Hoffman 1989 Cohort 1030 – Breast cancer incidence Doody 2000 Cohort 5466 – Breast cancer mortality Ronckers 2008 Cohort 3010 – Breast cancer Infante-Rivard 2000 Case-control 491 491 ALL Bartley 2010 Case-control 711/116 960/147 ALL; AML Rajaraman 2011 Case-control 2690 4858 All childhood cancers
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Risk of Leukemia or Lymphoma
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Risk of Brain Tumors
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Risk of Breast Cancer
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Fluoroscopy
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During Cardiac Catheterization
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During Other Medical Procedures
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CT Scans
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Limitations
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Future Investigation
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Conclusion
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