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  • Diagnostic Radiographic Studies Increase the Risk of Cancer in Pediatric Patients

    Neuro-Ophthalmology/Orbit
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    Compelling evidence based on populations exposed to low-dose radiation in Hiroshima and Nagasaki suggests that radiation exposure similar to that generated by even a single head, orbit, abdominal, or chest computed tomography (CT) presents a significant risk for the development of cancer cases in pediatric populations1-5(Figures 1 and 2). In fact, we may be causing a fatal case of cancer in one out of every 1600 pediatric CT scans. The risk is highest in very young infants with the greatest impact seen in girls and children undergoing multiple studies3(Figure 3). Ophthalmologists frequently order CT studies, yet discussions in the radiographic literature on this topic have not been common in the ophthalmology journals.6

    Reprinted from Hall EJ. Lessons we have learned from our children: cancer risks from diagnostic radiology. Pediatr Radiol. 2002;32(10):700-706
    Figure 1. Excess Relative Risk for Cancer Mortality in A-bomb survivors.

    Reprinted from Hall EJ. Lessons we have learned from our children: cancer risks from diagnostic radiology. Pediatr Radiol. 2002;32(10):700-706.
    Figure 2. Lifetime risk of fatal cancer scans.

    Reprinted from Hall EJ. Lessons we have learned from our children: cancer risks from diagnostic radiology. Pediatr Radiol. 2002;32(10):700-706
    Figure 3. Risk of Fatal Cancer.

    The concepts discussed are neither new nor my own, but have changed my practice of ophthalmology. The reader is encouraged to review a series of articles and discussions that most actively spanned a period from about 2000 to 2003 in the radiology literature.1-3 The initial discussions were riveting and generated repercussions as well as widespread changes in policy among radiologists and pediatricians.7 Based on the results of a recent survey assessing awareness of diagnostic radiation in patients, physicians, and radiologists, even the academic neuro-ophthalmologist or oculoplastic surgeon, ophthalmic specialists most likely to use CT scanning, would be challenged to discuss these germane issues.8

    CT Trends: Consensus on ALARA

    It would be remiss not to emphasize that CT is an invaluable imaging modality, with nearly 60 million CTs performed in the United States alone. Two to three million studies are performed yearly in the United States, with trends showing significant increases in scans in the pediatric population. Overall, CT represents 5% of medical imaging studies, but is responsible for nearly 2/3 of all medical radiation. Approximately 17% of pediatric CT is performed in the first 5 years of life. Small children have greater organ sensitivity to radiation, and experience a higher dose per organ in a given study. They subsequently have a lifetime to manifest a cumulative risk of radiation related cancer.

    Despite this, little consensus exists about how radiation dose should be measured, and the actual measurement is time-consuming and extremely complex. Absorbed radiation dose, determined by standardized measurements by a CT-dose phantom, must be determined for each protocol on each machine. There is interscanner difference among similar machines, and differences exist even within a single scanner over time.9 However, consensus does exist to follow as low as reasonably achievable (ALARA) exposure.7 Yet, surveys suggest that failure to correct for body size in pediatric cases was commonplace until these discussions broke.

    Magnitude of Risk: Effective Dose

    To understand the magnitude of risk, background concerning ionizing radiation is necessary. The term effective dose refers to a radiation dose quantity. It is a computed number based on combined organ dose, taking into account an organ-specific relative radio sensitivity. The effective dose is, therefore, an attempt to quantify biological damage based on deposition of ionizing radiation, as expressed as  sieverts (Sv) in the SI system, or radiation equivalent man (rem) in non-SI units. 1 Sv = 100 rem; 1 rem = 0.01 Sv or 10 millisieverts (mSv). Furthermore, in diagnostic radiology, exposure, absorbed dose and equivalent dose are all approximately equal in non-SI units (1 R ˜ 1 rad  ˜ 1 rem). This relationship may be quite different for nondiagnostic types of radiation.

    The CT generates ionizing energy, which produces a radiation dose distribution, with some organs receiving relatively high doses and others receiving only small amounts of scatter. The section dose corresponds to the energy equivalent in a defined volume as measured by a phantom cylinder of water scanned by a given protocol divided by the mass of the irradiated thickness. This section dose will vary by patient. Take for instance the head of a child versus an adult. The child’s head has a smaller dimension and a lower average tissue density compared with the adult head. The tissue attenuation in the less dense, smaller head is lower, and less attenuation causes a higher mean section dose, e.g., 30 milligray (mGy) increases to 40 mGy (adult head versus child head CT). On the other hand, the energy imparted is the product of section dose and the directly irradiated mass, such that although section dose is higher in the infant, energy imparted is higher in adults, who have greater mass.

    An effective dose can then be worked out as weighted sum of all exposed organs in the body, taking into account individual radiosensitivity as a weighting factor for each organ, with the most radiosensitive organs being bone marrow, breast, gonads, thyroid, and insensitive organs being skin and bone.

    Furthermore the effective dose is based on a dose per unit energy as a function of age. It turns out that the effective dose for a head CT is about 1.3 mSv or 130 mrem and doesn’t vary much in adults of different sizes. On the other hand, that same head scan may vary between 11 mSv in the 2 kg infant and 6 mSv in a 9 kg infant.3-5,9

    Radiation damage occurs as a threshold-related deterministic effect or a probabilistic stochastic effect. Deterministic effects are a result of cell killing and occur at a threshold dose: skin erythema at 5 Gy (500 rad); cataract formation at 2 Gy (200 rad) of acute dose or 5 Gy (500 rad) of chronic dose. Stochastic events occur as random or probabilistic effects such as future carcinogenesis. Whereas deterministic effects occur at a threshold dose and worsen with higher doses (e.g., skin erythema becomes skin necrosis at 30 Gy), the probability of a stochastic effect increases with increased dose, and the population incidence of the cancer will increase.

    Atomic Bomb Survivor Study

    In trying to quantify stochastic cancer risk of low-dose ionizing radiation, the atomic bomb (A-bomb) studies have proven that extraordinarily large cohorts are required with tens of thousands of patients. It may take up to 50 years to detect the excess cases occurring over and above the background normal rate of cancer development because the cancers occur in the same type of distribution as native cancers.1-2

    The best data comes from population studies of A-bomb survivors by the Radiation Effects Research Foundation. Study of the subset of survivors exposed to low doses (range of 0.005–0.2 Sv) generated data on 35,000 subjects with 5000 cancer cases. As detailed in Figure 1, there was a linear dose response with respect to relative risk of excess solid cancers even in the lowest dose range of 0 to 0.5 mSv gamma-ray dose equivalent. This is not hypothetical theory: The A-bomb survivors showed a statistically significant increase in solid cancer in the range of 5 to 100 (mean dose 29) mSv, and an increased risk for mortality due to solid cancer in the category 5 to 125 (mean dose 34) mSV.

    Other studies of radiographic in utero exposure also have concluded a dose of 10 mSv to embryo or fetus caused a quantifiable risk in early childhood solid and leukemic cancer.  Due to methodological difficulty, it is difficult to quantify risk to human population less than 10 mSV, and diagnostic radiation exposure may not completely mirror the effects seen in the A-Bomb survivors.1-5

    Critical Criteria: Conclusion

    In the quest to improve spatial and temporal resolution (image quality), the introduction of CT units with multirow detectors has contributed to a relatively high radiation exposure to patients disproportionate to the frequency of use.4 In addition, technical factors such as the overscanning of nontargeted organs at the superior or inferior limits of the study protocol and difference in exposure in pediatric versus adult patients as well as user-determined variables such as tube voltage, current, gantry rotation time, table speed, slice thickness, and imaging mode all add to the effective absorbed radiation dose. These factors contribute to the increased complexity in trying to maintain appropriate diagnostic image quality, yet minimize radiation dose. For instance, absorbed dose may be 50% higher in high-quality CT versus high-speed mode. 5,9-10

    Unfortunately, both children and adults may receive more radiation than needed for a given diagnostic study if CT parameters are not appropriately adjusted to the individual (FDA Pubic Notice 11/2001). It is critical for any physician willing to order a CT scan in a child to be confident that the referral institution has taken steps to optimize CT settings and follows the ALARA principle, which could include: reducing current; using tables based on patient weight, diameter, and anatomic region of interest; or increasing table increment in axial scans and pitch in helical scans.

    It is also critical that the clinician reduce ordering multiple scans, precontrast scans, and inappropriate referrals for CT. Based on these stochastic radiation risks, faced with the option of ordering a CT versus MRI in a clinical situation in which either could be sufficient, even if it requires a sedated or anesthetized examination, I have actively moved toward ordering the MRI.10

    References

    1. Hall HJ. Lessons we have learned from our children: cancer risks from diagnostic radiology.Pediatr Radiol. 2002;32(10):700-706.
    2. 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 SciUSA.2003;100(24):13,761-13,766.
    3. Huda W. Effective doses to adult and pediatric patients.Pediatr Radiol. 2002;32(4):272-279.
    4.

    Cohnen M, Poll LJ, Puettmann C, et al. Effective doses in standard protocols for multi-slice CT scanning.Eur Radiol. 2003;13(5):1148-1153.
    5. Huda W, Chamberlain CC, Rosenbaum AE, et al. Radiation doses to infants and adults undergoing head CT examinations.Med Phys. 2001;28(3):393-399.
    6. Mills DM, Tsai S, Meyer DR, et al. Pediatric ophthalmic computed tomographic scanning and associated cancer risk. Am J Ophthalmol.2006;142(6):1046-1053.
    7. No author. The ALARA (as low as reasonably achievable) concept in pediatric CT intelligent dose reduction. Multidisciplinary conference organized by the Society of Pediatric Radiology. August 18-19, 2001. Pediatr Radiol. 2002;32(4):217-313.
    8. Lee CI, Haims AH, Monico EP, et al. Diagnostic CT scans: assessment of patient, physician, and radiologist awareness of radiation dose and possible risks.Radiology. 2004;231(2):393-398.
    9. Theocharopoulos N, Damilakis J, Perisinakis K, et al. Estimation of effective doses to adult and pediatric patients from multislice computed tomography: A method based on energy imparted. Med Phys. 2006;33(10):3846-3856.
    10. Semelka RC, Armao DM, Elias J Jr, et al. Imaging strategies to reduce the risk of radiation in CT studies, including selective substitution with MRI.J Magn Reson Imaging. 2007;25(5):900-909.

    Author Disclosure

    Dr. Turbin states that he has no financial relationship with the manufacturer of any product discussed in this article or with the manufacturer of any competing product.