Impact of Nuclear Medicine Exposures to the American Population

Health Threat of Medical Ionizing Radiation

Impact of Nuclear Medicine Exposures

In October 2009, the U.S. Food and Drug Administration (FDA) alerted all healthcare facilities involved in performing brain perfusion computed tomography (CT) to ensure their patients were not being overexposed to ionizing radiation (Samson, 2009). This notice was in response to the discovery that 206 patients subjected to this procedure at the Cedars-Sinai Medical Center in Los Angeles had been exposed up to eight times the recommended dose. The immediate effects to some patients were skin reddening and hair loss, but the long-term effects could be an increased risk of cancer. Since the error was in the programmed settings for the CT equipment, none of the medical personnel bothered to check the actual radiation doses the patients were receiving. The absence of exposure monitoring allowed the equipment to perform at this setting for over a year and a half.

This event, together with other radiation overexposure scandals, led to publication of a series of investigative articles on the risk of medical radiation in the New York Times. Based on the article by Bogdanich (2010), there are a number of ways a patient can become exposed to unnecessary ionizing radiation. Should a dose miscalculation become part of a standard treatment procedure at a busy clinic or major medical center, dozens of patients could be overexposed repeatedly during treatment. Overworked medical professionals may overlook standard safety procedures and hospital budget constraints may degrade patient safety oversight protocols. According to some radiologists, advances in medical radiation equipment have outstripped the development of appropriate patient safety procedures. The relevant laws are lax in some states and rarely enforced in others. Reporting guidelines are frequently ignored, as are safety rules in some hospitals.

Even in clinics where the above problems are absent, patients are still at risk for being exposed to ionizing radiation unnecessarily or at dosages exceeding that required to produce an image of sufficient diagnostic quality (FDA, 2010). This is especially true for children seeking care at healthcare facilities without dedicated pediatric radiology equipment and personnel. This essay will examine the nature and extent of the health risk that medical radiation poses to patients, with an emphasis on pediatric care.

The Dramatic Growth of Medical Imaging in the United States

Medical imaging began in the late 19th century and almost immediately problems began to appear (reviewed by Linet et al., 2012). Medical imaging workers developed skin and blood cancer, in addition to other deleterious conditions, before realizing that both patients and radiologists needed protection from the ionizing radiation these devices produced. Radiation doses were reduced and protection devices developed by the 1950s that effectively eliminated the immediate health risks for workers and adult patients.

Following implementation of safety devices and procedures in the 1950s, the greatest danger recognized by the medical community was the cumulative effect of repetitive exposures (reviewed by Linet et al., 2012). However, studies examining the effects of radiation exposure on young children (reviewed by Laack et al., 2011) and fetuses in utero (reviewed by Linet et al., 2012) revealed that the health threat of medical radiation was much more complex than previously assumed. Given the dramatic revolution in medical imaging technologies over the past 30 years and the resulting increases in exposure frequency and dosage, the health threat this technology represents to the young is assumed to be considerable. Prior to the 1980s, medical radiation represented just 15% of the total radiation from all sources that the average U.S. citizen was exposed to each year. Current estimates suggest medical radiation now represents 50% of the ionizing radiation exposure each year.

The large increase in exposure to ionizing radiation is caused primarily by the increased use of CT scans (reviewed by Laack et al., 2011). From 1980 to 2007, the number of CT scans performed in the U.S. increased from about 3 million to almost 70 million per year. Not only were patients being exposed to ionizing radiation more often, the dose received was also higher. Compared to a standard chest X-ray, which exposes the patient to an average of 0.1 mSv (millisievert, a unit of measure representing the biological effects of ionizing radiation) of ionizing radiation, a standard CT scan of the chest will expose the patient to 7.0 mSv (ASRT, 2012). By comparison, ionizing radiation from natural and other manmade sources amounts to only 3.1 mSv per year.

Whole body CT scans have also become more common, due in part to efforts to identify unnoticed injuries in trauma patients (reviewed by Laack et al., 2011). Whole-body CT scans are particularly concerning, because the estimated average dose is 20.9 mSv. Since children are often trauma victims, the risk/benefit ratio for this demographic may favor limiting the use of whole-body scans to avoid short-term and long-term increases in cancer risk. One estimate suggests that the prevalent use of CT scans could be responsible for up to 2% of all cancers in the U.S. today.

Carcinogenic Effects of Ionizing Radiation

The radiation dose determines the level of risk for an adverse outcome (reviewed by Mettler, 2012). Below 0.05 to 0.1 Gy (Gray) the amount of harm caused is hard to quantitate, but it is believed to exist. Compared to Sv, the unit Gy is a measure of absorbed dose rather than the biological effect of a radiation dose. Between 0.05 and 1.0 Gy, leukemia and other cancers are believed to be the primary health risk. The risk of cancer was estimated to increase by 5% for every Sv of radiation exposure. If the route of exposure is through the skin, a single acute dose between 2 and 5 Gy can cause transient reddening of the skin and hair loss. Prolonged or permanent reddening of the skin can occur at doses between 10 and 15 Gy, in addition to permanent tissue damage. However, survival becomes an issue at these higher doses. For example, survival is unlikely at doses above 5 Gy without medical intervention and unlikely above 10 Gy with treatment.

Lower dosages can still pose a health hazard if inhaled or ingested, and some tissues are more radiation sensitive than others (reviewed by Mettler, 2012). Bone marrow, breast, thyroid, and salivary glands are highly susceptible to radiation exposure, while brain, kidney, and connective tissue have a lower cancer risk. Sterility is a common effect of radiation exposure, but does not occur in males until an acute dose exceeds 0.5 Gy. However, reduced fertility can result when exposed chronically to lower doses. For women, an acute dose of 10 Gy is required to cause sterility in females who have not reached puberty and 2 to 3 Gy for women over 40 years of age. Radiation of sufficient dosages can also cause cataracts and suppress the immune system.

Such high dosages rarely occur during diagnostic medical imaging procedures, but accumulated exposures over a period of years can become significant enough that the health risk must be considered (reviewed by Linet et al., 2012). As mentioned above, the per capita yearly dose of ionizing radiation from medical sources has increased from 0.53 mSv in 1980 to 3.0 mSv in 2006. Assuming a 5% increase in cancer risk for every Sv of exposure, this translates into an increase of cancer risk from 0.00265% to 0.015% per year. While this increase in risk seems negligible, over the course of a lifetime (80 years) the total increase is from 0.2% to 1.2%, or 6-fold. In addition, this risk is an average and therefore does not represent the actual increase in cancer risk for radiation sensitive tissues like the bone marrow or thyroid.

Radiation experts recently concluded that the adverse biological effects of ionizing radiation occur at all levels of exposure, even if they cannot be measured (reviewed by Linet et al., 2012). This linear, no threshold model implies that no exposure is the only exposure level that can eliminate the cancer risk associated with medical imaging. This conclusion is based on research findings, which revealed extremely low radiation exposures can induce base changes in DNA. These mutations may or may not represent a deleterious change in an important tumor suppressor gene, but over a period of years, the chance that a tumor-inducing mutation will occur is predicted to increases significantly under the linear, no-threshold model.

The carcinogenic effects of radiation exposure due to diagnostic imaging procedures are typically not realized immediately (reviewed by Linet et al., 2012). The latency period for the development of leukemias is between 2 to 5 years, although the latency period is shorter when the patient is a child. The type of leukemia that develops is affected by the amount of time that has passed since exposure, such that the risk of chronic myeloid leukemia decreases faster than the risk for acute myeloid leukemia. The latency period for solid tumors is at least 10 years; however, in contrast to the risk of leukemia, the risk for solid tumors continues to increase as the patient gets older. The radiation-induced solid tumors also tend to develop at the same age as tumors caused by other factors.

Risk vs. Benefit Calculations

In normal circumstances, exposure to medical radiation does no harm and provides a tremendous diagnostic advantage for treating physicians and thus patients. Imaging allows the physician to examine a patient internally without using an invasive procedure, such as surgery. This suggests physicians and radiologists must engage in a risk vs. benefit calculation when patients are exposed to substantial doses of ionizing radiation during treatment.

In the 1950 and 1960s, pregnant women were often exposed to abdominal radiologic imaging procedures to help the obstetrician gauge whether a normal delivery was possible (reviewed by Linet et al., 2012). A survey was eventually conducted that found an increased risk of pediatric cancer in the children born to these women [Risk Ratio (RR) 1.39, 95% CI, 1.31-1.47]. Since this finding was based on a survey of parents, the results languished under a cloud of skepticism until the findings were confirmed independently using medical records. It was estimated that infants that had undergone radiologic imaging during gestation experienced a 5.4-fold increased risk for pediatric cancer. Current estimates suggest the risk for this procedure has declined to 1.5- to 2.2-fold, due to lower radiation levels being used. In addition, the prevalence of in utero radiologic imaging has declined significantly due to the development and widespread use of ultrasonography.

For children and adolescents, multiple research studies have produced mixed results when trying to assess the risk of pediatric cancer (reviewed by Linet et al., 2012). Although it is generally believed that there is a small increase in pediatric cancer risk for children exposed to diagnostic radiation, few studies have been able to reach statistical significance. If there is a cancer risk, it would be for leukemia. In terms of the lifetime risk of cancer due to pediatric exposure to diagnostic radiation, what evidence that exists suggests the risk is real. For example, young women monitored for scoliosis and tuberculosis during childhood have an increased risk of developing breast cancer later in life (RR, 2.86, p = 0.058), but not lung cancer or leukemia.

Adults also suffer from an increased risk of cancer due to diagnostic radiation exposure (reviewed in Linet et al., 2012). The RRs for 3-month, 2-year, and 5-year follow-ups were 1.17 (95% CI, 0.8-1.8), 1.42 (95% CI, 0.9-2.2), and 1.04 (95% CI, 0.6-1.8) for leukemias other than chronic lymphocytic leukemia. These findings were generated from HMO medical records. Another study estimated the level of radiation received by the bone marrow and predicted a 1.4-fold increased risk of acute myeloid leukemia within 3 to 20 years following exposure. With respect to chronic myeloid leukemia, a number of studies have found a small increased risk during the 20-year period subsequent to radiation exposure.

Scientists have searched for a link between diagnostic radiation exposure and the emergence of solid tumors in adults, but only a few have reported statistically significant results (reviewed by Linet et al., 2012). Meningiomas and parotid tumors were linked to the number of full-mouth dental X-rays conducted before 1945 or prior to the age of 20. Adult tuberculosis patients undergoing repeated radiological examinations of their chest have an increased risk of breast cancer. In addition, elevated levels of chromosomal translocations were found in the white blood cells from radiology technicians.

These findings reveal real risks, but also a dearth of well-controlled studies. Linet and colleagues (2012) reported that such studies are underway, studies which hope to provide a clearer picture of the cancer risk caused by diagnostic radiation. Such studies should be more robust, not only because the science has improved, but because patients are being exposed to greater levels of ionizing radiation more frequently. In the meantime, radiologists and physicians are relying on the linear, no-threshold model for guidance.

Current risk estimates suggest the 70 million CT scans performed in 2007 in the U.S. could eventually cause 29,000 cancers (15,000-45,000) (reviewed by Linet et al., 2012). Half of this risk was attributed to abdominal and pelvic examinations. The most common cancer to result is expected to be lung cancer, followed by colon cancer and then leukemia. The cancer risk for specific procedures was also examined and whole-body CT scans between the ages of 45 to 70 years could cause cancer in 1 in 53 patients, mammograms in 1 in 1111 women, lung CTs in 1 in 435 males and 118 females, and CTs for coronary artery calcification in 1 in 2500 males and 1667 females.

These risk estimates can be used to calculate risk vs. benefit ratios, which in turn can be used to justify using or not using a radiologic diagnostic procedure. Of all the patients who enter a hospital emergency room, trauma patients will likely be exposed to significant amounts of diagnostic radiation. Laack and colleagues (2011) examined the medical records of 642 level II trauma patients in Rochester, Minnesota for treatment outcomes. The median radiation dose received was 24.7 mSv (interquartile range = 6.2-26.6), which did not differ substantially among the four age groups studied (15-19, 20-40, 41-60, and over 60). The primary radiologic examination was CT scans, including whole-body CTs. The largest doses were produced by CT scans of the abdomen and pelvis (14.1 mSv), thoracic spine (15.7 mSv), and whole-body (20.9 mSv). The maximum dose received among all patients was 54.75 mSv. The estimated increased risk of death from cancer due to CT scans was estimated to be 0.195% (0.053-0.218) for patients under 20 years of age, 0.137% (0.046-0.167) for patients between 20 and 40 years of age, 0.113% (0.030-0.126) for patients between 41 and 60 years of age, and 0.050% (0.022-0.085) for patients over the age of 60. Death due to trauma among these trauma patients was 0.6%. The patients who died had a median age of 90 and all died of intracranial injuries. No patients under 80 years of age died of trauma-related injuries. By comparison, the overall risk of death due to CT scans was just 0.1%.

The study by Laack and colleagues (2011) reveals how an evidence-based risk/benefit calculation can be conducted. All such studies need to consider age as a primary determining factor of risk. For example, the oldest patients in this study had the highest mortality risk and the lowest risk of CT scan-related cancer. For these patients, the risk/benefit calculation clearly indicates that CT scans should be done to enhance the quality of care that elderly trauma patients receive. The same conclusion cannot be reached for younger patients. Level II trauma patients between the ages of 15 and 19 are more likely to survive their injuries because of their age, but the estimated cumulative cancer risk is four times higher than for patients over the age of 60. Laack and colleagues (2012) suggest that efforts to reduce radiation exposure should therefore be focused on younger patients. The limitations to their study included an inability to determine if CT scans had saved any lives and the authors admit that if a single life had been saved in the youngest age group then the risk/benefit calculation would swing dramatically in favor of performing CT scans on young trauma patients.

Reconsidering the Linear, No-Threshold Model

Studies that examined the health of atomic blast survivors in Japan, suggests that exposures below 200 mSv did not cause an adverse effect over the course of their lifetime (reviewed by Jargin, 2012). Epidemiological studies examining other demographics have revealed the lower limit for adverse effects of ionizing radiation exposure is between 100-200 mSv. Jargin (2012) argues that there is substantial evidence to support the conclusion that low doses of radiation may not be a threat to human health and may even prove beneficial (hormesis). He cites a study that revealed cancer rates are lower for people living at higher elevations, where radiation from the sun and other interstellar sources is less diminished by the atmosphere. With respect to animal studies, exposure to 70-140 mGy per year of ionizing radiation increased the lifespan of mice. The transition zone for irradiated mice seems to be around 100 mGy per year, with cancer decreasing below this limit and increasing above it. If low doses of ionizing radiation are indeed protective against cancer, the mechanism involved is likely the induction of cellular DNA repair machinery by radiation-induced DNA damage. However, above a certain threshold, such a mechanism would predict that the rate of DNA damage exceeds the capacity of the repair machinery and mutations begin to accrue. If this theory is correct, then the linear, no-threshold model is inaccurate for low dose exposures typically received during medical imaging procedures.

Hendee and O'Connor (2012) would agree with Jargin's (2012) argument. They cite scientific evidence that suggests workers in the nuclear industry benefit from increased exposure to ionizing radiation, thus producing the so-called "healthy worker effect." They also argue that using data from the survivors of the nuclear bomb blasts in Japan to predict health outcomes from medical imaging is inappropriate. The health of the two groups is vastly different, as were the types of cancer endemic to Japanese citizens during WWII. They further cite a study that suggested low dose radiation exposure elevates immune system functioning, thus helping to lower the incidence of cancer. They also reviewed a more recent study that compared the colon cancer rates for Japanese citizens exposed or not exposed to the atomic bomb blasts during WWII, which revealed that a threshold model is the best predictor of their findings. The consensus seems to indicate that the threshold between cancer risk and benefit seems to be exposure to 100 mSv in a single dose. Hendee and O'Connor (2012) quote statements by the American Association of Physicists in Medicine and the Health Physics Society that essentially declare that exposures of 50 mSv or lower per year, apart from natural radiation exposure, has no effect on human health or is so miniscule as to be unmeasurable.

Campaign to Reduce Exposure

Despite the arguments in favor of a threshold model, which suggests single dose exposures to ionizing radiation below 50-100 mSv is not a threat to human health, government regulators have campaigned to eliminate unnecessary exposures to diagnostic radiological tests and minimize the level of exposure per test (FDA, 2010; FDA offers suggestions, 2011; FDA, 2012). This policy is based on the linear, no-threshold model and therefore assumes that any unnecessary exposure poses a threat to a patient's health.

Government efforts to reduce the amount of ionizing radiation depend on two criteria: justification and optimization (FDA, 2010). 'Justification' implies that any exposure should be medically necessary, while 'optimization' requires that medically necessary exposures be reduced to levels just sufficient to produce high quality images. Beyond these criteria, proper training and common sense are required to prevent unnecessary exposures and overexposures. There seems to be ample room for improvement, so these concerns appear to be justified. A study of medical clinics in the San Francisco Bay area revealed a 13-fold difference in radiation doses patients were being exposed to during identical procedures.

Standard exposure levels for specific diagnostic imaging tests have been established by the American College of Radiology and are called 'diagnostic reference levels' (FDA, 2010). Continued deviance from diagnostic reference levels is due in part to improper training and the lack of industry standards for exposure limit safeguards on imaging equipment (FDA offers suggestions, 2011). Of particular concern is the lack of training and equipment safeguards when it comes to pediatric radiology exams (FDA, 2010). The Alliance for Radiation Safety in Pediatric Imaging began two campaigns to reduce ionizing radiation exposures in pediatric populations, called the "Image Gently" and "Step Lightly" campaigns. The primary focus of these campaigns is to provide educational materials concerning child-appropriate use of CT scans and interventional fluoroscopy to medical professionals and parents.